αβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemia

L. N. Shelikhova; Шелихова Л. Н.; M. A. Ilushina; Илюшина М. А.; K. V. Semiglazova; Семиглазова К. В.; Zh. B. Shekhovtsova; Шеховцова Ж. Б.; D. A. Shasheleva; Шашелева Д. А.; R. D. Khismatullina; Хисматуллина Р. Д.; E. E. Kurnikova; Курникова Е. Е.; D. S. Pershin; Першин Д. С.; D. N. Balashov; Балашов Д. Н.; S. A. Radygina; Радыгина С. А.; P. E. Trakhtman; Трахтман П. Е.; I. I. Kalinina; Калинина И. И.; Y. O. Muzalevskii; Музалевский Я. О.; A. S. Kazachenok; Казаченок А. С.; V. V. Zaharova; Захарова В. В.; V. V. Brilliantova; Бриллиантова В. В.; Yu. V. Olshanskaya; Ольшанская Ю. В.; A. V. Panferova; Панферова А. В.; E. A. Zerkalenkova; Зеркаленкова Е. А.; D. D. Baidildina; Байдильдина Д. Д.; G. A. Novichkova; Новичкова Г. А.; A. G. Rumyantsev; Румянцев А. Г.; A. A. Mascha; Масчан А. А.; M. A. Maschan; Масчан М. А.

doi:10.24287/1726-1708-2019-18-2-11-21

αβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemia

Authors: Shelikhova L.N.¹, Ilushina M.A.¹, Semiglazova K.V.¹, Shekhovtsova Z.B.¹, Shasheleva D.A.¹, Khismatullina R.D.¹, Kurnikova E.E.¹, Pershin D.S.¹, Balashov D.N.¹, Radygina S.A.¹, Trakhtman P.E.¹, Kalinina I.I.¹, Muzalevskii Y.O.¹, Kazachenok A.S.¹, Zaharova V.V.¹, Brilliantova V.V.¹, Olshanskaya Y.V.¹, Panferova A.V.¹, Zerkalenkova E.A.¹, Baidildina D.D.¹, Novichkova G.A.¹, Rumyantsev A.G.¹, Mascha A.A.¹, Maschan M.A.¹
Affiliations:
1. Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation
Issue: Vol 18, No 2 (2019)
Pages: 11-21
Section: PROMISING STUDIES
Submitted: 28.06.2019
Accepted: 28.06.2019
Published: 28.06.2019
URL: https://hemoncim.com/jour/article/view/240
DOI: https://doi.org/10.24287/1726-1708-2019-18-2-11-21
ID: 240

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Abstract

Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

Keywords

chemorefractory acute myeloid leukemia, haploidentical hematopoietic stem cell transplantation, αβ-T-cell-depletion, immune recovery

About the authors

L. N. Shelikhova

Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation

Author for correspondence.
Email: lnik1975@mail.ru
ORCID iD: 0000-0003-0520-5630

Larisa N. Shelikhova, MD, hematologist, head.

117997, Moscow, Samory Mashela st., 1.

Russian Federation

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