Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-SCT) with Post-Transplant Cyclophosphamide for haematological malignancies: a single centre experience
Contact: Dr.Dmitry V.Motorin
Accepted 29 September 2016
For many patients with hematological malignancies, hematopoietic stem cells transplantation is the only potentially curative treatment option, but only 30% of patients have fully HLA-matched donor. In case of urgent need to transplant, use of alternative haploidentical donor can be the only chance for cure. For a long time, usage of haploidentical SCT was limited due to high rate of severe GVHD and graft failure. Introduction of GVHD prophylaxis with рost-transplant Cyclophosphamide (PT-Cy) allowed overcome this barrier [1, 2]. Unfortunately many patients relapse after transplant. In this case, different treatment strategies can be used for induction of remission .
Materials and methods
Since 2014, 38 patients underwent 44 Haplo-SCTs at our centre. Six patients received second haplo-SCT because of graft failure or relapse. Five patients were transplanted from the same donor and one patient from another donor. Mean age was 38 years (21-61). Twenty two patients were males, and 16 females. The most common diagnosis was acute leukemia. Patients had AML (N=15), CML (N=7), HL (N=6), ALL (N=2), Burkitt lymphoma (N=2), T-lymphoblastic lymphoma (N=2), AL with mixed phenotype (N=1), NKleukemia (N=1), PMBCL (N=1) and primary myelofibrosis (N=1). 25 patients had relapsed or refractory disease. 15 patients proceeded to transplant without remission. Conditioning regimens were: Flu-Cy-Mel (N=22), Bu-FluCy (N=10), Flu-Cy-TBI (N= 3), Flamsa-RIC (N=3), other regimens (N=6). PT-Cy, MMF and CsA were used for GVHD prophylaxis. Stem cell sources were either peripheral blood (N=37) or bone marrow (N=7). Mean transplant CD34+cell dose was 4.09 Mln/kg (0.96 – 12.78).
Mean time to engraftment was 27 days for platelets and 17 for neutrophils. 3 patients (7.8%) had primary transplant failure. Two of them had second transplantation from the same donor and one eventually engrafted. 8 patients proceeded to relapse (21%). Among them, 6 had acute leukemia (two had molecular relapse, and four, bone marrow relapse). Six patients were treated with DLI, azacitidine +DLI (in case of acute leukemia), 4 patients had second transplantation. Different chemotherapy regimens were used in relapse. Eventually, 6 patients achieved remission. 23 patients (61%) developed acute GVHD. 14 (37%) patients had Grade III-IV GVHD, all of them exhibited skin form, 7 (18%) patients had gastrointestinal form and 4 (11%) had hepatic form. Mean term of GVHD onset was 38 (13-130) days. 5 patients (13.2%) developed chronic GVHD (3 had skin damage, 1 had liver damage and 1 had muscle-skeletal form). Only 4 patients needed second-line GVHD treatment. Rate of hemorrhagic cystitis, a common complication of cyclophosphamide, was 8.9% (N=3). All cystitis episodes resolved on massive infusion therapy. By May 2016 OS of all patients was 55% (N=21), DFS was 47% (N=18). TRM was 16% (N=6). Rate of transplantrelated mortality (at < 30 days after transplantation) was 13% (N=5). Causes of death at late post-transplant period were as follows: infections (N=9), progression (N=3), GVHD (N=3), graft rejection (N=2).
Haplo-SCT is a possible alternative in patients without HLAcompatible donor. Conditioning regimen with Melphalan can be used instead of TBI-based regimens. GvHD prophylaxis with PT-Cy is feasible and effective. Different post-transplant strategies can be used for re-induction of remission in case of relapse. Disease status before transplantation has great influence on OS and PFS.
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2. Dietrich S, Finel H, Martinez C. Post-transplant cyclophosphamide-based haplo-identical transplantation as alternative to matched sibling or unrelated donor transplantation for non-Hodgkin lymphoma: a registry study by the European society for blood and marrow transplantation. Leukemia. 2016; 30(10):2086-2089.
3. Leo Luznik, Paul V. O’Donnell, J. Fuchs Ephraim. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical BMT. Semin Oncol .2012; 39(6):683-693
4. Amer M Zeidan, Patrick M Forde, Heather Symons. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014; 20(3): 314–318.
Bone marrow transplantation, haploidentical, t cell–repleted graf, cyclophosphamide, high-dose, post-transplant
Accepted 29 September 2016