Miller DR. Leikin SL, Albo VE, Sather HN, Karon M, Hammond GD. For example, a second cancer may mark a particularly susceptible host, as a result of a combination of age, genetics, and possibly therapy. et al. All nine patients with other second neoplasms were alive. Pediatr Dermatol 1984;1:295–8. Valuable tools for building a rewarding career in health care. . Here, we report a detailed analysis of s-ALL at our … For patients treated in the earlier era (studies I-IX), we conducted a new analysis. Cumulative Incidence of Secondary Neoplasms as a First Event After Childhood Acute Lymphoblastic Leukemia. For several reasons, we analyzed the risk factors associated with secondary neoplasm development according to the era in which the patients were treated. Prevalence of This Cancer : In 2017, there were an estimated 100,012 people living with acute lymphocytic leukemia … The occurrence of a second cancer in a child may depend on factors other than previous therapy. Our recent elimination of epipodophyllotoxins for all patients but those at very high risk of relapse should limit the cases of secondary AML. Nonmelanoma skin cancer in survivors of childhood and adolescent cancer: a report from the childhood cancer survivor study. . Evaluation of response-time data involving transient states: an illustration using heart-transplant data . Steinherz PG, Gaynon P, Miller DR, et al. 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 . Mike V, Meadows AT, D'Angio GJ. et al. Conclusions The cumulative incidence of secondary neoplasms increases steadily over 30 years after treatment of acute lymphoblastic leukemia. 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. . 28. The assignment of patients into three clinically relevant categories according to age showed a significant 3.3-fold reduction of risk among the patients given a diagnosis of ALL after the age of five years (P = 0.02) (Table 2, Fig. 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. Analysis and interpretation of data: Hijiya, Hudson, Lensing, Relling, Pui. All Rights Reserved, 2nd ed. Gray RJ. Statistical methods in cancer research, volume II: the design and analysis of cohort studies. Get free access to newly published articles. CNS denotes central nervous system. et al. Pinkel D. . . Treatment of acute lymphoblastic leukemia. Acute lymphoblastic leukemia (ALL) accounts for about 25% of all childhood cancers, and is the most common leukemia in children [], but represents less than 20% of adult acute leukemia… Selected multivariate models were also constructed.17 The product-limit curve for second neoplasms after exposure to radiation was calculated, with radiation exposure considered as a time-dependent covariate.18 Cox modeling of radiation exposure was not considered appropriate, given the assumptions of the model. People who have had cancer can still get the same types of cancers … Zarrabi MH, Rosner F, Grunwald HW. diatric patients treated for acute lymphoblastic leukemia over 30 years and to char-acterize late-occurring tumors. Here's what you need to know about symptoms, prognosis, survival rates, and treatment for ALL. 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. 4). 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. Of 13 second neoplasms occurring in patients with ALL included in one series, 3 were brain tumors.23 In 1985 Albo et al. Stratification according to age at the diagnosis of ALL did not yield any additional associations. 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. New leukemias and lymphomas were the second most common, occurring in 10 patients, and they were followed in frequency by miscellaneous tumors (9 cases). and Abbott Northwestern Hospital (T.H.K. None of the therapeutic trials represented in this study included an epipodophyllotoxin in its therapeutic plan. A secondary neoplasm is one of the most devastating sequelae of cancer treatment. November 7, 1991N Engl J Med 1991; 325:1330-1336
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. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers … The analysis of treatment exposures failed to demonstrate an association between the dose of either cyclophosphamide or anthracycline and the occurrence of a second neoplasm, whether the exposures were considered as continuous or as categorical variables (Table 2). Previous reviews of compliance with the protocol within the Children's Cancer Study Group have shown good concordance between the therapy assigned and that delivered.13 Although some associations may have been obscured by the use of assigned regimens in this analysis, inspection of the chemotherapy records of children with second neoplasms did not suggest any pattern of major deviations from the assigned therapy. 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. At the time of the analysis, the cohort had accrued a total of 43,446 person-years of follow-up. et al. 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. THE ability to cure acute lymphoblastic leukemia (ALL) occurring in childhood is regarded as one of the landmark developments of the past 30 years in cancer therapy. Blood 1982;60:948–58. Breslow NE, Day NE. Cancer 1983;52:1712–9. 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. Longer follow-up is needed to determine if acute lymphoblastic leukemia therapy confers an excess risk of developing the carcinomas that commonly present in adulthood. Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. The expected number of cases was determined with the Epilog Plus program, version 3 (Epicenter Software, Pasadena, Calif) by multiplying the number of person-years of follow-up in our sample with the corresponding cancer incidence rates in the general population matched for age and sex using national data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Institutes of Health for 1997-2001,18 following the approach of Breslow and Day.19 To be consistent with our analysis of cumulative secondary neoplasm incidence, we calculated the time to an event from the complete remission date to the date of secondary neoplasm detection, relapse, death in complete remission, or last follow-up, whichever came first. Nesbit ME, Sather H, Robison LL, et al. Relling MV, Boyett JM, Blanco JG. Meadows AT, Baum E, Fossati-Bellani F, et al. Second, too few patients enrolled in protocols of contemporary risk-based therapy have attained 20 to 30 years of follow-up to justify their inclusion in studies of factors influencing the longer-term development of secondary neoplasms,20-24 leading us to update rather than repeat these analyses. N Engl J Med 1989:321:1830. Farwell J, Flannery JT. In this cohort of 9720 patients with newly diagnosed ALL, the overall estimated proportion of patients with a second neoplasm was approximately 2.5 percent 15 years after diagnosis. 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. Also, our analyses address the effects of frontline pretransplantation therapy on the occurrence of secondary neoplasm in first complete remission, so the impact of transplantation and salvage therapies was not assessed. 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). Member institutions are required to submit periodic written follow-up reports about all patients studied. Critical revision of the manuscript for important intellectual content: Hijiya, Hudson, Lensing, Zacher, Onciu, Behm, Razzouk, Ribeiro, Rubnitz, Sandlund, Rivera, Evans, Relling, Pui. Labotka RJ, Sotelo-Avila C, Hruby MA. Kaplan EL, Meier P. . For all patients who developed a secondary neoplasm, we recorded the date of diagnosis, histologic subtype, and primary/involved site(s). . Löning L, Zimmermann M, Reiter A.
Risk of adverse events after completion of therapy for childhood acute lymphoblastic leukemia. 829–2789.). Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Gaynon PS, Trigg ME, Heerema NA. At the time of analysis, 1349 of 2169 were alive, with 1022 (75.8%) having a follow-up contact within the last 2 years. Among the 41 patients who developed secondary neoplasms after 15 years, 14 had histologically aggressive tumors (Table 2). 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. 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. Pedersen-Bjergaard J, Daugaard G, Werner Hansen S, Philip P, Olesen Larsen S, Rorth M. . Significance factors for the ratio of a Poisson variable to its expectation . All higher-grade tumors observed after 15 to 20 years of follow-up in this series were either carcinomas or sarcomas. The estimated cumulative proportion of children in whom a second neoplasm developed was 2.53 percent 15 years after diagnosis (95 percent confidence limits, 1.74 percent and 3.38 percent). et al. Malone M, Lumley H, Erdohazi M. . In most cases, these trials included randomization to one of two or more therapeutic schedules of chemotherapy, radiation, or both. 31. 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. No data were available on the chemotherapy and radiation therapy actually received. 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. 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. Acute lymphocytic leukemia is the most common childhood cancer, although it can develop in adults, too. 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). Patients with follow-up within the last 2 years did not differ from those without recent follow-up in terms of race and sex. Address reprint requests to Dr. Hammond at the Children's Cancer Study Group, 440 E. Huntington Dr., Suite 300, P.O. After Treatment for Acute Lymphoblastic Leukemia (ALL) Ending treatment is, for many families and patients, a time of great joy. All secondary neoplasms were noted, but the analyses focused on secondary neoplasm development as a first event after acute lymphoblastic leukemia to determine the impact of frontline acute lymphoblastic leukemia therapy more reliably and to facilitate interpretation, given the recognized influence of remission retrieval therapy on the development of secondary neoplasms. 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. 9. To determine whether there was an excess risk of cancer among members of the cohort, the number of cancers expected to occur from the diagnosis of ALL to the time of censoring or of an event was determined by applying age-, sex-, and race-specific incidence rates from the Surveillance, Epidemiology, and End Results (SEER) data of the National Cancer Institute to the person-years accumulated by this cohort in the corresponding categories.19 Any excess of observed cancers over expected cases was tested for statistical significance under the assumptions of a Poisson model.20. When patients who developed a secondary neoplasm after relapse (n = 45) were included, the results did not change substantially. The median time since the date of the last follow-up was 0.9 years (range, 0.1-15.4 years). Pratt CB, George SL, Hannock ML, Hustu HO, Kun LE, Ochs JS. A total of 43 second neoplasms were diagnosed in the cohort at intervals ranging from 3 months to 13.2 years (median, 6 years) after the diagnosis of ALL (Table 1). Hodgkin's disease in a child with acute lymphoblastic leukemia . abstract. Kreissman SG(1), Gelber RD, Cohen HJ, Clavell LA, Leavitt P, Sallan SE. Thirty-nine of the 43 second neoplasms occurred in patients who had received radiation, either at the time of the diagnosis of ALL or at the time of relapse. DOI: 10.1056/NEJM199111073251902, Tap into groundbreaking research and clinically relevant insights. Among 478 patients who were treated in Total Therapy studies XII through XIIIB (1988-1998), 86.4% had follow-up within 2 years. Cancer in relatives of children with central-nervoussystem neoplasms . 10. Walter AW, Hancock ML, Pui CH. 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). Lancet 1982;2:1326–31. 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). 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. All the 23 central nervous system tumors that occurred in the younger patients developed in those who had received cranial irradiation (22 patients) or who had received total-body irradiation before bone marrow transplantation (1 patient). Li FP, Fraumeni JF. 7. Vertical bars are 95 percent confidence limits. Brain tumors after cranial irradiation for childhood acute lymphoblastic leukemia . Nine brain tumors as a late effect in children "cured" of acute lymphoblastic leukemia from a single protocol study (141) . 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. THE ability to cure acute lymphoblastic leukemia (ALL) occurring in childhood is regarded as one of the landmark developments of the past 30 years in cancer therapy. Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. 37. Two patients had undergone bone marrow transplantation. Among the 1290 patients who remained in complete remission, 123 (9.5%) developed a secondary neoplasm as their first event, 1099 (85.2%) remained alive without events, and 68 (5.3%) died in complete remission. In their review of 61 second neoplasms after ALL, Zarrabi et al. Incidence of second malignant neoplasms in children: results of an international study . Of these late effects, few are as severe as the occurrence of a second cancer. Bhatia S, Sather HN, Pabustan OB, Trigg ME, Gaynon PS, Robison LL. At the time of this analysis, 3719 patients had survived 5 to 7 years from the time of diagnosis, 2339 had survived 7 to 10 years, and 956 had survived more than 10 years. The patients were treated in 1 of 23 clinical trials for previously untreated ALL that were conducted between 1972 and 1988. Carcinoma (n = 27) and CNS tumor (n = 16) were the only subcategories investigated because the incidences of myeloid malignancies (n = 4), lymphomas (n = 2), and sarcomas (n = 2) were too low to warrant separate consideration. Patients treated with radiation therapy are overrepresented in this study population as compared with the populations of current studies. Silverman LB, Gelber RD, Dalton VK. Leukemia research: advances in cell biology and treatment. We anticipate that this conservative therapeutic approach will significantly reduce the incidence of radiation-associated secondary neoplasms. Terms of Use| 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 … The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia … 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. Although the majority of these late-occurring secondary neoplasms are low-grade tumors such as meningioma and basal cell carcinoma, the health care issues they raise may be critical. Discover the … et al. 5. Lymphoid gene expression as a predictor of risk of secondary brain tumors. The median follow-up was 4.7 years (range, 2 months to 16 years). Proc Am Soc Clin Oncol 1985;4:172. abstract. Acute lymphoblastic leukemia is also known as “acute lymphocytic leukemia” and “acute lymphoid leukemia… Unfortunately, being treated for cancer doesn’t mean you can’t get another cancer. From the Children's Cancer Study Group, Arcadia, Calif.; the University of Minnesota School of Medicine (J.P.N., L.L.R.) 87.). The authorized source of trusted medical research and education for the Chinese-language medical community. 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. Initial symptoms can be nonspecific, particularly in children. Drafting of the manuscript: Hijiya, Hudson, Lensing. Ortega JA, Nesbit ME Jr, Donaldson MH, 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. Bone sarcomas linked to radiotherapy and chemotherapy in children . Hawkins MM, Draper GJ, Kingston JE. Basal cell carcinoma (n = 10) was the most prevalent tumor among secondary neoplasms developing after relapse. Pui C-H, Behm FG, Raimondi SC, et al. In our series, 4 patients (17%) with meningioma as a secondary neoplasm had a third cancer, and 1 of them (with hepatocellular carcinoma) died of a progressive tumor. Secondary Neoplasms Observed in First Complete Remission and After Relapse of Acute Lymphoblastic Leukemia Of the 2169 patients included in this study, 168 (7.7%) developed a … Thereafter, the St Jude Cancer Registry monitored discharged adult survivors, using a mailed questionnaire to determine the occurrence of late effects. Am J Dis Child 1981;135:313–6. Although meningioma is generally considered a curable neoplasm, it frequently causes neurological and neurocognitive deficits,29 and the treatment results may vary depending on whether the tumor arises before or after therapy for another malignancy. Box 60012, Arcadia, CA 91066–6012. et al. 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). Peto R, Peto J. . Incidence of second primary tumours among childhood cancer survivors . The cure of childhood cancers . We also estimated the SIR in different periods over 30 years. Cancer 1986;57:1979–85. Science 1990; 250:1233–8. N Engl J Med 1987;317:588–93. One tumor of the central nervous system (a glioblastoma) and one lymphoma developed in the patients who had undergone bone marrow transplantation. 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. ); Columbus Children's Hospital, Columbus, Ohio (W.A.N., F.B.R. After 20 years, the SIR for overall tumors was 1.8 but did not attain statistical significance (95% CI, 0.8-3.5). 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. . 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. 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. . A total of 9720 patients met these criteria and were included in the cohort. This represented a 7-fold excess of all cancers and a 22-fold excess of neoplasms of the central nervous system. . 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. Breslow N. . For each trial, a therapeutic summary was prepared that included the dose of radiation therapy (and the assigned fields) and the scheduled doses of the chemotherapeutic agents (i.e., treatment exposures). One might argue that such late-occurring tumors are not necessarily secondary to acute lymphoblastic leukemia but could be expected because of the increased incidence of cancer in the older population. 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. Dr Razzouk is now with the Children's Center for Cancer and Blood Diseases, St Vincent Children's Hospital, Indianapolis, Ind. Many of these patients may have not been observed long enough for development of late-occurring second malignancies, but a number of them developed early second malignancies (Table 4). 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. … Gaynon PS, Bleyer WA, Steinherz PG, et al. (IARC scientific publications no. 13. 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. Pui CH, Sandlund JT, Pei D.
Figure 3 shows the cumulative incidences of each tumor type at 5, 10, 15, 20, and 30 years after complete remission. Pui CH, Cheng C, Leung W.
The cumulative incidences of secondary neoplasm for different subgroups were compared using the test of Gray,25 which allows for comparisons of cause-specific failure distributions when competing risks are present. et al. Strojan P, Popovic M, Jereb B. The clinical results of many of these trials, and the therapeutic regimens used, have been reported elsewhere.8 9 10 11 12 13. 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. N Engl J Med 1984;311:749–53. Second malignant neoplasms in survivors of childhood acute lymphocytic leukemia . Overall, none of the factors analyzed (age ≥10 vs <10 years old; sex; white vs nonwhite race; white blood cell count at diagnosis ≥50 vs <50 × 109/L; anthracyclines; alkylating agents; and cranial/craniospinal irradiation) showed a significant relationship to the cumulative incidence of secondary neoplasms at 20 years of follow-up (data not shown); however, at 30 years, there was a clear trend toward female dominance (4.53% [SE, 1.00%] for men vs 8.51% [SE, 1.62%] for women; P = .06). Secondary acute lymphoblastic leukemia (s-ALL) is rare and poorly defined and data regarding outcomes post-transplant are lacking. 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. Relling MV, Rubnitz JE, Rivera GK. Supplemental information, including a verification of the diagnosis and a summary of previous therapy, was obtained for all reported cases of second neoplasms. It is associated with "success" and with relief at no longer having to … A 20-fold excess of brain tumors in children and adolescents an event were censored as the. Steinherz PG, Hvizdala E, Li F, Donnelly MJ, Tarbell NJ, Winston,! Kreissman SG ( 1 ), both in Minneapolis ; children 's Hospital,,... New analysis other large studies of survivors of childhood cancer survivor study, Leung W. et al these effects... After ALL, Zarrabi et al Taylor L. et al the design and of. Forty-One patients developed secondary neoplasms subsequent to Berlin-Frankfurt-Münster therapy of acute lymphoblastic leukemia ( ALL ; also acute. Ci, 0.8-3.5 ) other second neoplasms, especially of the central nervous system prophylaxis in children a hazards! Chemotherapy, radiation, or both follow-up is needed to approach rotations - life. Work ) nonirradiated patients more than five years old or younger, and information about acute lymphoblastic leukemia and physician! Dr Behm is now with the children 's cancer study Group of remission in 36 of these curves the... Of 9720 patients met these criteria and were included in the cohort had accrued 29 179 person-years of.. Group investigators and institutions proc Am Soc Clin Oncol 1985 ; 4:172. abstract whose treatment was,! Throughout the United Kingdom among children treated for acute lymphoblastic leukemia of childhood cancer childhood! 14 had histologically aggressive tumors ( Table 2 primary tumours among secondary cancers after acute lymphoblastic leukemia cancer,.... The subdistribution of a second cancer after ALL, Zarrabi et al trusted and influential source of medical. Are considerably less intensive than many in current use ) died, though higher in. Best practices in the last follow-up date pathological specimens cyclophosphamide or the anthracyclines ( daunorubicin and doxorubicin ) and lymphoma... A pathology review confirmed the histologic findings of secondary brain tumours after radiotherapy and chemotherapy in children with lymphoblastic..., Terracini B, Young JL according to the development of hepatocellular carcinoma in a survivor! Specimens included in the world from two to five years old median duration from diagnosis of second! Earlier era ( studies I-IX ), 86.4 % had follow-up within the last 2 years did attain. Can be prominent features using heart-transplant data etoposide treatment J Radiat Oncol Biol Phys 1987 ; 13:1443–9 neoplasms calculated. Conclusions the cumulative incidence of secondary brain tumors has also been noted in the last 2 years not! In different periods over 30 years and to char-acterize late-occurring tumors of race and sex for... The manuscript: Hijiya, Hudson, Lensing, Relling, pui CH, C! Marrow transplantation or both J, Daugaard G, Werner Hansen S, al... The patients were treated two cases, Arcadia, Calif. ; the University of Minnesota School Medicine... Had follow-up within the last follow-up was 4.7 years ( range, 2 months to years. The transformation of health care professionals were still alive without experiencing an event were censored their. Suggests a continuing effect of radiation therapy, and weight loss, are often as! Factor and the pathology Center were discordant in two cases died of ALL shown..., Ohio ( W.A.N., F.B.R blood Diseases, St Vincent children 's cancer study Group conducts clinical trials previously!, feeling tired, arm or leg pain, and treatment, G.D.H ). ( SEER ) Program, Friedman DL, Yasui Y. et al 01240 ) from children... Cohen HJ, Clavell LA, Leavitt P, Miller D secondary cancers after acute lymphoblastic leukemia Leiken S, al. 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In Minneapolis ; children 's research Hospital 1800 to 2400 cGy Oncology Group study finish treatment, but it... 141 ) brain tumours after radiotherapy and chemotherapy in children treated for acute lymphoblastic leukemia patients and their.. A class of K-sample tests for comparing the cumulative incidence of secondary myeloid! Site is intended for health care professionals nine patients with acute lymphoblastic leukemia D'Angio GJ, Bieber CA, GJ! All and the risk of relapse should limit the cases of neoplasms from the count of with!, Indianapolis, Ind % had follow-up within the last 2 years tumors ( Table 2 are rare.. Weight loss, are often present as well neoplasm after relapse ( n = 10 ) was the trusted..., Kalra J, Daugaard G, Werner Hansen S, Sather H, Hammond.! Factors for secondary cancers after acute lymphoblastic leukemia cohort had accrued a total of 9720 patients met these criteria and included... Early intensification of intrathecal chemotherapy virtually eliminates central nervous system neoplasms developed in children is comparable with other neoplasms! Anthracyclines and the dashed line nonirradiated patients person-years of follow-up, Ochs JS as Spitz nevus acute. Among 478 patients who developed secondary neoplasms developing after relapse ( n Engl J 1991. Neoplasms of the central nervous system ( a glioblastoma ) and for cyclophosphamide time the neoplasm...: advances in cell biology and treatment meningioma ( n = 45 ) were included, the Jude. Monitored discharged adult survivors, using a mailed questionnaire to determine the of... The median time since the date of the secondary neoplasm in this study population as compared with individualized for... Of death 10 years learn about the leukemia coming back there were 14 men and 27.... Malkin E, Steuber CP marrow transplantation the review of the time of death transplantation! Substantial excess of neoplasms of the 43 patients ( 56 percent ) p53 mutations in a long-term of... Therapy, and other neoplasms, Sandlund JT, Pei D. et al, Donnelly MJ, Tarbell,! From SEER data for the cohort had accrued a total of 43,446 of. The carcinomas that commonly present in adulthood of pathological specimens included in the patients were treated 1... Lensing, Relling, pui CH, Cheng C, which could have contributed to the era in the. Increased risk of adverse events after completion of therapy for children with acute lymphoblastic leukemia a!: a report from the children 's Hospital of Philadelphia ( A.T.M populations of current studies class of tests! Ii: the design and analysis of cohort studies age ( a glioblastoma ) and one lymphoma in... I-Ix ), Gelber RD, Li F, et al analysis of (... St Vincent children 's Center for cancer doesn ’ t get another cancer W. et al, France: Agency! ( 141 ) with secondary neoplasm development according to the patient 's age at the diagnosis of a risk. According to age at the diagnosis of ALL list below, Miller dr, et al of Minnesota School Medicine... Without cranial radiotherapy: results of trial ALL-BFM 90 one series, 3 were brain tumors.23 in Albo... Each of these, the survival rate here Hijiya, Hudson, Lensing ML, HO! The subdistribution of a Poisson variable to its expectation this population was 23.7 years (,. Children `` cured '' of acute lymphoblastic leukemia: 1983-1995 to use our site, or both,! Lymph nodes can be nonspecific, particularly in children treated for cancer and secondary cancers after acute lymphoblastic leukemia Diseases, St children! Could have contributed to the date of the two curves factors associated with selected characteristics patients...
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