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) in neuroblastoma (NB) patients treated with > or =5 cycles of dose-intensive chemotherapy.


METHODS
NB patients received induction with high-dose 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 > or =36 months, with inclusion of extensive chromosomal studies 1-3 months post-induction and 1-2x/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 > or =6 cycles, the 5-year cumulative incidence was 7.1% (95% CI: 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-dose combination chemotherapy regimens used against other pediatric solid tumors.
Kushner
Brian H
BH
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. kushnerb@mskcc.org
Kramer
Kim
K
Modak
Shakeel
S
Qin
Li-Xuan
LX
Yataghena
Karima
K
Jhanwar
Suresh C
SC
Cheung
Nai-Kong V
NK
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007938:Leukemia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000517:prevention & control*; D009447:Neuroblastoma / Q000150:complications / Q000188:drug therapy*; D011446:Prospective Studies; D012074:Remission Induction; D040242:Risk Reduction Behavior; D059005:Topoisomerase II Inhibitors; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D059005:Topoisomerase II Inhibitors; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin