Reduced morbidity and mortality in survivors of childhood acute lymphoblastic leukemia: A report from the childhood cancer survivor study

Stephanie B. Dixon, Yan Chen, Yutaka Yasui, Ching Hon Pui, Stephen P. Hunger, Lewis B. Silverman, Kirsten K. Ness, Daniel M. Green, Rebecca M. Howell, Wendy M. Leisenring, Nina S. Kadan-Lottick, Kevin R. Krull, Kevin C. Oeffinger, Joseph P. Neglia, Ann C. Mertens, Melissa M. Hudson, Leslie L. Robison, Gregory T. Armstrong, Paul C. Nathan

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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 longterm 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%] v 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.

Original languageEnglish (US)
Pages (from-to)3418-3429
Number of pages12
JournalJournal of Clinical Oncology
Issue number29
StatePublished - Oct 10 2020

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© 2020 by American Society of Clinical Oncology.


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