Successful low toxicity hematopoietic stem cell transplantation for high-risk adult chronic granulomatous disease patients.
BACKGROUND
Allogeneic hematopoietic stem cell transplantation for chronic granulomatous disease (CGD) is associated with a significant risk of transplant-related mortality. Adult age, overt infection, and residual inflammatory disease at transplant are major risk factors.


METHODS
Here we report the favorable outcome after bone marrow transplantation in three high-risk adult CGD patients (ages 18, 35, and 39) with severe disease-related complications (overt pneumonia, liver abscess, steroid-dependent granulomatous colitis, diabetes, restrictive lung disease, renal insufficiency, epilepsia). Bone marrow donors were human leukocyte antigen-matched related or unrelated. The conditioning regimen consisted of 2 x 4 mg/kg oral busulphan (d -3, -2), fludarabine 6 x 30 mg/qm (d -7 to -2), rabbit anti-T-cell-globulin (Fresenius) 4 x 10 mg/kg (d -4 to -1). Graft versus host disease prophylaxis consisted of cyclosporine A and mycophenolate-mofetil.


RESULTS
Mean neutrophil and platelet engraftment was observed at day +18.5 and +22.5, respectively. All infectious and inflammatory lesions resolved and restrictive lung disease improved. No signs of grade II-IV acute or chronic graft versus host disease were observed. With a follow-up of 12 to 27 months, all patients are alive and well with full donor chimerism, normalized superoxide production, and documented T- and B-cell function.


CONCLUSIONS
This modified reduced intensity conditioning protocol is a promising treatment modality for high-risk adult CGD patients.
Güngör
Tayfun
T
Division of Immunology/Hematology/BMT, University Children's Hospital, CH-8032 Zurich, Switzerland. Tayfun.Guengoer@kispi.unizh.ch
Halter
Jörg
J
Klink
Anne
A
Junge
Sonja
S
Stumpe
Katrin D M
KD
Seger
Reinhard
R
Schanz
Urs
U
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000502:physiology; D012129:Respiratory Function Tests; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D018183:Transplantation Chimera; D016896:Treatment Outcome