A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation

Abstract

We used a novel NF-08-TM transplant protocol based on intravenous busulfan, cyclophosphamide, fludarabine, and thiotepa in 82 consecutive patients with ␤-thalassemia major (TM), including 52 with allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors (UDs) with well-matched human leukocyte antigens and 30 with hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSDs). The median age at transplantation was 6.0 years (range, 0.6-15.0 years), and the ratio of male-to-female patients was 56:26. The median follow-up time was 24 months (range, 12-39 months). The estimated 3-year overall survival and TMfree survival were 92.3% and 90.4% in the UD-PBSCT group and 90.0% and 83.3% in the MSD-HSCT group. The cumulative incidences of graft rejection and grades III-IV acute graft-versus-host disease were 1.9% and 9.6%, respectively, in the UD-PBSCT group and 6.9% and 3.6%, respectively, in the MSD-HSCT group. The cumulative incidence of transplant-related mortality was 7.7% in the UD-PBSCT group and 10.0% in the MSD-HSCT group. In conclusion, UD-PBSCTs using the welltolerated NF-08-TM protocol show similar results to MSD-HSCTs and can be used to treat ␤-thalassemia patients in the absence of MSDs. (Blood. 2012;120(19): 3875-3881)

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010

“…For example, patients' clinical conditions and transplantation events, such as causes of transplant-related mortality, were not detailed. Several experiences, such as those of North America and the FarEast, [14][15][16][17][18][19] were also not reported to the EBMT registry. However, the EBMT ProMISe regulations and the large number of cases reported guarantee the accuracy of the data presented.…”

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

“…11 Subsequently, several centers worldwide have started their own transplant programs. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Recent results show that, with modern transplantation approaches, and careful patient selection, even better results could be obtained (Table 2). At the same time, however, survival without transplantation of TM patients has improved as the result both of a better understanding of the pathophysiology of iron overload and improvements in the medical therapy of TM; survival into the fourth or fifth decade of life is now possible for well-treated patients.…”

“…42 Using this approach, a suitable donor can be found in approximately one-third of Caucasian patients with TM; a higher probability could be expected in China because of the relatively genetic homogeneity of the Chinese population. 14 In addition, the risk of rejection can be reduced by selecting UD who do not have non-permissive mismatches at HLA-DPB1 locus in the host-versus-graft direction. 43 …”

“…[18][19][20] Recently, the fourth study reported from a Chinese group demonstrated no difference in terms of rate of acute and chronic GvHD using a novel conditioning regimen. 14 In 2003, Locatelli et al first reported the feasibility of using HLA-identical sibling cord blood (CB) for HSCT in TM. 34 This kind of allograft was associated with a decreased risk of both acute GvHD (aGvHD) and chronic GvHD (cGvHD) and of TRM, provided the CB unit had an adequate number of nucleated cells (i.e.…”

Conditioning regimens in allo-SCT for thalassemia major

“…27,30 PBSC grafts, when used, have been reported to be associated with faster engraftment and lower requirement of blood product support in the peri-transplant period 25,31,32 and have also been associated with a low incidence of graft rejection. 25,33 However, the risk of chronic GVHD is increased. 25,31,32 Larger prospective studies are required to confirm the benefit of PBSC over BM in these high-risk patients.…”