This Article Full Text Full Text (PDF) Erratum (v23,p5277) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laughton, S. J. Articles by Marshall, G. M. Search for Related Content PubMed PubMed Citation Articles by Laughton, S. J. Articles by Marshall, G. M. Social Bookmarking                            What's this?

Early Responses to Chemotherapy of Normal and Malignant Hematologic Cells Are Prognostic in Children With Acute Lymphoblastic Leukemia

From the Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, Randwick; and Children's Cancer Institute Australia for Medical Research, Sydney, Australia

Address reprint requests to Glenn M. Marshall, MD, Centre for Children's Cancer and Blood Disorders, Sydney Children's Hospital, High St, Randwick, Sydney, NSW 2031, Australia; e-mail: g.marshall{at}unsw.edu.au

PURPOSE: Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse.

PATIENTS AND METHODS: We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample.

RESULTS: We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse.

CONCLUSION: We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.

Supported by research grants from the National Health and Medical Research Council of Australia, New South Wales State Cancer Council, and the Sydney Children's Hospital Foundation, Joshua Holland Leukaemia Fund (S.J.L.).

Presented in part at the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 8, 2003.

Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children's Hospital, Randwick.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. R. Schultz, D. J. Pullen, H. N. Sather, J. J. Shuster, M. Devidas, M. J. Borowitz, A. J. Carroll, N. A. Heerema, J. E. Rubnitz, M. L. Loh, et al. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG) Blood, February 1, 2007; 109(3): 926 - 935. [Abstract] [Full Text] [PDF]

				N. M. Verrills, S. T. Po'uha, M. L. M. Liu, T. Y. E. Liaw, M. R. Larsen, M. T. Ivery, G. M. Marshall, P. W. Gunning, and M. Kavallaris Alterations in gamma-actin and tubulin-targeted drug resistance in childhood leukemia. J Natl Cancer Inst, October 4, 2006; 98(19): 1363 - 1374. [Abstract] [Full Text] [PDF]

				J. M. Rowe, G. Buck, A. K. Burnett, R. Chopra, P. H. Wiernik, S. M. Richards, H. M. Lazarus, I. M. Franklin, M. R. Litzow, N. Ciobanu, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993 Blood, December 1, 2005; 106(12): 3760 - 3767. [Abstract] [Full Text] [PDF]