Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism.
Based on the hypothesis that long-term fetomaternal microchimerism is associated with acquired immunologic hyporesponsiveness to noninherited maternal antigens (NIMAs) or inherited paternal antigens (IPAs), several groups have recently reported successful cases of non-T-cell-depleted hematopoietic stem cell transplantation (SCT) from HLA-haploidentical family members mismatched for NIMAs. In this study, we examined the outcomes of 35 patients with advanced hematologic malignancies who underwent HLA-2-antigen- or HLA-3-antigen-incompatible SCT from a microchimeric NIMA-mismatched donor. After standard-intensity or reduced-intensity preparative regimens, all patients had sustained hematopoietic recovery with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis. Grade II/IV acute GVHD occurred in 19 (56%) of 34 evaluable patients, while extensive chronic GVHD developed in 13 (57%) of 23 patients who could be evaluated. Multivariate analysis demonstrated that NIMA mismatch in the GVH direction was associated with a lower risk of severe grade III-IV acute GVHD when compared with IPA mismatch (P = .03). Fifteen patients were alive and 14 of them were disease-free with a median follow-up of 20 (range, 8 to 37) months. These results indicate that T cell-replete SCT from an HLA-haploidentical NIMA-mismatched donor can offer durable remission with an acceptable risk of GVHD in selected patients with advanced hematologic malignancies who lack immediate access to a conventional stem cell source.
Ichinohe
Tatsuo
T
Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. nohe@kuhp.kyoto-u.ac.jp.
Uchiyama
Takashi
T
Shimazaki
Chihiro
C
Matsuo
Keitaro
K
Tamaki
Shigehisa
S
Hino
Masayuki
M
Watanabe
Arata
A
Hamaguchi
Motohiro
M
Adachi
Souichi
S
Gondo
Hisashi
H
Uoshima
Nobuhiko
N
Yoshihara
Takao
T
Hatanaka
Kazuo
K
Fujii
Hiroshi
H
Kawa
Keisei
K
Kawanishi
Kazunobu
K
Oka
Koji
K
Kimura
Hideo
H
Itoh
Mitsuru
M
Inukai
Takeshi
T
Maruya
Etsuko
E
Saji
Hiroh
H
Kodera
Yoshihisa
Y
D000293:Adolescent; D000328:Adult; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007519:Isoantigens; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009679:Nuclear Family; D012042:Registries; D012189:Retrospective Studies; D016019:Survival Analysis; D014019:Tissue Donors; D018183:Transplantation Chimera
D007519:Isoantigens