Acute lymphoblastic leukemia occurring as a second malignant neoplasm in childhood: report of three cases and review of the literature.

1992 ◽  
Vol 10 (1) ◽  
pp. 156-163 ◽  
Author(s):  
S P Hunger ◽  
J Sklar ◽  
M P Link

PURPOSE The long-term effects of childhood cancer and its therapy are a problem of increasing concern. One of the most important of these late effects is the development of second malignant neoplasms (SMNs), which occur in approximately 8% of children within 20 years of diagnosis of a malignancy. These secondary cancers may result (individually or in combination) from increased genetic susceptibility, the mutagenic effects of chemotherapy and/or radiation therapy, or chance. Whereas the development of acute nonlymphocytic leukemia (ANLL) as an SMN is a well-recognized phenomenon, acute lymphoblastic leukemia (ALL) has been infrequently described as an SMN in either adults or children. PATIENTS AND METHODS We report three patients treated at our institution in whom ALL developed as an SMN after treatment for neuroblastoma, Wilms' tumor, and Hodgkin's disease. These cases prompted us to review the published literature for cases of secondary ALL in childhood. Patients whose initial malignancy was diagnosed at age less than 16 years were classified as pediatric patients. SMNs were defined as cancers of clearly distinct histologic type occurring 6 or more months after diagnosis of the first malignant neoplasm. RESULTS Including the three index cases, a total of 18 children with secondary ALL are reviewed, and the clinical features are discussed and compared with those of secondary ANLL. CONCLUSIONS This review summarizes the published case histories of secondary ALL. The data suggest that ALL represents approximately 5% to 10% of the cases of acute leukemia that arise as SMNs in both adults and children.

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 190-197 ◽  
Author(s):  
Lewis B. Silverman

Abstract Cure rates for children and adolescents with acute lymphoblastic leukemia (ALL) have improved dramatically over the last few decades. With this success has come increasing recognition of the adverse late effects of treatment. The significant long-term sequelae in the earliest cohort of long-term survivors treated in the 1970s and 1980s are well documented. To reduce the incidence of these late effects, the majority of pediatric patients treated on more contemporary regimens receive less intensive treatment than did those treated 30-40 years ago. However, current therapies are not risk free; children treated with contemporary regimens remain at risk for developing long-term toxicities, including cardiac dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms. One of the great challenges facing clinical investigators today is to identify interventions that will reduce the frequency and severity of long-term toxicities without adversely affecting cure rates. The use of dexrazoxane as a cardioprotectant (to prevent anthracycline-associated cardiotoxicity) and alternate-week dosing of dexamethasone (to reduce the risk of osteonecrosis) are examples of 2 such successful strategies. This article provides an overview of the long-term toxicities associated with current therapies and reviews results of clinical trials designed to minimize the burden of cure in long-term survivors.


2020 ◽  
Vol 7 (2) ◽  
pp. 115-119
Author(s):  
Yu. K. Toshina ◽  
Yu. V. Dinikina ◽  
A. S. Egorov ◽  
A. Yu. Smirnova ◽  
M. B. Belogurova

Neuroblastoma (NB) is the most common extra-cranial solid tumor in infants with the most heterogeneous clinical course to compare with other malignant diseases. Due to intensive multimodal anticancer treatment there are an increased number of survivors and issues related to long-term effects are becoming increasingly important. One of them is the risk of secondary malignant neoplasms. This article represents a clinical case of T-cell lymphoblastic leukemia in a child aged 2 years and 5 months who received combined antitumor therapy for NB with an intermediate risk group under the age of one year. We observed literature data to investigate the incidence of second malignant neoplasms in patients with NB for the period from 1948 to 2018 and analyzed risk factors.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hongnan Zhen ◽  
Zhikai Liu ◽  
Hui Guan ◽  
Jiabin Ma ◽  
Wenhui Wang ◽  
...  

ObjectiveRhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiotherapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN).MethodsThe Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis.ResultsThe 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR=1.95, 95% CI: 1.44 – 2.57, p < 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joints (SIR = 35.25) soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and all nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313 – 0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184 – 0.564. p < 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421 – 0.585, p < 0.001).ConclusionThis study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.


2013 ◽  
Vol 31 (19) ◽  
pp. 2469-2476 ◽  
Author(s):  
Kjeld Schmiegelow ◽  
Mette Frandsen Levinsen ◽  
Andishe Attarbaschi ◽  
Andre Baruchel ◽  
Meenakshi Devidas ◽  
...  

Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.


2018 ◽  
Vol 36 (6) ◽  
pp. 591-599 ◽  
Author(s):  
Maoxiang Qian ◽  
Xueyuan Cao ◽  
Meenakshi Devidas ◽  
Wenjian Yang ◽  
Cheng Cheng ◽  
...  

Purpose Germline TP53 variation is the genetic basis of Li-Fraumeni syndrome, a highly penetrant cancer predisposition condition. Recent reports of germline TP53 variants in childhood hypodiploid acute lymphoblastic leukemia (ALL) suggest that this type of leukemia is another manifestation of Li-Fraumeni syndrome; however, the pattern, prevalence, and clinical relevance of TP53 variants in childhood ALL remain unknown. Patients and Methods Targeted sequencing of TP53 coding regions was performed in 3,801 children from the Children’s Oncology Group frontline ALL clinical trials, AALL0232 and P9900. TP53 variant pathogenicity was evaluated according to experimentally determined transcriptional activity, in silico prediction of damaging effects, and prevalence in non-ALL control populations. TP53 variants were analyzed for their association with ALL presenting features and treatment outcomes. Results We identified 49 unique nonsilent rare TP53 coding variants in 77 (2.0%) of 3,801 patients sequenced, of which 22 variants were classified as pathogenic. TP53 pathogenic variants were significantly over-represented in ALL compared with non-ALL controls (odds ratio, 5.2; P < .001). Children with TP53 pathogenic variants were significantly older at ALL diagnosis (median age, 15.5 years v 7.3 years; P < .001) and were more likely to have hypodiploid ALL (65.4% v 1.2%; P < .001). Carrying germline TP53 pathogenic variants was associated with inferior event-free survival and overall survival (hazard ratio, 4.2 and 3.9; P < .001 and .001, respectively). In particular, children with TP53 pathogenic variants were at a dramatically higher risk of second cancers than those without pathogenic variants, with 5-year cumulative incidence of 25.1% and 0.7% ( P < .001), respectively. Conclusion Loss-of-function germline TP53 variants predispose children to ALL and to adverse treatment outcomes with ALL therapy, particularly the risk of second malignant neoplasms.


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