Reduced risk of secondary leukemia with fewer cycles of dose-intensive induction chemotherapy in patients with neuroblastoma Journal Article
| Authors: | Kushner, B. H.; Kramer, K.; Modak, S.; Qin, L. X.; Yataghene, K.; Jhanwar, S. C.; Cheung, N. K. V. |
| Article Title: | Reduced risk of secondary leukemia with fewer cycles of dose-intensive induction chemotherapy in patients with neuroblastoma |
| Abstract: | 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<sup>2</sup>)-doxorubicin (75 mg/m<sup>2</sup>)-vincristine (cycles 1, 2, 4, 6, 8), and high-dose cisplatin (200 mg/m<sup>2</sup>)-etoposide (600 mg/m<sup>2</sup>) (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 1-2x/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 ≥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. © 2009 Wiley-Liss, Inc. |
| Keywords: | adolescent; adult; cancer chemotherapy; child; controlled study; preschool child; school child; child, preschool; leukemia; young adult; major clinical study; cisplatin; doxorubicin; cancer growth; cancer risk; cancer radiotherapy; drug megadose; antineoplastic agent; prospective study; prospective studies; etoposide; antineoplastic combined chemotherapy protocols; drug administration schedule; health survey; cyclophosphamide; vincristine; drug antagonism; myelodysplastic syndrome; neuroblastoma; chemically induced disorder; remission; remission induction; drug administration; alkylating agents; dna topoisomerase (atp hydrolysing); risk reduction; chromosome analysis; chromosomal aberrations; topoisomerase ii inhibitors; dna topoisomerases, type ii; myelodysplastic syndromes; risk reduction behavior |
| Journal Title: | Pediatric Blood and Cancer |
| Volume: | 53 |
| Issue: | 1 |
| ISSN: | 1545-5009 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2009-07-15 |
| Start Page: | 17 |
| End Page: | 22 |
| Language: | English |
| DOI: | 10.1002/pbc.21931 |
| PUBMED: | 19148951 |
| PROVIDER: | scopus |
| PMCID: | PMC4079040 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: PBCEA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work