Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease

Biol Blood Marrow Transplant. 2012 Sep;18(9):1368-77. doi: 10.1016/j.bbmt.2012.02.002. Epub 2012 Feb 10.

Abstract

The curative potential of hematopoietic stem cell transplantation in patients with chronic granulomatous disease depends on availability of a suitable donor, successful donor engraftment, and maintenance of long-term donor chimerism. Twelve consecutive children (median age, 59.5 months; range, 8-140 months) with severe chronic granulomatous disease (serious bacterial/fungal infections pretransplantation; median, 3; range, 2-9) received myeloablative hematopoietic stem cell transplantation using sibling bone marrow ([SibBM]; n = 5), unrelated cord blood (UCB; n = 6), and sibling cord blood (n = 1) at our center between 1997 and 2010. SibBM and sibling cord blood were HLA matched at 6/6, whereas UCB were 5/6 (n = 5) or 6/6 (n = 1). Recipients of SibBM were conditioned with busulfan and cyclophosphamide ± anti-thymocyte globulin (ATG), whereas 6 of 7 cord blood recipients received fludarabine/busulfan/cyclophosphamide/ATG. Seven patients received granulocyte-colony stimulating factor-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but successfully underwent retransplantation with UCB. Highest acute graft-versus-host disease was grade III (n = 1). Extensive chronic graft-vs-host disease developed in 3 patients. All patients are alive with median follow-up of 70.5 months (range, 12-167 months) with high donor chimerism (>98%, n = 10; 94%, n = 1; and 92%, n = 1). Myeloablative hematopoietic stem cell transplantation led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of graft-vs-host disease regardless of graft source.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bone Marrow Transplantation*
  • Child
  • Child, Preschool
  • Cord Blood Stem Cell Transplantation*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Granulocytes / transplantation
  • Granulomatous Disease, Chronic / immunology
  • Granulomatous Disease, Chronic / mortality
  • Granulomatous Disease, Chronic / therapy*
  • Histocompatibility Testing
  • Humans
  • Infant
  • Male
  • Myeloablative Agonists / administration & dosage*
  • Quality of Life
  • Siblings
  • Transplantation Chimera / immunology
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • Myeloablative Agonists