A randomized phase III trial of myeloablative autologous peripheral blood stem cell (PBSC) transplant (ASCT) for high-risk neuroblastoma (HR-NB) employing immunomagnetic purged (P) versus unpurged (UP) PBSC: A Children's Oncology Group study.
10011 Background: ASCT improves outcome for HR-NB, but potential risk of reinfusion of viable tumor in PBSC could affect event-free survival (EFS). We assessed the impact of ASCT with immunomagnetic purging of PBSC, compared to UP product, on EFS, PBSC tumor content, engraftment, and ASCT toxicity. METHODS: Between 2/2001 and 3/2006, 489 eligible newly diagnosed HR-NB pts were randomized at study entry to have P or UP PBSC obtained and cryopreserved after 2 cycles of induction chemotherapy. Purging was performed centrally using carbonyl iron depletion of phagocytes followed by 2 cycles of magnetic beads with 5 anti-NB monoclonal antibodies. After 6 chemotherapy cycles, pts received melphalan (180-210 mg/m(2)), carboplatin (AUC 4.1 to max 1700 mg/m(2)), and etoposide (800-1352 mg/m(2)) based on GFR followed by PBSC support. Post-ASCT pts had radiation to primary and MIBG+ sites, then 6 cycles of 13-cis-retinoic acid. EFS and overall survival (OS) from enrollment [primary endpoint] were analyzed as intent-to- treat. RESULTS: Median age at study entry was 3.1 yrs (range 91 days-29 years), 44% of 392 tumors tested had MYCN amplification and 424 were INSS stage 4. There were 368 pts transplanted (178 P and 190 UP). Crossover from P to UP arm occurred in 30 pts and from UP to P arm in 5 pts. Only 5 pts (1 P and 4 UP) had NB detected in PBSC by immunocytology at collection, none after purging. RT- PCR analysis of tumor in PBSC products is ongoing. The median time to ANC>500 was 13 days for P and 11 days for UP (p= 0.0001). Toxic death following ASCT was 3.2%, (8 P, 4 UP) mainly due to infection. There was no difference in toxicities between arms. CONCLUSIONS: Centralized immunomagnetic purging of PBSC in the context of dose-intensive chemoradiotherapy and biologic therapy in first response did not impact EFS or OS at 2 years. RT-PCR analyses of PBSC products will determine if purging of rare tumor cells occurred. [Table: see text] No significant financial relationships to disclose.
Kreissman, SG; Villablanca, JG; Seeger, RC; Grupp, SA; London, WB; Maris, JM; Park, JR; Cohn, SL; Matthay, KK; Reynolds, CP
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