Second Malignant Neoplasms in Patients Treated for Childhood Leukemia: A Population‐based Cohort Study from the Nordic Countries

Abstract

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.

Osteosarcoma after allogeneic bone marrow transplantation. A report of four cases from the Cooperative Osteosarcoma Study Group (COSS)

“…22 Osteosarcoma following ALL, on the other hand, seems to be very rare. No osteosarcomas were detected in a population-based series of eight second malignant neoplasms in 895 childhood ALL patients, 23 none among 43 second neoplasms in 9720 children with ALL treated according to the therapeutic protocols of the Children's Cancer Study Group, 24 and only one of 52 second neoplasms among 5006 ALL patients observed by the BFM group until 1997 25 (corresponding to patient 1 from this report, Schrappe M, personal communication) was an osteosarcoma. Evidence suggestive of a familial cancer predisposition was present in two of our three ALL patients.…”

Glioblastoma after radiotherapy for childhood acute lymphoblastic leukemia: Review

“…Relling et al found that the incidence of brain tumors among in ALL children who received PCI was higher than in children who did not receive (9). Nygaard et al (28) reported that the estimated cumulative risk of developing secondary malignant neoplasms within 20 years was 2.9%. The corresponding risk for PCI-given ALL children was 8.1% compared to 0.3% for those who did not receive PCI.…”

Second malignancy after treatment of childhood acute myeloid leukemia

“…[29][30][31][32] The cumulative incidence was estimated to be approximately 2.5% at 15 years after the diagnosis of ALL. Irradiation is one of the most common risk factors for the development of a second malignancy after the treatment of ALL.…”

“…Irradiation is one of the most common risk factors for the development of a second malignancy after the treatment of ALL. [29][30][31][32][33][34] Three of the five second cancers and the third neoplasm reported herein occurred in the irradiated field. One of the patients developed a parotid gland carcinoma following autologous bone marrow transplantation (BMT) without irradiation.…”