Second neoplasms after acute lymphoblastic leukemia in childhood.

BACKGROUND 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. To determine the magnitude of this risk and identify possible risk factors for the development of second neoplasms, we studied a large cohort of children treated for ALL. METHODS AND RESULTS. 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. The median follow-up was 4.7 years (range, 2 months to 16 years). 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. This represented a 7-fold excess of all cancers and a 22-fold excess of neoplasms of the central nervous system. 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). An even higher risk, particularly of central nervous system tumors, was evident in children five years of age or less at the time of the diagnosis of ALL (P = 0.012). All central nervous system neoplasms developed in children who had previously undergone irradiation. There was no association with exposure to cyclophosphamide or anthracyclines. CONCLUSIONS There is a substantial excess of second neoplasms, especially of the central nervous system, among children treated for ALL. Children five years old or younger and those receiving radiation are at higher risk, especially for second tumors arising in the central nervous system.

[1]  L. Strong,et al.  Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. , 1990, Science.

[2]  F. Behm,et al.  Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. , 1989, The New England journal of medicine.

[3]  D. Parkin,et al.  The international incidence of childhood cancer , 1988, IARC scientific publications.

[4]  A. Sawitsky,et al.  Hepatocellular carcinoma in a long‐term survivor of acute lymphocytic leukemia , 1987, Cancer.

[5]  D M Green,et al.  Bone sarcomas linked to radiotherapy and chemotherapy in children. , 1987, The New England journal of medicine.

[6]  G. Draper,et al.  Incidence of second primary tumours among childhood cancer survivors. , 1987, British Journal of Cancer.

[7]  D. Pinkel General motors cancer research foundation prizes Charles F. Kettering prize curing children of leukemia , 1987 .

[8]  S. Sallan,et al.  Brain tumors after cranial irradiation for childhood acute lymphoblastic leukemia. A 13‐year experience from the Dana‐Farber cancer institute and the children's hospital , 1987, Cancer.

[9]  G. Hammond Keynote address: The cure of childhood cancers , 1986 .

[10]  M. Malone,et al.  Astrocytoma as a second malignancy in patients with acute lymphoblastic leukemia , 1986, Cancer.

[11]  A. Bleyer,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 Childrens Cancer Study Group. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  O. Oberlin,et al.  Second malignant neoplasms in children: an update from the Late Effects Study Group. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  A. Bleyer,et al.  Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (ALL). , 1984, International journal of radiation oncology, biology, physics.

[14]  J. Flannery,et al.  Cancer in relatives of children with central-nervous-system neoplasms. , 1984, The New England journal of medicine.

[15]  L. Dehner,et al.  Melanoma Masquerading as Spitz Nevus Following Acute Lymphoblastic Leukemia , 1984, Pediatric dermatology.

[16]  F. Rosner,et al.  Second neoplasms in acute lymphoblastic leukemia , 1983, Cancer.

[17]  R. Labotka,et al.  Hodgkin's disease in a child with acute lymphoblastic leukemia , 1983, Cancer.

[18]  Denis R. Miller,et al.  Prognostic factors and therapy in acute lymphoblastic leukemia of childhood: CCG‐141: A report from childrens cancer study group , 1983, Cancer.

[19]  A. Meadows,et al.  INCIDENCE OF SECOND MALIGNANT NEOPLASMS IN CHILDREN: RESULTS OF AN INTERNATIONAL STUDY , 1982, The Lancet.

[20]  P. Dyment,et al.  Equivalence of intrathecal chemotherapy and radiotherapy as central nervous system prophylaxis in children with acute lymphatic leukemia: a pediatric oncology group study , 1982 .

[21]  L. Robison,et al.  Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia: A Report from Children's Cancer Study Group. , 1982, Cancer research.

[22]  A. D. Mosijczuk,et al.  Second malignancy in acute lymphocytic leukemia. Review of 33 cases. , 1981, American journal of diseases of children.

[23]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[24]  A. Meadows,et al.  Patterns of second malignant neoplasms in children , 1977, Cancer.

[25]  D. Hammond,et al.  L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. , 1977, Cancer research.

[26]  N. Breslow Covariance analysis of censored survival data. , 1974, Biometrics.

[27]  J. Peto,et al.  Asymptotically Efficient Rank Invariant Test Procedures , 1972 .

[28]  John C. Bailar,et al.  202. Note: Significance Factors for the Ratio of a Poisson Variable to Its Expectation , 1964 .

[29]  H. Sather,et al.  Modified BFM therapy for children with previously untreated acute lymphoblastic leukemia and unfavorable prognostic features. Report of Children's Cancer Study Group Study CCG-193P. , 1988, The American journal of pediatric hematology/oncology.