Reduced Risk of Secondary Leukemia With Fewer Cycles of Dose-Intensive Induction Chemotherapy in Patients With Neuroblastoma

Background. We report a prospective study of secondary leukemia (SL)/myelodysplastic syndrome (MDS) ill neuroblastoma (NB) patients treated with >= 5 cycles of dose-intensive chemotherapy. Procedure. NB patients received induction with high-close cyclophosphamide (4,200 mg/m(2))-doxorubicin (75 mg/m(2))-vincristine (cycles 1, 2, 4, 6, 8), and high-dose cisplatin (200 mg/m(2))-etoposide (600 mg/m(2)) (cycles 3, 5, 7). Bone marrow was examined every 1-3 months for >= 36 months, with inclusion of extensive chromosomal Studies 1-3 months post-induction and 1-2 x/year thereafter. Results. One hundred eight four patients received 5 (n = 76), 6 (n = 45), 7 (n = 59), or 8 (n = 4) cycles. Eight patients developed SL/MDS (only one each in the 5- and 6-cycle groups), at 12-50 months, including two cases detected in Surveillance studies. Among 108 patients who received >= 6 cycles, the 5-year cumulative incidence was 7.1% (95% Cl: 2%, 12.2%), versus 0% among 54 patients who received 5 Cycles Without maintenance oral etoposide. Five-year Cumulative incidences were 1.46%, 2.28%, and 8.47%) among patients in the 5-, 6-, and 7-cycle groups, with fewer cycles having a significantly lower risk (P=0.048). There was no significant association of risk with potentially leukemogenic consolidative treatments (targeted radiotherapy, myeloablative therapy, and oral etoposide). Conclusions. Reducing the number of dose-intensive cycles significantly decreases the risk of SL/MDS, yielding 5-year rates matching the low range (0.4-2.2%) reported for moderate-close combination chemotherapy regimens used against other pediatric solid tumors. Pediatr Blood Cancer 2009;53:17-22. (C) 2009 Wiley-Liss, Inc.