Comparison of Reduced-Intensity and Myeloablative Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: A Meta-Analysis

Abstract

Currently, the indications to perform reduced-intensity conditioning allogeneic hematopoietic stem cell transplant (RIC-HCT) are based on data derived mainly from large registry and single-centre retrospective studies. Thus, at the present time, there is limited direct evidence supporting the current practice in selecting patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) for RIC versus myeloablative conditioning (MAC) transplants. To determine the relationship between dose intensity of conditioning regimen and survival outcomes after allografting in AML/ALL patients, we performed a meta-analysis of 23 clinical trials reported between 1990 and 2013 involving 15,258 adult patients that compare survival outcomes after RIC-HCT versus MAC-HCT. RIC-HCT resulted in comparable <2-year and 2-6 year overall survival (OS) rates post-transplantation even though the RIC-HCT recipients were older and had more active disease than MAC-HCT recipients. The 2-6 year progression-free survival (PFS), nonrelapse mortality, acute graft-versus-host disease (GvHD) and chronic GvHD rates were reduced after RIC-HCT, but relapse rate was increased. Similar outcomes were observed regardless of disease type and status at transplantation. Odds ratio for all outcomes remained comparable with or without performing separate analyses for the year of HCT and for retrospective versus prospective studies. Among RIC-HCT recipients, survival rates were superior if patients were in CR at transplantation. Significant inter-study heterogeneity for aGvHD data and publication bias for PFS data were observed. This meta-analysis showed no OS benefit of MAC-HCT over RIC-HCT across the entire cohort of patients suggesting that RIC-HCT could be an effective therapeutic option for AML/ALL patients who are ineligible for MAC-HCT and CR status is preferred before RIC-HCT.

Long-term survival and late events after allogeneic stem cell transplantation from HLA-matched siblings for acute myeloid leukemia with myeloablative compared to reduced-intensity conditioning: a report on behalf of the acute leukemia working party of European group for blood and marrow transplantation

“…In addition, the GRFS, which is a surrogate for quality of life analysis, was similar between the two regimens. Several retrospective analyses and meta-analyses supported these observations [4–9]. Luger et al reported in the largest such comparison from CIBMTR, including 3731 MAC and 1448 RIC/nonmyeloablative (NMA) recipients, that the 5-year OS rates were 34, 33, and 26 % after MAC, RIC, and NMA conditioning, respectively [5].…”

“…Several studies have shown similar survival of AML patients after SCT with RIC or MAC [3–9]. Most of these studies have shown that RIC is associated with reduced non-relapse mortality (NRM) but increased relapse rate, resulting in a similar leukemia-free survival (LFS) as MAC.…”

Personalized fludarabine dosing to reduce nonrelapse mortality in hematopoietic stem-cell transplant recipients receiving reduced intensity conditioning

“…Over the last decade, RIC regimens have allowed successful transplantation of patients who are heavily pretreated, older or have complicating comorbidities. (1-5) Fludarabine phosphate is an antitumor and immunosuppressive agent, and is a critical component of most RIC regimens in combination with other chemotherapeutics and/or total body irradiation (TBI).…”

Autologous Stem Cell Transplantation Is a Viable Postremission Therapy for Intermediate-Risk Acute Myeloid Leukemia in First Complete Remission in the Absence of a Matched Identical Sibling: A Meta-Analysis

“…Either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens were used before alloSCT. A meta-analysis published by Wahid et al [46] showed that there was no OS benefit with MAC over RIC regimens. However, for autoSCT, several reports showed that a high-dose cytarabine-containing regimen provided a favorable long-term RFS of 61–71% [35, 47].…”