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Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic Leukemia
Nobuko Hijiya, MD;
Melissa M. Hudson, MD;
Shelly Lensing, MS;
Margie Zacher, CCRP;
Mihaela Onciu, MD;
Fred G. Behm, MD;
Bassem I. Razzouk, MD;
Raul C. Ribeiro, MD;
Jeffrey E. Rubnitz, MD, PhD;
John T. Sandlund, MD;
Gaston K. Rivera, MD;
William E. Evans, PharmD;
Mary V. Relling, PharmD;
Ching-Hon Pui, MD
JAMA. 2007;297:1207-1215.
Context Little is known about the incidence of secondary neoplasms after 15 to 20 years in children and adolescents who were treated for acute lymphoblastic leukemia.
Objectives To investigate the cumulative incidence of secondary neoplasms in pediatric patients treated for acute lymphoblastic leukemia over 30 years and to characterize late-occurring tumors.
Design, Setting, and Patients Retrospective study of 2169 patients with acute lymphoblastic leukemia treated between 1962 and 1998 at St Jude Children's Research Hospital, Memphis, Tenn, who achieved complete remission and had a median follow-up time of 18.7 years (range, 2.4-41.3 years).
Main Outcome Measures Cumulative incidences of secondary neoplasms in first remission and standard incidence ratios of observed rates compared with rates of cancer development in the general US population.
Results Secondary neoplasms developed as the first event in 123 patients and comprised 46 myeloid malignancies, 3 lymphomas, 14 basal cell carcinomas, 16 other carcinomas, 6 sarcomas, 16 meningiomas, and 22 other brain tumors. The cumulative incidence of secondary neoplasm was 4.17% (SE, 0.46%) at 15 years and increased substantially after 20 years, reaching 10.85% (SE, 1.27%) at 30 years. When meningiomas and basal cell carcinomas were excluded, the overall cumulative incidence was 3.99% (SE, 0.44%) at 15 years and 6.27% (SE, 0.83%) at 30 years, representing a 13.5-fold increase in overall risk compared with the general population. The cumulative incidence of each tumor type at 30 years was 2.19% (SE, 0.32%) for myeloid malignancy, 0.17% (SE, 0.10%) for lymphoma, 3.00% (SE, 0.59%) for brain tumor, 4.91% (SE, 1.04%) for carcinoma, and 0.57% (SE, 0.37%) for sarcoma.
Conclusions The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. Although the majority of the late-occurring secondary neoplasms are low-grade tumors, the increase in incidence of more aggressive malignant neoplasms is significantly higher than expected in the general population. These results suggest that lifelong follow-up of acute lymphoblastic leukemia survivors is needed to ascertain the full impact of treatment and other leukemia-related factors on secondary neoplasm development.
Author Affiliations: Departments of Oncology (Drs Hijiya, Hudson, Razzouk, Ribeiro, Rubnitz, Sandlund, Rivera, and Pui), Biostatistics (Ms Lensing), Pharmaceutical Sciences (Drs Evans and Relling), Epidemiology and Cancer Control (Ms Zacher), and Pathology (Drs Onciu and Behm), St Jude Children's Research Hospital, and Departments of Pediatrics and Pharmaceutical Sciences and Pharmacy and the Center for Pediatric Pharmacokinetics and Therapeutics, College of Pharmacy, University of Tennessee Health Science Center (Drs Hijiya, Hudson, Behm, Razzouk, Ribeiro, Rubnitz, Sandlund, Rivera, Evans, Relling, and Pui), Memphis. Dr Behm is now with the Department of Pathology, University of Illinois–Chicago Medical Center, Chicago. Dr Razzouk is now with the Children's Center for Cancer and Blood Diseases, St Vincent Children's Hospital, Indianapolis, Ind.
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