Outcomes in Pediatric Patients with Engraftment Failure After Allogeneic Transplants

Graft failure is an uncommon but serious complication after allogeneic haematopoeitic stem cell transplantation (HSCT) and is an indication for a 2^nd HSCT. However, there are limited outcomes data for pediatric patients who undergo such therapy. We now report on 44 pediatric patients who had a 2^nd HSCT after graft failure following HSCT for malignant (n=14) or non-malignant diseases (n=30) at our institution between 2000-2012. Primary graft failure was defined as failure to achieve ANC >0.5x10 ⁹ /L for 3 consecutive days by day +30 (day +42 for cord donors) or donor chimerism <5% (n=22) and secondary graft failure was defined as loss of chimerism to <5% after having achieved >5%, or ANC persistently below 0.5x10 ⁹ /L or platelet count <20 x10⁹/L (n=23). The median age at first transplant was 6 yrs (range 1month to 21 years), 18 pts were transplanted from a matched or mismatched unrelated donor (MUD/MMUD); 16pts from haplo-identical donor (haplo), and 10 from a matched or mismatched related donor (MRD/MMRD). Donor stem cell products were: marrow for 26 patients; peripheral blood (PB) for 17 patients and a cord blood unit (CBU) for 1 patient. 26 patients received myeloablative conditioning (MAC); 17 reduced-intensity conditioning (RIC) and 1 patient received no conditioning. The median time between 1^st and 2^nd HSCT was 55 days (range: 30d-2587d) for patients with malignancies and 66 days (range: 33d-1846d) for patients with non-malignant disorders. The donor was the same for both the 1^st and 2^nd transplant for 34 pts. More patients received PB stem cell products for their second transplant (marrow product=17, PB=25, CBU=2). At the time of 2^nd HSCT, 24 had RIC, 8 had MAC and 12 had no conditioning. 31 patients engrafted after the 2^nd HSCT. The overall survival for patients who underwent a 2^nd HSCT was 61% (27/44) with a median overall survival of 3.8 years (range: 0.2yrs to >10 yrs) and better survival for patients with non-malignant (21/30) versus malignant disease (6/14). There was no difference in survival between patients with primary versus secondary graft failures. Infection was the primary cause of death (9/17). For 13 patients who failed to engraft after 2^nd HSCT, 3 patients died and 10 patients received a 3^rd HSCT of whom 5 patients survive. Thus 61% of pediatric patients can achieve graft salvage from a second transplant, and half of the continuing graft failures can be rescued by a third HSCT.