Title

Reduced Morbidity and Mortality in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study

Authors

Stephanie B. Dixon, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.
Yan Chen, School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
Yutaka Yasui, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.
Ching-Hon Pui, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.
Stephen P. Hunger, Division of Oncology and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA.
Lewis B. Silverman, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
Kirsten K. Ness, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.
Daniel M. Green, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.
Rebecca M. Howell, Radiation Physics Department, The University of Texas at MD Anderson Cancer Center, Houston, TX.
Wendy M. Leisenring, Cancer Prevention and Clinical Statistics Programs, Fred Hutchinson Cancer Research Center, Seattle, WA.
Nina S. Kadan-Lottick, Department of Pediatric Hematology/Oncology, Yale Cancer Center, New Haven, CT.
Kevin R. Krull, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.
Kevin C. Oeffinger, Department of Medicine, Duke University, Durham, NC.
Joseph P. Neglia, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN.
Ann C. Mertens, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA.
Melissa M. Hudson, Department of Oncology, St Jude Children's Research Hospital, Memphis, TN.
Leslie L. Robison, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.
Gregory T. Armstrong, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN.
Paul C. Nathan, Division of Hematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Abstract

PURPOSE: Risk-stratified therapy, which modifies treatment on the basis of clinical and biologic features, has improved 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) to 90%, but its impact on long-term toxicity remains unknown. METHODS: We assessed all-cause and health-related late mortality (including late effects of cancer therapy), subsequent malignant neoplasms (SMNs), chronic health conditions, and neurocognitive outcomes among 6,148 survivors of childhood ALL (median age, 27.9 years; range, 5.9-61.9 years) diagnosed between 1970 and 1999. Therapy combinations and treatment intensity defined 6 groups: 1970s-like (70s), standard- or high-risk 1980s-like (80sSR, 80sHR) and 1990s-like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Cumulative incidence, standardized mortality ratios, and standardized incidence ratios were compared between treatment groups and with the US population. RESULTS: Overall, 20-year all-cause late mortality was 6.6% (95% CI, 6.0 to 7.1). Compared with 70s, 90sSR and 90sHR experienced lower health-related late mortality (rate ratio [95% CI]: 90sSR, 0.2 [0.1 to 0.4]; 90sHR, 0.3 [0.1 to 0.7]), comparable to the US population (standardized mortality ratio [95% CI]: 90sSR, 1.3 [0.8 to 2.0]; 90sHR, 1.7 [0.7 to 3.5]). Compared with 70s, 90sSR had a lower rate of SMN (rate ratio [95% CI], 0.3 [0.1 to 0.6]) that was not different from that of the US population (standardized incidence ratio [95% CI], 1.0 [0.6 to 1.6]). The 90sSR group had fewer severe chronic health conditions than the 70s (20-year cumulative incidence [95% CI], 11.0% [9.7% to 12.3%] 22.5% [19.4% to 25.5%]) and a lower prevalence of impaired memory (prevalence ratio [95% CI], 0.7 [0.6 to 0.9]) and task efficiency (0.5 [0.4 to 0.7]). CONCLUSION: Risk-stratified therapy has reduced late morbidity and mortality among contemporary survivors of standard-risk ALL, represented by 90sSR. Health-related late mortality and SMN risks among 5-year survivors of contemporary, standard-risk childhood ALL are comparable to the general population.

Publication Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

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