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.
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.
Pediatric Blood and Marrow Transplantation Program, Duke University Medical Center, Durham, North Carolina 27710, USA. priti.tewari@duke.edu
Priti
P
Tewari
Paul L
PL
Martin
Adam
A
Mendizabal
Suhag H
SH
Parikh
Kristin M
KM
Page
Timothy A
TA
Driscoll
Harry L
HL
Malech
Joanne
J
Kurtzberg
Vinod K
VK
Prasad
D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control*; D006098:Granulocytes / Q000637:transplantation; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D011788:Quality of Life; D035781:Siblings; D018183:Transplantation Chimera / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
D019653:Myeloablative Agonists