The median period of follow-up of the patients still alive at the time of this analysis was 4.7 years (range, 2 months to 16 years). Of these late effects, few are as severe as the occurrence of a second cancer. Bassal M, Mertens AC, Taylor L. At the time of analysis, 1349 of 2169 were alive, with 1022 (75.8%) having a follow-up contact within the last 2 years. et al. Radiation exposure appears to be associated with a continued risk of second neoplasms up to 15 years after the diagnosis of ALL. . National Cancer Institute. Thus, although accrual to the cohort continued into 1988, patients treated more recently and more aggressively have had a much more limited period at risk. 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). . Previous studies have demonstrated a low incidence of secondary neoplasm during the first 10 to 15 years after the treatment of childhood acute lymphoblastic leukemia.9-11,27 Data on the longer-term incidence of secondary neoplasms has been limited by relatively incomplete and short follow-up times in the majority of published studies.9-11,27 We demonstrate herein that the cumulative incidence of secondary neoplasms in patients remaining in complete remission does not reach plateau at 20 years but continues to increase. After Treatment for Acute Lymphoblastic Leukemia (ALL) Ending treatment is, for many families and patients, a time of great joy. Some limitations to the current study should be noted. 4). 4. Pratt et al. 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. . Statistical methods in cancer research, volume II: the design and analysis of cohort studies. For example, a second cancer may mark a particularly susceptible host, as a result of a combination of age, genetics, and possibly therapy. Prepare to become a physician, build your knowledge, lead a health care organization, and advance your career with NEJM Group information and services. We anticipate that this conservative therapeutic approach will significantly reduce the incidence of radiation-associated secondary neoplasms. Gaynon PS, Trigg ME, Heerema NA. Thus, the combination of T-cell ALL and these particular chemotherapeutic agents may increase the risk of a secondary myeloid leukemia.37 An increased frequency of secondary leukemia has been noted among other groups of patients exposed to epipodophyllotoxins as well.38 Some cases of secondary ANLL may not have been included among the second neoplasms reported here, particularly if they were classified as relapses of ALL. . . One meningioma was excluded from the count of observed neoplasms (see text). 7. Conclusions The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. Other large studies of survivors of childhood cancer have noted a similar excess of brain tumors. The second patient developed t(4;11)(q21;q23), which differed from the complex translocation involving chromosomes 3, 8, and 18 at the time of initial diagnosis 3.5 years earlier. 32. Pui CH, Cheng C, Leung W. Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. 13. 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. Drafting of the manuscript: Hijiya, Hudson, Lensing. . 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. Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. The median follow-up was 4.7 years (range, 2 months to 16 years). Some late effects may be treated or … 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). Author information: (1)Department of Pediatric Oncology, Dana-Farber Cancer … Likewise, basal cell carcinomas are often locally invasive, and their multiple occurrence is common.28 Indeed, the clinical significance of these “low-grade” tumors occurring as secondary neoplasms should not be underestimated. et al. et al. Member institutions are required to submit periodic written follow-up reports about all patients studied. Incidence of second primary tumours among childhood cancer survivors . The ratios of observed to expected numbers of cancers were also increased for leukemias and lymphomas (10 observed vs. 2.56 expected, P<0.05) and for miscellaneous tumors (9 observed vs. 5.07 expected, P>0.05). Coccia PF. Hodgkin's disease in a child with acute lymphoblastic leukemia . 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. Valuable tools for building a rewarding career in health care. Pratt CB, George SL, Hannock ML, Hustu HO, Kun LE, Ochs JS. When the observed number of malignancies was less than 20, exact CIs for a Poisson-distributed variable were computed by multiplying SIRs with tabulated multipliers, which vary for the number of events (eg, secondary neoplasms); otherwise, the Byar approximation was used by applying a formula to the observed and expected number of secondary neoplasms.19 Three tumors developing in first complete remission were in fact third neoplasms but were considered as first events in SIR calculations because they arose after low-grade malignancies not included or only recently included in SEER descriptions. et al. We found that 43 second neoplasms occurred among the children in the cohort, including 24 neoplasms of the central nervous system, 10 new leukemias and lymphomas, and 9 other neoplasms. Among 478 patients who were treated in Total Therapy studies XII through XIIIB (1988-1998), 86.4% had follow-up within 2 years. Biometrics 1964;20:639–43. Stratification according to age at the diagnosis of ALL did not yield any additional associations. Chemotherapy (including anthracyclines and alkylating agents) and cranial/craniospinal irradiation were coded for each patient on the basis of protocol-specified doses and schedules, using an intention-to-treat rationale. JAMA 1982;247:2692–4. Second cancers (new types of cancer) or other conditions, such as brain tumors, thyroid cancer, acute myeloid leukemia, and myelodysplastic syndrome. 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). et al. The solid line represents irradiated patients, and the dashed line nonirradiated patients. Pui CH, Evans WE. Zarrabi MH, Rosner F, Grunwald HW. 31. Although most of them were not high-grade tumors and the prognosis after secondary neoplasms was favorable (10 of 14 were alive at the time of analysis), this patient population also had high morbidity. For some people with acute lymphocytic leukemia (ALL), treatment can get rid of all of the leukemia cells. Of 13 second neoplasms occurring in patients with ALL included in one series, 3 were brain tumors.23 In 1985 Albo et al. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. Among the 41 patients who developed secondary neoplasms after 15 years, 14 had histologically aggressive tumors (Table 2). Get free access to newly published articles. For patients whose treatment was unclear, this approach was combined with a chart review. Figure 1 illustrates the latency from the time of diagnosis of acute lymphoblastic leukemia to the development of a secondary neoplasm in the 123 patients who had this complication as a first event. Cancer 1987;59:1506–8. In each of these, the second neoplasm was categorized on the basis of the central review. 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. 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 . Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers … Cancer 1983;52:846–50. Government Leaders and Prioritization of SARS-CoV-2 Vaccines, Vaccinating Children against Covid-19 — The Lessons of Measles, Case 2-2021: A 26-Year-Old Pregnant Woman with Ventricular Tachycardia and Shock, Polypill with or without Aspirin in Persons without Cardiovascular Disease, Post-Transcriptional Genetic Silencing of. 20. 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. Improved outcome in childhood acute lymphoblastic leukaemia with reinforced early treatment and rotational combination chemotherapy. 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. did note a suggestion of an increased risk of both solid tumors and hematologic cancers, but they were unable to conclude that a truly increased risk existed.5 In a 1985 review by the Late Effects Study Group of 292 patients in whom second neoplasms developed, leukemia was the eighth most common initial diagnosis after retinoblastoma, Hodgkin's disease, soft-tissue sarcomas, Wilms' tumor, central nervous system tumors, neuroblastoma, and bone sarcomas.23 Despite this, there are multiple reports of second neoplasms after ALL, many of which have recently appeared in the literature.24 25 26 27 28 Few studies have attempted to describe the overall risk of a second neoplasm among children with ALL. For all patients who developed a secondary neoplasm, we recorded the date of diagnosis, histologic subtype, and primary/involved site(s). Indeed, when these 2 neoplasms are excluded, the incidence of CNS tumors reaches a plateau at 15 years (1.17% [SE, 0.25%]) (Figure 3), while the rate of increase of carcinoma development from 15 to 30 years after induction slows considerably (0.39% [SE, 0.16%] to 2.16% [SE, 0.63%] vs 0.51% [SE, 0.18%] to 4.91% [SE, 1.04%] for all carcinomas) (Figure 3). 38. Cancer in relatives of children with central-nervoussystem neoplasms . 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). Non-menaloma skin cancer … Acute lymphoblastic leukemia (ALL) is a type of blood cancer. 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. N Engl J Med 1989:321:1830. 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. Significance factors for the ratio of a Poisson variable to its expectation . 36. Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. 2. Pedersen-Bjergaard J, Daugaard G, Werner Hansen S, Philip P, Olesen Larsen S, Rorth M. . Sullivan MP, Chen T, Dyment PG, Hvizdala E, Steuber CP. However, there was nearly complete concordance between the pathological diagnosis assigned at the patient's institution and the diagnosis assigned by the reviewing pathologist for all patients studied by both. Author Contributions: Dr Hijiya and Ms Lensing had full access of all the data in this study and take responsibility of integrity of the data and accuracy of data analysis. Tucker MA, D'Angio GJ, Boice JD Jr, et al. 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. 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. Five, 10, and 15 years after diagnosis, the actuarial estimated cumulative proportions of patients with a second neoplasm were 0.3 percent (95 percent confidence limits, 0.19 percent and 0.48 percent), 1.52 percent (95 percent confidence limits, 1.11 percent and 2.11 percent), and 2.53 percent (95 percent confidence limits, 1.74 percent and 3.38 percent), respectively. Learn about the acute lymphocytic leukemia survival rate here. No data were available on the chemotherapy and radiation therapy actually received. 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