melphalan and Stomatitis

Oral mucositis (OM) is known to be the most common and challenging side effect of conditioning chemotherapy in haematopoietic cell transplant (HCT). This side effect causes significant morbidity and may delay the treatment plan, as well as increase therapeutic expenses. There are few clinical trials in the literature that indicate any kind of treatment or prevention methods are effective. Therefore, the aim of this study is to perform a systematic review of literature and examine the effectiveness of oral cryotherapy (OC) in management of chemotherapy-induced OM in patients with haematological malignancies undergoing a HCT.. A systematic literature search was conducted, using the electronic databases PubMed, Embase, MEDLINE and Scopus. A total of 322 papers were identified and 9 papers were analysed based on defined inclusion and exclusion criteria. The quality of the chosen primary studies was appraised using the COCHRANE risk of bias assessment tool.. Nine randomized controlled trials, analysing 658 participants; control group (n = 289, age mean ± SD; 41.15 ± 21) and treatment group (n = 369, age mean ± SD; 39.15 ± 20), were included in this systematic review. Seven studies had significantly addressed the effectiveness of OC (p value < 0.05), in reducing the incidence of developing severe OM in the adult population undergoing HCT, especially when the conditioning regimen protocols included high dose of alkylating agent such as melphalan.. This review supports the use of OC for prevention of OM in patients undergoing HCT, with high-dose of melphalan conditioning protocols. It is recommended that more studies be conducted to compare efficacy and duration of OC with other chemotherapeutic agents with relatively short plasma half-lives. The heterogeneity of the trials demonstrated the need to regulate the validated assessment tools and similar interventions that would enable comparisons and analyses of treatment effects based on well-designed RCTs.

Topics: Adult; Antineoplastic Agents; Cryotherapy; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Stomatitis

Oral mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative oral mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence.. To assess the effects of oral cryotherapy for preventing oral mucositis in patients with cancer who are receiving treatment.. We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases.. We included parallel-design randomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website.. Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format.. We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop oral mucositis).The results were similar for moderate to severe oral mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH).Severe oral mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9).Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, nu. We are confident that oral cryotherapy leads to large reductions in oral mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of oral cryotherapy to reduce oral mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce oral mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe oral mucositis in these adults.This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.

Topics: Adult; Antineoplastic Agents; Cryotherapy; Fluorouracil; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mouth Diseases; Myeloablative Agonists; Neoplasms; Pain; Randomized Controlled Trials as Topic; Stomatitis

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Prognosis; Risk Factors; Stomatitis; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous

Photobiomodulation therapy (PBMT) is widely used in oncology settings, but lack of assessment standardization is the main barrier to optimization of clinical protocols. This study analyzed three PBMT protocols for preventing oral and oropharyngeal mucositis (OM) in patients undergoing chemotherapy (CT) and/or hematopoietic stem cell transplantation (HSCT). This is a preliminary randomized blind clinical trial. Group 1 received intraoral prophylactic PBMT, Group 2 received intraoral and oropharyngeal PBMT, and Group 3 received intraoral, oropharyngeal, and extraoral PBMT. The applications were from the first day of CT to day + 10. Clinicodemographic data, CT regimens, types of HSCT, hematological exams, occurrence/severity of OM, odynophagia, and OM-related opportunistic infections were assessed. Sixty participants (age range: 18-74 years) were included; 70% of them underwent CT and 30% HSCT. About 43.3% of patients had OM, while odynophagia was reported by 23.3%. Both Groups 1 and 2 revealed better results. Multivariate analysis showed that HSCT directly influenced the occurrence of OM. Individuals who had undergone allogeneic HSCT were 1.93 times more likely to develop OM (p < 0.001). Group 3 exhibited a higher frequency of OM, albeit of lower grades. This group consisted of half the population who had undergone HSCT, had the highest percentage of melphalan use, and had the lowest mean leukocyte count. The three proposed protocols were effective in preventing and reducing OM, with good tolerance and no reported adverse effects. PBMT is a safe and effective approach to OM prophylaxis in adults undergoing CT/HSCT.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Hematopoietic Stem Cell Transplantation; Humans; Low-Level Light Therapy; Melphalan; Middle Aged; Mucositis; Randomized Controlled Trials as Topic; Stomatitis; Young Adult

The conditioning therapy used in connection with haematopoietic stem cell transplantation (HSCT) can induce painful oral mucositis, which has negative impacts on patient quality of life and survival, as well as on health-care costs. While cooling of the oral mucosa (cryotherapy) is regarded as standard prophylaxis against oral mucositis, the long duration of the treatment affects compliance owing to side effects. In this prospective, randomised trial, 94 patients (62 males/32 females; median age 59 years, range 34-69) with a diagnosis of myeloma who were undergoing autologous HSCT were randomised 1:1 to receive cryotherapy for 7 h (N = 46) or 2 h (N = 48). Oral mucositis was evaluated prospectively. No significant difference was observed with respect to the proportion of patients who showed grades 3 and 4 toxicity according to the WHO scale (2.1 and 4.3% for 2 and 7 h, respectively; 95% CI -0.09 to 0.049; p = 0.98) as between the groups. Two hours of cryotherapy was as effective as 7 h in terms of protecting against severe oral mucositis in connection with autologous HSCT for myeloma. This trial is registered with ClinicalTrials.gov (NCT03704597).

Topics: Adolescent; Adult; Aged; Autografts; Cryotherapy; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prospective Studies; Stem Cell Transplantation; Stomatitis

Topics: Administration, Intravenous; Adult; Aged; Busulfan; Female; Humans; Infections; Male; Melphalan; Middle Aged; Multiple Myeloma; Stem Cell Transplantation; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Venous Insufficiency; Young Adult

Topics: Adult; Aged; Cryotherapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Prospective Studies; Stomatitis; Transplantation, Autologous

High-dose melphalan followed by autologous stem cell transplantation remains the standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 h) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate that 2-h is at least as effective as 6-h cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified that fat-free mass, hematocrit, and creatinine clearance were significant covariates, as reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Creatinine; Cryotherapy; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Large Neutral Amino Acid-Transporter 1; Male; Melphalan; Middle Aged; Multiple Myeloma; Polymorphism, Genetic; Stomatitis; Survival Rate; Time Factors

Melphalan followed by hematopoietic stem-cell transplantation (HSCT) is the standard treatment for multiple myeloma and other hematopoietic neoplasms. However, high doses of melphalan cause severe oral mucositis (OM). The objective was to verify the efficacy of cryotherapy plus laser therapy on reduction of OM severity. HSCT patients undergoing melphalan chemotherapy (n = 71) were randomly divided into two groups according to OM treatment: oral cryotherapy performed with ice chips for 1 h 35 min followed by low-level laser therapy (InGaAIP, 660 nm, 40 mW, 6 J/cm(2) ) (n = 54) and laser therapy alone with the same protocol (n = 17). A control group (n = 33) was composed of HSCT patients treated with melphalan who received no specific treatment for OM. OM scores and clinical information were collected from D0 to D + 11. The cryotherapy/laser therapy group showed the lowest OM scores (maximum Grade I) and the lowest mean number of days (8 days) with OM in comparison with the other groups (p < 0.001). OM Grades III and IV were present with high frequency only in the control group. The association of cryotherapy with laser therapy was effective in reducing OM severity in HSCT patients who underwent melphalan conditioning.

Topics: Adolescent; Adult; Aged; Child; Cryotherapy; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Laser Therapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Prospective Studies; Retrospective Studies; Stomatitis; Time Factors; Treatment Outcome; Young Adult

Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events). Based on investigators' assessment of mucositis using the World Health Organization (WHO) oral toxicity scale, 75% of patients had a shift in mucositis score from WHO grade 0 at baseline to a higher grade on study, of which 13% of patients reported WHO grade 3 as the worst post-treatment mucositis over the course of the study; there were no reports of WHO grade 4 mucositis during the study. This study confirms the efficacy and accept

Topics: Adult; Aged; Cyclodextrins; Drug Administration Schedule; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Myeloablative Agonists; Propylene Glycol; Severity of Illness Index; Solubility; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Melphalan 200 mg/m(2) is the standard conditioning regimen for patients with multiple myeloma (MM) with normal renal function (NRF) undergoing autologous stem cell transplant (ASCT). In an effort to escalate the dose of melphalan and to improve the efficacy, we designed a dose-escalation study of melphalan in conjunction with palifermin in patients with NRF, with the hope that a higher dose of melphalan can be administered with an acceptable degree of oral mucositis (OM). We enrolled 19 patients (18 evaluable) with NRF. Dose-escalation of melphalan administered on day -2 began at 200 mg/m(2) with palifermin administered at a fixed dose of 60 mcg/kg/day. Palifermin was given as an i.v. bolus on day -5, -4, and -3, and then on day +1, +2, and +3. Subsequent dose escalations of melphalan were done at 20 mg/m(2) increments up to a maximum dose of 280 mg/m(2). Of 18 evaluable patients, there were no treatment-related deaths by day 100. The median age was 48.5 years (range, 33-65 years). The most common adverse events related to palifermin included rash (18 events, no ≥ grade 3 events), elevation of amylase (10 events, 4 were grade 3 but asymptomatic), and lipase (5 events, 2 were grade 3 but asymptomatic), edema (11 events, no ≥ grade 3). The overall incidence of OM grade 3 was 44% (8/18) with a median duration of severe mucositis of 5 days (range, 3-6 days). Eleven patients (61%) required opioid analgesics. None of the patients received total parenteral nutrition (TPN)/nasogastric feeding. Two of 6 patients who were given melphalan 280 mg/m(2) did not develop OM. Cardiac dose-limiting toxicity (DLT) in the form of atrial fibrillation did occur in 1 of 6 patients treated with melphalan 280 mg/m(2). Palifermin has permitted safe dose escalation of melphalan up to 280 mg/m(2), thus reaching the cumulative dosage of melphalan administered in tandem ASCT. This higher dose of melphalan has the potential to improve the efficacy and, hopefully, outcomes of patients with MM with a single ASCT. A phase 2 trial is necessary to better delineate the antimyeloma efficacy of this regimen.

Topics: Adult; Aged; Cytoprotection; Female; Fibroblast Growth Factor 7; Humans; Kidney; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Stem Cell Transplantation; Stomatitis; Transplantation, Autologous

This randomized-controlled trial studied the efficacy of palifermin in a chemotherapy-only, high-dose Melphalan (HDM) transplant setting, to reduce oral mucositis (OM) and its sequelae measured by patient-reported outcomes (PRO) and medical resource use. Palifermin, relative to placebo was given either pre-/post-HDM or pre-HDM in patients with multiple myeloma (MM) undergoing auto-SCT at 39 European centers. Oral cavity assessment (WHO) and PRO questionnaires (oral mucositis daily questionnaire (OMDQ) and EQ 5D) were used in 281 patients (mean age 56, ± s.d.=8 years). 57 patients received placebo. One hundred and fifteen subjects were randomized to pre-/post-HDM receiving palifermin on 3 consecutive days before HDM and after auto-SCT and 109 patients were randomized to pre-HDM, receiving palifermin (60 μg/kg/day) i.v. for 3 consecutive days before HDM. There was no statistically significant difference in maximum OM severity. Severe OM occurred in 37% (placebo), 38% (pre-/post-HDM) and 24% (pre-HDM) of patients. No significant difference was observed with respect to PRO assessments or medical resource use, but more infections and fever during neutropenia were reported in pre-/post-HDM vs placebo (for example, 51 and 26%). To conclude, palifermin was unable to reduce OM or OM-related patient's burden in MM transplant patients.

Topics: Adolescent; Adult; Aged; Autografts; Female; Fibroblast Growth Factor 7; Follow-Up Studies; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Stem Cell Transplantation; Stomatitis; Transplantation Conditioning

High-dose melphalan 140 mg/m2 is the standard of care for patients with multiple myeloma (MM) with renal insufficiency (RI). Palifermin as a cytoprotective agent has demonstrated efficacy in reducing the intensity and duration of oral mucositis (OM) in patients who receive intensive chemotherapy/radiotherapy. There is no prospective data on the use of palifermin in patients with MM with RI.. creatinine clearance ≤60 mL/minute/1.73 m2, age >18 years, no dialysis, no active OM, and a suitable candidate for autologous stem cell transplant (ASCT). Melphalan dose ranged from 140 to 200 mg/m2 and escalated at the increment of 20 mg/m2. Six dosages of palifermin 60 mcg/kg/day were given intravenously between day -5 to day +3. Dose escalations were to stop if dose-limiting toxicities (DLTs) occurred at melphalan dose in ≥2 of 3 patients, with that dose declared as the maximal administered dose and the level below where ≤1 of 6 patients had DLTs was considered the maximally tolerated dose (MTD). Nineteen patients were enrolled from June 2007 to June 2011. Data on 15 evaluable patients is reported as 4 patients were removed. Median age was 59 years (range, 36-67 years). The overall incidence of OM ≥ grade 3 was 53% (8 of 15) and a median duration of ≥grade 3 OM was 6.5 days (range, 3-42 days). One patient in L2 (melphalan 160 mg/m2) developed atrial fibrillation on day +9. Two patients in L4 (melphalan 200 mg/m2) developed grade 4 OM, hence reaching DLT. No DLT was observed in 6 patients enrolled in L3 (melphalan 180 mg/m2). Palifermin has permitted safe dose escalation of melphalan up to 180 mg/m(2) in patients with RI.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Creatinine; Cytoprotection; Drug Administration Schedule; Drug Therapy, Combination; Female; Fibroblast Growth Factor 7; Hematopoietic Stem Cell Transplantation; Humans; Injections, Intravenous; Male; Melphalan; Middle Aged; Multiple Myeloma; Renal Insufficiency, Chronic; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

Oral mucositis (OM) still represents a significant complication of hematopoietic stem cell transplantations (HSCT). Observational studies focusing on risk factor definitions are still warranted.. A total of 126 patients participated in this observational study after autologous HSCT with the BEAM and HD-l-PAM 200mg/m(2) conditioning regimens. Basic clinical and laboratory variables and their impact on OM were assessed.. Age, gender, body mass index, and baseline absolute neutrophil counts were not shown to have any negative impact on OM development. The multivariate analysis revealed oral cryotherapy non-provision as being the most significant predictor for OM incidence (p < 0.0001), followed by BEAM conditioning regimen (p = 0.007), OM in a patient's history (p = 0.002) and lower number of days since the last chemotherapy (p = 0.025). The cryotherapy was remarkably effective both in the single high-dose melphalan 200mg/m(2) conditioning regimen (18% OM in cryotherapy vs. 68% without it, p<0.0001) and in the multidrug BEAM (melphalan 140mg/m(2)) regimen (38% vs. 86%, p=0.006).. Oral cryotherapy should be implemented into supportive care management in patients treated with high-dose melphalan short-infusion chemotherapy. Large and well-designed randomized trials are necessary to obtain more significant and reliable results and understanding regarding OM risk factors.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cryotherapy; Cytarabine; Dose-Response Relationship, Drug; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Prospective Studies; Risk Factors; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Oral mucositis (OM) is an unresolved problem among patients treated with a high-dose therapy supported by hematopoietic stem cell transplantation (HSCT). We tested the ability of supersaturated calcium phosphate mouth rinse (Caphosol) to ameliorate oral mucosal injury induced by a conditioning regimen.. Thirty-two patients with hematologic malignancies were treated with Caphosol to prevent OM during HSCT procedures. The conditioning regimens for 16 patients were BGNU 300 mg/m2, day 6; ARA-C 200 mg/m2 daily, days 5, 4, 3, 2; VP-16 200 mg/m2 daily, days 5, 4, 3, 2; L-PAM 140 mg/m2, day 1 (BEAM) and for 16 patients, MEL 200 (non-Hodgkin's lymphoma). A control group was composed of 24 consecutive patients, who had been treated with HSCT before Caphosol was available. The source of the graft was autologous peripheral blood.. Among patients treated with Caphosol no one had to receive total parenteral nutrition. Among the BEAM group no one experienced III to IV degree OM compared with 40% of the control group. The median OM duration was 2.25 days versus controls of 8.6, (P<.001); only one patient received opioids versus 100% of controls. In the MEL 200 group, 93.7% of patients developed 0 to II degree OM vs 94% of the control group (P=.74) with median duration of 1, 73 days versus 2.42 for the controls (P=.73). In both control and Caphosol cohorts one patient received opioids.. Caphosol may reduce the incidence, severity, and duration of oral mucositis and decrease the number of days with painkillers among patients treated with a BEAM but not a Mel 200 regimen.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Calcium Phosphates; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mouthwashes; Multiple Myeloma; Stomatitis; Transplantation Conditioning; Treatment Outcome; Young Adult

ATL-104 is a potent mitogen for epithelial cells of the gastrointestinal tract. In animal models, ATL-104 aids regeneration of the gastrointestinal tract after treatment with chemotherapeutic agents. The effect of ATL-104 on mucositis in patients requiring high-dose melphalan or BEAM before peripheral blood SCT (PBSCT) was investigated in a randomized, placebo-controlled, double-blind, two-part study. Patients were randomized to ATL-104 (50, 100 or 150 mg) or placebo once daily for 3 days before chemotherapy and 3 days after PBSCT. Part one of the study was a dose-escalation design; part two was a parallel group design using all three ATL-104 doses. Patients were followed up for 28 days post-treatment. Severity of signs and symptoms were assessed and used to calculate scores for standard toxicity rating scales (WHO, Western Consortium for Cancer Nursing Research (WCCNR)). Sixty-three patients were treated. Treatment with ATL-104 substantially reduced the median duration of severe oral mucositis (WHO grade 3 or 4) compared with placebo (median duration: ATL-104 groups 2 or 3 days, placebo 10.5 days). The effect of ATL-104 on the incidence of severe oral mucositis was inconclusive. Similar results were obtained using the WCCNR Scale. Adverse events (AEs) were predominantly mild or moderate in intensity. Gastrointestinal AE were most common.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Double-Blind Method; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Male; Melphalan; Middle Aged; Mouthwashes; Phytohemagglutinins; Pilot Projects; Placebos; Recombinant Proteins; Stomatitis

We evaluated the efficacy and toxicity of adding 9 Gy of total body irradiation (TBI), in three single daily fractions of 3 Gy, to the reduced intensity regimen of fludarabine 30 mg/m2 i.v. x 4 days and melphalan 140 mg/m2 i.v. x 1 day in advanced pediatric hematologic malignancies. Twenty-two acute lymphoblastic leukemia (ALL), six acute myeloid leukemia (AML), and one non-Hodgkin lymphoma patients were transplanted. Of these, 13 were beyond second remission, and five had prior hematopoietic stem cell transplant (HSCT). Twenty-one donors were unrelated, of which 19 were from cord blood (CB) units. Three of the eight related donors were genotypically disparate. Oral mucositis and diarrhea were the most common toxicities. Twenty-seven patients achieved neutrophil engraftment (median 16 days), and 23 had platelet engraftment (median 42 days). One patient had primary graft failure. Seven patients died of non-relapse causes in the first 100 days. With a median follow-up of 52 months, seven of 22 ALL, five of six AML, and one of one lymphoma patients are alive and in remission. The regimen of TBI, fludarabine, and melphalan allows the engraftment of allogeneic hematopoietic stem cells (including mismatched CB). It was fairly well tolerated in pediatric patients, even for second transplants. Its efficacy requires further evaluation.

Topics: Adolescent; Child; Child, Preschool; Combined Modality Therapy; Diarrhea; Female; Graft Survival; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Mouth Mucosa; Stomatitis; Survival Rate; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

Forty patients with multiple myeloma scheduled to receive melphalan 200 mg/m(2) followed by autologous stem cell transplantation were randomly assigned to receive oral cryotherapy or room temperature normal saline rinses 30 min before and for 6 h after high-dose therapy. Patients were evaluated for the development of mucositis using the National Cancer Institute grading system as well as evaluation of secondary measures such as days of total parenteral nutrition (TPN), narcotic use, hospitalization, weight loss and resumption of oral caloric intake for 28 days after transplant. Patients self-scored their pain, swallowing, drinking, eating, sleeping and taste alterations for 28 days. The primary end point of this trial was the incidence of grades 3-4 mucositis. Compared to the normal saline group, patients using cryotherapy experienced less grade 3-4 mucositis, 14 vs 74%, P=0.0005. Patients receiving cryotherapy also had statistically lower uses of narcotics and TPN, although there were no differences in length of hospitalization or weight loss. Patient-reported pain was significantly lower and activities were significantly better in the cryotherapy group.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Cryotherapy; Female; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Pain; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Stomatitis; Transplantation, Autologous

the aim of this paper was to review the initial use of Palifermin(rHu-KGF1) in a single institution, for the prevention of oral mucositis in high-dose chemotherapy and stem cell transplantation.. the case records of the first five patients treated with Palifermin at the Royal Adelaide Hospital Cancer Centre were reviewed, and incidence,severity and duration of the oral mucositis were recorded, as well as demographics and toxicities.. two of the five patients developed grade 4 mucositis, and the remaining three patients developed grade 2 mucositis. Palifemin was well tolerated with only one patient developing a rash.. the severity of oral mucositis was less than would be expected in these patients without anti-mucositis therapy. Palifermin was well tolerated. Obviously this single institution report is from a very small cohort of patients, but it is encouraging for the ease of use of this drug in the future.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cancer Care Facilities; Carmustine; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Drug Administration Schedule; Drug Eruptions; Female; Fibroblast Growth Factor 7; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Melphalan; Middle Aged; Podophyllotoxin; Primary Prevention; Severity of Illness Index; South Australia; Stomatitis; Time Factors; Transplantation Conditioning; Treatment Outcome

In this prospective multicentre trial, 90 patients undergoing autologous stem cell transplantation (ASCT) were randomised to receive (n=43) or not receive (n=47) amifostine 910 mg/m(2) prior to melphalan 200 mg/m(2). Patients were monitored for regimen-related toxicity, engraftment, supportive care, response and survival. Both groups underwent ASCT at a median of 8 months from diagnosis and were matched for disease characteristics, prior therapy and pre-ASCT disease responsiveness. Amifostine infusional side-effects were frequent, occurring in 65% of patients, but of mild severity. Amifostine use was associated with a reduction in the median grade of oral mucositis (1 vs 2, P=0.01) and the frequency of severe (WHO grades 3 or 4) mucositis (12 vs 33%, P=0.02), but no reduction in the requirement for parenteral nutrition or analgesic use. Conversion to complete remission post-ASCT occurred in 30 and 14% of the amifostine and control groups, respectively (P=0.09). With a median follow-up of 35 months, there was no statistically significant difference between the median progression-free or overall survival times for the two groups. We conclude that amifostine can be safely administered prior to high-dose melphalan and significantly reduces the frequency and severity of therapy-induced oral mucositis.

Topics: Adult; Aged; Amifostine; Cytoprotection; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Prospective Studies; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

Antimicrobial solutions are widely used in the nursing care of chemotherapy induced oral mucositis (OM). There is little evidence, however, supporting their use for reducing mucosal damage. In our study, 132 patients were randomized to use normal saline (n=65) or povidone-iodine diluted 1:100 (n=67) mouthwashes for OM prophylaxis and treatment after high-dose chemotherapy comprising BEAM or HD-L-PAM followed by autologous peripheral stem cell transplantation. The study groups were well balanced in respect of age, sex, chemotherapy and the number of CD34+ cells in the graft. No significant difference was found between the groups in respect of OM characteristics, fever of unknown origin (FUO) and other infections. The antimicrobial solution was less tolerable for patients. OM occurred significantly more often in females than in males (86% vs 60%, P=0.0016) and was worse and of longer duration. The mechanical effect of mouthwashes might have a certain importance in FUO prevention. When indicating oral rinses, the patient's individual preference and tolerance of solutions offered should be considered.

Topics: Adult; Aged; Anti-Infective Agents, Local; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Humans; Male; Melphalan; Middle Aged; Mouth Mucosa; Mouthwashes; Peripheral Blood Stem Cell Transplantation; Povidone-Iodine; Sex Factors; Sodium Chloride; Stomatitis; Transplantation, Autologous

High-dose melphalan (HDM) has been adopted as standard therapy in the treatment of multiple myeloma. This treatment is associated with non-selective cytotoxicity, causing oral mucositis as the major non-hematological side-effect. Amifostine is a cytoprotector which prevents toxicity induced by anticancer therapy. We prospectively compared two groups of patients who either received (group A, n = 21) or did not receive (group B, n = 20) amifostine (740 mg/m(2)) before HDM (200 mg/m(2)) followed by autologous peripheral blood progenitor cell transplantation. The occurrence of severe oral mucositis was significantly decreased in group A in comparison to group B (33% vs 65%, P < 0.05). Six patients in group A required opioid analgesic therapy during a mean period of 4.8 days as compared to eight patients for 6.5 days in group B (P = NS). Delayed vomiting was less frequent in group A (43% vs 70%, P = 0.07) and significantly less severe in group A (grade 2-4) vomiting: two patients vs nine patients, P < 0.02). No difference was observed between the two groups in either hematological toxicity after HDM or in response rate. Grade I emesis was the only immediate side-effect observed after amifostine administration. We conclude that amifostine can reduce mucositis induced by HDM.

Topics: Adult; Aged; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Female; Graft Survival; Humans; Kinetics; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

We conducted a phase I/II trial, to evaluate the efficacy and safety of an intravenous liposomal formulation of busulphan (LBu) as a myeloablative agent for stem cell transplantation (SCT). The liposomal busulphan was administered as a 3 h infusion twice daily over 4 consecutive days. Six adults received 1.6-2 mg/kg/dose and 18 children received 1.8-3 mg/kg/dose. Pharmacokinetic parameters were studied after the first and the last dose of busulphan. No significant difference in clearance, AUC, elimination half-lives or distribution volume between the first and the last dose was found in either groups. A significantly (P < 0.005) higher clearance was observed in children after the first and the last dose (3.61 and 3.79 ml/min/kg, respectively) compared to adults (2.40 and 2.33 ml/min/kg, respectively). The elimination half-lives after the first and the last dose were significantly (P < 0.005) shorter in children (2.59 and 2.72 h, respectively) compared to adults (3.35 and 3.61 h, respectively). Clearance correlated significantly with age. However, no significant correlation with age was observed when clearance was adjusted to the body surface area. Two cases of VOD following a total dose of 24 mg/kg were observed. Six patients experienced mucositis. No other organ toxicity was observed. We conclude that intravenous liposomal busulphan pharmacokinetics is age dependent. A dosage schedule based on body surface area should be used especially in young children to reduce the age-dependent difference in kinetics. An intravenous liposomal dose of busulphan of 500 mg/m(2) is suggested to reach a similar systemic exposure and myeloablative effect in both children and adults. Moreover, the novel liposomal form of busulphan showed a favorable toxicity profile and seems safe as a part of the high-dose therapy prior to SCT.

Topics: Adult; Age Factors; Busulfan; Child; Cyclophosphamide; Drug Administration Schedule; Drug Carriers; Female; Genetic Diseases, Inborn; Graft vs Host Disease; Half-Life; Hematologic Neoplasms; Hepatic Veno-Occlusive Disease; Humans; Immunosuppressive Agents; Infant; Infusions, Intravenous; Liposomes; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Peripheral Blood Stem Cell Transplantation; Stomatitis; Transplantation Conditioning

To evaluate feasibility and potential efficacy of amifostine (AMI) in the prevention of toxicities associated with high-dose melphalan (MEL), ten myeloma patients received AMI 910 mg/m2 in 15 min infusion preceding MEL 200 mg/m2 followed by stem cell infusion (AMI group). Hematologic and extra-hematologic toxicities as well as the need for supportive care observed in the AMI group were compared with ten myeloma patients treated in an identical protocol but without AMI. Hypotension was the most important adverse event of AMI infusion. No differences were observed in the time of engraftment between the AMI group and the control group neither was there any difference in the need for supportive care. Oral mucositis grade >2 was observed in 30% of the patients in both groups. Diarrhea grade >2 occurred only in two AMI patients but in five control patients. AMI preceding high-dose MEL is feasible, although adverse events are observed in some patients. Whether AMI could reduce the gastrointestinal toxicity associated with high-dose MEL can be reliably assessed only in prospective randomized trials.

Topics: Adult; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Feasibility Studies; Female; Graft Survival; Humans; Hypotension; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Pilot Projects; Stomatitis; Transplantation, Autologous

The role of more intense conditioning for second transplant was evaluated in myeloma patients achieving at least partial remission (PR) after first transplant with melphalan at 200 mg/m2. Forty-three patients received more intensive conditioning for the second transplant. Nineteen patients received cyclophosphamide 120 mg/kg along with melphalan 200 g/m2 (MEL-CY; group 1) while 24 patients received total body irradiation (1125 cGy) in conjunction with melphalan 140 mg/m2 (MEL-TBI; group 2). Forty-three matched control patients were identified from 450 patients receiving melphalan alone for second transplant (MEL200; group 3). Engraftment and toxicities were comparable among the groups with the exception of increased treatment-related mortality of 8% in group 2 compared to none in groups 1 and 3 (P = 0.07). Despite identical CR rates of 74, 71 and 70%, respectively, in groups 1, 2 and 3 (P = 1.0), event-free survival (median: 27, 15 and 61; P < 0.0001) and overall survival (median: 39, 25 and 76 months; P = 0.003) were significantly decreased in patients receiving more intensive conditioning (groups 1 and 2). Lymphocyte recovery, evaluated as a surrogate for immune recovery, was inferior in more intensively treated patients (groups 1 and 2 compared to group 3). Our findings suggest that more intense conditioning appears to have no benefit in patients responding to their first cycle of high-dose therapy and may even be detrimental in this setting. Bone Marrow Transplantation (2000) 25, 483-487.

Topics: Antigens, CD34; Antineoplastic Agents, Alkylating; beta 2-Microglobulin; Cohort Studies; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Evaluation Studies as Topic; Fever; Graft Survival; Humans; Lymphocyte Count; Melphalan; Multiple Myeloma; Pneumonia; Prognosis; Sepsis; Stomatitis; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Topics: Adolescent; Bone Marrow Transplantation; Cataract; Child; Child, Preschool; Disease-Free Survival; Female; Fever; Follow-Up Studies; Gonadal Disorders; Graft Survival; Human Growth Hormone; Humans; Infant; Male; Melphalan; Mouth Mucosa; Neutrophils; Platelet Count; Pneumocystis Infections; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Sepsis; Stomatitis; Survival Rate; Thyroxine; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Whole-Body Irradiation

Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extrahaematological toxicity after high-dose therapy (HDT) has never been investigated. We compared two historical groups of patients who either received (group A, n = 35) or did not receive (group B, n = 33) amifostine (740 mg/m2) before high-dose (HD) melphalan, followed by autologous infusion of peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this dose level. Emesis grade 1-2 was the most important side-effect, but the interruption of infusion was never required. The incidence and median duration of severe mucositis (grade 3-4) was 21% and 0 d (range 0-11 d) in group A and 53% and 7 d (range 0-11 d) in group B. The duration of analgesic therapy was also significantly lower in group A (0 d; range 0-12) than in group B (6 d, range 0-20) (P = 0.0001). Severe diarrhoea (3% vs. 25%; P = 0.01) and emesis (9% vs. 34%; P = 0.01) were also reduced in group A in comparison with group B. No differences were observed between the two groups for haematological recovery. This retrospective study strongly suggests that amifostine can reduce severe mucositis and the use of analgesic drugs in this setting. A randomized study is warranted to confirm these preliminary results.

Topics: Adolescent; Adult; Aged; Amifostine; Analgesics, Opioid; Antineoplastic Agents, Alkylating; Blood Cell Count; Diarrhea; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mouth Mucosa; Pain; Radiation-Protective Agents; Retrospective Studies; Stomatitis; Treatment Outcome; Vomiting

The purpose of the study was to determine the maximum tolerated dose of continuous infusion of high-dose VP-16 in combination with high-dose melphalan (HDM) for conditioning before autologous bone marrow transplantation (ABMT). Thirteen children (median age 27 months) with stage IV neuroblastoma were treated with high-dose VP-16 and HDM followed by ABMT as consolidation treatment. All had previously received conventional chemotherapy with a mean number of six drugs. Surgery of the primary tumor had been performed in 12/13. We performed a dose-escalating study of VP-16 from 1800 mg/m2/72 h with 300 mg/m2/72 h dose increments according to toxicity. VP-16 was administered as a 72-h i.v. infusion. Melphalan (140 mg/m2/day) was administered once as an i.v. push. VP-16 pharmacokinetics were analyzed in 12 patients. Five children received 1800 mg/m2/72 h of VP-16, five received 2100 mg/m2/72 h and three, 2400 mg/m2/72 h. The mean duration of granulocytopenia (< 0.5 x 10(9)/1) was 24 days and thrombocytopenia (< 50 x 10(9)/1) was 36 days. No major infectious complications occurred. Gastrointestinal (GI) toxicity was the dose-limiting toxicity. Five severe manifestations of GI toxicity in three patients led us to consider 2400 mg/m2/72 h as the MTD. The mean VP-16 clearance rate was 17.3 ml/min/m2 with continuous infusion. A mean steady-state plasma concentration of 24.2 micrograms/ml (s.d. = 2) and 28.3 micrograms/ml (s.d. = 1.9) was achieved at the 1800 mg/ml and 2100 mg/m2 dose levels, respectively, GI toxicity is dose limiting when VP-16 at 2400 mg/m2/72 h, is associated with HDM. When given as a continuous i.v. infusion, at 2100 mg/m2/72 h, VP-16 associated with HDM is well tolerated before ABMT in young heavily pre-treated children.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Diarrhea; Dose-Response Relationship, Drug; Doxorubicin; Etoposide; Female; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Melphalan; Neuroblastoma; Neutropenia; Remission Induction; Salvage Therapy; Stomatitis; Transplantation Conditioning; Vincristine

Topics: Administration, Oral; Adult; Cryotherapy; Female; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Prospective Studies; Stomatitis

Renal impairment (RI) used to exclude multiple myeloma (MM) patients from autologous stem cell transplantation (ASCT) for safety concerns. Here, we retrospectively reviewed 34 consecutively transplanted patients with creatinine clearance < 60 ml/min at ASCT in recent 5 years at our institution. Busulfan/cyclophosphamide and high-dose melphalan were both employed as conditioning regimens. We found 62% grade 1-2 oral mucositis, 12% grade 3 oral mucositis, 48% grade 3 infection, 8% grade ≥ 4 infection, 50% grade 1 transient creatinine increase, 15% cardiac adverse events, and 12% engraftment syndrome. One case of secondary platelet graft failure and 1 case of transplantation-related mortality were observed. Interleukin-6 concentration was elevated among patients with increased body temperature and/or N-terminal pro-brain natriuretic peptide during engraftment, and close monitoring of these markers may help to predict susceptibility to cardiac events and engraftment syndrome. Adverse events occurred frequently, but the majority were manageable in this cohort. ASCT would further deepen the anti-myeloma efficacy and slightly ameliorated renal function. With a median follow-up of 26.2 months post transplantation (range: 1.6-74.8 months), the median progression-free survival (PFS) and overall survival (OS) post-transplantation of patients undergoing first-line transplantation were not reached; the median PFS post-transplantation of patients undergoing rescue transplantation was 19.2 months and the median OS was not reached.

Topics: Creatinine; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Retrospective Studies; Stem Cell Transplantation; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM).. In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.. A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.. The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.. The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

Topics: Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Proteome; Proteomics; Quality of Life; Stomatitis; Stomatitis, Aphthous

Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens.. Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis.. Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (β = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use.. Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Topics: Cryotherapy; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Methotrexate; Retrospective Studies; Stomatitis; Transplantation Conditioning

It has been reported that expression of OCT3 enhanced the sensitivity to melphalan in cells, indicative of potential roles of OCT3 in melphalan transport. Herein we investigated the association of select single nucleotide polymorphisms in SLC22A3 (gene encoding OCT3) with clinical outcomes in multiple myeloma (MM) patients with hematopoietic autologous stem cell transplants followed by high-dose melphalan therapy.. Melphlan concentrations in blood samples from 108 MM patients were measured using liquid chromatography-tandem mass spectrometry (LC-MS/ΜS); genotypes of rs2048327, rs1810126, and rs3088442 in these patients were determined using quatitive RT-PCR assays.. Rs3088442 A variant-carriers had a significantly increased risk of severe oral mucositis in comparison with homozygous rs3088442 G-carriers with adjusted odds ratio of 4.00 (95% CI=1.25-14.7; p=0.027). Rs3088442 A carriers tended to have lower creatinine clearance (p=0.10) and higher maximum plasma concentration of melphalan (p=0.07).. OCT3 might be involved in melphalan transport in MM patients.

Topics: Adult; Aged; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Organic Cation Transport Proteins; Polymorphism, Single Nucleotide; Stem Cell Transplantation; Stomatitis; Transplantation, Autologous

Oral mucositis is a common complication during haematopoietic stem cell transplantation (HSCT). This study aimed to assess the incidence of severe mucositis in patients undergoing different HSCT regimens.. This single-centre retrospective study reviewed daily oral assessment for 467 consecutive patients who underwent different transplant regimens for matched unrelated or related allogeneic HSCT with post-transplant methotrexate, haploidentical or mismatched HSCT with post-transplant cyclophosphamide (PTCy), or autologous HSCT. Oral care and cryotherapy with melphalan were used. Patient demographic data, oral mucositis WHO grade, use of total parenteral nutrition (TPN) and patient-controlled analgesia (PCA) were collected.. Grade 3-4 oral mucositis was common in myeloablative total body irradiation (TBI)-based regimens cyclophosphamide/ TBI (CyTBI) (71%) and fludarabine/ TBI (FluTBI) with PTCy (46%), as well as reduced-intensity fludarabine/melphalan (FluMel) (43%) and carmustine/etoposide/cytarabine/melphalan (BEAM) autologous HSCT (41%). In contrast, grade 3-4 oral mucositis was less common in reduced-intensity haploidentical regimen melphalan/fludarabine/TBI with PTCy (19%), all non-myeloablative regimens (0-9%) and high-dose melphalan autologous HSCT (26%). TPN and PCA use were correlated to oral mucositis severity.. Severe oral mucositis was associated with myeloablative TBI, methotrexate and melphalan in combination with methotrexate and in BEAM. Use of PTCy was preferable over methotrexate to prevent oral mucositis.

Topics: Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Melphalan; Methotrexate; Retrospective Studies; Stomatitis; Transplantation Conditioning

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

Topics: Hematopoietic Stem Cell Transplantation; Humans; Longitudinal Studies; Melphalan; Multiple Myeloma; Stomatitis; Transplantation, Autologous

Cryotherapy is a conventional method for preventing melphalan-induced oral mucositis (OM) in adult patients. We retrospectively examined the clinical benefits of cryotherapy in 41 pediatric patients undergoing autologous stem cell transplantation using a melphalan-etoposide-carboplatin regimen. Twenty-two patients received cryotherapy. The cumulative incidence of grade 3-4 OM was significantly lower in the cryotherapy group (57.1%) than in the noncryotherapy group (89.5%; P = .041). Multivariate analyses identified cryotherapy and the melphalan dose as independent factors for the lower occurrence of OM. The present study demonstrates the clinically significant efficacy of cryotherapy for preventing melphalan-induced OM in pediatric patients.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Combined Modality Therapy; Cryotherapy; Dose-Response Relationship, Drug; Etoposide; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Melphalan; Neoplasms; Prognosis; Retrospective Studies; Stomatitis; Transplantation, Autologous; Young Adult

One explorative observational study in two parts was performed to examine early salivary changes in relation to oral mucositis (OM) in multiple myeloma patients treated with high-dose melphalan and autologous haematopoietic stem cell transplantation (HSCT). As cryotherapy was introduced after part A as regular care, its effect on OM could be evaluated.. Unstimulated whole-mouth saliva (UWS) and stimulated whole-mouth saliva (SWS) were collected, and OM was scored with the Oral Mucositis Nursing Instrument (OMNI) at days -3, 0, 4, 7, 11 and 14 after HSCT. Salivary flow rate, total protein (BCA), mucin 5B, albumin (western blot), total IgA, lactoferrin and myeloperoxidase levels (ELISA) were determined.. Trends of decreasing UWS and SWS flow rates and total IgA levels were observed. At days 7 and 11, increases in lactoferrin and albumin levels were found in UWS and SWS. A positive correlation was found between OMNI scores and albumin and lactoferrin levels in SWS (R. Compositional changes in saliva reflecting inflammation were found in the first days after HSCT, and the use of cryotherapy in the second part was associated with decreased OM severity.

Topics: Adult; Aged; Albumins; Cryotherapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin A; Lactoferrin; Male; Melphalan; Middle Aged; Mucin-5B; Multiple Myeloma; Myeloablative Agonists; Peroxidase; Saliva; Severity of Illness Index; Stomatitis; Transplantation, Autologous

In the present study, we compared the incidence and severity of oral mucositis among patients undergoing allogeneic hematopoietic stem cell transplantation after fludarabine-based regimens with busulfan 12.8 mg/kg (FB12.8), with busulfan less than or equal to 9.6 mg/kg (FB9.6), and with melphalan 140 mg/m

Topics: Adult; Aged; Busulfan; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Melphalan; Middle Aged; Stomatitis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Young Adult

The present study outlines the clinical impact and risk factors of oral mucositis in 79 patients with multiple myeloma following high-dose melphalan for autologous transplant. All patients underwent daily prophylactic low-level indium gallium aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm

Topics: Adult; Aged; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Logistic Models; Low-Level Light Therapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Risk Factors; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p < 0.001). The median oral mucositis severity, assessed using the WHO oral toxicity scale from grade 0-4, experienced in the no group was 2.5 vs. 2 in the cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

Topics: Cryotherapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infusions, Parenteral; Length of Stay; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Narcotics; Pain Management; Parenteral Nutrition, Total; Practice Guidelines as Topic; Retrospective Studies; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

Toxicity of the oral and gastrointestinal mucosa induced by high-dose melphalan is a clinical challenge with no documented prophylactic interventions or predictive tests. The aim of this study was to describe molecular changes in human oral mucosa and to identify biomarkers correlated with the grade of clinical mucositis.. Ten patients with multiple myeloma (MM) were included. For each patient, we acquired three buccal biopsies, one before, one at 2 days, and one at 20 days after high-dose melphalan administration. We also acquired buccal biopsies from 10 healthy individuals that served as controls. We analyzed the biopsies for global gene expression and performed an immunohistochemical analysis to determine HLA-DRB5 expression. We evaluated associations between clinical mucositis and gene expression profiles. Compared to gene expression levels before and 20 days after therapy, at two days after melphalan treatment, we found gene regulation in the p53 and TNF pathways (MDM2, INPPD5, TIGAR), which favored anti-apoptotic defense, and upregulation of immunoregulatory genes (TREM2, LAMP3) in mucosal dendritic cells. This upregulation was independent of clinical mucositis. HLA-DRB1 and HLA-DRB5 (surface receptors on dendritic cells) were expressed at low levels in all patients with MM, in the subgroup of patients with ulcerative mucositis (UM), and in controls; in contrast, the subgroup with low-grade mucositis (NM) displayed 5-6 fold increases in HLA-DRB1 and HLA-DRB5 expression in the first two biopsies, independent of melphalan treatment. Moreover, different splice variants of HLA-DRB1 were expressed in the UM and NM subgroups.. Our results revealed that, among patients with MM, immunoregulatory genes and genes involved in defense against apoptosis were affected immediately after melphalan administration, independent of the presence of clinical mucositis. Furthermore, our results suggested that the expression levels of HLA-DRB1 and HLA-DRB5 may serve as potential predictive biomarkers for mucositis severity.

Topics: Aged; Biopsy; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Gene Expression Regulation; Hematopoietic Stem Cell Transplantation; HLA-DRB5 Chains; Humans; Immunohistochemistry; Male; Melphalan; Middle Aged; Mouth Mucosa; Multiple Myeloma; Stomatitis

High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems, cancer treatment may have to be interrupted or delayed. In this study, we looked beyond OM's known risk factors of renal function and melphalan dose with a genome-wide association study (GWAS) to evaluate whether genetic variants in conjunction with clinical risk factors influence predisposition for OM.. Genotyping was performed using Illumina HumanOmni1-Quad v1.0 BeadChip and further assessed for data quality. We tested 892,589 germline single-nucleotide polymorphisms (SNPs) for association with OM among 972 Caucasian patients treated with high-dose melphalan and ASCT in Total Therapy clinical trials (TT2, TT3, TT4) for newly diagnosed MM. Statistical analyses included t tests, stepwise regression modeling, and logistic regression modeling to find baseline clinical factors and genotypes associated with OM.. We found that 353 (36.3 %) patients had grades 2-4 OM. Type of treatment protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were associated with grades 2-4 OM. The addition of these SNPs increased sensitivity in detecting grades 2-4 OM cases to 52 %.. These SNPs may be important for their roles in inflammatory pathways, epithelial healing, and chemotherapy detoxification.

Topics: Adult; Aged; Antineoplastic Agents; Combined Modality Therapy; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Polymorphism, Single Nucleotide; Risk Factors; Stomatitis; Transplantation, Autologous

Topics: Anti-Bacterial Agents; Cohort Studies; Cryotherapy; Female; Fever of Unknown Origin; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Intestinal Mucosa; Male; Melphalan; Prospective Studies; Risk Assessment; Severity of Illness Index; Stomatitis; Transplantation, Autologous; Treatment Outcome

Bu-Mel as preparative therapy prior to autologous stem cell rescue was recently shown to be superior to the conventional CEM regimen for HR NBL in Europe. There are no data available on the feasibility and toxicity of Bu-Mel as consolidation therapy following the COG-type induction regimens used in North America. We report early complications and outcomes of patients with HR NBL who received Bu-Mel for consolidation following COG-based induction. Retrospective analysis of all patients who had received Bu-Mel as preparative regimen prior to stem cell rescue for HR NBL was carried out. Toxicity, outcomes, and any delays to receiving radiation or anti-GD2 antibody therapy were analyzed. Six patients undergoing PBSCT had received Bu-Mel. The treatment was well tolerated. Mucositis was the main toxicity; three patients had developed neutropenia fever and none developed pulmonary toxicity. One patient had developed moderate SOS that responded to conservative management. All patients were able to receive and tolerate post-transplant local radiotherapy and ch.14.18 anti-GD2 antibody therapy without any delays. All patients are alive with no disease recurrence. The Bu-Mel regimen is well tolerated and is feasible post-COG-type induction platform.

Topics: Busulfan; Child; Child, Preschool; Consolidation Chemotherapy; Female; Humans; Infusions, Intravenous; Male; Melphalan; Neuroblastoma; Peripheral Blood Stem Cell Transplantation; Recurrence; Retrospective Studies; Stomatitis; Treatment Outcome

Mucositis is a common complication of high-dose melphalan (HDM) used before autologous stem cell transplantation (ASCT) for multiple myeloma (MM). Mucositis rates are influenced by previous chemotherapy (CT) exposure. We examined the effect of induction therapy before ASCT on ASCT mucositis rates.. Patients undergoing first 200 mg/m(2) HDM ASCT were assessed. Those receiving < 200 mg/m(2), or those with previous ASCT were excluded. Patients were evaluated depending on type of induction therapy (CT, immunomodulatory drug [IMiD], or proteasome inhibitor [PI]) before ASCT. A case record review was performed and data collected on response to induction, rates of Grade 3/4 mucositis, and days of total parenteral nutrition (TPN) or parenteral opiate analgesia.. One hundred twenty-eight patients with ASCT were assessed. Induction therapy was CT- (n = 62), IMiD- (n = 51), or PI-based (n = 15) therapy. Patient characteristics were overall similar, including median age, MM stage, and CD34(+) cell dose. IMiD-based therapy patients had lower rates of mucositis (33% vs. 53%; P = .03) and less opiate requirements (10% vs. 31%; P = .02) compared with those treated with CT. Rates of mucositis and opiate use in the PI group were not different to the CT cohorts (33% vs. 53%; P = .6 and 13% vs. 31%; P = .13), likely due to concurrent anthracycline exposure. TPN usage was similar (CT, 42%; IMiD, 35%; and PI, 20%), as was neutropenia duration and antibiotic usage.. Patients treated with IMiD-based regimens before HDM ASCT had significantly lower rates of mucositis than those treated with CT-based therapy. There were too few patients who received PI therapy to evaluate the effect.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Staging; Severity of Illness Index; Steroids; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Oral mucositis (OM) is a common complication of conditioning regimens with high-dose melphalan (HDmel). This retrospective cohort study analyzes the impact of oral cryotherapy (OC) or room temperature saline rinses on the prevention of OM in patients with multiple myeloma (MM) or lymphoid neoplasias submitted to autologous stem cell transplantation (ASCT) in a single center.. From August 2006 to July 2011, 134 consecutive patients were enrolled. Two consecutive groups were included: Non-OC (August 2006 to April 2009, 68 patients) and OC (May 2009 to July 2011, 66 cases). MM cases (78, 58%) received HDmel as the conditioning regimen and 56 patients (42%) with lymphoma received BEAM.. The non-OC and OC groups were comparable for the main clinicobiologic features and type of neoplasia. OM was more frequent and severe in patients receiving BEAM as the conditioning therapy. The group of OC showed less frequent and less severe mucositis and fewer days on antibiotics. No differences were observed in the duration of OM, need for parenteral nutrition and narcotics, and the length of hospital stay on comparison with the OC and non-OC groups. By multivariate analyses, OC was an independent favorable prognostic factor for OM development.. This study shows that OC is more effective than saline rinses in the prevention of OM in patients with lymphoma and myeloma receiving conditioning regimens with HDmel for ASCT.

Topics: Adult; Aged; Female; Hematopoietic Stem Cell Transplantation; Humans; Hypothermia, Induced; Incidence; Lymphoma; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Prognosis; Retrospective Studies; Stomatitis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Topics: Adult; Aged; Cryotherapy; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Stomatitis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine

Stomatitis, including oral mucositis and ulcerations induced by HSV-reactivation are major sources of morbidity after high-dose (HD) chemotherapy and subsequent autologous hematopoietic stem cell transplantation (SCT). While increased synthesis of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-α)-as well as reactivation of viral infections have frequently been observed in this setting, data on their association with the severity of mucositis is limited.. Fifteen patients with Hodgkin's or non-Hodgkin's lymphoma receiving HD conditioning chemotherapy and autologous SCT were assessed with respect to oral pain and severity of stomatitis on day -6, 0, +5 to +7, +13 to +15, and +100. On the same dates, IL-1 and TNF-α were quantified in saliva and screening for a wide range of viral pathogens was carried out by cell culture and PCR and complemented by serological analyses. t Tests were used to assess potential associations between these variables.. All but one patient had a positive HSV IgG titer at baseline. Reactivation as confirmed by HSV PCR was observed in seven patients (50%). There was a significant association between the presence of HSV in saliva samples and severity of stomatitis (t test, p = 0.015). The highest concentration of TNF-α and IL-1 coincided with the maximum intensity of stomatitis, but the association was not significant.. We found a significant association between the presence of HSV in saliva samples and severity of stomatitis in patients receiving HD chemotherapy and subsequent autologous SCT. While acyclovir prophylaxis has become standard for patients undergoing allogeneic SCT, this issue has not been sufficiently explored for other chemotherapy regimens. Based on our findings, conduction of a well-powered controlled randomized trial may be warranted.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Cytokines; Female; Herpesvirus 1, Human; Herpesvirus 2, Human; Hodgkin Disease; Humans; Inflammation; Interleukin-1; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Podophyllotoxin; Saliva; Severity of Illness Index; Statistics as Topic; Stem Cell Transplantation; Stomatitis; Transplantation, Autologous; Tumor Necrosis Factor-alpha; Young Adult

Oral mucositis (OM) is a common toxic side effect among patients receiving high-dose chemotherapy (CT) with autologous stem cell transplantation (ASCT) for hematologic malignancies. The aim of this study was to investigate changes in submucosal microcirculation in myeloma patients receiving high-dose CT with ASCT by assessing capillary density and microvascular structural integrity.. Ten consecutive patients with multiple myeloma who underwent first-time CT treatment with high-dose melphalan (200 mg/m(2)) and ASCT were included in this study. Baseline buccal mucosa capillary density, expressed as the mean number of capillaries +/- SD per mm(2) (cpll/mm(2)), was measured with sidestream dark-field imaging after treatment was performed, after 30 and 60 minutes, and then on days 2, 4, 6, 8, and 14. A linear mixed model was used to examine capillary density over time and a P value of <.05 was considered to be statistically significant.. Baseline mucosal capillary density was 19 +/- 2.4 cpll/mm(2). Mucosal capillary density after melphalan infusion after 30 and 60 minutes and on days 2 and 4 showed no statistically significant differences. A decrease in capillary density with statistical significance was observed on days 6 (10 +/- 3.0 cpll/mm(2); P < .01) and 8 (12 +/- 4.9 cpll/mm(2); P < .01). On day 14, capillary density returned to near baseline value.. High-dose CT alters microvascular structural integrity and dysregulates tissue perfusion in the oral mucosa by decreasing the number of perfused submucosal capillaries in the oral mucosa. The findings of this investigation suggest that acute CT toxicity alters oral microcirculation and may be an important mechanism responsible for driving early mucosal barrier disturbances associated with CT-induced OM.

Topics: Antineoplastic Agents, Alkylating; Capillaries; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Linear Models; Male; Melphalan; Microscopy, Polarization; Microscopy, Video; Middle Aged; Mouth Mucosa; Mucositis; Multiple Myeloma; Radiography; Stomatitis; Young Adult

We undertook a retrospective analysis of a cohort of 67 patients with multiple myeloma who had received an autologous haematopoietic SCT (HSCT) following high-dose melphalan to explore the impact of mucositis on the systemic inflammatory response. A homogenous group of 16 patients without a documented infection and a group of 30 patients with bacteraemia were identified for whom complete data on neutropenia, an inflammatory response, infectious complications and mucositis were available. All patients showed a similar course of events with an inflammatory response coinciding with the occurrence of significant mucositis, regardless of the presence or absence of infection. The only differences between the two groups were significantly higher maximum C-reactive protein (CRP) levels and lower citrulline levels for patients with bacteraemia, suggesting a causative role for mucositis in the occurrence of bacteraemia. Statistical analysis showed a significant association over time between citrulline levels, to a lesser extent bacteraemia, but not neutropenia, and the inflammatory response measured by CRP. These data suggest that the inflammatory response after conditioning for a HSCT is the result of the chemotherapy-induced mucositis and independent of neutropenia. Though primary inflammation appeared due to mucositis, infections resulting from mucosal barrier injury and neutropenia aggravated the inflammatory response.

Topics: Antineoplastic Agents, Alkylating; Bacteremia; C-Reactive Protein; Citrulline; Cohort Studies; Combined Modality Therapy; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Retrospective Studies; Stomatitis

The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral mucositis (SOM; WHO Oral Toxicity Scale grade 3-4) and local and systemic clinical sequelae and medical resource use. SOM occurred in 44% of patients. The duration of SOM (mean 5.3 days) correlated with time to neutrophil engraftment. The following parameters increased gradiently with maximum grade of oral mucositis: duration of pain score >or=4, opioid use, dysphagia score >or=4, total parenteral nutrition (TPN) use, incidence and/or duration of fever and infection, and duration of antibiotic use. SOM increased the duration of TPN use by 2.7 days (P<0.001), opioids by 4.6 days (P<0.001), and antibiotics by 2.4 days (P=0.045). SOM prolonged hospital stay by 2.3 days (P=0.013) in MM patients, but not in NHL patients (who tended to have a longer hospital stay). In conclusion, this analysis of prospectively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting.

Topics: Adult; Aged; Analgesics, Opioid; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Male; Medical Audit; Melphalan; Middle Aged; Multiple Myeloma; Prospective Studies; Risk Factors; Stem Cell Transplantation; Stomatitis; Transplantation Conditioning

The fludarabine (FLU)/melphalan (MEL) conditioning regimen containing FLU and high-dose MEL was analyzed in comparison with the BU/CY2 regimen to characterize oral mucositis (OM) and risk factors. OM incidence significantly varied between BU/CY2 and FLU/MEL (100 vs 78%, P=0.004), but the incidence of severe OM grades 3-4 WHO and kinetics of OM were fully comparable. Patients with OM persisting on day +21 had more acute GVHD (68 vs 32%, P=0.005), which tended to occur earlier than among those without such prolonged OM. Multivariate analysis showed significant dependency of acute GVHD on severity and prolonged duration of OM and significant correlation between OM severity and its prolonged duration. Body surface area-based dosing in the FLU/MEL regimen led to a wide range of MEL doses administered per kilogram body weight (2.5-5.2 mg/kg, median 3.5). In multivariate analysis, MEL dose per kilogram of body weight was found to be a significant predictor of OM incidence and severity. Female gender and lower body mass index were less important variables than the fact that the actual dose of MEL administered per kilogram of body weight was relatively high when the dosage was calculated on the basis of body surface area.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Busulfan; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Melphalan; Middle Aged; Prospective Studies; Risk Factors; Stomatitis; Transplantation Conditioning; Vidarabine; Young Adult

The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation.. Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 mg/m(2) chemotherapy, respectively, in 25 European centers. OM assessments were made daily until 30 days after transplantation or hospital discharge. High quality of OM assessment was ensured by an intensive training program.. Severe OM occurred in 46% (95% CI, 36% to 56%) of patients with MM and 42% (95% CI, 32% to 53%) of patients with NHL, with a mean duration of 5.3 days (95% CI, 4.4 to 6.1 days) and 5.5 days (95% CI, 4.5 to 6.7 days), respectively. Time from start of conditioning to peak OM score was 12.1 +/- 2.6 and 14.6 +/- 2.4 days. Severe OM risk and/or duration was significantly associated with higher chemotherapy dose per kilogram of body weight and poor performance status, but in contrast with some previous reports, this was not related to age.. Severe OM is more common in the transplantation setting than previously reported, justifying effective preventative and therapeutic measures.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Carmustine; Cytarabine; Dose-Response Relationship, Drug; Etoposide; Europe; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Lymphoma, Non-Hodgkin; Male; Medical Audit; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Prospective Studies; Research Design; Risk Assessment; Risk Factors; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

The purpose of this study was to assess the relationship between oral mucositis (OM) and adverse clinical and economic outcomes of autologous hematopoietic stem-cell transplantation (HSCT) following high-dose melphalan (Alkeran) conditioning in patients with multiple myeloma. A retrospective study of 115 consecutive autologous HSCT recipients with multiple myeloma who received high-dose melphalan conditioning before transplantation was undertaken at a single academic center. OM severity was assessed twice weekly using a validated scale beginning 3-4 days following conditioning and continuing until hospital discharge or day 28, whichever occurred first. OM was graded, based on presence/extent of erythema/ulceration across eight oropharyngeal sites, as follows: 0 = no erythema or ulceration; I = erythema but no ulceration; II = ulceration, 1 site; III = ulceration, 2 sites; IV = ulceration, 3 sites; and V = ulceration, > or = 4 sites. Analyses examined the relationship between worst OM grade and selected clinical and economic outcomes, including days with fever, days of total parenteral nutrition (TPN),days of parenteral narcotic therapy, incidence of significant infection, and inpatient days and charges. The mean age of study subjects was 54 years; 19 patients (17%) received total-body irradiation, and 55 patients (48%) experienced OM grade > or = II (ie, ulceration). The worst OM grade was significantly (P < 0.05) associated with numbers of days of TPN and parenteral narcotic therapy, length of hospitalization, and total inpatient charges. Worst OM grade was not associated with the number of febrile days or the risk of significant infection. OM is associated with worse clinical and economic outcomes in multiple myeloma patients undergoing autologous HSCT following high-dose melphalan conditioning.

Topics: Analysis of Variance; Antineoplastic Agents, Alkylating; Boston; Costs and Cost Analysis; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Length of Stay; Male; Melphalan; Middle Aged; Multiple Myeloma; Oral Ulcer; Parenteral Nutrition, Total; Retrospective Studies; Severity of Illness Index; Stomatitis; Time Factors; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Study on the normal saline vs povidone-iodine mouthwashes for oral mucositis (OM) prophylaxis in patients after high-dose chemotherapy comprising bischloroethyl nitrosourea etoposide ara-C melphalan (BEAM) or high-dose melphalan (HD-L-PAM) followed by autologous peripheral stem cell transplantation indicated that females have higher a incidence of OM compared to men, as reported by [Vokurka et al. 13:554-558, (2005)]. The multivariable analysis of larger cohort of 148 patients compliant with the original study protocol confirmed female gender to be an independent risk factor and predictor for OM. The HD-L-PAM (200 mg/m2) conditioning regimen revealed to be more toxic compared to BEAM as for incidence of OM grades 3-4 World Health Organization score. Body mass index, age, mouthwash solution used, and CD34+ cell number in the autologous graft were verified not to have an impact on OM incidence in this group of patients.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Humans; Incidence; Male; Melphalan; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Oral Ulcer; Peripheral Blood Stem Cell Transplantation; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Sex Factors; Stomatitis; Transplantation, Autologous

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P < 0.01). These results suggest that 60-min oral cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

Topics: Administration, Oral; Adult; Cryotherapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Japan; Male; Melphalan; Middle Aged; Myeloablative Agonists; Stomatitis; Transplantation, Homologous

Topics: Antineoplastic Agents, Alkylating; Cryotherapy; Female; Humans; Male; Melphalan; Multiple Myeloma; Pain; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Stomatitis; Transplantation, Autologous

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucose Oxidase; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Kidney Diseases; Lactoperoxidase; Male; Melphalan; Middle Aged; Models, Theoretical; Multiple Myeloma; Muramidase; Myeloablative Agonists; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Cryotherapy; Female; Humans; Leukemia; Lymphoma; Male; Melphalan; Middle Aged; Stem Cell Transplantation; Stomatitis

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis.. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration.. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001).. These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

Topics: Antineoplastic Agents, Alkylating; Cryotherapy; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Japan; Male; Melphalan; Middle Aged; Stomatitis

Despite the best available agents to prevent mucositis, most patients receiving high-dose chemoradiotherapy regimens experience severe mucositis, and new therapies are needed. In this study, we evaluated the safety and tolerability of a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM) chemotherapy. PV701 mouthwash (15 mL x 13.5 mg/mL) was administered 6 times a day for 12 days, from day--6 to day +5, to patients with lymphoma, who were given BEAM on day--6 to day--2, with autologous stem cells infused on day 0. Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The severity and duration of OM, the duration of enteral/parenteral feeding, the requirement for intravenous opiates, and admission to intensive care were recorded. Outcomes were also compared with those of historical control patients. Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose-limiting toxicities were observed. Compared with 89 historical controls, the 9 PV701-treated patients had significantly less frequent grade 2 or 3 OM ( P=.0006) and had grade>or=3 OM for an estimated 5 fewer days ( P=.0003). There was a reduction in the need for enteral/parenteral feeding ( P=.012), its duration ( P=.010), and its frequency ( P=.022) and in the duration of intravenous opiates ( P=.0006). We conclude that PV701 mouthwash is readily administered with minimal side effects at a dose of 1215 mg/d, and further investigation of this agent is warranted.

Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cattle; Complex Mixtures; Cytarabine; Dose-Response Relationship, Drug; Female; Growth Substances; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Milk; Mouth Mucosa; Mouthwashes; Podophyllotoxin; Stomatitis

Topics: Antineoplastic Agents, Alkylating; Cryotherapy; Dose-Response Relationship, Drug; Humans; Melphalan; Neoplasms; Stomatitis

Children with Wilms tumor who have a particular risk of failure at relapse or at primary diagnosis were treated with high-dose chemotherapy (HDC) and autologous peripheral blood stem cell rescue in order to improve their probability of survival. From April 1992 to December 1998, 23 evaluable patients received HDC within the German Cooperative Wilms Tumor Studies. Nineteen were given melphalan, etoposide and carboplatin (MEC); the others received different regimens. The dose of carboplatin was adjusted according to renal function. Indications for HDC were high-risk relapse in 20 patients, bone metastases in two patients and no response in one patient. Fourteen of 23 patients are alive after a median observation time of 41 months, 11 of 14 in continuous complete remission, three in CR after relapse post HDC. The estimated survival and event-free survival for these patients are 60.9% and 48.2%. Twelve children relapsed after HDC; nine of them died within 12 months and three are surviving from 20 to 33 months after relapse. The main toxicities were hematologic, mucositis and renal (tubular dysfunction; intermittent hemodialysis in one patient). There were no toxic deaths. About half of the children suffering from Wilms tumor with very unfavorable prognostic factors survive disease-free after HDC for over 3 years. Besides hematological toxicity, mucositis and infections, renal function is at risk during HDC. With dose adjustment on glomerular filtration rate, however, no permanent renal failure was observed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Etoposide; Female; Germany; Hematologic Diseases; Humans; Ifosfamide; Infant; Kidney Diseases; Kidney Neoplasms; Life Tables; Lung Neoplasms; Male; Melphalan; Peripheral Blood Stem Cell Transplantation; Prognosis; Stomatitis; Survival Analysis; Thiotepa; Transplantation, Autologous; Wilms Tumor

The aim of the present study was to evaluate the correlation between the number of CD34+ cells transfused and the duration of hypoplasia, and the relationship between various CD34+ subsets (CD34+/33-; CD34+/38-; CD34+/ HLA-DR-; CD34+/Thy-1+) and engraftment kinetics in a series of patients with breast cancer treated with high doses of thiotepa and melphalan.. We treated 42 consecutive patients: 19 in an adjuvant context (>= 4 positive axillary nodes) and 23 for metastatic disease. A combination of thiotepa 600 mg/m(2) and melphalan 140-160 mg/m(2) was administered as the conditioning regimen. All patients received peripheral blood progenitor cells (PBPC) and growth factors for hematopoietic rescue.. In univariate analysis, we found a significant relationship between the number of CD34+ cells reinfused and the time to hematologic recovery and the duration of hospital stay. We observed an inverse correlation between the number of CD34+ cells reinfused and the units of platelets transfused. Cox multivariate analysis confirmed that the number of CD34+ cells reinfused is the most effective predictor of time to hematologic recovery. CFU-GM resulted to be a better predictor of the duration of hospitalization.. We found a significant relationship between the number of PBPC reinfused and the time to hematologic recovery after high doses of thiotepa and melphalan. In our experience, the numbers of subsets of CD34+ cells infused did not give compared additional information to that provided by the total number of CD34+ cells infused.

Topics: Adult; Analysis of Variance; Antigens, CD34; Breast Neoplasms; Female; Graft Survival; Hospitalization; Humans; Melphalan; Middle Aged; Mouth Mucosa; Platelet Transfusion; Stomatitis; Thiotepa

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made. Peripheral blood stem cell collection was performed with either cyclophosphamide 5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15 microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received autotransplant as front-line therapy, while the last two patients were treated in relapse, which occurred following prior autologous stem cell transplantation in support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha-interferon (No. 6). High-dose chemotherapy administered as preparation to transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6) or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage. Following transplant, prompt and sustained recovery of hematopoiesis was documented in all the patients; 500 PMN/microI and 20000 platelets/microI were reached after a median of 13 and 14 days, respectively. None of the patients suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive disease (patient No. 3). Renal function either improved or remained stable throughout the transplant period. All the patients but one responded to therapy, three of them are progression free after 2, 15 and 26 months; two relapsed after 16 and 4 months and one died from cholangiocarcinoma 7 months after transplant, while still in remission. Although our experience is limited so far, these results appear promising and support the investigational use of myeloablative therapy in MM patients with chronic renal failure.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Cholangiocarcinoma; Combined Modality Therapy; Creatinine; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Hyperbilirubinemia; Immunologic Factors; Interferon-alpha; Kidney Failure, Chronic; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Multiple Myeloma; Neoplasms, Second Primary; Remission Induction; Renal Dialysis; Safety; Stomatitis; Survival Analysis; Transplantation, Autologous; Treatment Outcome; Vincristine

Topics: Adolescent; Adult; Child; Cryotherapy; Humans; Ice; Melphalan; Middle Aged; Mouth Mucosa; Stomatitis

Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4 myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen males and 11 females, aged 27-53 years (median 39.5 years) received oral busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17 patients and severe mucositis in 22. There was no evidence of cardiotoxicity, nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive disease. Twenty-three patients engrafted with the median duration of neutropenia (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x 10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related complications. Of 15 evaluable patients with active disease at BMT, 9 responded and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months) later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival at 36 months was 64% and 58%, respectively, while for the entire group of 24 patients these values were 39% and 34%. Busulphan and melphalan is a safe and inexpensive conditioning regimen for autologous BMT with acceptable toxicity and substantial antitumour activity particularly against lymphomas.

Topics: Actuarial Analysis; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Purging; Bone Marrow Transplantation; Busulfan; Combined Modality Therapy; Female; Gastrointestinal Diseases; Humans; Male; Melphalan; Middle Aged; Neoplasms; Neutropenia; Remission Induction; Stomatitis; Survival Analysis; Thrombocytopenia; Transplantation, Autologous; Treatment Outcome

We report a case of extramedullary plasmacytoma that appeared in an uncharacteristic manner as an ulcerative stomatitis affecting particularly the tongue and buccal mucosa. The lesions were associated with a transient lichenoid skin rash. The literature is reviewed and comparisons made between this tumor and the related plasma cell dyscrasias of multiple myeloma and monoclonal gammopathy.

Topics: Aged; Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Lichenoid Eruptions; Melphalan; Mouth Neoplasms; Plasmacytoma; Stomatitis; Ulcer

The authors report a case of stomatitis, in a patient receiving antimitotic therapy, which was found to be due to an acute leukosis. They feel that patients on antimitotics who develop stomatitis should have a white cell count to exclude leukosis, which is not a very rare finding today.

Topics: Antineoplastic Agents; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Female; Gingivitis; Humans; Leukocytes; Melphalan; Middle Aged; Stomatitis; Vincristine