Improved clinical outcomes of high risk β thalassemia major patients undergoing a HLA matched related allogeneic stem cell transplant with a treosulfan based conditioning regimen and peripheral blood stem cell grafts

Abstract

Improving clinical outcomes among high risk Class III β thalassemia major patients (Class IIIHR) receiving an allogeneic SCT remains a challenge. From October, 2009 a treosulfan based regimen (TreoFluT) was used for all consecutive Class III patients (n = 50). The clinical outcomes were compared with the historical conventional busulfan (BuCy) based regimen (n = 139). Use of TreoFluT was associated with a significantly reduced incidence of sinusoidal obstruction syndrome (SOS) among Class IIIHR cases (78% to 30%; P = 0.000) and early TRM (46% to 13%; p = 0.005). There was also a trend towards better engraftment in the Class IIIHR subset (P = 0.055). However, the use of bone marrow (BM) as source of stem cells along with the TreoFluT regimen was associated with 50% early mixed chimerism which reduced to 8.5% with the use of a peripheral blood stem cell graft (PBSC). Use of a PBSC graft was not associated with a significant increase in the incidence of acute or chronic graft versus host disease (GVHD). The overall and event free survival was significantly better among the Class IIIHR subset with the use of TreoFluT Vs. BuCy (86.6 ± 7.3 Vs. 39.4 ± 6.8%; P = 0.002 and 77.8 ± 8.8 Vs. 32.4 ± 6.5%; P = 0.003 respectively). A TreoFluT conditioning regimen with a PBSC graft can significantly improve clinical outcomes of Class IIIHR patients.

Figure 1. Analysis of day 28 chimerism and survival in different subsets.

(A) Day 28 chimerism comparing patients conditioned with aTreoFluT regimen and receivingeither a bone marrow graft (Treo BM) or a peripheral blood stem cell graft (Treo PBSC); NE = not evaluated; indicates cases that had died prior to day 28 and were hence: not evaluated. ▴ Filled triangles indicates cases that had an event defined as either graft rejection or death. △ Empty triangles indicate cases that did not have an event defined as either graft rejection or death (B) Overall survival of all Class III patients conditioned with either a TreoFluT (Treo) or a busulfan based regimen (Bu/Cy) (C) Event free survival of all Class III patients conditioned with either a TreoFluT (Treo) or a busulfan based regimen (Bu/Cy) (D) Overall survival of all Class IIIHR patients conditioned with either a TreoFluT (Treo) or a busulfan based regimen (Bu/Cy) (E) Event free survival of all Class IIIHR patients conditioned with either a TreoFluT (Treo) or a busulfan based regimen (Bu/Cy).