Summary:A total of 31 consecutive patients with hematologic malignancies who were considered poor candidates for TBI underwent allogeneic stem cell transplantation after conditioning with fludarabine and melphalan. A total of 25 matched sibling recipients received fludarabine 25 mg/ m 2  5 days and melphalan 70 mg/m 2  2 days. For unrelated and haploidentical donor recipients, fludarabine was increased to 30 mg/m 2 and ATG 30 mg/kg  4 days was added. Graft-versus-host disease prophylaxis consisted of tacrolimus and mini methotrexate. All patients engrafted. Regimen-related toxicity was considerable and included mainly renal, hepatic and mucosal toxicity. There were seven regimen-related-deaths including two VOD, two pulmonary, one renal, one cardiac and one mucosal toxicity. One case of fatal pulmonary toxicity death could be attributed to pre-existing pulmonary damage. Progression-free survival at 12 months was 44% (90% CI: 30-58%) for recipients of HLA-identical sibling transplants and 33% (90% CI: 21-45%) for all patients. In conclusion, the fludarabine-melphalan regimen leads to consistent engraftment. The regimen-related toxicity is considerable and cannot be explained solely by patient selection. Cardiac toxicity is emerging as a unique toxicity of this regimen. Despite toxicity, fludarabinemelphalan has considerable activity and leads to durable remission in a proportion of patients. Bone Marrow Transplantation (2003) 32, 471-476. doi:10.1038/sj.bmt.1704166 Keywords: fludarabine; melphalan; nonmyeloablative; transplantation Patients with advanced hematologic malignancies are considered incurable with conventional chemotherapy, but can occasionally be cured with allogeneic transplantation. The impact of allogeneic transplantation is unfortunately limited because of high recurrence rates and due to treatment-related complications in patients with considerable comorbidities. A number of new preparative regimens have been evaluated, which avoid the use of full-dose TBI.1-3 For patients considered ineligible for TBI, we studied the fludarabine-melphalan preparative regimen and report our experience in 31 consecutive patients. This regimen was developed specifically for patients with advanced hematologic malignancies. 1 We confirmed its ability to induce engraftment but observed considerable regimen-related toxicity associated with this regimen that could not be explained solely by patient selection. Patients and methods Patients and protocolPatients were eligible if they had hematologic malignancies including acute and chronic leukemia and myeloproliferative disorders, non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma. Patients with acute leukemia in first remission were enrolled only if they had unfavorable cytogenetics.Additional eligibility criteria included, Karnofsky performance status greater than or equal to 60%, bilirubin less than or equal to 2 mg/dl, creatinine less than 1.5 times normal.Patients were enrolled on this protocol only if they were considered ineligible for TBI, because o...
Summary:Severe regimen-related toxicity often complicates second transplant procedures performed in patients with hematological malignancies that have relapsed after an initial hematopoietic stem cell (HSC) transplant. Therefore, we studied the safety and efficacy of a reduced-intensity fludarabine and melphalan based conditioning regimen in 11 patients who had relapsed following an autologous (n = 7) or allogeneic (n = 4) HSC transplant. All patients received allogeneic peripheral blood HSC from either an HLA-identical (n = 7) or an HLA-mismatched (n = 4) relative. Diagnoses included AML (n = 9), ALL (n = 1), or Hodgkin's disease (n = 1). Only one patient was in complete remission at the time of second transplant. The median interval between first transplant and relapse was 163 days (range 58-1885). Recipients of HLA-mismatched transplants received antithymocyte globulin in addition to fludarabine and melphalan as part of the conditioning regimen. All 11 patients received acute GVHD prophylaxis consisting of tacrolimus and methotrexate. Ten of 11 patients achieved hematopoietic engraftment with a median time to absolute neutrophil count Ͼ0.5 × 10 9 /l and to platelet count of Ͼ20 × 10 9 /l of 14 and 19 days, respectively. All engrafting patients achieved 100% donor chimerism on initial analysis, except for one with persistent leukemia at day +19. Two patients experienced grade 3 regimen-related toxicity, manifesting as acute renal failure. Acute GVHD grades 2-4 occurred in two recipients and chronic GVHD in four. The 100-day mortality from all causes was 36%. Ten of 11 patients (91%) died a median of 140 days (range 9-996) after the second transplant. The causes of death included relapse (n = 5), sepsis (n = 4), and idiopathic pneumonia syndrome (n = 1). One patient with AML survives in remission at 880 days post-transplant. We conclude that fludarabine-and melphalan-based conditioning promotes full donor chimerism, even following Hematopoietic stem cell (HSC) transplantation has improved the likelihood of disease-free survival for many patients with hematological disorders. Nevertheless, relapse remains the major cause of treatment failure following HSC transplantation performed in patients with advanced hematological malignancies. 1,2 The prospects for patients relapsing after an HSC transplant are limited. Donor leukocyte infusion (DLI) has been demonstrated to be effective in patients with chronic myelogenous leukemia (CML), but has met with limited success in highly proliferative malignancies, such as acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). 3,4 Second HSC transplants using allogeneic donors are often attempted, but are fraught with complications. Regimen-related toxicity is usually prohibitive and outcomes are adversely affected by high rates of infection and graft-versus-host disease (GVHD). 2,5-14 Moreover, relapse is common following a second HSC transplant, particularly for patients not in remission at the time of transplantation. Outcomes are particularly poor for patients ...
Fludarabine was utilized in the conditioning regimen of 30 adult patients undergoing an allogeneic hematopoietic stem cell transplant. In 18 patients it was combined with full-dose busulfan (FluBu) as a myeloablative regimen and in 12 cases with melphalan (FluMel) as a reduced intensity conditioning (RIC) regimen. Patients in the FluBu group were younger than in the FluMel group (P ¼ 0.03). Of 30 patients, 24 received peripheral blood stem cells (PBSC) whereas six patients in the FluBu group received bone marrow cells. The hematological toxicity of each regimen was evaluated by analyzing the kinetics of the neutropenia induced by preparative regimens and the time to recovery of the absolute neutrophils count (ANC) and platelets post transplantation. In PBSC transplants, the median day of severe neutropenia (o500 ANC/ll) occurred on day þ 6 after the FluBu regimen and on day þ 3 after FluMel (P ¼ ns), whereas both groups had a duration of severe neutropenia of 9 days and a comparable time for ANC and platelet engraftment. Extra-hematological toxicities were also comparable in the two groups. These findings suggest that the hematological and extra-hematological toxicities induced by fludarabine/full-dose i.v. busulfan are similar to those induced by a standard RIC regimen such as fludarabine/melphalan.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.