Allogeneic Stem Cell Transplantation for CML in Accelerate or Blastic Phase

Patients with advanced chronic myeloid leukemia (CML) in accelerate (AC) or blastic phase (BC) have a dismal prognosis despite the use of tyrosine kinase inhibitors (TKI). Here we report our experience for allogeneic stem cell transplantation (ASCT) in advanced and phase of CML. Between July 1990 and May 2012 88 patients with a median age of 36 years (range 7-76) received allogeneic stem cell transplantation from related (n=34) or unrelated (n=54) donors , including 19 HLA-mismatched donors after myeloablative (n=54) or reduced intensity (n= 34) conditioning. Stem cell source was bone marrow (n=37) or peripheral blood stem cells (n=51). GvHD prophylaxis consisted of calcineurin inhibitor plus short course MTX or MMF. Most of the patient received additional ATG as GvHD prophylaxis (84%).The majority of patient (75%) received TKIs before ASCT. 50% received one TKI, 8 received 2 TKIs and 2 received 3 TKI before ASCT. At time of transplantation 34 patient achieved a second or subsequent chronic phase, 28 were in accelerate and 25 in blastic phase. Overall the median number of blasts at time of ASCT was 18.75% (range 5-58%) and the time from diagnosis to transplantation was 27 months (range 3-296).

No primary graft failure was observed. The incidence of acute graft versus host disease (GvHD) grade II to IV was 43% and of severe grade III/IV GvHD was 28%. Forty-two percent of the patient experienced chronic GvHD.

The non-relapse mortality (NRM) at 1 and 5 years was 22% (95% CI; 14-30%) and 23% (95%CI: 13-33%), respectively. In a multivariate analysis (MVA) only higher number of transplanted CD34+ cells were associated with a lower risk of NRM (HR 0.850, 95%CI: 0.729-0.992, p=0.04). The cumulative incidence of relapse at 5 years was 43% (95% CI: 31-55%). In a MVA age > 40 years (HR 2.272, 95%CI: 1.112-4.645, p=0.024) and Reduced intensity conditioning (HR 2.034, 95%CI: 0.998-4.144, p=0.051) were significant factors for higher risk of relapse. After a median follow-up of 91 months (r., 52-133) the estimated 5 and 10 year overall survival was 44% (95% CI: 32-56) and 40% (95% CI: 28-52%), respectively. In an univariate analysis overall survival was significantly influenced by stem cell source, gender, CD34 transplanted cell number and blastic phase at time of transplantation. However, the only significant factor for improved survival in a MVA was a higher number of transplanted CD34+ cells (HR 0.916, 95%CI: 0.844-0.916, p=0.038).