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

摘要

The curative potential of hematopoietic stem cell transplantation (HSCT) in patients with chronic granulomatous disease (CGD) depends upon 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) with severe CGD (serious bacterial/fungal infections pre-transplant, median 3; range, 2–9) received myeloablative HSCT using sibling bone marrow (SibBM; n=5), unrelated cord blood (UCB; n=6), and sibling cord blood (SibCB; n=1) at our center between 1997–2010. SibBM and SibCB were HLA matched at 6/6 while UCB were 5/6 (n=5) or 6/6 (n=1). Recipients of SibBM were conditioned with Busulfan and Cyclophosphamide (Bu/Cy) + ATG while 6 of 7 CB recipients received Fludarabine/Bu/Cy/ATG. Seven patients received G-CSF-mobilized granulocyte transfusions from directed donors. The first 2 UCB recipients had primary graft failure but were successfully re-transplanted with UCB. Highest acute GvHD was grade III (n=1). Extensive chronic GvHD developed in 3 patients. All patients are alive with median follow-up of 70.5 (range 12–167) months with high donor chimerism (>98%, n=10; 94%, n=1; and 92%, n=1). Myeloablative HSCT led to correction of neutrophil dysfunction, durable donor chimerism, excellent survival, good quality of life, and low incidence of GvHD regardless of graft source.