Haploidentical hematopoietic stem cell transplantation in the treatment of children and adolescents with resistant forms of acute leukemia

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the effective methods of treatment of patients with malignant disorders of hematopoietic system. Because of absence of related and unrelated donors at the majority of Russian patients, search for alternative grafts for allo-HSCT is actual now. HSCT from partially HLA-matched related (haploidentical, haplo-HSCT) is the fast and universal method of treatment. Fifty six children and young adults 1–21 years old (age median – 9 years old) with resistant forms of acute lymphoblastic leukemia (ALL) (n = 32) and acute myeloid leukemia (AML) (n = 24) were transplanted with haploidentical donor from December 2007 to June 2013. In preparative therapy and graft-versus-host disease (GvHD) prevention the following regimens were used: myeloablative conditioning regimen (MAC) + Antithymocyte Immunoglobulin (ATGAM) (n = 20), MAC + Cyclophosphamide (CpH) (n = 5), reduce-intensity regimen (RIC) +
ATGAM (n = 14), RIC + Alemtuzumab (n = 4), RIC + CpH (n = 13). All patients received base immunosuppressive therapy with Tacrolimus and Cyclosporin A. The following types of haplo-transplants were used: combination of stimulated with G-CSG unmanipulated bone marrow (BM) and peripheral blood stem cells (PBSC) with positive CD34+ selection (n = 23) or stimulated with G-GSF unmanipulated BM (n = 33). Overall survival (OS) in this group of patients was 33.3 %. Statistically better OS (р = 0.03) was revealed in a group of patients transplanted with G-CSF stimulated unmanipulated BM – 45.5 % versus 13 % in case of combined transplant. Other factors influenced on the results of haplo-HSCT (age, status at the moment of HSCT, conditioning regimen, posttransplant therapy, engraftment, cells dose) are described in the article.

1. Зубаровская Л.С., Фрегатова Л.М., Афанасьев Б.В. Трансплантация гемопоэтических стволовых клеток при гемобластозах. В кн.: Клиническая онкогематология под ред. М.А. Волковой, 2-е издание. М., 2007. [Zubarovskaya L.S., Fregatova L.M., Afanasiev B.V. Hematopoietic stem cell transplantation. In: Clinical oncohematology. M.A. Volkova (ed.). M.: Medicine, 2007. (In Russ.)].

2. Kekre N., Antin J.H. Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist. Blood 2014;123(3):334–43.

3. Bitan M., He W., Zhang M.-J. et al. Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens. Blood 2014;123(10):1615–20.

4. Wang Y., Chang Y.-J., Xu L.-P. et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood 2014;124:843–50.

5. Zecca M., Strocchio L., Pagliara D. et al. HLA-haploidentical T-cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia. Biol Blood Marrow Transplant 2014;20(4):571–6.

6. Lang P., Teltschik H., Feuchtinger T. et al. Transplantation of CD3/CD19 depleted allografts from haploidntical family donors in paediatric leukaemia. Brit J Haematol 2014;165(5):688–98.

7. Martelli M.F., Di Ianni M., Ruggeri L. et al. “Designed” grafts for HLAhaploidentical stem cell transplantation. Blood 2014;123(7):967–73.

8. Handgretinger R., Klingebiel T., Lang P. et al. Megadose transplantation of purified peripheral blood CD34+ progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant 2001;27(8):777–83.

9. Huang X.J. Current status of haploidentical stem cell transplantation for leukemia. J Hematol Oncol 2008;1:27.

10. Luznik L., O’Donnell P.V., Symons H.J. et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, post transplantation cyclophosphamide. Biol Blood Marrow Transplant 2008;14:641–50.

11. Sawada A., Shimizu M., Isaka K. et al. Feasibility of HLA-haploidentical hematopoietic stem cell transplantation with posttransplantation cyclophosphamide for advanced pediatric malignancies. Pediatr Hematol Oncol 2014;31(8):754–64.

12. Liu H.-D., Xu L.-P., Liu K.-Y. et al. Long-term outcomes of unmanipulated haploidentical HSCT for paediatric patients with acute leukaemia. Bone Marrow Transplant 2013;48:1519–24.

13. Adriana S., Valeria C.G., Roseane G. et al. Haploidentical hematopoietic stem cell transplantation with reduced intensity conditioning, T-cell replete grafts and osttransplant cyclophosphamide in pediatrics. Blood 2013;122:5510.

14. Raiola A.M., Dominietto A., Ghiso A. et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant 2013;19:117–22.

15. Ciurea S.O., Mulanovich V., Saliba R.M. et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2012;18:1835–44.

16. Chang Y.J., Zhao X.Y., Xu L.P. et al. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplant for myelodysplastic syndrome and acute myeloid leukemia evolving from myelodysplastic syndrome. Leuk Lymphoma 2013;54(12):2671–7.

17. Martelli M.F., Di Ianni M., Ruggeri L. et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood 2014;124:638–44.

18. Chang Y.-J., Zhao X.-Y., Huang X.-J. Immune reconstitution haploidentical hematopoitic stem cell transplantation. Biol Blood Marrow Transplant 2014;20:440–9.

19. Shimoni A. Haploidentical stem-cell transplant: the challenge of immune reconstitution. Leuk Lymphoma 2013;54(12):2579–80.