melphalan and Mucositis

CAMT is a bone marrow failure syndrome that usually presents with isolated thrombocytopenia soon after birth. HSCT is curative, and MAC is associated with increased transplant-related morbidity and mortality, especially in the unrelated setting. We used a RIC regimen with alemtuzumab, fludarabine, and melphalan in a seven-month-old patient with CAMT who underwent a MUD HSCT. The transplant was well tolerated with few complications. Neutrophil and platelet engraftment occurred on day +12 and +29, respectively, and she had 100% donor chimerisms on days +19.

Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Blood Platelets; Congenital Bone Marrow Failure Syndromes; Female; Hematopoietic Stem Cell Transplantation; Hepatic Veno-Occlusive Disease; Humans; Infant; Melphalan; Methylprednisolone; Mucositis; Neutrophils; Thrombocytopenia; Transplantation Conditioning; Vidarabine

Topics: Antineoplastic Agents, Alkylating; Double-Blind Method; Head and Neck Neoplasms; Health Services Needs and Demand; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mucositis; Needs Assessment; Randomized Controlled Trials as Topic; Severity of Illness Index; United States

A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical tomotherapy, with promising results.. This study was a prospective multicenter phase 1 trial that aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >15 days, grade 4 thrombopenia >28 days, and all other grade 4 nonhematologic toxic effects except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion.. Thirteen patients were included; only 1 DLT at the third escalated dose level (12 Gy) was observed, whereas 1 patient was treated at 14 Gy with no adverse events. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3-4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of these 13 patients, 38.5% were in very good partial response and 30.8% were in complete response. Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up.. Total marrow irradiation provides good results with a good tolerance profile at first relapse in MM and makes it possible to increase the dose delivered to the planning target volume while sparing organs at risk. This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required.

Topics: Bone Marrow; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Mucositis; Multiple Myeloma; Prospective Studies; Radiotherapy, Intensity-Modulated; Recurrence; Transplantation, Autologous; Whole-Body Irradiation

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

This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P=0.025 and 78.1 vs 100%, P=0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P=0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Diarrhea; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Transplantation Conditioning; Treatment Outcome; Vomiting

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m

Topics: Aged; Cytogenetics; Disease-Free Survival; Female; Hematopoietic Stem Cell Mobilization; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Stem Cell Transplantation; Transplantation, Autologous; Treatment Outcome

High-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m(2)) to high-dose MEL (140 mg/m(2)) before a second ASCT, in a tandem ASCT strategy, in 64 patients with "de novo" MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Female; Fever; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Neutrophils; Prospective Studies; Survival Analysis; Thiotepa; Transplantation Conditioning; Transplantation, Autologous

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

Whether the intensity of the conditioning regimen affects febrile neutropenia (FN) and severe bacterial infections (SBIs) is not well established. We analyzed the risk factors (RFs) for the development of FN and SBI in the first 100d post-transplant in 195 consecutive adult recipients of a reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (RIC-allo).. The RIC regimens consisted of fludarabine plus melphalan (62%) or busulphan (38%) (FluMel or FluBu). SBIs include pneumonia, urinary tract infections, and bacteremia.. FN occurred in 141 patients (72%), always in the first 30d post-allo-RIC. However, a SBI occurred in only 27 patients (14%) during this early post-transplant period (

Topics: Adult; Bacterial Infections; Busulfan; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Mucositis; Mycophenolic Acid; Myeloablative Agonists; Neutropenia; Retrospective Studies; Risk Factors; Time Factors; Transplantation Conditioning; Transplantation, Homologous

With the eventual goal of reducing relapse and thus improving overall survival in selected lymphoma patients, a Phase I study was performed using the cytoprotectant amifostine to permit safe dose-augmentation of melphalan in the carmustine (BCNU), etoposide, cytarabine (arabinosylcytosine), and melphalan (BEAM) regimen before autologous hematopoietic stem cell transplantation. Between 30 July 2003 and 25 November 2008, a total of 32 lymphoma patients were entered, of which 28 were evaluable. We found the melphalan dose in BEAM could be safely escalated to at least 260 mg/m², a substantial increase from the usual dose of 140 mg/m² in BEAM while the trial was terminated early due to poor accrual, no maximal tolerated dose or dose-limiting toxicity was found. A Phase II trial is planned.

Topics: Adult; Aged; Amifostine; Antineoplastic Combined Chemotherapy Protocols; Atrial Fibrillation; Carmustine; Combined Modality Therapy; Cytarabine; Cytoprotection; Dose-Response Relationship, Drug; Etoposide; Female; Humans; Lymphoma; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Mucositis; Pancytopenia; Peripheral Blood Stem Cell Transplantation; Postoperative Complications; Transplantation Conditioning; Transplantation, Autologous; Young Adult

The underlying mechanism of high-dose therapy (HDT)-related oral mucositis (OM) may be partly mediated by alterations in the normal salivary composition. This study evaluated salivary antioxidant and immunological capacities observed in myeloma patients suffering from HDT-related OM, and assessed potential contribution of these factors to OM development. Twenty-five consecutive myeloma patients treated with melphalan 200 mg/m(2) followed by autologous SCT were enrolled. Patients underwent a daily assessment for OM, and salivary samples were collected on days -3 and +7 of transplantation and analyzed for secretory IgA and antioxidant capacity. The degree of mucosal damage was assessed by measuring the salivary carbonyl and albumin (Alb) levels. OM, reported in 96% of patients, appeared to be most severe on 8 day after transplantation (range: +2 to +14). Clinical mucositis was associated with significant reduction in salivary secretory IgA (54%; P=0.05), and antioxidant activity, measured by total antioxidant status (40%; P=0.0004), antioxidant capacity (ImAnOx) (23%; P=0.002) and uric acid level (51%; P=0.006). The increase found in salivary Alb (119%; P=0.024) and carbonyl (28%; P=0.047) levels, indicates mucosal and oxidative damage, respectively. These salivary changes might enhance mucositis development and symptoms. Therapeutic interventions, enhancing antioxidative and immunological activities need to be investigated.

Topics: Adult; Aged; Albumins; Antineoplastic Agents; Antioxidants; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin A; Male; Melphalan; Middle Aged; Mouth; Mucositis; Multiple Myeloma; Oxidative Stress; Saliva; Transplantation, Autologous

Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m2) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m2. Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 microg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal; C-Reactive Protein; Dexamethasone; Disease-Free Survival; Drug Evaluation; Female; Humans; Interleukin-6; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Myeloablative Agonists; Pilot Projects; Stem Cell Transplantation; Transplantation, Autologous

High-dose chemotherapy before autologous transplantation is a therapeutic option as consolidation in primary or relapsed lymphoma. Even if BEAM conditioning is generally used, alternative conditioning regimens have been published. The purpose of this study was to assess the outcome of 177 adult patients with lymphoma whose conditioning treatment included a BAM (busulfan, aracytine, and melphalan) regimen. With a median follow-up of 17.4 months, 2-year estimates of overall survival and progression-free survival for the entire group were 87% and 70.5%, respectively. Mucositis was the main reported complications and infectious episodes were described in 80.2% of patients. According to multivariate analysis, high performance status and age at diagnosis were adverse factors for survival and increased the risk of disease relapse and death. Despite its limitations, this retrospective study suggests that BAM combination is a valid conditioning regimen in lymphoma patients, with an acceptable rate of toxicity.

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Cytarabine; Female; France; Humans; Lymphoma; Male; Melphalan; Middle Aged; Mucositis; Multivariate Analysis; Prognosis; Retrospective Studies; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous

The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Carboplatin; Child; Child, Preschool; Cohort Studies; Etoposide; Female; Hepatic Veno-Occlusive Disease; Humans; Hypertension, Pulmonary; Infant; Kidney Diseases; Male; Melphalan; Mucositis; Myeloablative Agonists; Neuroblastoma; Pancytopenia; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Young Adult

Mucositis is a common side effect of cancer therapies that causes painful, erythematous lesions to develop in the gastrointestinal tract. These lesions can lead to malnutrition, increased risk for serious infection, prolonged hospital stays, and reduced quality of life. Oral cryotherapy, or the use of ice chips to cool the mucous membranes during bolus chemotherapy infusions (e.g., 5-fluorouracil [Adrucil®] and melphalan [Alkeran®]), is the most readily accessible and cost-effective intervention available. Although many factors may contribute to the development of mucositis during cancer treatment, studies have found a reduction in the incidence and the severity of mucositis with the use of oral cryotherapy.


Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cryotherapy; Female; Fluorouracil; Humans; Ice; Male; Melphalan; Middle Aged; Mucositis; Neoplasms

A bortezomib-containing regimen followed by high-dose therapy and autologous stem cell transplant (ASCT) is considered the standard of care for front-line therapy in younger patients with newly diagnosed multiple myeloma (MM). We analyzed the results of ASCT with an intravenous busulfan 9.6 mg/kg and melphalan 140 mg/m2 (ivBUMEL) preparative regimen in 47 patients with newly diagnosed MM who had received bortezomib-based combinations as pre-transplant induction. The overall response rate and complete response after transplant were 100% and 49%, respectively. With a median follow-up of 24.5 months, median overall survival and progression-free survival have not been reached. Mucositis and febrile neutropenia were the most frequent toxicities observed. No case of sinusoidal obstruction syndrome was observed and there was no transplant-related mortality. These results suggest that front-line induction therapy with a bortezomib-based combination followed by ASCT with ivBUMEL is an effective and well-tolerated therapeutic approach for transplant eligible patients with MM.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Busulfan; Combined Modality Therapy; Febrile Neutropenia; Female; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Stem Cell Transplantation; Survival Analysis; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

The matched-control study failed to show a clinical relevant impact of palifermin on intestinal mucositis, although there was a reduced inflammatory response and less febrile neutropenia among patients who had no bacteraemia.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; C-Reactive Protein; Carmustine; Case-Control Studies; Cytarabine; Etoposide; Febrile Neutropenia; Female; Fibroblast Growth Factor 7; Hematopoietic Stem Cell Transplantation; Humans; Inflammation; Intestinal Mucosa; Male; Melphalan; Middle Aged; Mucositis; Neutropenia; Young Adult

Intravenous high-dose melphalan has a short half-life, and application of this single drug in MM transplant favors the use of stem cells without cryopreservation, for wider use in general and in resource-limited settings in particular.. Ninety-two patients with MM were given high-dose melphalan and rescued with granulocyte colony stimulating factor (G-CSF) mobilized noncryopreserved autologous PBSC, in our hospital during the past 18 years. Stem cells were mobilized with 4 days of G-CSF, harvested (median CD34 dose, 2.9 × 10(6)/kg) and then stored at 4°C in a refrigerator for a median of 2 days (range, 1-5 days) before reinfusion.. Median time to neutrophil (> 500/mm(3)) and platelet (> 20,000/mm(3)) engraftment were 10 and 14 days respectively. There was no graft failure. Mucositis grade 3/4 was seen in 66 patients (72%). Transplant-related mortality at 100 days was 3.2%. The overall response to transplant was 88% and improvement compared with pretransplant status was seen in 48%. The median overall survival (OS) and progression-free survival (PFS) were 61.7 months and 35.4 months respectively; independent predictors of survival were Eastern Cooperative Oncology Group Performance Status and hemoglobin for OS and chemosensitive disease and remission status after transplant for PFS.. We conclude that high-dose chemotherapy and autologous transplant with noncryopreserved PBSC is a simple, effective, and safe method for MM with equivalent results, and that cryopreservation is not necessary. It reduces the cost of transplant and avoids dimethyl sulfoxide toxicity.

Topics: Administration, Intravenous; Adult; Aged; Antineoplastic Agents, Alkylating; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Humans; India; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Outcome Assessment, Health Care; Peripheral Blood Stem Cell Transplantation; Proportional Hazards Models; Transplantation, Autologous; Young Adult

In the 1960s, it was reported that infectious complications were the main cause of fever during neutropenia that followed hematopoietic stem cell transplant (HSCT). More recently, mucositis has become recognized as an important determinant of the inflammatory response and infectious complications.. The objective of this prospective study was to determine the impact of intestinal mucositis, as measured by plasma citrulline, and neutropenia on the systemic inflammatory response (C-reactive protein) and the occurrence of bacteremia among 2 cohorts of HSCT recipients: 1 composed of 18 patients who had been treated with a myeloablative (MA) regimen (high-dose melphalan) and the other involving 19 patients who had received the non-myeloablative (NMA) regimen (fludarabine and cyclophosphamide). Blood cultures were obtained for surveillance from admission onwards as well as at the onset of fever.. The MA regimen induced severe intestinal mucositis manifest by citrullinemia <10 μmol/L, which was accompanied by an inflammatory response, and bacteremia affected 8 (44%) of 18 patients and coincided with the nadir of citrullinemia. By contrast, those who had been treated with the NMA regimen did not develop severe intestinal mucositis, had a moderate inflammatory response, and only 2 (11%) of the 19 patients developed bacteremia. However, both groups experienced profound neutropenia and its duration was significantly longer for those receiving the NMA regimen.. This study suggests that severe intestinal mucositis, i.e., citrullinemia <10 μmol/L, defines the period of risk of bacteremia better than does neutropenia, and that measuring plasma citrulline may prove useful in deciding who needs empirical antimicrobial therapy and when.

Topics: Adult; Aged; Bacteremia; C-Reactive Protein; Citrulline; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucositis; Myeloablative Agonists; Neutropenia; Prospective Studies; Transplantation Conditioning; Vidarabine

Mucositis is a known complication following use of chemotherapy, but fatal mucositis is unusual and management of such cases may be challenging. Pathologically there is denudation of mucosa of gastrointestinal tract. Severe cases can develop ileus and even perforation of bowel wall. We report here a case of multiple myeloma who developed World Health Organization grade 4 gut mucositis following the use of high dose melphalan with the expulsion of "intestine-like" material.

Topics: Fatal Outcome; Humans; Intestinal Mucosa; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Myeloablative Agonists; Stem Cell Transplantation; Transplantation Conditioning

High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) is considered standard in the treatment of patients with relapsed or refractory aggressive peripheral T cell lymphoma (PTCL). However, the optimal salvage regimen before ASCT has not yet been established. We retrospectively analyzed 31 patients with relapsed or refractory aggressive PTCL after anthracycline-based first-line chemotherapy who received either DexaBEAM (dexamethasone, carmustine, etoposide, cytarabine, and melphalan; n = 16) or ICE (ifosfamide, carboplatin, and etoposide; n = 15) regimen as first salvage chemotherapy followed by HDT/ASCT. The overall response rate (OR) was significantly higher for patients treated with DexaBEAM (69 %; 95 % confidence interval 46.0-91.5 %) as compared to the ICE group (20 %; 95 % confidence interval -0.2-40.2 %; P = 0.01), with higher complete response (CR; 38 %; 95 % confidence interval 13.8-61.2 %; vs. 7 %; 95 % confidence interval -6.0-19.6 %) as well as partial response (PR; 31 vs. 13 %) rate. Changing regimen due to failure of first salvage therapy, 12 patients initially receiving ICE still achieved an OR of 58 % (33 % CR, 25 % PR) with DexaBEAM as second salvage therapy, whereas in three patients receiving ICE after DexaBEAM failure, only one achieved an OR (1 PR). Median progression-free survival was significantly higher in the DexaBEAM group (6.4 vs. 2 months; P = 0.01). Major adverse event in both groups was myelosuppression with higher but tolerable treatment-related toxicity for patients in the DexaBEAM group. For all patients proceeding to HDT/ASCT, a 3-year overall survival was 50 %. Together, considering the limitations of the retrospective design of the evaluation and the small sample size, our data suggest that DexaBEAM salvage chemotherapy is superior to ICE for patients with relapsed or refractory aggressive PTCL for remission induction prior to autologous transplantation, with higher but manageable treatment-related toxicity.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carmustine; Combined Modality Therapy; Cytarabine; Dexamethasone; Disease-Free Survival; Drug Evaluation; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hematopoietic Stem Cell Mobilization; Humans; Ifosfamide; Kaplan-Meier Estimate; Lymphoma, T-Cell, Peripheral; Male; Melphalan; Middle Aged; Mucositis; Peripheral Blood Stem Cell Transplantation; Preoperative Care; Retrospective Studies; Salvage Therapy; Transplantation, Autologous; Treatment Outcome; Young Adult

Topics: Adult; Busulfan; Drug Administration Schedule; Female; Fibroblast Growth Factor 7; Gastric Mucosa; Hodgkin Disease; Humans; Intestinal Mucosa; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Retrospective Studies; Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

We developed a new high-dose combination of infusional gemcitabine with busulfan and melphalan for lymphoid tumors. Gemcitabine dose was escalated by extending infusions at a fixed rate of 10 mg/m(2)/min in sequential cohorts, in daily, 3-dose or 2-dose schedules. Each gemcitabine dose immediately preceded busulfan (adjusted targeting area under the curve 4,000 μM/min(-1)/day × 4 days) or melphalan (60 mg/m(2)/day × 2 days). We enrolled 133 patients (80 Hodgkin lymphoma [HL], 46 non-Hodgkin lymphoma [NHL], 7 myeloma), median 3 prior regimens; primary refractory disease in 63% HL/45% NHL and positron emission tomography positive tumors at transplantation in 50% patients. Two patients died from early posttransplantation infections. The major toxicity was mucositis. The daily and 3-dose schedules caused substantial cutaneous toxicity. In contrast, the 2-dose schedule was better tolerated, which allowed us to extend the infusions from 15 to 270 minutes. Pretransplantation values of C-reactive protein, B-type natriuretic peptide, ferritin, or haptoglobin did not correlate with toxicity. Overall response and complete response rates were 87%/62% (HL), 100%/69% B large-cell lymphoma (B-LCL), 66%/66% (T-NHL), and 71%/57% (myeloma). At median follow-up of 24 months (range, 3-63 months), the event-free/overall survival rates were 54%/72% (HL), 60%/89% (B-LCL), 70%/70% (T-NHL), and 43%/43% (myeloma). In conclusion, gemcitabine/busulfan/melphalan is a feasible regimen with substantial activity against a range of lymphoid malignancies. This regimen merits further evaluation in phase II and III trials.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Deoxycytidine; Drug Administration Schedule; Female; Follow-Up Studies; Gemcitabine; Hematopoietic Stem Cell Transplantation; Humans; Infusions, Intravenous; Lymphoma; Male; Melphalan; Middle Aged; Mucositis; Recurrence; Survival Rate; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

Lower alimentary tract mucositis is a serious complication of chemotherapy. The aim of the study was to determine the incidence, risk factors, and mortality of lower alimentary tract mucositis in a homogeneous population of patients with newly diagnosed myeloma receiving similar antineoplastic therapy and standardized supportive care.. Lower alimentary tract mucositis was evaluated among 303 consecutive patients with myeloma (2004-2007) enrolled in a clinical trial consisting of induction chemotherapy, tandem melphalan-based autologous stem cell transplantation (ASCT), and consolidation. Lower alimentary tract mucositis was defined as neutropenia-associated grade II-IV enteritis/colitis. Pretreatment risk factors were examined including body surface area (BSA), serum albumin (albumin), and estimated creatinine clearance (CrCl). Multiple logistic regression model was used to compute adjusted odds ratio (OR) and 95% confidence intervals (CI).. Forty-seven (15.5%) patients developed lower alimentary tract mucositis during 1529 courses of chemotherapy (including 536 melphalan-based ASCT). Pre-enrollment BSA <2 m² (OR, 2.768; 95% CI, 1.200-6.381; P = .0169) increased the risk for lower alimentary tract mucositis, whereas higher albumin was protective (OR, 0.698; 95% CI, 0.519-0.940; P = .0177). Pretransplant variables associated with lower alimentary tract mucositis were BSA <2 m² (OR, 4.451; 95% CI, 1.459-13.58, P = .0087) and estimated CrCl <60 mL/min (OR, 3.493; 95% CI, 1.173-10.40; P = .0246). Higher albumin level conferred protection (OR, 0.500; 95% CI, 0.304-0.820; P = .0061). No lower alimentary tract mucositis-related death was observed.. Lower alimentary tract mucositis is not uncommon among a homogenous population of oncology patients undergoing sequential courses of chemotherapy including melphalan-based ASCT but does not contribute to mortality. Lower BSA, renal function, and albumin are associated with increased risk for lower alimentary tract mucositis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Surface Area; Colitis; Enteritis; Female; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Kidney; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Risk Factors

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 retrospectively determined whether a 3-day short course of palifermin could reduce the toxicity of high-dose therapy (HDT) and autologous blood stem-cell transplantation (ASCT) in patients with multiple myeloma (MM).. Sixty-seven consecutive patients received 60 mug/kg palifermin for 3 days before HDT with melphalan 200 or 140 mg/m(2) for patients with renal failure (group A). Granulocyte colony-stimulating factor (G-CSF) was applied after ASCT. Data on haematopoietic reconstitution and toxicity were compared with two previously published patient groups from our institution who had received pegfilgrastim but not palifermin (group B, n = 21) and patients who had received neither palifermin nor G-CSF (group C, n = 21).. In group A, patients with renal failure had a significantly higher risk for severe mucositis (64% versus 16%, P < 0.002). Patients with normal renal function who received palifermin experienced significantly less days of hospitalisation (P < 0.05) and less need for narcotic analgesia (P < 0.05), parenteral nutrition (P < 0.05) and erythrocyte transfusions (P < 0.05) in comparison with groups B and C. Time to haematopoietic reconstitution was not compromised by the use of palifermin.. In conclusion, a short 3-day course of palifermin may be able to reduce the toxicity of HDT and ASCT in patients with MM. Patients with impaired renal function at the time of HDT need additional strategies to further reduce the incidence of severe mucositis.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Female; Fibroblast Growth Factor 7; Filgrastim; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm Staging; Palliative Care; Peripheral Blood Stem Cell Transplantation; Polyethylene Glycols; Recombinant Proteins; Retrospective Studies; Survival Rate; Transplantation, Autologous; Treatment Outcome

Topics: Drug Administration Schedule; Exanthema; Fibroblast Growth Factor 7; Humans; Melphalan; Morphine; Mouth Mucosa; Mucositis; Multiple Myeloma; Pain; Recombinant Proteins; Stem Cell Transplantation; Treatment Outcome

Busulfan, combined with therapeutic drug monitoring-guided dosing, is associated with higher event-free survival (EFS) rates due to fewer graft failures/relapses and lower toxicity. The optimal target area under the curve (AUC) and dosing schedule of intravenous busulfan in children undergoing hematopoietic stem cell transplantation (HSCT) remain unclear, however. We conducted a retrospective analysis of the association between busulfan exposure and clinical outcome in 102 children age 0.2 to 21 years who received busulfan 1 or 4 times daily before undergoing HSCT (46 malignant and 56 nonmalignant indications). EFS and overall survival after a median of 2 years of follow-up were 68% and 72%, respectively. EFS was optimal when the exposure of busulfan (AUC) was 78 mg x h/L (95% confidence interval=74 to 82 mg x h/L). Acute graft-versus-host disease (aGVHD) grade II-IV occurred more frequently with greater busulfan exposure. The addition of melphalan was an independent risk factor; melphalan use combined with high busulfan exposure (AUC >74 mg x h/L) was associated with high incidences of aGVHD (58%), veno-occlusive disease (66%), and mucositis grade III-IV (26%). Dosing frequency (1 or 4 times daily) was not related to any outcome. In conclusion, dose targeting of busulfan to a narrow therapeutic range was found to increase EFS in children. Adding melphalan to optimal busulfan exposure is associated with a high incidence of toxicity.

Topics: Adolescent; Area Under Curve; Busulfan; Child; Child, Preschool; Drug Interactions; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Infant; Melphalan; Mucositis; Retrospective Studies; Survival Analysis; Treatment Outcome; Young Adult

This study was done to evaluate the frequency and severity of mucositis in the early period of stem cell transplantation (SCT) and the relation of conditioning regimens with mucositis.. Patients with hematologic or solid tumors who underwent conditioning regimen were asked to score mucositis severity daily from the first day to the tenth day of reinfusion. Patient-reported scoring was performed according to a five-grade scale (0: no symptom; 1: mild; 2: moderate; 3: severe; 4: very severe). Total mucositis score (TMS) was defined as the addition of daily mucositis scores for 10 days. A total of 68 SCT (58 autologous and 10 allogeneic) patients, 48 men (71%) and 20 women (29%) were included to the study. Median age of patients was 32.5 (range 15-78) years. The most frequent three diagnosis were non-Hodgkin's lymphoma (37%, n = 25), Hodgkin's lymphoma (12%, n = 8), and multiple myeloma (12%, n = 8). BEAM (n = 27), ICE (n = 17), melphelan 200 mg/m(2) (M200)(n = 8), and TBI+C (total body irradiation + cyclophosphamide) (n = 16) were used as conditioning regimens.. All of the patients experienced mucositis at any grade. TMS in the sixth day was higher than TMS in the first day (p < 0.05). TMS was not related to the diagnosis or gender (p > 0.05). TMS at ICE regimen in the first 5 days after transplantation was more severe than BEAM regimen. TMS at TBI+C regimen was higher than TMS at BEAM regimen from day 4 to day 10 (p < 0.05). The mean percentages of patients who scored severe or very severe mucositis in 10 days was 7.4% in BEAM, 8.9% in ICE, 12.5% in M200, and 31.2% in TBI+C groups.. Patients experience mucositis frequently following conditioning regimen and SCT. The necessity and the timing of prophylaxis for mucositis change due to the type of conditioning regimens.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Ifosfamide; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Neoplasms; Severity of Illness Index; Whole-Body Irradiation; Young Adult

Oral and/or intestinal mucositis is a severe complication of hematopoietic SCT. Keratinocyte growth factor (KGF) has proven activity in the prevention of oral mucositis. We examined the efficacy of KGF in the prevention of intestinal mucositis. From January 2006 until December 2007, 35 consecutive patients underwent autologous SCT (auto-SCT) in our institution. A total of 15 consecutive patients who underwent auto-SCT from March 2007 to December 2007 received KGF for the prevention of mucositis and were included in the study group A, whereas 20 consecutive patients treated from January 2006 to March 2007, were included in the historical control group B. Oral and intestinal mucositis were significantly less severe in group A (P=0.002 and P<0.001, respectively). These results were confirmed with the use of video-capsule endoscopy. Patients in group A had a significantly lower incidence of neutropenic fever (P=0.026). Severe intestinal mucositis was significantly associated with a higher incidence of documented infections too (P=0.019). KGF is effective in the prevention of intestinal mucositis in patients undergoing auto-SCT. Patients with severe intestinal mucositis run a higher risk to develop infections.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capsule Endoscopy; Carmustine; Cytarabine; Female; Fibroblast Growth Factor 7; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Intestinal Diseases; Male; Melphalan; Middle Aged; Mucositis; Podophyllotoxin; Transplantation, Autologous

High-dose chemotherapy and haematopoietic stem cell (HSC) transplantation is considered standard therapy in patients with chemosensitive relapsed diffuse large B cell lymphoma (DLBCL). BCNU (carmustine), etoposide, cytarabine and melphalan (BEAM) is a widely used standard DLBCL conditioning regimen. The practice of basing chemotherapy doses on body surface area (BSA) is empirical and the best biometric parameter to dose chemotherapy is unknown. Weight-based dosing has been suggested to better predict toxicity of the conditioning regimen. We correlated the dose/weight ratio with toxicity and overall outcome in a uniform cohort of 80 consecutive patients receiving HSC transplant for relapsed DLBCL at Mayo Clinic, Rochester, MN following BSA-dosed BEAM conditioning chemotherapy. Melphalan dose was used as surrogate for the entire regimen. Median age at the time of transplant was 62 (26-77) years; 65% were males. The median melphalan dose was 3.2 mg/kg (range 2.2-4.5). Patients who received >3.6 mg/kg of melphalan were more likely to have grade 3 or 4 mucositis (44.4% vs. 9.8%, P = 0.001) and prolonged hospitalization (median 13 vs. 7 d; P = 0.04). Dose/weight ratio did not correlate with cumulative incidence of relapse (P = 0.3) or survival (P = 0.8). Transplant physicians should consider limiting the dose of BEAM to the equivalent of 3.6 mg/kg of melphalan.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Carmustine; Chi-Square Distribution; Cohort Studies; Cytarabine; Drug Administration Schedule; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Length of Stay; Lymphoma, Large B-Cell, Diffuse; Male; Melphalan; Middle Aged; Mucositis; Recurrence; Risk; Statistics, Nonparametric; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome

The incidence of mucositis caused by autologous hematopoietic stem cell transplantation (AHSCT) is relatively high. The severe painful mucositis can reduce the quality of life of patients obviously. Transdermal fentanyl is efficient in treating chronic pain of cancer, and also can relieve the severe pain of mucositis resulted from chemotherapy. This study was to investigate the efficacy and safety of transdermal fentanyl for the severe painful mucositis caused by AHSCT.. A total of 22 malignant tumor patients suffered from severe mucositis caused by high dose chemotherapy combined AHSCT. The analgesic degree before and after treatment was evaluated by the scores of Visual Analogue Scale (VAS) (range 0-10). The median VAS scores of all patients were above 4 (moderate to severe pain) before the administration of transdermal fentanyl. The quality of life before and after treatment was evaluated by the Standard of Quality of Life drew up in China in 1990. The adverse events after treatment were evaluated by Common Toxicity Criteria formulated by National Cancer Institute of the USA.. The median VAS score has been decreased from baseline at 6 (4-9) to 3.5 (0-9) on Day 3, 2 (0-6) on Day 5, 0.5 (0-8) on Day 7, 0 (0-6) on Day 10, and 0 (0-5) on Day 15 after treatment (P<0.001). The overall response rate was 100%, while the complete response rate was 45.5%. The quality of life of the patients was improved significantly (P<0.01). The adverse events after treatment of transdermal fentanyl included dizziness, somnolence, dysuria, mild and transient nausea, vomiting, discomfort of stomach, and so on. All the adverse events disappeared within several days after proper managements. Neither severe adverse event nor drug addiction was found.. Transdermal fentanyl has good analgesic effect on painful severe mucositis induced by AHSCT. It is convenient and well tolerated, and could improve quality of life significantly.

Topics: Administration, Cutaneous; Adolescent; Adult; Analgesics, Opioid; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Child, Preschool; Combined Modality Therapy; Cytarabine; Female; Fentanyl; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Non-Hodgkin; Male; Melphalan; Middle Aged; Mucositis; Pain; Pain Measurement; Podophyllotoxin; Quality of Life; Transplantation, Homologous; Young Adult

Since 1997, 32 newly diagnosed multiple myeloma patients responsive to DAV chemotherapy were autografted with idarubicin-intensified busulphan-melphalan (ida-bu-mel). Main endpoints of the study were transplant-related toxicity, overall survival (OS) and progression-free survival (PFS). The results were compared with a historical control group of 38 patients treated with the 'standard' bu-mel regimen. Concerning time to engraftment, no significant difference was observed between the two groups, while toxicity was significantly higher in the intensive conditioning group, regarding grade IV mucositis, duration of profound neutropenia, incidence of infections and platelet requirement. Five-year OS and PFS are 73 versus 78% and 37 versus 48% for the intensive and standard regimen, respectively (p value not significant). The ida-bu-mel schedule appears to be a feasible and effective regimen for newly diagnosed multiple myeloma patients; nevertheless, no apparent benefit in OS and PFS arises from the comparison with a historical control treated with standard bu-mel, which is better tolerated and at least equally effective.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Busulfan; Dacarbazine; Female; Graft Survival; Humans; Idarubicin; Infections; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Neutropenia; Nimustine; Peripheral Blood Stem Cell Transplantation; Transplantation Conditioning; Transplantation, Autologous; Vincristine

We describe the results of a clinical trial to evaluate the feasibility and toxicity of autologous hematopoietic stem cell transplantation (auto-HSCT) for patients with progressive multiple sclerosis (MS). Fifteen patients (all patients with secondary progressive MS) were enrolled. The median expanded disability status scale (EDSS) score at baseline was 6.0 (range, 4.5-7.5). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. In 9 patients, CD34+ cell selection was performed with a CliniMACS cell selection system, and 6 patients accepted infusion of unmodified peripheral blood stem cells. The modified BEAM (carmustine, teniposide, cytarabine, and melphalan) was the sole conditioning regimen used. The adverse effects included infections, mucositis, transient hepatotoxicity, and diarrhea. Three patients had flares of neurologic deterioration during mobilization, 8 patients had the same manifestation during transplantation, and 2 patients had similar flares within 3 months of transplantation. Six patients experienced continuous neurologic improvement after transplantation, 5 patients experienced neurologic progression, and 4 patients had stabilization of their disease. The confirmed progression-free rate was 63.8% at 49 months. The results of lymphocyte purging were no better than for no purging. Auto-HSCT proved to be safe and beneficial for some MS patients. Further studies are needed to establish the merit of this procedure for MS patients.

Topics: Adult; Antigens, CD34; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Diarrhea; Disease-Free Survival; Female; Hematopoietic Stem Cell Mobilization; Humans; Liver Diseases; Lymphocyte Depletion; Male; Melphalan; Middle Aged; Mucositis; Multiple Sclerosis; Peripheral Blood Stem Cell Transplantation; Podophyllotoxin; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous