Haploidentical Stem Cell Transplantation (HAPLO-HSCT) with Post-Transplant Cyclophosphamide (PT-CY) As Gvhd Prophylaxis in High Risk Hematologic Malignancies: Bone Marrow or Peripheral Blood Progenitors Render Same Results

Introduction: Allogeneic transplantation is the only curative option for patients with high risk hematologic malignancies. Only one third of them have an HLA identical sibling donor and around 60-70% will find an unrelated donor, that´s why HAPLO-HSCT offers a therapeutic option to most of these patients with the advantages of quick availability, easy programation and logistics, and a committed donor. Bone marrow (BM) or peripheral blood stem cells (PBSC) could be used as graft source but it´s not established if any of them offer significant advantages.

Patients and methods: We retrospectively evaluated the results of HAPLO-HSCT with reduced conditioning regimens and GVHD prophylaxis based on PT-CY (50 mg/kg on days +3 and +4) and a calcineurin inhibitor plus mycophenolate from day +5 performed in GETH centers, with focus on the graft source.

Results: From Dec-2007, 118 HAPLO-HSCT have been done in 17 centers. Median age was 36 years (16-67), 64% were males and all were in advanced phases of their disease or presented high risk features (Hodgkin´s 43%, AML/ALL/MDS 36%, NHL/mieloma/others 21%). Previous HSCT had been employed in 64% (autologous 66, allogeneic 19), and in 36% the HAPLO-HSCT was their first transplant. Disease status at HAPLO-HSCT was CR in 44%, with persistent disease in 55%. BM was the graft source in 48 patients (41%) and PBSC in 70 (59%), non T-cell depleted in all cases. The haploidentical donor was the patient´s mother (28%), father (10%), siblings (44%) or offspring (18%). Baltimore´s reduced conditioning (RIC) including 200cGy was employed in 15% and RIC based on IV busulfan in 85% (44% with 3.2 mg/kg on day -2 (BUX1), and days -3 and -2 (BUX2) in 41%). Median neutrophils engraftment was reached at day +18 (13-45) and platelets >20K at day +26 (11-150), without significant differences (NS) between BM and PBSC.

Main toxic complications were grade II-III mucositis in 36%, febrile neutropenia in 75% and CMV reactivations in 62%. Transplant related mortality rate (TRM) at 1 year was 19% with BM vs 23% with PBSC (NS). Day +100 grade II-IV acute GVHD cumulative incidence (CI) was 46% vs 48% , and grade III-IV was 15% and 10% with BM and PBSC respectively. Chronic GVHD CI at 1 year was 40% vs 24% (NS), being extensive in 16% and 9% (NS) respectively. No differences in acute or chronic GvHD CI were seen when comparing BM against PBSC. After a median follow-up of 10 months (3-61), estimated event-free survival (EFS) and overall survival (OS) at 18 months were 41% and 59% respectively. CI of relapse or progression was 29%. No significant differences in TRM, EFS, OS and relapse incidence were detected between BM and PBSC.

Conclusions: HAPLO-HSCT with PT-CY in the treatment of high risk hematologic malignancies, offers long-lasting remissions with manageble toxicity and GVHD, employing either BM or PBSC that render similar results as graft source.