melphalan and Fever

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinra, minimized the duration and intensity of mucosal barrier injury and accompanying clinical symptoms, including diarrhea, weight loss and fever in rats. 16S analysis of fecal microbiome demonstrated a more stable composition in rats receiving anakinra, with reduced pathogen expansion. In parallel, we report through Phase IIA investigation that anakinra is safe in stem cell transplant patients with multiple myeloma after HDM. Ramping-up anakinra (100-300 mg administered intravenously for 15 days) did not cause any adverse events or dose limiting toxicities, nor did it change time to neutrophil recovery. Our results reinforce that strengthening the mucosal barrier may be an effective supportive care strategy to mitigate local and systemic clinical consequences of HDM. We are now conducting a Phase IIB multicenter, placebo-controlled, double-blinded trial to assess clinical efficacy of anakinra (AFFECT-2).Trial registration: ClinicalTrials.gov identifier: NCT03233776.

Topics: Animals; Fever; Hematopoietic Stem Cell Transplantation; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Melphalan; Multiple Myeloma; Rats; Tumor Microenvironment

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

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

High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2-4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5-8.5) and 64 (39-73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525-531.

Topics: Adolescent; Adult; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Carmustine; CD4-CD8 Ratio; Cytarabine; Etoposide; Female; Fever; Follow-Up Studies; Graft Survival; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infections; Leukapheresis; Lymphocyte Subsets; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Sclerosis; Neutropenia; Prognosis; Severity of Illness Index

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

In a Nordic multi-centre trial, 583 previously untreated multiple myeloma patients were randomized to receive melphalan-prednisone or melphalan-prednisone+ interferon alpha-2b at a dose of 5 million units subcutaneously, 3 d/week. A quality-of-life study was integrated into the trial, using the EORTC QLQ C-30 questionnaire supplemented with 11 questions concerning interferon toxicity. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 90% of the patients participated in the quality-of-life study, and 83% completed all questionnaires submitted to them. During the first year of treatment the patients on interferon reported significantly more fever, chills, dry skin, fatigue, pain, nausea/vomiting and appetite loss than the control patients. There was a moderate reduction of the global quality-of-life score and slight, non-significant, reductions of physical, emotional, cognitive, social and role functioning scores. After the first year there were no statistically significant differences in any toxicity, symptom or quality-of-life score, except for an increased frequency of dizziness in the interferon group. As only 60% of the patients remained on interferon after 24 months, our data probably underestimate the potential toxicity of the drug. Although there was no significant survival benefit for the interferon patients, a 5-6 months prolongation of the response and plateau phase duration was observed. However, by intention-to-treat analysis, there was no late quality-of-life benefit for the interferon patients to compensate for the early impairment. Thus, the clinical significance of the plateau-phase prolongation is uncertain.

Topics: Activities of Daily Living; Aged; Antineoplastic Combined Chemotherapy Protocols; Fatigue; Feeding and Eating Disorders; Fever; Humans; Interferon alpha-2; Interferon-alpha; Melphalan; Multiple Myeloma; Nausea; Pain; Prednisone; Quality of Life; Recombinant Proteins; Social Behavior; Vomiting

Interferon (INF) has been incorporated as part of maintenance therapy after high dose treatment in order to make remissions more durable. In this study we have compared peripheral blood stem cell transplant (PBSCT) versus autologous bone marrow transplant (ABMT) with respect to INF tolerance. Thirty nine PBSCT patients have been compared to 37 ABMT patients for INF tolerance. This is followed by a comparison of 15 PBSCT patients versus 21 ABMT patients for engraftment details, response and survival. INF was started at a median of 61 days in the PBSCT and 58 days in the ABMT patients (P = NS). It was well tolerated in both groups without a significant difference in toxicity in the two arms. Engraftment was more rapid in the PBSCT patients with platelet recovery being significantly faster. Response and survival showed a favourable trend for ABMT patients though statistical significance was not reached and the cost of PBSCT was 12% cheaper. We were thus able to conclude that PBSCT grafts were as durable and could tolerate INF just as well as ABMT. Engraftment was more rapid and the procedure of PBSCT was also cheaper. Further studies with a larger group of patients will be required before comments on the efficacy of treatment can be made.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Disease-Free Survival; Fatigue; Female; Fever; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Life Tables; Male; Melphalan; Middle Aged; Multiple Myeloma; Pain; Recombinant Proteins; Remission Induction; Survival Analysis; Thrombocytopenia; Transplantation, Autologous; Treatment Outcome

The objectives of this study were to compare the costs of managing lymphoma patients who underwent mini-BEAM salvage chemotherapy with G-CSF prophylactic support against a group of similar patients without growth factors. Methods used included: 1) A retrospective chart review was conducted to estimate the average length of hospitalization and resource consumption for the management of fever and neutropenia in the two groups of patients and 2) An economic analysis was then performed from a hospital perspective which considered only institutional resource utilization. Costs of antibiotic support and monitoring, lab tests as well as G-CSF were calculated. Results demonstrated that overall, patients who received prophylactic G-CSF after chemotherapy required 2 fewer hospital days compared to controls. The administration of G-CSF resulted in a savings of approximately $1580/patient relative to control. When the initial G-CSF expenditure was included in the analysis, the total net cost/patient was similar between the two groups. In conclusion, the results of the current study support the routine use of G-CSF in patients receiving salvage chemotherapy with mini-BEAM. The initial G-CSF expenditure would be offset by reduced hospitalization.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Fever; Granulocyte Colony-Stimulating Factor; Hodgkin Disease; Humans; Length of Stay; Lymphoma, Non-Hodgkin; Melphalan; Neutropenia; Retrospective Studies; Salvage Therapy

The influence of interferon-induced fever on oral melphalan pharmacokinetics has been studied in 10 myeloma patients in a randomized crossover design. The melphalan dose (0.25 mg/kg) was given alone and 5 hours after the administration of human interferon alpha (7 x 10(6) IU/m2), respectively. The plasma concentration of melphalan was determined by liquid chromatography with fluorometric detection after derivatization of melphalan with N-acetylcysteine. The area under the plasma concentration-time curve (AUC) was significantly lower (p = 0.02) when melphalan was given with interferon. There was a significant negative correlation (p = 0.008) between body temperature and dose normalized AUC, whereas no effect was noticed on the maximum plasma concentration (Cmax) and on the time to obtain Cmax. The rate of elimination showed a tendency (p = 0.06) to increase with increasing body temperature. It is suggested that the cytotoxicity of the drug is most probably enhanced because of the higher alkylating activity of the compound at elevated body temperatures.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Body Temperature; Drug Interactions; Female; Fever; Half-Life; Humans; Interferon Type I; Male; Melphalan; Metabolic Clearance Rate; Middle Aged; Multiple Myeloma; Prednisone

Conditioning therapy with high-dose melphalan (HDM) is associated with a high risk of gut toxicity, fever and infections in haematopoietic stem cell transplant (HSCT) recipients. However, validated preclinical models that adequately reflect clinical features of melphalan-induced toxicity are not available. We therefore aimed to develop a novel preclinical model of melphalan-induced toxicity that reflected well-defined clinical dynamics, as well as to identify targetable mechanisms that drive intestinal injury.. Male Wistar rats were treated with 4-8 mg/kg melphalan intravenously. The primary endpoint was plasma citrulline. Secondary endpoints included survival, weight loss, diarrhea, food/water intake, histopathology, body temperature, microbiota composition (16S sequencing) and bacterial translocation.. Melphalan 5 mg/kg caused self-limiting intestinal injury, severe neutropenia and fever while impairing the microbial metabolome, prompting expansion of enteric pathogens. Intestinal inflammation was characterized by infiltration of polymorphic nuclear cells in the acute phases of mucosal injury, driving derangement of intestinal architecture. Ileal atrophy prevented bile acid reabsorption, exacerbating colonic injury via microbiota-dependent mechanisms.. We developed a novel translational model of melphalan-induced toxicity, which has excellent homology with the well-known clinical features of HDM transplantation. Application of this model will accelerate fundamental and translational study of melphalan-induced toxicity, with the clinical parallels of this model ensuring a greater likelihood of clinical success.

Topics: Animals; Bacterial Translocation; Bile Acids and Salts; Fever; Gastrointestinal Microbiome; Hematopoietic Stem Cell Transplantation; Inflammation; Intestinal Diseases; Male; Melphalan; Microbiota; Neutropenia; Rats; Rats, Wistar; Transplantation Conditioning; Transplantation, Autologous

Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT.. Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT.. The incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age ≥60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05).. G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Aged; Antineoplastic Agents, Alkylating; Female; Fever; Granulocyte Colony-Stimulating Factor; Humans; Incidence; Male; Melphalan; Middle Aged; Multiple Myeloma; Odds Ratio; Patient Readmission; Progression-Free Survival; Risk Factors; Stem Cell Transplantation; Transplantation, Autologous

Chromosomally integrated human herpesvirus 6 (ciHHV-6) can be transmitted via allogeneic hematopoietic cell transplantation. To date, only a few cases have been reported. Here, we report a case identified as transmission of ciHHV-6 via cord blood transplantation. Distinguishing transmission of ciHHV-6 from HHV-6 reactivation in cases with high titer of HHV-6 DNA load after transplantation is important to prevent unnecessary exposure to antiviral drugs that could be toxic.

Topics: Acyclovir; Antibiotic Prophylaxis; Antiviral Agents; Busulfan; Child, Preschool; Chromosomes, Human, Pair 22; Cord Blood Stem Cell Transplantation; DNA, Viral; Exanthema; Fetal Blood; Fever; Herpesvirus 6, Human; Humans; Immunocompromised Host; Male; Melphalan; Myeloablative Agonists; Roseolovirus Infections; Transplantation Conditioning; Unrelated Donors; Valacyclovir; Valine; Viral Load; Virus Integration

Aggressive treatment with high-dose i.v. melphalan followed by auto-SCT (HDM/SCT) is effective in inducing hematological and clinical remissions, and in extending survival in AL amyloidosis. Tandem cycles of HDM/SCT have been shown to increase hematologic complete response rates in patients with AL amyloidosis. Between April 1994 and July 2008, 57 patients with AL amyloidosis at the Boston University Medical Center were treated with a second cycle of HDM/SCT after failing to achieve a complete response after a first transplantation. A total of 11 of 57 patients (19%) treated with tandem transplantation developed high fever 12-24 h after melphalan administration. The average peak temperature was 39.1 degrees C. Other clinical features include hypotension, acute renal failure and skin rash. No infectious etiology was identified. One of the patients had serum available for measurement of cytokines before, during and after the febrile reaction. The concentration of several pro-inflammatory cytokines, including IL-6 and TNFalpha, increased significantly, showing a clear physiological response correlating with the clinical findings. We conclude that an unusual cytokine-mediated febrile reaction can occur in patients with AL amyloidosis exposed to a second cycle of high-dose melphalan, which we have termed a 'melphalan recall' reaction.

Topics: Adult; Amyloidosis; Antineoplastic Agents, Alkylating; Cytokines; Female; Fever; Humans; Male; Melphalan; Middle Aged; Paraproteinemias; Stem Cell Transplantation; Transplantation Conditioning

A 45-year-old woman was referred to our hospital with acute renal failure and pyrexia. In August 2005, the patient was diagnosed with IgA-λ type multiple myeloma with chromosome 13 deletion, and received three cycles of vinclistine, adriamycin and dexamethasone followed by high-dose melphalan-based autologous peripheral stem cell transplantation: this resulted in remission 2 months before admission to our hospital. Serum IgA concentration was within the normal limit, but an excess of myeloma cells in bone marrow was confirmed. Immunoelectrophoresis revealed BJP-λ production with no IgA-λ. The patient received several courses of chemotherapy with mechanical ventilation and regular hemodialysis. The progression of the illness was rapid: multiple organ failure promptly developed and the patient died 2 months after admission. Autopsy revealed deposition of light chain λ protein in multiple organs. We report this unusual case of aggressive myeloma recognized shortly after successful autologous transplantation.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 13; Dexamethasone; Doxorubicin; Female; Fever; Humans; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Remission Induction; Transplantation, Autologous; Vincristine

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 brief period of neutropenia and limited nonmarrow toxicity after high-dose melphalan (HDM) provide a rationale for outpatient treatment.. Our experience with HDM (140-200 mg/m(2)) in 90 consecutive transplant episodes was retrospectively reviewed. Most patients were treated in an outpatient setting. Patients without a primary care provider (PCP) were electively admitted before the anticipated onset of neutropenia. Ceftriaxone was added to ciprofloxacin at the onset of neutropenia. All febrile patients were admitted.. The median time from peripheral blood progenitor cell infusion to onset of neutropenia was 5 days (range, 4-6 days), and the mean duration of neutropenia was 5 days (range, 4-7 days). Thirty-eight transplants (42%) were performed entirely in the outpatient setting. The mean duration of hospitalization was 2.2 days in patients not electively admitted. The use of ceftriaxone was associated with a decreased risk for fever (39% vs. 79%) and reduced duration of hospitalization (1.6 days vs. 4.5 days) for nonelectively admitted patients. There was no treatment-related mortality.. Ambulatory therapy with HDM is safe and can be achieved in a general outpatient setting. The predictable time to neutropenia allows even poor candidates for outpatient therapy to be admitted electively on Day +4. The apparent beneficial effect of ceftriaxone needs to be confirmed in randomized trials.

Topics: Adult; Aged; Ambulatory Care; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents, Alkylating; Bacteremia; Ceftriaxone; Dose-Response Relationship, Drug; Fever; Hospitalization; Humans; Incidence; Length of Stay; Melphalan; Middle Aged; Multiple Myeloma; Neutropenia; Retrospective Studies; Staphylococcal Infections; Stem Cell Transplantation

Treatment of patients with AL amyloidosis with high-dose melphalan and autologous peripheral blood stem cells (PBSC) produces hematologic remissions in approximately 40% of evaluable patients, accompanied by improvements in organ disease and quality of life. These patients, who frequently have amyloid deposits in bone marrow blood vessels and interstitium and impaired function of kidneys, liver, spleen, and heart, represent an unusual population for stem cell transplantation, with unique problems. To identify factors influencing engraftment rates after chemotherapy and autologous granulocyte colony-stimulating factor (G-CSF)-mobilized PBSC reinfusion, we studied a group of 225 patients. The median time to neutrophil engraftment was 10 days (range, 8-17 days). In a multivariate analysis, the factors positively affecting the rate of neutrophil engraftment were CD34+ stem cell dose, female gender, and minimal prior alkylator therapy. The median time to platelet engraftment was 13 days (range, 7-52 days). Factors positively affecting platelet engraftment, in addition to CD34+ cell dose, included preserved renal function and the absence of neutropenic fever. The conditioning dose of intravenous melphalan was not found to be an independent predictive factor for hematopoietic recovery. Thus, in this patient population, organ function and host and hematopoietic factors influence engraftment after PBSC rescue.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Antigens, CD34; Antineoplastic Agents, Alkylating; Blood Platelets; Female; Fever; Graft Survival; Humans; Kinetics; Male; Melphalan; Middle Aged; Neutrophils; Peripheral Blood Stem Cell Transplantation; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Sex Factors; Transplantation, Autologous

We describe here an extremely rare case of primary amyloidosis which presented moderate pleural effusion and high fever. A 71-year-old man was admitted to our hospital because of exertional dyspnea, fatigue and fever. A chest X-ray showed right-sided moderate pleural effusion. A thoracocentesis revealed an exudative pleural effusion. Cytology and cultures of the effusion were negative. External drainage failed to control the effusion. To determine the etiology of the effusion and fever, bronchoscopy was performed. Biopsies of the tracheal wall showed amyloid deposition. The pleural effusion might have been due to the inflammation and the disturbed lymphatic drainage caused by the amyloid deposition. Treatment with melphalan (6 mg) and prednisolone (35 mg) for 4 days every 6 weeks decreased the fever and alleviated his symptoms.

Topics: Aged; Amyloidosis; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Bronchoscopy; Dyspnea; Exudates and Transudates; Fever; Humans; Lung Diseases; Male; Melphalan; Pleural Effusion; Prednisolone; Treatment Outcome

Infectious complications were retrospectively analyzed in 129 transplants, performed in 90 patients, to identify characteristics that qualify breast cancer patients for outpatient-based PBSCT. Thirty-one cases (24%) did not develop fever. Of the remaining 98 cases, 84.7% developed fever during severe neutropenia. On univariate analysis, disease stages II-III, first PBSCT, mucositis grades II-IV and the use of two alkylators were associated with a higher risk of fever development. The latter two factors also affected fever occurrence on multivariate analysis. A longer median time to fever onset was observed in patients conditioned with single as compared to double alkylating agent-containing regimens (respectively 8th vs 6th day, P < 0.00001). As compared with metastatic breast cancer (MBC), high risk breast cancer showed a 2.3-fold increased risk of developing early fever during neutropenia (CI 2.3-3.8), remaining the only variable still significant on multivariate analysis (P = 0.0039). Combination antibiotic therapy was equivalent to single agent therapy. Patients suffering from microbiologically documented fever were at higher risk of undergoing second-line antibiotic therapy. In conclusion, MBC patients treated with a conditioning regimen containing only one alkylating agent and adequate prophylaxis for mucositis may qualify for outpatient-based PBSCT on the basis of a lower risk of infection.

Topics: Adult; Aged; Ambulatory Care; Anti-Bacterial Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Combined Modality Therapy; Cyclophosphamide; Docetaxel; Drug Therapy, Combination; Female; Fever; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Infection Control; Infections; Inflammation; Melphalan; Middle Aged; Mitoxantrone; Mucous Membrane; Multivariate Analysis; Neutropenia; Paclitaxel; Patient Selection; Retrospective Studies; Risk; Taxoids; Thiotepa; Transplantation Conditioning

The incidence of long-term (> or = 3 months) neuropathy in 350 melanoma patients treated with single normothermic or 'mild' hyperthermic perfusion with melphalan in the period 1978 to 1990 was studied. Long-term neuropathy was encountered in 14 patients; in 10/51 patients (20%) after perfusion at the axillary level and in 4/247 patients (2%) after perfusion at the iliac level. After brachial and femoro-popliteal perfusions no long-term neuropathy was observed. Neuropathy, mainly consisting of paresis/paralysis of the hand and/or fingers, anaesthesia, and/or paraesthesiae, improved over a mean period of 16 (3-43) months in eight patients, but three patients still had serious neuropathy one year after perfusion. In another six patients little improvement was seen and four died with permanent neuropathy. Acute regional toxicity after perfusion and the application of 'mild' hyperthermia did not seem to influence the incidence of long-term neuropathy. This complication is probably a result of the isolating Esmarch rubber bandage being applied too tightly during perfusion at a proximal level. At the axillary level, where the brachial plexus lacks the protection from enveloping tissues, nerve damage is especially prone to occur. We recommend applying this bandage no tighter than is necessary to maintain the isolation of the circuit. This implies meticulous surgical isolation of the vascular system and accurate monitoring of leakage.

Topics: Adolescent; Adult; Aged; Arm; Chemotherapy, Cancer, Regional Perfusion; Female; Fever; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Paralysis; Paresis; Peripheral Nervous System Diseases; Retrospective Studies; Sensation Disorders; Skin Neoplasms; Time Factors

Topics: Adult; Bone Marrow Transplantation; Cyclophosphamide; Epilepsy, Tonic-Clonic; Fever; Graft vs Host Disease; Humans; Leukemia, Erythroblastic, Acute; Male; Melphalan; Mitoxantrone; Multiple Myeloma; Purpura, Thrombotic Thrombocytopenic; Whole-Body Irradiation

The effects of the alkylating cytostatic drug PTC on the production of radiation-induced single-strand breaks in DNA, and on the repair in L cells incubated at 37 degrees or 42 degrees C were studied. The same amount of SSB is obtained when the cells are treated simultaneously with PTC and hyperthermia as when irradiated with 2 500 rad, but different rate in the rejoining was observed. There is no potentiation of SSB formation by pretreatment of cells with 10 microgram PTC/ml for 2 hours at 42 degrees C before irradiation, but in these cells less effective repair occurs. The effect of PTC on the rejoining of SSB induced with 2 500 rad depends on the drug's concentration and post-incubation time.

Topics: Alkylating Agents; Animals; DNA; DNA Repair; Fever; Humans; In Vitro Techniques; L Cells; Melphalan; Peptichemio; Radiation Dosage; Time Factors

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Topics: Aged; Bone Marrow; Bone Marrow Examination; Cell Count; Cells, Cultured; Drug Evaluation; Drug Resistance; Female; Fever; Hemoglobins; Humans; Immunoglobulin G; Immunoglobulin lambda-Chains; Interferons; Melphalan; Multiple Myeloma; Neoplasm Recurrence, Local; Thrombocytopenia

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Chlorpromazine; Cyclophosphamide; Female; Fever; Humans; Liver Neoplasms; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Melphalan; Middle Aged; Nasopharyngeal Neoplasms; Nausea; Neoplasm Recurrence, Local; Olivomycins; Thiotepa; Thrombocytopenia; Tonsillar Neoplasms; Vomiting