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Reduced risk of secondary leukemia with fewer cycles of dose‐intensive induction chemotherapy in patients with neuroblastoma
Author(s) -
Kushner Brian H.,
Kramer Kim,
Modak Shakeel,
Qin LiXuan,
Yataghena Karima,
Jhanwar Suresh C.,
Cheung NaiKong V.
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21931
Subject(s) - medicine , etoposide , cumulative incidence , vincristine , induction chemotherapy , cumulative dose , cyclophosphamide , gastroenterology , chemotherapy , surgery , transplantation
Background We report a prospective study of secondary leukemia (SL)/myelodysplastic syndrome (MDS) in neuroblastoma (NB) patients treated with ≥5 cycles of dose‐intensive chemotherapy. Procedure 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 ≥36 months, with inclusion of extensive chromosomal studies 1‐3 months post‐induction and 1–2×/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% 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. Pediatr Blood Cancer 2009;53:17–22. © 2009 Wiley‐Liss, Inc.