Allogeneic stem cell transplantation using myeloablative and reduced-intensity conditioning in patients with major histocompatibility complex class II deficiency

Biol Blood Marrow Transplant. 2010 Jun;16(6):818-23. doi: 10.1016/j.bbmt.2010.01.002. Epub 2010 Jan 14.

Abstract

Major histocompatibility complex class II (MHC II) deficiency is a rare combined immunodeficiency disease. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment. Between June 1994 and February 2007, 30 children with MHC II deficiency underwent a total of 33 HSCT procedures. Median age at HSCT was 27 months. The stem cell source was unmanipulated bone marrow from HLA-identical related donors in 26 patients, one HLA antigen-mismatched bone marrow in 3 patients, and unrelated umbilical cord blood in 1 patient. Conditioning was with one of 3 myeloablative regimens--regimen A (18 patients): busulfan (Bu), cyclophosphamide (Cy), and etoposide; regimen B (2 patients): Bu, Cy, and antithymocyte globulin (ATG); or regimen C (1 patient): CY and total body irradiation (TBI)--or with a reduced-intensity regimen (12 patients): fludarabine, melphalan, and ATG. The median CD34 cell dose was 8.3 x 10(6)/kg. Twenty patients experienced immune reconstitution and had sustained engraftment ranging from 9% to 100% for lymphoid lines and from 5% to 100% for myeloid lines that were significant to cure the disease. The overall disease-free survival rate was 66% and 76% after HLA-identical HSCT, with a median follow-up of 6.3 years, which is higher than previously reported. In HLA-identical transplant recipients, reliable donor stem cell engraftment and immune reconstitution were achieved through myeloablative or reduced-intensity conditioning. Further studies and long-term follow-up are needed to determine the appropriate conditioning regimen.

MeSH terms

  • Blood Cell Count
  • Bone Marrow Transplantation / adverse effects
  • Bone Marrow Transplantation / methods
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Graft Survival / immunology
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / prevention & control
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Histocompatibility / immunology
  • Histocompatibility Antigens Class II*
  • Humans
  • Immunoglobulin G / blood
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / surgery*
  • Infant
  • Infant, Newborn
  • Lymphocyte Count
  • Lymphocytes / cytology
  • Lymphocytes / immunology
  • Male
  • Myeloablative Agonists / therapeutic use*
  • Retrospective Studies
  • Transplantation Chimera / immunology
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • HLA Antigens
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Myeloablative Agonists