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Onkologie Apr 1990The symptomatology and outcome of three of our own cases with Melphalan overdose are presented. The literature regarding Melphalan overdose and its toxicity when given... (Review)
Review
The symptomatology and outcome of three of our own cases with Melphalan overdose are presented. The literature regarding Melphalan overdose and its toxicity when given in normal and high doses is reviewed. Two of our cases with injection of less than 100 mg/m2 recovered from marrow aplasia within 3 weeks without major complications. The third patient died 6 days after injection of 290 mg/m2 Melphalan, probably due to cardiac arrhythmia before complete marrow failure had established. After intravenous application of more than 125 mg/m2 gastrointestinal side effects such as hemorrhagic diarrhea or even bowl perforation may be observed. These, together with a syndrome of inadequate ADH-secretion and electrolyte disturbances were the predominant clinical problems and the reasons for early death before infectious or bleeding complications due to prolonged marrow aplasia occur. Therapeutic measures are discussed. Due to the lack of a clinically useful antidote and detoxification method only symptomatic treatment is recommended. Colony stimulating factors such as GM-CSF G-CSF may improve the prognosis of moderate to severe Melphalan overdose.
Topics: Bone Marrow; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Infusions, Intravenous; Medication Errors; Melphalan; Middle Aged; Ovarian Neoplasms
PubMed: 2197588
DOI: 10.1159/000216734 -
British Journal of Cancer Jul 1994In 14 consecutive patients with recurrent melanoma of the lower limb a total of 35 biopsies were taken at the end of perfusion treatment to assess melphalan tissue...
In 14 consecutive patients with recurrent melanoma of the lower limb a total of 35 biopsies were taken at the end of perfusion treatment to assess melphalan tissue concentrations in tumour, skin/subcutis and muscle tissue. In tumour tissue (n = 12) the mean melphalan concentration was 6.8 micrograms g-1, which was significantly higher than that of healthy skin/subcutis (3.2 micrograms g-1; n = 10), but equal to that of muscle tissue (6.5 micrograms g-1; n = 13). The correlation between melphalan concentration in the tissues and the concentration in the perfusate was studied. The latter was assessed in the form of melphalan peak concentration and the area under the curve (AUC0-->60) of the melphalan concentration-time curve. Tumour concentration proved to be correlated linearly with AUC0-->60 (R = 0.6, P = 0.002) and muscle concentration with melphalan peak concentration (R = 0.8, P = 0.04). There was no relation between skin/subcutis concentrations and the perfusate parameters. Further research is warranted to study the relationship between melphalan tissue concentration, tumour response and regional toxicity.
Topics: Chemotherapy, Cancer, Regional Perfusion; Chromatography, High Pressure Liquid; Female; Humans; Leg; Male; Melanoma; Melphalan; Middle Aged; Muscles; Skin; Skin Neoplasms
PubMed: 8018528
DOI: 10.1038/bjc.1994.266 -
Lancet (London, England) Nov 1983
Topics: Humans; Melphalan; Multiple Sclerosis
PubMed: 6139546
DOI: 10.1016/s0140-6736(83)91240-0 -
Bone Marrow Transplantation Jul 2019High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations...
High-dose melphalan is the standard conditioning regimen for patients with AL amyloidosis receiving autologous stem cell transplantation. Conventional formulations require propylene glycol (PG) as a co-solvent and melphalan has limited solubility and chemical stability after reconstitution, with potential risks for propylene glycol-related complications. Captisol-stabilized propylene glycol-free (PG-free) melphalan has been developed with improved solubility and chemical stability. We compared a cohort of patients with AL amyloidosis receiving PG melphalan (n = 96) to those receiving PG-free melphalan (n = 48) as conditioning for autologous stem cell transplantation. Median time to neutrophil and platelet engraftment was the same; 14 days PG melphalan vs 14 days PG-free melphalan, p = 0.73 and 16 days PG melphalan vs 16 days PG-free melphalan, p = 0.52, respectively. Hospitalization rate was similar in both cohorts, 68% PG melphalan vs 58% PG-free melphalan, p = 0.27. All-cause mortality at 100 days was not statistically significant, 3% PG melphalan vs 2% PG-free melphalan, p > 0.99. Overall response rate (ORR) and rates of complete response (CR) were similar (ORR 93% PG melphalan vs 94% PG-free melphalan, p > 0.99 and CR 39% PG melphalan vs 32% PG-free melphalan, p = 0.46). PG-free melphalan showed a comparable safety and efficacy profile to PG melphalan in patients with AL amyloidosis receiving stem cell transplantation.
Topics: Aged; Antineoplastic Agents, Alkylating; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Transplantation Conditioning; Transplantation, Autologous
PubMed: 30390060
DOI: 10.1038/s41409-018-0388-x -
Investigational New Drugs 1983A pharmacokinetic study of high dose intravenous melphalan, 180 mg/m2, was performed in eight patients. Plasma levels of melphalan declined in a biexponential fashion...
A pharmacokinetic study of high dose intravenous melphalan, 180 mg/m2, was performed in eight patients. Plasma levels of melphalan declined in a biexponential fashion with a mean terminal half-life (t 1/2 beta) of 61 min (range 40.3-132.8 min). Estimated peak concentrations ranged from 5.45 to 16.57 mcg/ml. The average volume of distribution at steady state (Vdss) and clearance were 0.479 +/- 0.164 l/kg and 6.73 +/- 1.60 ml/min/kg, respectively. These kinetic parameters are similar to those reported from studies using lower doses of melphalan.
Topics: Adult; Half-Life; Humans; Kinetics; Male; Melphalan; Middle Aged; Tumor Stem Cell Assay
PubMed: 6678879
DOI: 10.1007/BF00177417 -
Biology of Blood and Marrow... Sep 2018Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those...
Melphalan-Based Reduced-Intensity Conditioning is Associated with Favorable Disease Control and Acceptable Toxicities in Patients Older Than 70 with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.
Allogeneic hematopoietic stem cell transplantation (alloHCT) is offered increasingly to elderly patients with hematologic malignancies. However, outcome data in those who are 70 years or older are limited, and no standard conditioning regimen has been established for this population. In this retrospective study we evaluated the outcome of 53 consecutive patients aged 70 years and older who underwent alloHCT with melphalan-based reduced-intensity conditioning (RIC) at City of Hope. Engraftment was prompt, with median time to neutrophil engraftment of 15 days. More than 95% of patients achieved complete donor chimerism within 6 weeks from HCT, consistent with the "semiablative" nature of this regimen. With a median follow-up of 31.1 months, the 2-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) were 68.9%, 63.8%, and 17.0%, respectively. Cumulative incidence of relapse at 1 and 2 years was 17.0% and 19.3%, respectively. One hundred-day cumulative incidence of grades II to IV acute graft-versus-host disease was 37.7% (grades III to IV, 18.9%), and 2-year cumulative incidence of chronic graft-versus-host disease was 61.9% (extensive, 45.9%). The only significant predictor for poor OS was high/very high disease risk index. Transplant-related complications and morbidities observed here did not differ from the commonly expected in younger patients treated with RIC. In conclusion, alloHCT with a melphalan-based conditioning regimen is associated with acceptable toxicities and NRM, lower incidence of relapse, and favorable OS and PFS in patients aged 70 years or older.
Topics: Aged; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Retrospective Studies; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous
PubMed: 29753158
DOI: 10.1016/j.bbmt.2018.04.029 -
Bone Marrow Transplantation Aug 2019Cardiac deposition of misfolded light chains is the leading cause of morbidity and mortality in patients with immunoglobulin (AL) amyloidosis. Cardiac defibrillators can...
Cardiac deposition of misfolded light chains is the leading cause of morbidity and mortality in patients with immunoglobulin (AL) amyloidosis. Cardiac defibrillators can be used in the management of patients with advanced cardiac amyloidosis, but data concerning the use of these devices in patients undergoing treatment with high-dose melphalan followed by autologous peripheral blood stem cell transplantation (HDM/SCT) is limited. Herein we describe a single-institution experience of HDM/SCT in 15 patients with cardiac defibrillators. During the peri-transplant period, five of these patients (33%) had detectable cardiac arrhythmias and two patients (13%) had implantable cardiac defibrillator (ICD) discharges. Thirteen of the 14 evaluable patients (93%) achieved at least a partial hematologic response. Transplant-related mortality was 6.7% and median overall survival was 40.8 months, with multiple patients achieving an overall survival of >10 years. These data highlight the feasibility of HDM/SCT in patients with an ICD due to advanced cardiac AL amyloidosis, but highlight the need for additional research to appropriately determine which patients will benefit from this aggressive therapy.
Topics: Adult; Amyloidosis; Antineoplastic Agents, Alkylating; Defibrillators; Female; Heart; Humans; Male; Melphalan; Middle Aged; Peripheral Blood Stem Cell Transplantation
PubMed: 30664726
DOI: 10.1038/s41409-019-0440-5 -
Blood Jul 1970
Topics: Aged; Anemia, Sideroblastic; Blood Platelets; Female; Hemoglobinometry; Humans; Leukocyte Count; Leukopenia; Male; Melphalan; Polycythemia Vera; Primary Myelofibrosis
PubMed: 5421745
DOI: No ID Found -
American Journal of Clinical Oncology Aug 2003The purpose of this study was to determine the response to melphalan in patients with recurrent epithelial ovarian cancer after platinum-based therapy. This...
The purpose of this study was to determine the response to melphalan in patients with recurrent epithelial ovarian cancer after platinum-based therapy. This retrospective observational study analyzed 10 patients with recurrent epithelial ovarian carcinoma treated with melphalan between August 1995 and April 2001. All had received primary platinum-based therapy. Nine of the 10 patients had chemosensitive disease. All but one patient had received one or more second-line therapies prior to melphalan. The median time to recurrence after first-line therapy was 26 months (range, 3-68). Treatment with melphalan resulted in 2 (20%) complete responses and 1 (10%) partial response (response rate, 30%; 95% CI 8%, 65%). The median progression-free interval after initiation of melphalan therapy was 8 months (range, 3-23). The most common side effects were grade I thrombocytopenia (20% of courses) and grade II leukopenia (18% of courses). The use of melphalan as palliative chemotherapy in patients with recurrent ovarian cancer results in response rates similar to those reported with other more expensive agents. Melphalan at the doses reported here has a favorable toxicity profile.
Topics: Administration, Oral; Antineoplastic Agents, Alkylating; Female; Humans; Melphalan; Neoplasm Recurrence, Local; Ovarian Neoplasms; Palliative Care; Platinum Compounds; Retrospective Studies; Salvage Therapy; Survival Analysis
PubMed: 12902900
DOI: 10.1097/01.COC.0000027269.06091.E9 -
Recenti Progressi in Medicina Sep 1968
Review
Topics: Aged; Diagnosis, Differential; Female; Humans; Male; Melphalan; Middle Aged; Plasmacytoma; gamma-Globulins
PubMed: 4192432
DOI: No ID Found