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Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m2 (Mel-100, n = 62) versus 140 mg/m2 (Mel-140, n = 283) in combination with Flu. Median age at allo-HCT was 66 years and media…

Melphalan induced germ cell toxicity and dose-dependent effects of β-aminoisobutyric acid in experimental rat model: Role of oxidative stress, inflammation and apoptosis.

The success of chemotherapy regimens has led to an increase in cancer survival rate over the last decades. Melphalan has been widely used for the treatment of several types of cancers despite its gonadotoxic effects. Due to its ability to cause mutations in the spermatogonial stem cells and spermatids, melphalan can exert a negative impact on male reproductive health in young cancer survivors. β-aminoisobutyric acid (BAIBA), a myokine released by skeletal muscles, has been reported to have beneficial effects in diabetic nephropathy, cardiomyopathy and hepatic toxicity. However, the exact role …

Single-center retrospective study assessing the efficacy and safety of BeEAM (bendamustine, etoposide, cytarabine, melphalan) as conditioning regimen for autologous hematopoietic stem cell transplantation.

One of the most widely accepted conditioning regimens for hematopoietic stem cell transplantation (HSCT) is BEAM (carmustine, etoposide, cytarabine, melphalan). However, a recent increase in the cost of carmustine has limited its use bringing our institution to replace carmustine with bendamustine. This observational retrospective single-center study aims to report the efficacy and safety of the BeEAM regimen. 55 patients with diffuse large B-cell lymphoma (47%), Hodgkin lymphoma (25%), mantle cell lymphoma (25%), or follicular lymphoma (2%) were included. Progression-free survival (PFS) at 24…

A novel pro-oxidant combination of resveratrol and copper reduces transplant related toxicities in patients receiving high dose melphalan for multiple myeloma (RESCU 001).

BACKGROUND: Transplant related toxicity is a major therapeutic challenge. We have previously reported that the toxicity of chemotherapy is l … μg). The dose was given twice daily with the first dose administered 48 hours before administering melphalan and continued until day +21 post-transplant. Common Terminology Criteria for Adverse Events version 4.02 was used to assess toxicities which included oral mucositis, nausea, vomiting and diarrhea. Measurement of inflammatory cytokines was done by EL …

Allogeneic hematopoietic cell transplantation using fludarabine plus myeloablative busulfan and melphalan confers promising survival in high-risk hematopoietic neoplasms: a single-center retrospective analysis.

OBJECTIVES: Optimal selection of pretransplant conditioning is crucially vital for improving survival and quality-of-life of patients who receive allogeneic hematopoietic cell transplantation (allo-HCT), particularly in those with high-risk diseases. In this study, we evaluated the efficacy and safety of recently-developed reduced-toxicity myeloablative regimen that combines fludarabine, intravenous busulfan, and melphalan (FBM). METHODS: We conducted a single-center retrospective analysis of 39 patients (23 with myeloid neoplasms and 16 with lymphoid neoplasms), with a median age of 50 (rang…

Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study.

INTRODUCTION: Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who receiv…

Prospective oral mucositis audit: oral mucositis in patients receiving high-dose melphalan or BEAM conditioning chemotherapy--European Blood and Marrow Transplantation Mucositis Advisory Group.

PURPOSE: The Prospective Oral Mucositis Audit assessed the incidence, duration, and determinants of severe oral mucositis (OM; WHO oral toxicity scale grades 3 to 4) in patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) receiving high-dose conditioning chemotherapy before autologous stem-cell transplantation. PATIENTS AND METHODS: Patients with MM (n = 109; mean age, 57 +/- 8 years) or NHL (n = 88; mean age, 50 +/- 13 years) were treated with high-dose melphalan (200 mg/m(2)) or carmustine 300 mg/m(2), etoposide 800 mg/m(2), cytarabine 800 to 1,600 mg/m(2), and melphalan 140 …

Complete remission of previously intractable peripheral cutaneous T-cell lymphoma of the lower extremity using isolated hyperthermic limb perfusion with melphalan (1-phenylalanine mustard).

The patient is a 74-year-old woman first diagnosed with a peripheral cutaneous T-cell lymphoma (PCTCL) in April of 1994. Initially she prese … atening progression of the disease in 2001, she underwent isolated hyperthermic limb perfusion with melphalan (1-phenylalanine mustard). Although limb preservation could not be achieved, this treatment resulted in complete clinical and pathological regression of the lesions of the perfused extremity.

High-dose melphalan-based chemotherapy and autologous stem cell transplantation after second look laparotomy in patients with chemosensitive advanced ovarian carcinoma: long-term results.

The importance of dose intensity has been suggested in ovarian carcinoma. We retrospectively evaluated the long-term results of melphalan-based high-dose chemotherapy (HDC) with hematopoietic rescue in a unicentric series of 33 patients with advanced ovarian cancer sensitive to first-line chemotherapy. Before HDC, treatment with debulking surgery and platinum-based chemotherapy was followed by second-look operation (SLO). HDC consisted of melphalan (n = 8), melphalan and cyclophosphamide (n = 9), or melphalan, etoposide and carboplatinum (n = 16). Toxicity was mainly hematological. One death o…

Assessing Outcomes in Patients With Multiple Myeloma Postautologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200 mg/m2 versus 140 mg/m2.

BACKGROUND: No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence. OBJECTIVE: To evaluate efficacy and safety of standard dose (200 mg/m2 = Mel200) versus reduced dose 140 mg/m2 = Mel140) of melphalan in patients with MM undergoing ASCT. DESIGN: A single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS…

P1680: HEALTH-RELATED QUALITY OF LIFE IN TRANSPLANT-INELIGIBLE REAL-LIFE MULTIPLE MYELOMA PATIENTS TREATED WITH FIXED-DURATION BORTEZOMIB-MELPHALAN-PREDNISONE VS. CONTINUOUS LENALIDOMIDE-DEXAMETHASONE

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… Nine 42-day cycles (12 months [mo] of therapy) of bortezomib-melphalan-prednisone (VMP) and continuous treatment with lenalidomide-dexamethasone (Rd) represented the standard-of-care treatments for transplant-ineligible (NTE) newly diagnosed (ND)MM pts before the introduction of daratumumab upfront. …

Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide.

We compared the health-related quality-of-life of patients with newly diagnosed multiple myeloma aged over 65 years or transplant-ineligible in the pivotal, phase III FIRST trial. Patients received: i) continuous lenalidomide and low-dose dexamethasone until disease progression; ii) fixed cycles of lenalidomide and low-dose dexamethasone for 18 months; or iii) fixed cycles of melphalan, prednisone, thalidomide for 18 months. Data were collected using the validated questionnaires (QLQ-MY20, QLQ-C30, and EQ-5D). The analysis focused on the EQ-5D utility value and six domains pre-selected for the…

Durable second complete remissions with oral melphalan in hypocellular Acute Myeloid Leukemia and Refractory Anemia with Excess Blast with normal karyotype relapsing after intensive chemotherapy.

We treated six patients who had relapsed after intensive chemotherapy, presenting initially with AML or RAEB, a hypocellular marrow and normal karyotype, and who were deemed unsuitable for re-induction with intensive chemotherapy, with low dose oral melphalan. Three of six patients achieved complete hematological response with no significant toxicity and with a duration of 12, 8 and 3+ months respectively. These three patients had received only two prior courses of chemotherapy each, in contrast to non-responders who were more heavily pre-treated. Low dose melphalan is highly effective therapy…

Bortezomib salvage followed by a Phase I/II study of bortezomib plus high-dose melphalan and tandem autologous transplantation for patients with primary resistant myeloma.

We conducted a Phase 1/2 study of bortezomib administered in combination with high-dose melphalan followed by tandem autologous transplants in patients with primary resistant multiple myeloma. Thirty patients received two cycles of salvage bortezomib followed by stem cell mobilization with granulocyte colony-stimulating factor and harvest. Melphalan 100 mg/m(2) per day on two consecutive days was administered, immediately followed by one dose of bortezomib (dose escalation) and stem cell infusion. The median beta 2-microglobulin was 4·35 mg/l (range: 1·8-11·4); albumin was 37 g/l (range: 3·1-4…

Veno-occlusive disease of the liver after high-dose cytoreductive therapy with busulfan and melphalan for autologous blood stem cell transplantation in multiple myeloma patients.

Veno-occlusive disease of the liver (VOD) is a potentially severe complication of high-dose cytoreductive therapy (HDT) used for stem cell transplantation (SCT). This complication is uncommon after HDT for autologous SCT (ASCT) in patients with multiple myeloma (MM). The Spanish Myeloma Group/PETHEMA conducted a study (MM2000) for patients with newly diagnosed MM consisting of induction with alternating VBMCP/VBAD chemotherapy followed by intensification with busulfan/melphalan (Bu/MEL) with a second high-dose therapy procedure in patients not achieving at least near-complete remission with th…

Double high-dose therapy for Hodgkin's disease with dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP) prior to high-dose melphalan and autologous stem cell transplantation.

We previously reported a 50% (95% CI = 33-76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin's disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. Since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASC…

Netupitant/palonosetron is effective for preventing chemotherapy-induced nausea and vomiting in high-dose melphalan conditioning before autologous stem cell transplantation: A real-world analysis.

High-dose melphalan (HDM) is the standard conditioning regimen before autologous stem cell transplantation (ASCT) in plasma cell malignancies. Despite prophylactic antiemetics, chemotherapy-induced nausea and vomiting (CINV) remains a prevalent challenge. We retrospectively compared the efficacy of netupitant and palonosetron (NEPA) plus dexamethasone with that of serotonin receptor antagonist (5-HT3RA)-based regimens (the control group) for patients receiving HDM. The primary endpoint was complete resolution (CR) of CINV in the acute (0-24 hours) and delayed (24-168 hours) phases. Secondary e…

P12 HEALTH-RELATED QUALITY OF LIFE IN FRAIL AND INTERMEDIATE-FIT PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH DOSE-ADJUSTED MELPHALAN-PREDNISONE-BORTEZOMIB (MPV)

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