T-cell-replete haploidentical stem cell transplantation using low-dose antithymocyte globulin in children with relapsed or refractory acute leukemia
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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.
KeywordsAcute leukemia Haploidentical hematopoietic stem cell transplantation Relapse Children Graft-versus-host disease
Stem cell transplantation
- R/R AL
Refractory/relapsed acute leukemia
Mixed lineage leukemia
Granulocyte-colony stimulating factor
Peripheral blood stem cells
FMS like tyrosine kinase- internal tandem duplication
Myeloid natural killer cell precursor leukemia
Acute lymphoblastic leukemia
Acute myeloid leukemia
Human leukocyte antigen
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.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- 3.Tallen G, Ratei R, Mann G, Kaspers G, Niggli F, Karachunsky A, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010;28:2339–47.CrossRefPubMedGoogle Scholar
- 8.Balduzzi A, Valsecchi MG, Uderzo C, De Lorenzo P, Klingebiel T, Peters C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. Lancet. 2005;366:635–42.CrossRefPubMedGoogle Scholar
- 15.Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–73.CrossRefPubMedGoogle Scholar
- 18.Ikegame K, Yoshida T, Yoshihara S, Daimon T, Shimizu H, Maeda Y, et al. Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non-complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant. 2015;21:1495–505.CrossRefPubMedGoogle Scholar
- 19.Mochizuki K, Kikuta A, Ito M, Sano H, Akaihata M, Kobayashi S, et al. Feasibility of tacrolimus, methotrexate, and prednisolone as a graft-versus-host disease prophylaxis in non-T-cell-depleted haploidentical hematopoietic stem cell transplantation for children. Clin Transplant. 2011;25:892–7.CrossRefPubMedGoogle Scholar
- 24.Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transpl. 2011;17:821–30.CrossRefGoogle Scholar
- 26.Liu J, Xu LP, Bian Z, Chang YJ, Wang Y, Zhang XH, et al. Differential impact of two doses of antithymocyte globulin conditioning on lymphocyte recovery upon haploidentical hematopoietic stem cell transplantation. J Transl Med. 2015;13:391. https://doi.org/10.1186/s12967-015-0748-x.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.O’Hare P, Lucchini G, Cummins M, Veys P, Potter M, Lawson S, et al. Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience. Bone Marrow Transpl. 2017. https://doi.org/10.1038/bmt.2017.3 (e-pub ahead of print 20 February 2017).
- 31.Jaiswal SR, Chakrabarti A, Chatterjee S, Ray K, Chakrabarti S. Haploidentical transplantation in children with unmanipulated peripheral blood stem cell graft: the need to look beyond post-transplantation cyclophosphamide in younger children. Pediatr Transplant. 2016;20:675–82.CrossRefPubMedGoogle Scholar