Allogeneic hematopoietic stem cell transplantation from a 2-HLA-haplotype-mismatched family donor for posttransplant relapse: a prospective phase I/II study

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 th...

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Published in:	Bone marrow transplantation (Basingstoke) Vol. 56; no. 1; pp. 70 - 83
Main Authors:	Ikegame, Kazuhiro, Kaida, Katsuji, Fukunaga, Keiko, Osugi, Yuko, Yoshihara, Kyoko, Yoshihara, Satoshi, Ishii, Shinichi, Fujino, Satoshi, Yamashita, Takaya, Mayumi, Azusa, Maruyama, Satoshi, Teramoto, Masahiro, Inoue, Takayuki, Okada, Masaya, Tamaki, Hiroya, Ogawa, Hiroyasu, Fujimori, Yosihiro
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-01-2021 Nature Publishing Group
Subjects:	631/67/1990/283/1897 692/308/2779/109/1941 Acute lymphoblastic leukemia Acute myeloid leukemia Cancer Cell Biology Cytarabine Donors Fludarabine Globulins Graft versus host reaction Graft vs Host Disease - prevention & control Haplotypes Hematology Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Histocompatibility antigen HLA Humans Internal Medicine Irradiation Leukemia Lymphatic leukemia Lymphoma Medical prognosis Medicine Medicine & Public Health Melphalan Methylprednisolone Mycophenolate mofetil Mycophenolic acid Myeloid leukemia Non-Hodgkin's lymphoma Prophylaxis Prospective Studies Public Health Radiation Recurrence Relapse Risk factors Stem cell transplantation Stem Cells Tacrolimus Thymocytes Transplantation Transplantation Conditioning Japan
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0268-3369 1476-5365
DOI:	10.1038/s41409-020-0980-8