This association held for carcinoma incidence (2.14% [SE, 0.72%] for men vs 5.52% [SE, 1.35%] for women; P = .07). For some people with acute lymphocytic leukemia (ALL), treatment can get rid of all of the leukemia cells. Learn about the acute lymphocytic leukemia survival rate here. . 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. Information and tools for librarians about site license offerings. Zwerdling T, Dothage J. Meningiomas in children and adolescents. Pui CH, Sandlund JT, Pei D. 24. Lymphoid gene expression as a predictor of risk of secondary brain tumors. Patients whose first event (eg, secondary neoplasm or relapse) occurred before the planned initiation of a specific therapy considered in the analysis (eg, cranial/craniospinal radiation) were included in the analysis but coded as not having received that therapy because the exposure would not have affected the risk of a first event. This study did not confirm the recent report of an excess of ANLL after childhood ALL.7 Secondary myeloid leukemia developed in only 2 of 9720 patients during this period of observation. et al. 29. 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. 1. A secondary neoplasm is one of the most devastating sequelae of cancer treatment. N Engl J Med 1984;311:749–53.  et al. Pui CH, Ribeiro RC, Hancock ML. Ortega JA, Nesbit ME Jr, Donaldson MH, et al. Case Records of the Massachusetts General Hospital, Changing Hand Color after Carpal Tunnel Injection, At the Cusp — Reimagining Infective Endocarditis Care amid the Opioid Epidemic, Who Goes First? . Effective forms of treatment for acute lymphoblastic leukemia (ALL) in childhood now result in survival rates above 70 percent at five years, but the treatments are potentially carcinogenic. Bailar JC III, Ederer F. . Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms . Five of these were isolated relapses in the central nervous system, and two were isolated marrow relapses. Our website uses cookies to enhance your experience. Overall, a total of 6.13 neoplasms would have been expected, and 42 were observed (ratio of observed to expected cases, 6.85; P<0.05). 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. ; Peter Coccia, M.D., University of Nebraska Medical Center, Omaha; and Donald Norris, M.D., Cleveland Clinic Foundation, Cleveland. Some treatments for children’s cancer increase the risk of secondary cancers. Finally, the remaining proportion of the increased long-term risk is for secondary neoplasm development, represented by 2 cases of sarcoma diagnosed in patients who had been followed up for 30 and 31 years. Cancer 1983;51:1041–9. This is called a second cancer. Covariance analysis of censored survival data . Littman P, Coccia P, Bleyer A, et al. Design, Setting, and Patients Retrospective study of 2169 patients with acute lymphoblastic leukemia … The markedly increased risk in the youngest patients raises questions about the role of age, therapy, and genetics in the occurrence of these second neoplasms. Get free access to newly published articles. Meadows AT, Robison LL, Neglia JP, Sather H, Hammond D. . 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. Silverman LB, Gelber RD, Dalton VK. Because of the wide differences in treatment regimens and incidence rates of late-occurring secondary neoplasms between patients treated before and after 1979, we evaluated risk factors by separate methods. There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. Indeed, the significance of host-related genetic risk factors for secondary neoplasm was recognized recently using gene expression profiles for the diagnostic bone marrow specimens.32,33 Patients found to have high genetic susceptibility to secondary neoplasms will likely receive special consideration and long-term follow-up in the future. 40. Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. Bogni A, Cheng C, Liu W. Lifetime Risk of Developing Cancer: Approximately 0.1 percent of men and women will be diagnosed with acute lymphocytic leukemia at some point during their lifetime, based on 2015–2017 data. In fact, a recent report from the Childhood Cancer Survivor Study31 indicates that young survivors of childhood cancers have increased risk of developing carcinomas that typically present in later adulthood. Interestingly, we did not observe a high incidence of cancers common in mid and late adulthood, such as colon, breast, and lung cancers, which could reflect the relatively young age of our cohort (median, 24.8 years[ range, 6.1-52.5 years]). For all patients who developed a secondary neoplasm, we recorded the date of diagnosis, histologic subtype, and primary/involved site(s). Overall, the survival rate for the cohort was 71 percent 5 years after diagnosis and 64 percent after 10 years. The diagnosis of a second neoplasm was the first event after the successful induction of remission in 36 of these 43 patients. Figure 3 shows the cumulative incidences of each tumor type at 5, 10, 15, 20, and 30 years after complete remission. 21. In the irradiated patients, the pattern in which second neoplasms occurred showed no evidence of reaching a plateau 15 years after diagnosis, as compared with the pattern in the nonirradiated group, in which a plateau appeared to develop early. J Am Stat Assoc 1958;53:457–81. Cancer 1987;60:2548–52. All patients but 1 with Hodgkin disease received cranial/craniospinal irradiation for acute lymphoblastic leukemia. N Engl J Med 1989:321:136–42. No association was seen between sex or race and the occurrence of a second neoplasm. The Children's Cancer Study Group conducts clinical trials in cooperation with member institutions throughout the United States and Canada. 87.). The risk for high-grade tumors, especially carcinomas, significantly exceeds the risk in the general population, underscoring the need for continued careful follow-up of acute lymphoblastic leukemia survivors. Among the five patients with previous central nervous system relapses, four had central nervous system tumors (medulloblastoma, primitive neuroectodermal tumor, glioblastoma, and low-grade astrocytoma) and one had thyroid cancer. Of 13 second neoplasms occurring in patients with ALL included in one series, 3 were brain tumors.23 In 1985 Albo et al. Curing children of leukemia . Potential long-term toxic effects in children treated for acute lymphoblastic leukemia . Ten years after the diagnosis, the estimated risks of a second neoplasm among the irradiated and nonirradiated patients were 1.6 percent and 0.3 percent, respectively. All higher-grade tumors observed after 15 to 20 years of follow-up in this series were either carcinomas or sarcomas. The reviews by the institution and the Pathology Center were discordant in two cases. It is associated with "success" and with relief at no longer having to … We dedicate this article to the late Charles Pratt, MD, who made substantial contributions in the study of subsequent malignancies in pediatric cancer survivors. Kimball Dalton VM, Gelber RD, Li F, Donnelly MJ, Tarbell NJ, Sallan SE. Previous studies of second neoplasms among patients with ALL have been primarily descriptive or have focused on selected subgroups of patients or second neoplasms.5 6 7 To investigate the occurrence of second neoplasms among a large population with childhood ALL, the Children's Cancer Study Group undertook a retrospective evaluation of 9720 patients with newly diagnosed ALL who were treated in clinical trials since 1972. Kalbfleisch J, Prentice RL. Astrocytoma as a second malignancy in patients with acute lymphoblastic leukemia . Pui CH, Cheng C, Leung W. We also thank from St Jude Children's Research Hospital: Michael Hancock, Cheng Cheng, PhD, Yinmei Zhou, Deqing Pei, and Stan Pounds, PhD, for suggestions and assistance in the statistical analysis; Joseph Khoury, MD, for discussions regarding histological classification; Annette Stone and Pam Hays for data collection; Julie Groff for assistance with figures; and Jeana Cromer for administrative assistance. Kaplan EL, Meier P. . Introduction. The largest excess occurred in the case of central nervous system tumors; 23 such tumors occurred, whereas 1.06 were expected (ratio, 21.7; P<0.05). However, even with exclusion of basal cell carcinomas, there remains an impressive increase in carcinoma incidence between 25 and 30 years after induction, reflecting cases of more aggressive malignant neoplasms (Figure 3). The Operations Office is responsible for determining patient eligibility, for randomization (when necessary), and for quality assurance and follow-up of the patients studied. The growth of a large population of "cured" survivors of ALL coincides with the development of late-occurring consequences of this diagnosis and its therapy. N Engl J Med 1987;317:588–93. Secondary meningioma tends to have aggressive biological behavior and to recur.30 Moreover, if a patient survives secondary meningioma, the probability of subsequent tumor may be increased. The risk of this complication varies among long-term survivors with different histologic subtypes of cancer at diagnosis.8 For pediatric patients with acute lymphoblastic leukemia, the reported cumulative risk of secondary neoplasm ranges from 1.2% to 3.3% after 10 to 15 years of follow-up9-11; however, it is not clear whether the incidence of secondary neoplasms reaches a plateau at 15 to 20 years or continues to increase. The median age of acute lymphoblastic leukemia diagnosis was 4.0 years (range, 2 months to 18 years). The relatively rapid increase in incidence at 20 years after complete remission can be attributed largely to the late development of meningiomas and basal cell carcinomas. All Rights Reserved, 2nd ed. International incidence of childhood cancer. Bassal M, Mertens AC, Taylor L. These cases were treated as a competing event, similar to relapse of acute lymphoblastic leukemia, in this analysis. 28. Hepatocellular carcinoma in a long-term survivor of acute lymphocytic leukemia .  et al. Pratt et al. Silverberg E, Boring CC, Squires TS. Data on patients who died of ALL were censored as of the time of death. Proc Am Soc Clin Oncol 1985;4:172. abstract. Incidence of second malignant neoplasms in children: results of an international study . Malkin E, Li FP, Strong LC, et al. Pedersen-Bjergaard J, Daugaard G, Werner Hansen S, Philip P, Olesen Larsen S, Rorth M. . To estimate the probability of secondary neoplasms in first complete remission, the cumulative incidence (with standard error) was calculated for all patients achieving complete remission.17 Competing events were relapse (including central nervous system [CNS] and testicular disease), secondary acute lymphoblastic leukemia, and death in first complete remission. However, these trends did not reach statistical significance at the P = .05 level. J R Stat Soc [A] 1972;135:185–206. The construction of multivariate models that included the patient's age at the diagnosis of ALL and the assigned therapy did not suggest any interaction. Pui C-H, Behm FG, Raimondi SC, et al. Mosijczuk AD, Ruymann FB. doi:10.1001/jama.297.11.1207. 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. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Fried M, Kalra J, Hardi CF, Sawtisky A. . Asymptotically efficient rank invariant test procedures . Some limitations to the current study should be noted. To compare secondary neoplasm incidence rates with rates of cancer development in the general US population, we used standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Hodgkin's disease in a child with acute lymphoblastic leukemia . There was a suggestion of fewer second neoplasms among the patients assigned to receive higher doses of anthracycline, but the trend was not statistically significant. Int J Radiat Oncol Biol Phys 1987;13:1443–9. No data were available on the chemotherapy and radiation therapy actually received. Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery. The overall pattern of risk for these cancers is shown in Figure 1. The estimated cumulative risk for radiation exposure is shown in Figure 4 (with the patients irradiated at the time of relapse being transferred to the exposed group as of the time of radiation). Second Neoplasms after Acute Lymphoblastic Leukemia in Childhood. et al. As expected, this ratio was highest for overall tumors in the first 5 years of follow-up (SIR, 335.1; 95% CI, 232.8-436.7), reflecting the overwhelming impact of myeloid leukemias (SIR, 3951.7; 95% CI, 2782.9-5448.9). . Eighteen patients had third malignant neoplasms: acute myeloid leukemia (n = 3), basal cell carcinoma (n = 4), squamous cell carcinoma (n = 2), thyroid carcinoma (n = 2), meningioma (n = 3), other CNS tumors (n = 2), hepatocellular carcinoma (n = 1), and melanoma (n = 1). However, as demonstrated by SIR analysis, the risk of solid tumor development was still 2.4-fold higher than in the age- and sex-matched general population after 2 decades of follow-up. Cranial or craniospinal radiation was part of the therapy for some or all patients in all but six studies. A class of K-sample tests for comparing the cumulative incidence of a competing risk. The results of the Cox proportional-hazards analysis of selected characteristics are shown in Table 2. et al. Author information: (1)Department of Pediatric Oncology, Dana-Farber Cancer … Abstract. This process was successful in assigning all but 3.1 percent of the patients (305) to radiation regimens and in assigning all but 4.2 percent (413) to chemotherapy regimens. When a specific tumor type was analyzed, other types of secondary neoplasms were also treated as competing events. Dr Razzouk is now with the Children's Center for Cancer and Blood Diseases, St Vincent Children's Hospital, Indianapolis, Ind. reported a 4.7 percent risk of acute nonlymphocytic leukemia (ANLL) six years after therapy in a group of 733 patients.7. Blood 1982;60:948–58. Other solid tumors were no more frequent than expected in the general population in the first 5 years (SIR, 14.8; 95% CI, 0.4-82.4) but became significant when the SIR reached 17.3 (95% CI, 3.6-50.4) in years 6 to 10 of follow-up and remained significant for the duration of follow-up (SIRs, 9.8 [95% CI, 4.5-18.6] in years 11-20 and 2.4 [95% CI, 1.1-4.5] after 20 years). German-Austrian-Swiss ALL-BFM Study Group. In the subgroups with CNS tumors or carcinomas (excluding meningiomas and basal cell or squamous cell carcinomas), only patients who did receive cranial/craniospinal irradiation had SIRs that were significantly different from those in the general population, reinforcing the results shown in Table 4. JAK2 V617F Acute Lymphoblastic Leukemia Secondary to Myeloproliferative Neoplasms (MPNs) or After Lenalidomide Exposure: Case Report and Review of the Literature Previous Article Nelarabine in Adult Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia… ALL occurs in the United States at an annual rate of 32 cases per 1 million children under the age of 15, or more than 2000 new cases each year.3 Population-based data indicate that patients with ALL diagnosed between 1980 and 1985 have a five-year survival rate of 70.7 percent.4 Thus, there are approximately 1500 patients annually who become long-term survivors of childhood ALL. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. 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