Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

Abstract

BackgroundPrimary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML.MethodsThe current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate.ResultsHSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality.ConclusionsHSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0498-8) contains supplementary material, which is available to authorized users.

Prognostic significance of recurring chromosomal abnormalities in transplanted patients with acute myeloid leukemia

“…Notwithstanding the incorporation of novel innovative molecular risk stratification models into modern prognostication schemas of AML patients [8,19,20], baseline cytogenetic studies still serve as an invaluable prognostic tool for prediction of outcome at key clinical time points during the therapeutic sequence of AML patients [7]. Indeed, cytogenetic abnormalities have been previously established as robust predictors of the risk of primary induction resistance [21], risk of relapse [22,23], and outcome following transplant for primary refractory disease [24]. Yet, to what extent these chromosomal abnormalities impact on patients undergoing allo-HSCT has not been fully addressed hitherto.…”

A gut microbiota score predicting acute graft-versus-host disease following myeloablative allogeneic hematopoietic stem cell transplantation

“…Acute graft‐versus‐host disease (aGVHD) remains a major cause of death for patients who undergo allogeneic hematopoietic stem cell transplantation (allo‐HSCT) . Approximately one‐third of patients fail to response to initial corticosteroid therapy, and survival is poor among the remaining patients . Mortality is associated with clinical severity in current grading systems.…”

“…1,2 Approximately one-third of patients fail to response to initial corticosteroid therapy, and survival is poor among the remaining patients. [2][3][4] Mortality is associated with clinical severity in current grading systems.…”

“…Once aGVHD occurs, serious complications, such as infections and organ dysfunction, may appear subsequently, resulting in high mortality of recipients after allo-HSCT. [2][3][4] So it is necessary to predict aGVHD occurrence to take proper measures preemptively for patients. Recently, gut microbiota serving as a biomarker for predicting aGVHD have been studied.…”

Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants

“…[1][2][3] With increasing use of unrelated donors (URDs) for allogeneic HCT, large studies have evaluated outcomes for patients with sibling donor vs URD, with most demonstrating similar longterm survival among the 2 donor groups. [4][5][6][7][8][9][10][11][12][13][14] However, when given the option of a sibling donor or URD, sibling donors are typically preferred for convenience and possibly to reduce GVHD and to improve survival. Both donor-recipient sex mismatching and the effect of donor parity have been evaluated as possible influences on transplant morbidity and mortality.…”