Haploidentical Stem Cell Transplantation (HAPLO-HSCT) With High Dose Cyclophosphamide Post-Transplant (HD-CY) As Gvhd Prophylaxis In High Risk Hematologic Malignancies: Multicentric Spanish Experience
Authors: Gayoso Jorge , Balsalobre Pascual , Kwon Mi , Pascual María Jesús , Castilla-Llorente Cristina , Serrano David , Caballero Dolores , Pérez-Simón Jose Antonio , Bermudez Arancha , Rovira Montserrat , Anguita Javier , Pérez-Corral Ana , Heras Inmaculada , Solano Carlos , Figuera Angela , Sampol Antonia , Ferra Christelle , Herrera Pilar , González Marta Sonia , Montesinos Pau , Buno Ismael , Diez-Martin Jose Luis 
Published: October 2019

Abstract

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.

Patients and methods
We retrospectively evaluate the results of HAPLO-HSCT with reduced conditioning or myeloablative regimens and GVHD prophylaxis based on HD-CY (50 mg/kg on days +3 and +4) and a calcineurin inhibitor plus mycophenolate from day +5 performed in GETH centers.

Results
From Dec-2007, 80 HAPLO-HSCT have been done in 14 centers. Median age was 37 years (16-66), 67.5% were males and all were in advanced phases of their disease or presented high risk features (29 Hodgkin´s, 22 AML, 9 ALL, 8 MDS, 5 NHL, 4 myeloma and 2 myelofibrosis). Previous HSCT has been employed in 65%, autologous in 38 and allogeneic in 15 (5 siblings, 3 unrelated and 7 cord blood transplants), and in 35% the HAPLO-HSCT was their first transplant. Disease status at HAPLO-HSCT was CR in 45%, with persistent disease in 55%. Bone marrow was the graft source for 51% and peripheral blood for 49%, non T-cell depleted in all cases. The haploidentical donor was the patient´s mother (21), father (7), brother/sister (35) or offspring (17). Non-myeloablative conditioning was employed in 77.5% and myeloblative in 22.5%. Median neutrophils engraftment was reached at day +18 (13-45) and platelets >50K at day +27 (11-150). Main toxic complications were grade II-III muchositis in 36%, febrile neutropenia in 75% and CMV reactivations in 62%, with a transplant related mortality rate of 12.5% at day +100 and 19% at 6 months post-transplant. Acute GVHD grade II-IV affected to 24/73 patients at risk (33%), with grade III-IV in 10/73 (14%). Chronic GVHD was present in 12/51 (24%), being extensive in 6/51 (12%). After a median follow-up of 9 months (0.3-49), 26/80 patiens have died due to relapse in 13, infections in 10 and GVHD in 3 cases. Event-free survival and overall survival at 1 year were 48% and 60% respectively. Immune reconstitution was fast and complete in those evaluated.

Conclusions
HAPLO-HSCT with HD-CY is a useful tool in the treatment of high risk hematologic malignancies, rendering long-lasting remissions with limited toxicity, low GVHD incidence and early immune reconstitution.

Disclosures:
No relevant conflicts of interest to declare.