Fludarabine Melphalan reduced-intensity conditioning allotransplanation provides similar disease control in lymphoid and myeloid malignancies: analysis of 344 patients

Abstract

This was an Australasian Bone Marrow Transplant Recipient Registry (ABMTRR)-based retrospective study assessing the outcome of Fludarabine Melphalan (FluMel) reduced-intensity conditioning between 1998 and 2008. Median follow-up was 3.4 years. There were 344 patients with a median age of 54 years . In all, 234 patients had myeloid malignancies, with AML (n ¼ 166) being the commonest indication. There were 110 lymphoid patients with non-hodgkins lymphoma (NHL) (n ¼ 64) the main indication. TRM at day 100 was 14% with no significant difference between the groups. OS and disease-free survival (DFS) were similar between myeloid and lymphoid patients (57 and 50% at 3 years, respectively). There was no difference in cumulative incidence of relapse or GVHD between groups. Multivariate analysis revealed four significant adverse risk factors for DFS: donor other than HLAidentical sibling donor, not in remission at transplant, previous autologous transplant and recipient CMV positive. Chronic GVHD was associated with improved DFS in multivariate analysis predominantly due to a marked reduction in relapse (HR:0.44, P ¼ 0.003). This study confirms that FluMel provides durable and equivalent remissions in both myeloid and lymphoid malignancies. Disease stage and chronic GVHD remain important determinants of outcome for FluMel allografting.

Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse

“…Therefore, consideration of transplant conditions is important when assessing the results of chimerism analysis. No significant differences in transplant outcomes were reported between melphalan doses of 140 and 120 mg/m 2 in a recent large study in which most patients received PBSCT conditioned with FM [25]. Thus, a melphalan dose of 120 mg/m 2 in combination with fludarabine is likely an acceptable preparative regimen when peripheral blood stem cells are used as the stem cell source.…”

Allogeneic Hematopoietic Stem Cell Transplantation after Conditioning Regimens with Fludarabine/melphalan or Fludarabine/busulfan for Patients with Hematological Malignancies: A Single-center Analysis

“…Fludarabinebased regimens have been used as conditioning regimens for allo-HSCT in patients who must avoid cyclophosphamide toxicity or high-dose total body irradiation (TBI). Although fludarabine-based regimens with melphalan or busulfan have been widely used (2)(3)(4)(5)(6)(7)(8), and there have been several retrospective reports comparing the two regimens (9)(10)(11), there have been no randomized, controlled trials to compare these two regimens. We believed that an understanding of the current status is important to conduct prospective trials in the future.…”

Outcomes following second allogeneic haematopoietic transplants using fludarabine–melphalan conditioning

“…No other factors reached significance for OS or DFS. We compared this series with a recently reported comparison group receiving their first Flu-Mel allografts with identical conditioning in the same time period, 7 matched for age, sex and diagnosis. There was no difference in 5-year OS (48 vs 40% for first vs second, P ¼ 0.5) or 5-year DFS (40 vs 27%, P ¼ 0.5).…”

“…5,6 No series has reported the outcomes in patients conditioned purely with fludarabinemelphalan (Flu-Mel), which is presently the commonest RIC regimen used in Australasia. 7 Here, we report a series of patients receiving allo-HCT2 using Flu-Mel conditioning. Cumulative incidence curves were constructed with appropriate events as competing risks.…”

“…8,9 An Australian study reporting the outcomes of Flu-Mel first transplants found NRM of 22% after 1 year, with 3-year OS and DFS of 57 and 50%, respectively. 7 We compared outcomes of allo-HCT2 recipients with those from the original Flu-Mel data set, finding no differences in survival. Although encouraging, this may reflect a positive bias in those selected as fit for allo-HCT2.…”