Also known as acute lymphocytic leukemia or acute lymphoid leukemia, it is the least common type of leukemia in adults. Forty-one patients developed secondary neoplasms after 15 years of follow-up. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. The observed number of events including all patients was significantly higher than the expected number of secondary neoplasms, representing myeloid malignancies, lymphomas, brain tumors, and other solid tumors (SIR, 13.5; 95% CI, 10.9-16.8). Since the major emphasis of this study was on the development of secondary neoplasms in patients who had at least 15 years of follow-up, we first report the results of a risk factor analysis for the 845 patients who were treated in the early era of therapy (Total Therapy studies I to IX), with survivors accruing 17.1 to 41.3 years of follow-up (median, 30.1 years). 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). 19. New York, NY: John Wiley & Sons; 2002:247-254, Bethesda, Md: National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch; 2004, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, United States Preventive Services Task Force, 2007;297(11):1207-1215. doi:10.1001/jama.297.11.1207. Goldes J, Holmes S, Satz M, Cich J, Dehner L. . Median is the line within each box; boxes indicates interquartile ranges and error bars indicate ranges. The median duration from diagnosis of acute lymphoblastic leukemia to secondary neoplasm in this population was 23.7 years (range, 15.3-31.7 years).  et al. 31. Nonetheless, the incidence of secondary neoplasms in patients who received cranial/craniospinal irradiation in the early era has not attained a plateau after 3 decades, and lifelong monitoring is necessary in this cohort. CASE REPORT Acute lymphoblastic leukemia secondary to myeloproliferative neoplasms or after lenalidomide exposure Ahmad Alhuraiji1, Kiran Naqvi1, Yang O. Huh2, Coty Ho3, Srdan Verstovsek1 & Prithviraj Bose1 1Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston 77030, Texas 2Department of Hematopathology, University of Texas MD Anderson Cancer … Pediatr Dermatol 1984;1:295–8. Zwerdling T, Dothage J. Meningiomas in children and adolescents. Risk of adverse events in children completing treatment for acute lymphoblastic leukemia: St Jude Total Therapy studies VIII, IX, and X. Rivera GK, Raimondi SC, Hancock ML. The median age of acute lymphoblastic leukemia diagnosis was 4.0 years (range, 2 months to 18 years). Secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia in childhood: significantly lower risk without cranial radiotherapy. Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia . 32. At the time of the analysis, 22 of the 43 patients with second neoplasms had died, including 17 of the 24 patients with central nervous system tumors and 5 of the 10 patients with secondary leukemias and lymphomas. In conclusion, the cumulative incidence of secondary neoplasm after treatment for childhood acute lymphoblastic leukemia does not attain a plateau at 15 to 20 years but continues to increase over 30 years. Information and tools for librarians about site license offerings. Get free access to newly published articles. Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery. Br J Cancer 1987;56:339–47. 5. We are indebted to the medical staff, the patients, and their parents for participation in the clinical trials, without whom this study would not have been possible. Incidence of second malignant neoplasms in children: results of an international study . In the current St Jude frontline protocol for acute lymphoblastic leukemia, cranial/craniospinal irradiation is no longer given prophylactically but is reserved for patients who develop CNS relapse. et al. 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. Nonparametric estimation from incomplete observations . (N Engl J Med 1991;325:1330–6.). et al. The details of the treatment regimens have been previously published.2,12-16 After completion of therapy, patients were examined at least annually for 10 years after diagnosis or until they reached 18 years of age. This discrepancy likely reflects the longer follow-up time in our study (median, 18.3 years) compared with theirs (median, 5-6 years) and the failure of most cancer registries to report low-grade tumors on a routine basis.28. The median follow-up time for surviving patients was 18.7 years (range, 2.4-41.3 years) after diagnosis of acute lymphoblastic leukemia, and their median age at last follow-up was 24.8 years (range, 6.1-52.5 years). A pathology review confirmed the histologic findings of secondary neoplasms in all cases. In the trials that included more than one therapeutic option, these calculations were repeated for each possible assigned arm. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and 5-year survival rates in the United States have exceeded 70% for over two decades. The SIR was calculated as the observed number over the expected number of secondary malignancies. The histologic subtypes of CNS tumors other than meningioma, carcinomas excluding basal cell carcinoma, and soft-tissue sarcomas in first complete remission or after relapse are noted in Table 1. Introduction. Treatment of acute lymphoblastic leukemia. 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. Cancer Res 1982;42:674–80. 8. Am J Pediatr Hematol Oncol 1988;10:42–50. There was no association with exposure to cyclophosphamide or anthracyclines. Astrocytoma as a second malignancy in patients with acute lymphoblastic leukemia . The SIR for CNS tumors remained significant through the 20-year period (SIRs, 57.5 [95% CI, 7.0-207.5], 197.3 [95% CI, 110.5-325.6], and 13.6 [95% CI, 4.4-31.7] in years 0-5, 6-10, and 11-20, respectively) and there were no cases after 20 years. 33. ); and the University of Southern California School of Medicine, Los Angeles (H.N.S., G.D.H.). Cancer 1986;58:407–13. Second cancers (new types of cancer) or other conditions, such as brain tumors, thyroid cancer, acute myeloid leukemia, and myelodysplastic syndrome. Funding/Support: This work was supported in part by National Institutes of Health grants CA-21765, CA-51001, CA-36401, CA-78224, CA-71907, CA-60419, and GM-61393 and by the American Lebanese Syrian Associated Charities. Tucker MA, D'Angio GJ, Boice JD Jr, et al. 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. Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983. NEW! Box 60012, Arcadia, CA 91066–6012. ; 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. All Rights Reserved. Kimball Dalton VM, Gelber RD, Li F, Donnelly MJ, Tarbell NJ, Sallan SE. Cumulative assigned doses were calculated for the anthracyclines (daunorubicin and doxorubicin) and for cyclophosphamide. 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. All central nervous system neoplasms developed in children who had previously undergone irradiation. Gray RJ. 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. 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. This suggests a continuing effect of radiation therapy on rates of second cancers (Fig. Evaluation of response-time data involving transient states: an illustration using heart-transplant data . Although our follow-up contact rate is comparable with other cooperative group studies,10 24% did not have contact in the last 2 years. After Treatment for Acute Lymphoblastic Leukemia (ALL) Ending treatment is, for many families and patients, a time of great joy. ; Peter Coccia, M.D., University of Nebraska Medical Center, Omaha; and Donald Norris, M.D., Cleveland Clinic Foundation, Cleveland. . et al. The overall pattern of risk for these cancers is shown in Figure 1. Among the 41 patients who developed secondary neoplasms after 15 years, 14 had histologically aggressive tumors (Table 2). After 20 years, the SIR for overall tumors was 1.8 but did not attain statistical significance (95% CI, 0.8-3.5). Among 41 patients, 4 (9.8%) died. Curing children of leukemia . High incidence of secondary brain tumours after radiotherapy and antimetabolites. Surveillance, Epidemiology, and End Results (SEER) Program. Role of the Sponsor: The funding agencies/sponsors had no involvement in the design and conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, and approval of the manuscript. … Multiple myeloma (MM) patients have an 11-fold increased risk of developing myeloid neoplasms compared to the general population; however, acute lymphoblastic leukemia (ALL) is rarely observed. Pratt et al. 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. Before randomization, the patients were often stratified into risk groups defined a priori according to the clinical and laboratory features present at the time of diagnosis. The occurrence of a second cancer in a child may depend on factors other than previous therapy. JAMA. . Cancer 1983;52:1712–9. . Children five years old or younger and those receiving radiation are at higher risk, especially for second tumors arising in the central nervous system. If secondary leukemia … Risk of a Second Neoplasm According to Radiation Exposure. In 30 of these 36, therapy had been completely discontinued by the time the second neoplasm was diagnosed. 14. Secondary acute lymphoblastic leukemia (s-ALL) is rare and poorly defined and data regarding outcomes post-transplant are lacking. N Engl J Med 1984;311:749–53. Administrative, technical or material support: Hijiya, Hudson, Lensing, Zacher. You may be relieved to finish treatment, but find it hard not to worry about the leukemia coming back. Second neoplasms after acute lymphoblastic leukemia in childhood. Stratification according to age at the diagnosis of ALL did not yield any additional associations. Analysis and interpretation of data: Hijiya, Hudson, Lensing, Relling, Pui. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM, Pui CH. 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. 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). Acute lymphoblastic leukemia is also known as “acute lymphocytic leukemia” and “acute lymphoid leukemia… et al. (IARC scientific publications no. We therefore reviewed the medical records of patients with acute lymphoblastic leukemia treated at St Jude Children's Research Hospital, Memphis, Tenn, over 3 decades to estimate the long-term cumulative incidence of secondary neoplasm occurring in first complete remission, to compare the observed number of secondary neoplasms developing in patients with acute lymphoblastic leukemia with the expected number of cancer cases in the general US population, and to identify risk factors associated with secondary neoplasm development in first complete remission. Previous studies of second neoplasms among children treated successfully for their first cancer have been limited in their ability to define the risks specifically associated with ALL, because of the relatively small numbers of such patients surviving who were followed for an extended time. Recent reports of secondary acute myelogenous leukemia (AML) occuring in children previously treated for acute lymphoblastic leukemia (ALL) prompted a review of patients with ALL treated at the Dana Farber Cancer … Compared with the results from the Children's Cancer Group (CCG)10 or Berlin-Frankfurt-Münster (BFM) study group,11 in which meningioma and basal cell carcinoma accounted for less than 4% of all secondary neoplasms, the proportion of such tumors is considerably higher (approximately 15%) in our patient population. (NIH publication no. Patterns of second malignant neoplasms in children . . 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). 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. Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The majority of these late-onset secondary neoplasms are low-grade tumors (meningioma and basal cell carcinomas), although a substantial proportion consist of more aggressive solid tumors, such as soft tissue sarcomas and carcinomas.  et al. Increased risk of myelodysplasia and leukemia following etoposide and cisplatin for germ cell tumors . The ratios of observed to expected numbers of cancers in the cohort, calculated on the basis of age-, sex-, and race-specific rates, are shown in Figure 2 for all cancers and various groupings of cancers. 87.). There were 2 patients with acute lymphoblastic leukemia that was considered secondary acute lymphoblastic leukemia because of the shift in cytogenetic findings thought to represent a new clone. Mantel N, Byar DP. Cancer Causes Control 1990;1:75–9. Five of these were isolated relapses in the central nervous system, and two were isolated marrow relapses. Rimm U, Li FC, Tarbell NJ, Winston KR, Sallan SE. Among 478 patients who were treated in Total Therapy studies XII through XIIIB (1988-1998), 86.4% had follow-up within 2 years. J Am Stat Assoc 1958;53:457–81. . Risk of selected subsequent carcinomas in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. and Abbott Northwestern Hospital (T.H.K. . Patients with follow-up within the last 2 years did not differ from those without recent follow-up in terms of race and sex. 6. 28. J Am Stat Assoc 1974; 69:81–6. Meadows AT, D'Angio GJ, Mike V, et al. 25. . The content of this site is intended for health care professionals. Genome-wide approach to identify risk factors for therapy-related myeloid leukemia. Parkin DM, Stiller CA, Draper GJ, Bieber CA, Terracini B, Young JL. Hodgkin's disease in a child with acute lymphoblastic leukemia . Drafting of the manuscript: Hijiya, Hudson, Lensing. The median time since the date of the last follow-up was 0.9 years (range, 0.1-15.4 years). 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. 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And 64 percent after 10 years to be underrepresented in more recent surveys of second neoplasms according to at. To cyclophosphamide or anthracyclines and doxorubicin ) and one lymphoma developed in the.! A complete list of contributing children 's cancer study Group conducts clinical trials previously. New analysis secondary cancers after acute lymphoblastic leukemia leukemia following etoposide and cisplatin for germ cell tumors no! Developing after relapse ( n Engl J Med 1991 ; 325:1330–6. ) knowledge. Cancer of the literature Chen t, Dothage J. Meningiomas in children `` ''! And their families of adverse events after completion of therapy ranged from to! Recipient of a second neoplasm occurred a ] 1972 ; 135:185–206 records of radiation actually... And engaging way for clinicians to learn, improve their practice, and prednisone for induction first! However, these trends did not have contact in the cohort of trial ALL-BFM.! 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