ISSN 1866-8836
Клеточная терапия и трансплантация

Haploidentical Hematopoietic Stem Cell Transplantation (Haplo-SCT) with Post-Transplant Cyclophosphamide for haematological malignancies: a single centre experience

Dmitry V.Motorin, Renat S.Badaev, Diana V.Babenetskaya, Nataliya A.Ilyina, Tatyana O.Silina, Georgiy G.Baratashvili, Vladimir V.Ivanov, Yuliya A.Alexeeva, Andrey Yu. Zaritskey
Federal Almazov North-West Medical Research Centre, Saint Petersburg, Russia.

Contact: Dr.Dmitry V.Motorin
E-mail: almazov-bmt@mail.ru
doi 10.18620/ctt-1866-8836-2016-5-3-51-53
Submitted 20 September 2016
Accepted 29 September 2016

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Cellular Therapy and Transplantation (CTT)
Volume 5, Number 3
Contents 

Summary

Introduction

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 [4].

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).

Results

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).

Conclusion

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.

References

1. Kanakry CG, de Lima MJ, Luznik L. Alternative donor allogeneic hematopoietic cell transplantation for acute myeloid leukemia. SeminHematol. 2015;52(3):232-242.

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.

Keywords

Bone marrow transplantation, haploidentical, t cell–repleted graf, cyclophosphamide, high-dose, post-transplant


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