Unrelated umbilical cord blood transplant for osteopetrosis

Severe osteopetrosis is a uniformly fatal disease that affects infants and young children. Stem cell transplantation can be curative since the patient's defective osteoclasts are replaced by functional donor osteoclasts. Due to encroachment of cranial nerves leading to blindness and deafness, rapid intervention is necessary to decrease morbidity. We have investigated use of unrelated umbilical cord blood (UUCB) as the source of stem cells for 7 patients with osteopetrosis who lacked matched family donors. Sufficiently matched UUCB units were identified for all 7 osteopetrosis patients referred to our center. Four patients received UCB units with 2 antigen mismatches, while 2 patients received a single antigen mismatched unit. The median age at the time of transplant was 7-months (range 4-27) and the median mononuclear cell dose was 10xlOe7 cells/kg (range 2.3-21.1xlOe7). All patients were prepared with Busulfan, Cyclophosphamide and ATG. Steroids and Cyclosporine were used for GvHD prophylaxis. All évaluable cases engrafted with a median time to ANC 500 of 22 days (range 12-68). Five patients had grade I-I1 acute GvHD, while 2 had limited chronic GvHD which responded to therapy. Five of seven patients are currently alive, with a median follow-up of 23 months (range 1-49). Our results show that use of UUCB for severe osteopetrosis is an effective treatment for patients who lack matched family donors. The advantages of UUCB are low risk of chronic GvHD and the rapidity of identifying a match. For osteopetrosis patients, it is critical to begin transplantation as soon as possible after diagnosis to decrease the risk of cranial nerve damage. Age MNC Match ANC Pit. RBC aGvHD cGvHD Survival (Mo) (10e7/kg) 500 Indep. Indep. 7 2.3 5/6 12 23 30 D limited 23 mo 13 5.9 4/6 20 67 56 None None 49 mo 27 12.3 4/6 21 150 151 0 None 23 mo 5 5.6 5/6 23 47 39 None limited 12 mo 8 18.3 4/6 40 ME ME u NE died d 92 6 10.0 6/6 68 NE NE IINE died dl 10 4 21.1 4/6 Too early TE TE TE TE 1 mo.

Duke Scholars

Author Paul Langlie Martin Pediatrics, Transplant and Cellular Therapy