Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism

Blood. 2004 Dec 1;104(12):3821-8. doi: 10.1182/blood-2004-03-1212. Epub 2004 Jul 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cause of Death
  • Child
  • Child, Preschool
  • Feasibility Studies
  • Female
  • Graft vs Host Disease / etiology
  • Haplotypes
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Histocompatibility Testing*
  • Histocompatibility*
  • Humans
  • Isoantigens*
  • Male
  • Middle Aged
  • Mothers
  • Nuclear Family
  • Registries
  • Retrospective Studies
  • Survival Analysis
  • Tissue Donors
  • Transplantation Chimera*

Substances

  • Isoantigens