Beneficial and harmful effects of anthracyclines in the treatment of childhood acute lymphoblastic leukaemia: A systematic review and meta-analysis Journal Article


Authors: Yetgin, S.; Ozbek, N. Y.; Masera, G.; Valsecchi, M. G.; Dacou, V.; Loening, L.; Schrappe, M.; Zimmermann, M.; Henze, G.; Von Stackelberg, A.; Gadner, H.; Mann, G.; Attarbaschi, A.; Brandalise, S. R.; Carroll, W. L.; Gaynon, P.; Boyett, J. M.; Nachman, J.; Devidas, M.; Sather, H. N.; Escherich, G.; Janka, G.; Gelber, R. D.; Sallan, S. E.; Pieters, R.; Bierings, M.; Kamps, W. A.; Otten, J.; Suciu, S.; Viana, M. B.; Baruchel, A.; Auclerc, M.; Perez, C.; Solidaro, A.; Stark, B.; Steinberg, D.; Koizumi, S.; Tsurusawa, M.; Zintl, F.; Schiller, I.; Matsuzaki, A.; Eden, T. O. B.; Lilleyman, J. S.; Richards, S.; Steinherz, P. G.; Steinherz, L.; Kochupillai, V.; Bakhshi, S.; Ortega, J. J.; Appelbaum, F. R.; Cheng, C.; Pei, D.; Pui, C. H.; Kukure, P.; Nakazawa, S.; Tsuchida, M.; Elphinstone, T.; Evans, V.; Gettins, L.; Hicks, C.; MacKinnon, L.; Morris, P.; Wade, R.
Article Title: Beneficial and harmful effects of anthracyclines in the treatment of childhood acute lymphoblastic leukaemia: A systematic review and meta-analysis
Abstract: Anthracyclines are used to treat childhood acute lymphoblastic leukaemia (ALL) but non-randomized studies suggest that cardiotoxicity may be a problem. Individual patient data from trials in childhood ALL that randomized anthracyclines or methods of reducing cardiotoxicity were analysed by standard meta-analysis methods. Results were grouped and combined according to: addition of an anthracycline to standard therapy, type of anthracycline, mode of administration, and the use of a cardioprotectant. Data from 958 patients in 4 trials, recruiting between 1972 and 1984, showed that addition of an anthracycline reduced bone marrow relapse and, non-significantly, non-bone marrow relapse, resulting in an increased relapse-free interval. However there was a non-significant increase in induction failures, and in deaths in first remission. Event-free survival at 5 years was 56.7% with anthracycline versus 52.8% without (Odds Ratio = 0.91; 95% Confidence Interval = 0.76-1.10; P = 0.3). There were no significant differences found in other treatment comparisons. The limited data from trials did not demonstrate differences in clinically evident cardiotoxicity. Anthracyclines are effective against bone marrow relapse but have not been shown to significantly increase event free survival in childhood ALL. The evidence on type of anthracycline, method of administration or use of cardioprotectant was insufficient to be able to rule out important differences.
Keywords: cardiotoxicity; anthracycline; children; induction therapy; meta-analysis; randomized; term-follow-up; risk-factors; clinical heart-failure; acute; leukaemia; childhood all; liposome-encapsulated doxorubicin; lymphocytic-leukemia; conventional doxorubicin; multicenter trial
Journal Title: British Journal of Haematology
Volume: 145
Issue: 3
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2009-01-01
Start Page: 376
End Page: 388
Language: English
ACCESSION: ISI:000265009100012
DOI: 10.1111/j.1365-2141.2009.07624.x
PROVIDER: wos
PMCID: PMC2812732
PUBMED: 19236609
Notes: --- - Article - "Source: Wos"
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MSK Authors
  1. Peter G Steinherz
    179 Steinherz