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

S Fadilah S. Abdul Wahid, Nor Azimah Ismail, Mohd Razif Mohd-Idris, Fariza Wan Jamaluddin, Nor Rafeah Tumian, Sze Wei Yap, Norasiah Muhammad, Ming Lai Nai

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2535-2552
Number of pages18
JournalStem Cells and Development
Volume23
Issue number21
DOIs
Publication statusPublished - 1 Nov 2014

Fingerprint

Hematopoietic Stem Cell Transplantation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Hematopoietic Stem Cells
Meta-Analysis
Transplants
Transplantation
Graft vs Host Disease
Disease-Free Survival
Survival
Survival Rate
Publication Bias
Homologous Transplantation
Registries
Retrospective Studies
Odds Ratio
Clinical Trials
Prospective Studies
Recurrence
Mortality

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

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. / S. Abdul Wahid, S Fadilah; Ismail, Nor Azimah; Mohd-Idris, Mohd Razif; Jamaluddin, Fariza Wan; Tumian, Nor Rafeah; Yap, Sze Wei; Muhammad, Norasiah; Nai, Ming Lai.

In: Stem Cells and Development, Vol. 23, No. 21, 01.11.2014, p. 2535-2552.

Research output: Contribution to journalArticle

@article{480723e23b9f46a488c41ce8afd799a4,
title = "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.",
author = "{S. Abdul Wahid}, {S Fadilah} and Ismail, {Nor Azimah} and Mohd-Idris, {Mohd Razif} and Jamaluddin, {Fariza Wan} and Tumian, {Nor Rafeah} and Yap, {Sze Wei} and Norasiah Muhammad and Nai, {Ming Lai}",
year = "2014",
month = "11",
day = "1",
doi = "10.1089/scd.2014.0123",
language = "English",
volume = "23",
pages = "2535--2552",
journal = "Stem Cells and Development",
issn = "1547-3287",
publisher = "Mary Ann Liebert Inc.",
number = "21",

}

TY - JOUR

T1 - Comparison of reduced-intensity and myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia and acute lymphoblastic leukemia

T2 - A meta-analysis

AU - S. Abdul Wahid, S Fadilah

AU - Ismail, Nor Azimah

AU - Mohd-Idris, Mohd Razif

AU - Jamaluddin, Fariza Wan

AU - Tumian, Nor Rafeah

AU - Yap, Sze Wei

AU - Muhammad, Norasiah

AU - Nai, Ming Lai

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84913620645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84913620645&partnerID=8YFLogxK

U2 - 10.1089/scd.2014.0123

DO - 10.1089/scd.2014.0123

M3 - Article

C2 - 25072307

AN - SCOPUS:84913620645

VL - 23

SP - 2535

EP - 2552

JO - Stem Cells and Development

JF - Stem Cells and Development

SN - 1547-3287

IS - 21

ER -