Allogeneic transplantation for patients with high-risk or refractory neuroblastoma.

9552 Background: While the survival of high-risk neuroblastoma patients has improved with myeloablative chemotherapy (MAC) and 13-cis retinoic acid, 60% of children fail this approach, thus other strategies are needed. As a potential platform for future immunologic-based therapies, we report a retrospective, single-center experience using allogeneic hematopoietic stem cell transplantation (allo-HSCT) following MAC for high risk or recurrent neuroblastoma (NB). METHODS: Between June 1994 and November 2007, 17 pediatric patients with high risk or recurrent NB underwent allo-HSCT: allograft sources were related bone marrow (MRD) in 10 patients (pts) and unrelated umbilical cord blood (UCB) in 7 pts. At initial diagnosis the median age was 3.5 years, 16 pts had stage 4 and 1 patient had stage 3 disease. N-myc was amplified in 4 of the 12 pts with available N-myc status. Prior to allo-HSCT, 4 pts were in CR and 7 pts had failed autologous HSCT. Median time from NB diagnosis to allo-HSCT was 14.9 months. Regarding MAC, 7 pts received total body irradiation (TBI)-based regimens: (5 TBI/melphalan (Mel) and 2 TBI/thiotepa), 6 pts received cyclophosphamide (Cy)-based regimens (5 Cy/Mel and 1 Cy-thiotepa), 1 received carboplatin /etoposide/melphalan (CEM), and 3 pts received therapeutic I-131MIBG based regimens (MIBG /CEM in 1, MIBG /campath /Mel in 1, and MIBG/TBI/Mel in 1). RESULTS: The median day to neutrophil engraftment (ANC > 500) was 10.5 days for MRD BMT and 22 days for UCBT. The median day to platelet engraftment (plt >20k) for MRD BMT was 29.5 days and for UCBT was 62 days. Acute GVHD (grades I-IV) was seen in 6 patients: 3 grade-I skin, 1 grade-II skin, and 2 grade-III involving both skin and gut. Eleven pts (65%) died at a median of 377 days post-allo-HSCT: 2 infections (PCP pneumonia, Pseudomonal sepsis), 2 MSOF, 1 leukemic relapse (child with recurrent NB and secondary AML) and 6 NB progression. Six patients (5 MRD, 1 UCB) are long-term survivors with overall survival of 35% at 10 years. CONCLUSIONS: Allo-HSCT provided durable remission in a very high risk group of NB patients. Therefore a strategy that incorporates early allografting with targeted immunologic therapy should be investigated for refractory or ultra-high risk NB patients.

Duke Scholars

Author Paul Langlie Martin Pediatrics, Transplant and Cellular Therapy

Author Joanne Kurtzberg Pediatrics, Transplant and Cellular Therapy