Unmanipulated Haploidentical Blood and Marrow Transplantation in High Risk Hematologic Malignancies

Introduction: allogeneic haploidentical identical stem cells transplantation (SCT) is currently a salvage procedure in patients with hematologic malignancies at high risk and who have no HLA identical donor. The new modalities of haploidentical transplantation without in vitro T depletion of the donor, seem to allow rapid immune reconstitution and reduce the incidence of graft versus host disease (GVHD). This retrospective study presents the short-term results of this procedure in a single-center series, using a unmanipulated graft involving both bone marrow and peripheral blood stem cells after exposure to G-CSF donor.

Material and Methods: From May 2013 to March 2015, 15 allografts SCT HLA-haploidentical were used in 14 pts with hematological malignancies (3 AML, 9 ALL, one acute CML and one lymphoblastic NHL). The median age is 24 years with a sex ratio of 2,5. Median time diagnosis-transplant is 27 months (2-74). At the time of transplant, 8 pts were in second complete remission and 3 pts in blast phase. The donor used was one of the two ascendants (father: 5, mother: 2) or sibling (brother: 5, sister: 3), median donors age 38 years (17-65). The degree of compatibility (HLA A, B and DR) is 3/6 (8 cases), 4/6 (6 cases) and 5/6 (1 case). CMV status between donor/recipient was high risk in 14 cases. ABO incompatibility is major in 3 cases, minor in 4 cases. The conditioning regimen associated Busilvex 9.6 mg/kg; Aracytine 8 g/m²; Endoxan 3.6 g/m². The prevention of GVHD involved the Cyclosporine-Methotrexate association, MMF and Thymoglobulin 10 mg/kg. All pts received an association of bone marrow transplant and peripheral blood stem cells (from the donor receiving first G-CSF at a dose of 5 μg/kg) with a total average rate of NC: 8,9.10⁸/kg , CD34: 11.29 10⁶/kg (1,43-18,25), MNC: 8,9.10⁸/kg (4.80-17.97), CD3: 3,61 10⁸/kg (0.04-14), CD4: 1.36 10⁸/kg (0,02-7.53), CD8: 1.24 10⁸ (0,36-7.53). A second haploidentical allogeneic transplantation (from another donor) with Fluadarabine-Melphalan conditioning, was required in a pt who presented early rejection.

Results: aplasia was observed in all pts with average duration of 21 days (15-21). The output is seen aplasia average J17 (12-23). No cases of VOD was observed. One pt presented an early rejection and received a second haploidentical transplantation. Acute GVHD occurred in 9 pts (64.2%) including 8 (57%) of grade II-IV; a chronic GVHD in 2 pts (18%) of extensive form. Seven pts (46%) developed CMV reactivation occurred in average d44 (35-67). Three cases of hemorrhagic cystitis (one grade 4) are observed on average d47 (30-75). Three pts (21%) relapsed four months after transplantation (all in blast phases at the time of graft). After a median follow-up of 11 months (4-25), 8 pts (58%) are alive and 6 pts (42%) died (digestive aGVH: 1, severe infection: 2, hemorrhagic cystitis: 1, relapse: 2). The actuarial overall survival and event-free survival at 28 months are 42.4% and 37.5% respectively.

Conclusion: The results of the allogeneic SCT using unmanipulated haploidentical from the marrow and peripheral blood, after a myeloablative conditioning, seem encouraging in pts with hematological malignancies at advanced stages.