Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. Nesbit ME, Sather H, Robison LL, et al. Finally, although our analyses include all patients with acute lymphoblastic leukemia enrolled in St Jude studies between 1962 and 1998, some of our estimates, particularly those investigating temporal trends, are based on small sample sizes and have wide confidence intervals, which indicates lack of precision requiring careful interpretation. Cancer 1987;59:1683–91. Simone J, Aur RJ, Hustu HO, Pinkel D. “Total therapy” studies of acute lymphocytic leukemia in children: current results and prospects for cure.  et al. reported nine brain tumors among 896 children treated in one study by the Children's Cancer Study Group30; additional tumors of the central nervous system developed subsequently in several other children in that study and are included in this series. Analysis and interpretation of data: Hijiya, Hudson, Lensing, Relling, Pui. Dr Pui is an American Cancer Society professor. Discover the … ; William Woods, M.D., University of Minnesota Health Sciences Center, Minneapolis; Thomas Williams, M.D., University of Texas Health Sciences Center, San Antonio; Anna Meadows, M.D., Children's Hospital of Philadelphia; Peter Steinherz, M.D., Memorial Sloan-Kettering Cancer Center, New York; Robert Weetman, M.D., James Whitcomb Riley Hospital for Children, Indianapolis; Mark Greenberg, M.B., Ch.B., Hospital for Sick Children, Toronto; Richard O'Brien, M.D., University of Utah Medical Center, Salt Lake City; Harvey Cohen, M.D., Strong Memorial Hospital, Rochester, N.Y.; Paul Rogers, M.D., University of British Columbia, Vancouver; Robert Wells, M.D., Children's Hospital Medical Center, Cincinnati; Jerry Finklestein, M.D., Harbor/UCLA and Miller Children's Medical Center, Torrance and Long Beach, Calif.; Stephen Feig, M.D., University of California Medical Center, Los Angeles; Raymond Tannous, M.D., University of Iowa Hospitals and Clinic, Iowa City; David Tubergen, M.D., Children's Hospital of Denver; Gerald Gilchrist, M.D., Mayo Clinic, Rochester, Minn.; Allan Pyesmany, M.D., Izaak Walton Killam Hospital for Children, Halifax, Nova Scotia; Herbert Cooper, M.D., University of North Carolina, Chapel Hill; Milton Donaldson, M.D., University of Medicine and Dentistry of New Jersey, Camden; Arnold Freeman, M.D., Children's Mercy Hospital, Kansas City, Mo. This included operative and pathology reports, records of radiation therapy, and information about the patient's treatment and outcome. Non-menaloma skin cancer … We undertook a retrospective cohort study of 9720 children who had been given a diagnosis of ALL between June 1972 and August 1988 and had been treated according to the therapeutic protocols of the Children's Cancer Study Group. Lymphoid gene expression as a predictor of risk of secondary brain tumors. No association was seen between sex or race and the occurrence of a second neoplasm. The overall pattern of risk for these cancers is shown in Figure 1. Cumulative assigned doses were calculated for the anthracyclines (daunorubicin and doxorubicin) and for cyclophosphamide. Tumors of the central nervous system were the most common second neoplasms among children five years of age or younger at the time of the diagnosis of ALL, with miscellaneous neoplasms more common in older children. . Learn about the acute lymphocytic leukemia survival rate here. ); and the University of Southern California School of Medicine, Los Angeles (H.N.S., G.D.H.). Nineteen new secondary neoplasms were diagnosed in these groups since publication of the studies, but in each analysis the risk factors retained their original importance. Vertical bars are 95 percent confidence limits. Prognostic factors and therapy in acute lymphoblastic leukemia of childhood: CCG-141 . New York: John Wiley, 1980:14–5. Meadows AT, Robison LL, Neglia JP, Sather H, Hammond D. . Pratt CB, George SL, Hannock ML, Hustu HO, Kun LE, Ochs JS. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. These cases were treated as a competing event, similar to relapse of acute lymphoblastic leukemia, in this analysis. Among the 123 patients who developed a secondary neoplasm as their first event, acute myeloid leukemia represented the most common subtype, occurring in 37 patients (30.1%), followed by CNS tumors other than meningioma (22 patients [17.9%]), meningioma (16 patients [13.0%]), carcinoma (excluding basal cell carcinoma) (16 patients [13.0%]), and basal cell carcinoma (14 patients [11.4%]). Hammond GD. Nonparametric estimation from incomplete observations . Cancer 1983;51:1041–9. Bone sarcomas linked to radiotherapy and chemotherapy in children . . These institutions are required to register all new patients who have a diagnosis of cancer with the Operations Office, and they generally enter all eligible patients in active clinical trials. Three patients (1 each with acute myeloid leukemia, transitional cell carcinoma, and hepatocellular carcinoma) died of secondary neoplasms, and a patient with meningioma died after developing hepatocellular carcinoma as a third neoplasm. et al. For some people with acute lymphocytic leukemia (ALL), treatment can get rid of all of the leukemia cells. 27. Statistical comparison of these curves by the log-rank test or Cox modeling was inappropriate, given the early crossover of the two curves. Figure 2 depicts the cumulative incidence of secondary neoplasms in all patients with this complication as the first event after complete remission induction: 4.17% (SE, 0.46%) at 15 years, increasing to 5.37% (SE, 0.55%) at 20 years and to 10.85% (SE, 1.27%) at 30 years. Fine JP, Gray RJ. Pui CH, Dodge RK, Look AT. Albo V, Miller D, Leiken S, Sather H, Hammond D. . During this time, some people with CLL may develop a new, unrelated cancer later. Conclusions The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. © 2021 American Medical Association. Table 2 summarizes the 14 patients with neoplasms excluding meningioma (n = 15) and basal cell carcinoma (n = 12). et al. … sign up for alerts, and more, to access your subscriptions, sign up for alerts, and more, to download free article PDFs, sign up for alerts, customize your interests, and more, to make a comment, download free article PDFs, sign up for alerts and more, Archives of Neurology & Psychiatry (1919-1959), JAMAevidence: The Rational Clinical Examination, JAMAevidence: Users' Guides to Medical Literature, FDA Approval and Regulation of Pharmaceuticals, 1983-2018, Global Burden of Skin Diseases, 1990-2017, Health Care Spending in the US and Other High-Income Countries, Life Expectancy and Mortality Rates in the United States, 1959-2017, Medical Marketing in the United States, 1997-2016, Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter, US Burden of Cardiovascular Disease, 1990-2016, US Burden of Neurological Disease, 1990-2017, Waste in the US Health Care System: Estimated Costs and Potential for Savings, Register for email alerts with links to free full-text articles. The overall risk of second neoplasms in the cohort and in specific subgroups was calculated by Kaplan–Meier life-table methods.14 , 15 Ninety-five percent confidence intervals for point estimates on these curves were calculated by the method of Kalbfleisch and Prentice for life-table events of low frequency.16 Cox proportional-hazards analysis was used to analyze the exposures that involved continuous variables and for the categorical analysis of selected subgroups of patient characteristics and treatment assignments. ; Peter Coccia, M.D., University of Nebraska Medical Center, Omaha; and Donald Norris, M.D., Cleveland Clinic Foundation, Cleveland. Development and preliminary findings of Children's Cancer Study Group protocols (161, 162 and 163) for low-, average- and high-risk acute lymphoblastic leukemia in children. To determine the occurrence of second neoplasms within this cohort, the principal investigators were each sent a listing of all eligible patients with ALL who had been registered in an ALL clinical trial by their institutions and affiliates. et al. 35. 24. Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia . Malkin E, Li FP, Strong LC, et al. Gaynon PS, Trigg ME, Heerema NA. et al. 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. Valuable tools for building a rewarding career in health care. Some late effects may be treated or … If secondary leukemia … A 2.8-fold excess risk of hematopoietic neoplasms was reported among siblings of children with tumors of the central nervous system, and an 8-fold increase in risk among siblings of children with medulloblastoma.33 Moreover, central nervous system tumors and leukemias are part of the Li—Fraumeni syndrome,34 in which germline mutations of the p53 gene have recently been identified.35 Central nervous system tumors in young children have been suggested as a marker of familial susceptibility to cancer.36 Thus, the increased prevalence of such tumors in long-term survivors of ALL may reflect a complex interaction between a genetic and a temporal susceptibility of the host, combined with the effects of therapy. Despite the persistent influence of therapeutic factors such as cranial/craniospinal irradiation,22,24 epipodophyllotoxins,20 and alkylating agents8 on secondary neoplasm induction, the pathogenesis of these cancers is almost certainly multifactorial. Follow-up dates for any patients seen after October 1, 1988, were recoded to that date, and patients who had a second neoplasm thereafter were recoded as having no second neoplasm on the closing date of the study. Improved disease-free survival of children with acute lymphoblastic leukemia at high risk for early relapse with the New York regimen — a new intensive therapy protocol: a report from the Children's Cancer Study Group . Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs … Because very few patients not assigned to receive radiation therapy have been followed more than seven years after diagnosis, it is impossible at present to know whether the apparent reduction of risk in the nonirradiated patients will continue or whether there will be more second neoplasms later. Introduction. Of the 2169 patients included in this study, 168 (7.7%) developed a secondary neoplasm. Previous Presentation: This study was presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 14, 2005, Orlando, Fla. Acute lymphoblastic leukemia is the most common cancer in children and adolescents, with almost 4000 new cases diagnosed in the United States each year.1 It is also one of the most curable pediatric cancers: survival rates for patients treated with contemporary risk-based protocols now exceed 80%,1-5 and most of these survivors are cured (no evidence of disease for at least 10 years).6,7 Accordingly, characterization of long-term outcomes in acute lymphoblastic leukemia patients who remain in first complete remission for at least a decade has assumed increasing importance, especially in view of the long life expectancy of this survivor population. In this cohort of 9720 patients, 2637 (27.1 percent) had died at the time of analysis, 6644 (68.4 percent) were still alive and were being followed at the treating institution or another institution belonging to the Children's Cancer Study Group, and 439 (4.5 percent) were reported by the primary institution as being lost to follow-up.