Haploidentical Stem Cell Transplantation (HAPLO-HSCT) with Busulfan (BUX) Based Reduced Intensity Conditioning (RIC) Regimens and Post-Transplant Cyclophosphamide (PT-CY) As Gvhd Prophylaxis in Patients with Relapsed or Refractory Hodgkin Lymphoma (HL)

Introduction: HAPLO-HSCT is a therapeutic option for patients with high risk hematologic neoplasms with the advantages of quick availability, easy programation and logistics, and a committed donor. It has shown promissing results in patients diagnosed with relapsed or refractory Hodgkin´s lymphoma (HL) at least comparable to allogeneic transplant from siblings or unrelated donors (Burroughs LM et al. Biol Blood Marrow Transplant 2008; 14:1279-1287).

Patients and Methods: We retrospectively evaluate the results of HAPLO-HSCT with IV Busulfan (BUX) based RIC regimens (Fludarabine 30 mg/m2 x5 days (-6 to -2), Cyclophosphamide14,5 mg/kg x2 days (-6 to -5), BUX 3,2 mg/kg x 1 (BUX1)or 2 days (BUX2) on days -3 to -2) 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 to patients diagnosed with relapsed or refractory HL.

Results From March-2009, 43 HAPLO-HSCT have been performed in patients diagnosed with relapsed or refractory HL in 11 GETH centers. Median age was 31 years (17-53), 67% were males and all were in advanced phases of their disease,  after a median of 4 prior treatment lines (2-8). Autologous HSCT was previously employed in 79%, and allogeneic HSCT in 7%. Five patients (11.5%) have received more than 2 prior transplants.  Disease status at HAPLO-HSCT evaluated by PET was complete remission in 14 (32%) and persistent disease in 29 (68%). Bone marrow was employed in 11 (26%) and peripheral blood in 32 (74%), without T-cell depletion in all cases. The haploidentical donor was patient´s mother (20), father (3), siblings (19) or daughter (1). The RIC regimens employed were BUX1 in 14 (32.5%) and BUX2 in 29 patients (67.5%). Median neutrophils engraftment was day +18 (13-44) and platelets >20K was day +26 (13-150). Graft failure with autologous reconstitution happened only in 1 patient (2.5%). The day +100 cumulative incidence (CI) of non-relapse mortality (NRM) was 7% (3/43)  and 16% (7/43) at 1 year post-transplant. The day +100 CI of grade II-IV acute GVHD was 43%, and grade III-IV was 14.5%. Chronic GVHD CI was 26.5% at 1 year, being extensive in 6%. After a median follow-up for survivors of 13 months (3-60), the event-free survival (EFS) was 59.5% and overall survival (OS) was 84%. The 1-year CI of relapse or progression was 25%. Factors related with better 1-year EFS were CR prior to HAPLO-HSCT (93% vs 45%; p=0.017) and receiving less than 4 treatment lines prior to HAPLO-HSCT (100% vs 51.5%; p=0.018). No significant differences were seen when comparing BUX1 against BUX2 in terms of NRM, EFS or OS.

Conclusions: HAPLO-HSCT with PT-CY and BUX based RIC conditioning in relapsed or refractory HL patients, renders long-lasting remissions with acceptable toxicity and GVHD, obtaining better results in those transplanted in CR and with less than 4 treatment lines prior to HAPLO-HSCT.