High-dose chemotherapy and autologous peripheral blood stem cell transplantation with BCVAC regimen followed by maintenance chemotherapy for children with very high risk acute lymphoblastic leukemia
Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended treatment for children with very high risk acute lymphoblastic leukemia (ALL), but it requires adequate institutional infrastructure, experience, and expertise, especially for alternative donor HSCT. We review our experience with high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (APBSCT), followed by post-APBSCT maintenance chemotherapy for children with very high risk ALL. Between August 1997 and November 2012, our institute was not successful with HLA-haploidentical HSCT. Thus, if patients lacked HLA-matched allogeneic donors or cord blood donors, we treated them with HDCT and APBSCT with carmustine, etoposide, cytarabine, and cyclophosphamide, followed by post-APBSCT maintenance chemotherapy with vincristine, oral prednisolone, methotrexate, and 6-mercaptopurine.Ten patients underwent HDCT and APBSCT due to relapse, biphenotype leukemia, Philadelphia translocation, MLL rearrangement, hypodiploidy, and initial white blood cell count above 20.0 × 109/L. At a median 7.4 years from HDCT to APBSCT, overall survival (OS) was 70.0% ± 14.5% and event-free survival (EFS) was 70.0% ± 14.5%. Adverse events were tolerable, without treatment-related mortality.This historical analysis may be a useful reference when allogeneic HSCT including alternative donor HSCT cannot be performed for children with very high risk ALL.
KeywordsLeukemia Transplantation Autologous Maintenance chemotherapy
This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1420250) and was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3A9D3026905).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest. The authors alone are responsible for the content and writing of this article.
- 1.Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, et al. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. Biol Blood Marrow Transplant. 2012;18:505–22.CrossRefPubMedGoogle Scholar
- 3.Powles R, Mehta J, Singhal S, Horton C, Tait D, Milan S, et al. Autologous bone marrow or peripheral blood stem cell transplantation followed by maintenance chemotherapy for adult acute lymphoblastic leukemia in first remission: 50 cases from a single center. Bone Marrow Transplant. 1995;16:241–7.PubMedGoogle Scholar
- 7.Badell I, Munoz A, Ortega JJ, Martinez A, Madero L, Bureo E, et al. Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983–1998. Bone Marrow Transplant. 2005;35:895–901.CrossRefPubMedGoogle Scholar
- 12.Takaue Y, Watanabe A, Murakami T, Watanabe T, Kawano Y, Kuroda Y, et al. High-dose chemotherapy and blood stem cell autografts for children with first relapsed acute lymphoblastic leukemia: a pilot study of the Children’s Cancer and Leukemia Study Group of Japan (CCLSG). Med Pediatr Oncol. 1994;23:20–5.CrossRefPubMedGoogle Scholar
- 13.Lee JW, Kang HJ, Kim S, Lee SH, Yu KS, Kim NH, et al. Favorable outcome of hematopoietic stem cell transplantation using a targeted once-daily intravenous busulfan-fludarabine-etoposide regimen in pediatric and infant acute lymphoblastic leukemia patients. Biol Blood Marrow Transplant. 2015;21:190–5.CrossRefPubMedGoogle Scholar