Safety and Efficacy of Haploidentical Stem Cell Transplantation for Advanced Chronic Myeloid Leukemia

Background: Allogeneic stem transplantion in Chronic Myeloid Leukemia (CML) is reserved for patients who have accelerated phase (AP), are in blast crisis (BP), chronic phase CML patients that have failed second-generation tyrosine kinase inhibitors (TKIs), and those who have developed resistant mutations to TKI such as T315I. Haploidentical hematopoietic Stem Cell transplantation (HaploSCT) is an alternative treatment option for patients without a matched donor. Post-transplant cyclophosphamide (PTCy), in addition to tacrolimus and mycophenolate, has been effective in preventing GVHD and was associated with lower treatment-related mortality in this type of transplant. However, outcomes for patients with CML using this approach are unknown, we therefore report on our experience using haploidentical transplantation for a cohort of advanced CML patients treated at our institution.

Patients and Methods: We performed a retrospective chart review of patients with advanced CML who received a haploidentical stem cell transplant at the MD Anderson Cancer Center after January 2009. The objectives of this analysis were to determine rates of engraftment, incidence of GVHD, treatment-related mortality, relapse rates and survival. The conditioning regimen consisted of melphalan 140mg/m2 (1 patient had 100mg/m2), thiotepa 5-10 mg/kg and fludarabine 160mg/m2 total dose. GVHD prophylaxis consisted of post-transplant cyclophosphamide followed by tacrolimus and MMF as previously reported. All but one patient received bone marrow as stem cell source.

Results: Ten patients with advanced CML were treated during this time period. The median number of prior medical therapies including TKIs was 3. All patients engrafted neutrophils after a median of 18 days, with 100% donor cells on chimerism, and achieved remission post-transplant. Acute grade 2-4 GVHD occurred in 30% (no grade 3 -4), and overall chronic GVHD occurred in 37.5% of evaluable patients. Four patients relapsed and died, ¾ who were not in chronic phase at the time of transplant.  No patient died of treatment-related mortality. 71% of patients transplanted in second chronic phase remained in molecular remission at the last follow-up. After a median follow-up of 22 months median PFS had not been reached; 6 patients (60%) are alive, 5 are in complete molecular remission and one with low level PCR positivity (Figure 1).

Conclusion: Our results suggest that HaploSCT can produce durable complete remissions with minimal toxicity for patients with advanced CML, and that treatment outcomes are comparable with matched transplantation as recently reported by us in abstract format by Ahmed et al. Larger studies, with longer follow-up and comparison to other donor sources are needed to better assess this approach.

Figure 1: Progression-free survival for patients with advanced CML treated with a haploidentical transplant at MD Anderson Cancer Center.