Outcomes of thalassemia patients undergoing hematopoietic stem cell transplantation by using a standard myeloablative versus a novel reduced-toxicity conditioning regimen according to a new risk stratification

Biol Blood Marrow Transplant. 2014 Dec;20(12):2066-71. doi: 10.1016/j.bbmt.2014.07.016. Epub 2014 Jul 23.

Abstract

Improving outcomes among class 3 thalassemia patients receiving allogeneic hematopoietic stem cell transplantations (HSCT) remains a challenge. Before HSCT, patients who were ≥ 7 years old and had a liver size ≥ 5 cm constitute what the Center for International Blood and Marrow Transplant Research defined as a very high-risk subset of a conventional high-risk class 3 group (here referred to as class 3 HR). We performed HSCT in 98 patients with related and unrelated donor stem cells. Seventy-six of the patients with age < 10 years received the more conventional myeloablative conditioning (MAC) regimen (cyclophosphamide, busulfan, ± fludarabine); the remaining 22 patients with age ≥ 10 years and hepatomegaly (class 3 HR), and in several instances additional comorbidity problems, underwent HSCT with a novel reduced-toxicity conditioning (RTC) regimen (fludarabine and busulfan). We then compared the outcomes between these 2 groups (MAC versus RTC). Event-free survival (86% versus 90%) and overall survival (95% versus 90%) were not significantly different between the respective groups; however, there was a higher incidence of serious treatment-related complications in the MAC group, and although we experienced 6 graft failures in the MAC group (8%), there were none in the RTC group. Based on these results, we suggest that (1) class 3 HR thalassemia patients can safely receive HSCT with our novel RTC regimen and achieve the same excellent outcome as low/standard-risk thalassemia patients who received the standard MAC regimen, and further, (2) that this novel RTC approach should be tested in the low/standard-risk patient population.

Keywords: Myeloablative; Reduced toxicity; Thalassemia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Busulfan / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Myeloablative Agonists / administration & dosage
  • Risk Factors
  • Survival Rate
  • Thalassemia / mortality*
  • Thalassemia / therapy*
  • Transplantation Conditioning / methods*
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Myeloablative Agonists
  • Cyclophosphamide
  • Vidarabine
  • Busulfan
  • fludarabine