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Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study.
Bone Marrow Transplant. 2020 Jun 20 [Online ahead of print]BM

Abstract

HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation.

Authors+Show Affiliations

Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. kame@hyo-med.ac.jp.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Department of Hematology-Oncology, Chiba Cancer Center, Chiba, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. Division of Hematology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32564055

Citation

Ikegame, Kazuhiro, et al. "Allogeneic Hematopoietic Stem Cell Transplantation From a 2-HLA-haplotype-mismatched Family Donor for Posttransplant Relapse: a Prospective Phase I/II Study." Bone Marrow Transplantation, 2020.
Ikegame K, Kaida K, Fukunaga K, et al. Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study. Bone Marrow Transplant. 2020.
Ikegame, K., Kaida, K., Fukunaga, K., Osugi, Y., Yoshihara, K., Yoshihara, S., Ishii, S., Fujino, S., Yamashita, T., Mayumi, A., Maruyama, S., Teramoto, M., Inoue, T., Okada, M., Tamaki, H., Ogawa, H., & Fujimori, Y. (2020). Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study. Bone Marrow Transplantation. https://doi.org/10.1038/s41409-020-0980-8
Ikegame K, et al. Allogeneic Hematopoietic Stem Cell Transplantation From a 2-HLA-haplotype-mismatched Family Donor for Posttransplant Relapse: a Prospective Phase I/II Study. Bone Marrow Transplant. 2020 Jun 20; PubMed PMID: 32564055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study. AU - Ikegame,Kazuhiro, AU - Kaida,Katsuji, AU - Fukunaga,Keiko, AU - Osugi,Yuko, AU - Yoshihara,Kyoko, AU - Yoshihara,Satoshi, AU - Ishii,Shinichi, AU - Fujino,Satoshi, AU - Yamashita,Takaya, AU - Mayumi,Azusa, AU - Maruyama,Satoshi, AU - Teramoto,Masahiro, AU - Inoue,Takayuki, AU - Okada,Masaya, AU - Tamaki,Hiroya, AU - Ogawa,Hiroyasu, AU - Fujimori,Yosihiro, Y1 - 2020/06/20/ PY - 2019/12/28/received PY - 2020/06/12/accepted PY - 2020/05/20/revised PY - 2020/6/22/entrez PY - 2020/6/22/pubmed PY - 2020/6/22/medline JF - Bone marrow transplantation JO - Bone Marrow Transplant. N2 - HLA haploidentical hematopoietic stem cell transplantation (HSCT), i.e., HSCT from a 1-HLA-haplotype-mismatched family donor, has been successfully performed even as a second transplantation for posttransplant relapse. Is the haploidentical the limit of HLA mismatches in HSCT? In order to explore the possibility of HLA-mismatched HSCT from family donors beyond haploidentical relatives, we conducted a prospective phase I/II study of 2-HLA-haplotype-mismatched HSCT (2-haplo-mismatch HSCT). We enrolled 30 patients with posttransplant relapse (acute myeloid leukemia: 18, acute lymphoblastic leukemia: 11, non-Hodgkin lymphoma: 1). 2-haplo-mismatch HSCT was performed as the second to sixth transplantations. The donors were siblings (n = 12), cousins (n = 16), and second cousins (n = 2). The conditioning regimen consisted of fludarabine, cytarabine, melphalan, low-dose anti-thymocyte globulin, and 3 Gy of total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, methylprednisolone, and mycophenolate mofetil. All patients achieved neutrophil engraftment, except for a case of early death. The cumulative incidences of grades II-IV and III-IV acute GVHD were 36.7% and 16.7%, respectively. The overall survival at 1 year, relapse, and non-relapse mortality rates was 30.1%, 38.9%, and 44.3%, respectively. Considering the poor prognosis of posttransplant relapse, 2-haplo-mismatch HSCT can be an alternative option in a second or third transplantation. SN - 1476-5365 UR - https://www.unboundmedicine.com/medline/citation/32564055/Allogeneic_hematopoietic_stem_cell_transplantation_from_a_2-HLA-haplotype-mismatched_family_donor_for_posttransplant_relapse:_a_prospective_phase_I/II_study L2 - http://dx.doi.org/10.1038/s41409-020-0980-8 DB - PRIME DP - Unbound Medicine ER -
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