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T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia

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Abstract

We evaluated the efficacy and toxicity of T-cell-replete haploidentical stem cell transplantation (TCR-haploSCT) using low-dose antithymocyte globulin (ATG) in children with refractory/relapsed (R/R) acute leukemia. From October 2009 to April 2016, 39 consecutive patients with R/R acute leukemia who underwent TCR-haploSCT were included. At the time of TCR-haploSCT, 17 patients were in complete remission (CR), but 22 had active disease. Thirty-three patients received a myeloablative regimen and six received a reduced-intensity conditioning regimen. Graft-versus-host disease (GvHD) prophylaxis comprised tacrolimus, methotrexate, prednisolone, and low-dose ATG (thymoglobulin 2.5 mg/kg). Neutrophil engraftment (> 0.5 × 109/L) was 95% after a median of 13 days. The median follow-up period was 527 days, with mean 3-year overall and disease-free survival rates of 45.1% [standard deviation (SD), ± 8.5%) and 33.8% (SD, ± 7.9%), respectively. The cumulative incidence of acute GvHD was 73.0%, but that of grade III–IV acute GvHD was 34.1%. The 3-year cumulative incidences of relapse and transplant-related mortality were 50.3 and 15.9%, respectively. Age < 10 years at transplantation was associated with a better overall survival in the multivariate analysis. These data suggest that TCR-haploSCT using a low-dose ATG combined with the GvHD prophylaxis described here has a significant anti-leukemic activity, particularly in younger patients.

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Abbreviations

SCT:

Stem cell transplantation

ATG:

Antithymocyte globulin

R/R AL:

Refractory/relapsed acute leukemia

TCR:

T-cell-replete

GvHD:

Graft-versus-host disease

GvL:

Graft-versus-leukemia

PTCY:

Post-transplantation cyclophosphamide

MLL:

Mixed lineage leukemia

CMV:

Cytomegalovirus

G-CSF:

Granulocyte-colony stimulating factor

TRM:

Transplant-related mortality

PBSCs:

Peripheral blood stem cells

CR:

Complete remission

FLT3-ITD:

FMS like tyrosine kinase- internal tandem duplication

M/NKL:

Myeloid natural killer cell precursor leukemia

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

HLA:

Human leukocyte antigen

EBV:

Epstein–Barr virus

SD:

Standard deviation

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Acknowledgements

We wish to thank all the clinicians and nurses who helped to support the care of patients in this study. We also thank the technicians at the Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University Hospital, especially Mr. Satoshi Ono for his help with the HLA typing and Mr. Shunichi Saito for CD34+ and CD3+ cell assays. We would like to thank Editage (http://www.editage.ip) for English language editing.

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Authors and Affiliations

  1. Department of Pediatric Oncology, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan

    Hideki Sano, Kazuhiro Mochizuki, Shogo Kobayashi, Yoshihiro Ohara, Masaki Ito, Tomoko Waragai, Nobuhisa Takahashi & Atsushi Kikuta

  2. Department of Blood Transfusion and Transplantation Immunology, Fukushima Medical University Hospital, Fukushima, Japan

    Kazuhiko Ikeda & Hitoshi Ohto

Authors
  1. Hideki Sano
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  2. Kazuhiro Mochizuki
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  3. Shogo Kobayashi
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  4. Yoshihiro Ohara
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  5. Masaki Ito
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  10. Atsushi Kikuta
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Correspondence to Atsushi Kikuta.

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Sano, H., Mochizuki, K., Kobayashi, S. et al. T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia. Int J Hematol 108, 76–84 (2018). https://doi.org/10.1007/s12185-018-2423-5

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  • DOI: https://doi.org/10.1007/s12185-018-2423-5

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