Second malignant neoplasms (SMN) in childhood acute lymphoblastic leukemia (ALL): Primitive neuroectodermal tumor of bone (PNET) with p53 mutation

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 8173-8173
Author(s):  
C. R. Suarez ◽  
A. B. Raj ◽  
S. J. Bertolone
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Primitive Neuroectodermal Tumor ◽  
Lymphoblastic Leukemia ◽  
P53 Mutation ◽  
Neuroectodermal Tumor ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Second Malignant Neoplasms

scholarly journals Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

2013 ◽  
Vol 31 (19) ◽  
pp. 2469-2476 ◽  
Author(s):  
Kjeld Schmiegelow ◽  
Mette Frandsen Levinsen ◽  
Andishe Attarbaschi ◽  
Andre Baruchel ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Brain Tumors ◽  
Hodgkin Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Collaborative Study ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Monosomy 7 ◽  
Myeloid Malignancies ◽  
Second Malignant Neoplasms

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.

Treatment of Metastatic Ewing's Sarcoma or Primitive Neuroectodermal Tumor of Bone: Evaluation of Combination Ifosfamide and Etoposide—A Children's Cancer Group and Pediatric Oncology Group Study

2004 ◽  
Vol 22 (14) ◽  
pp. 2873-2876 ◽  
Author(s):  
James S. Miser ◽  
Mark D. Krailo ◽  
Nancy J. Tarbell ◽  
Michael P. Link ◽  
Christopher J.H. Fryer ◽  
...  
Keyword(s):  
Primitive Neuroectodermal Tumor ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Lung Metastases ◽  
Neuroectodermal Tumor ◽  
Malignant Neoplasms ◽  
Cancer Group ◽  
Improved Outcomes ◽  
Second Malignant Neoplasms ◽  
Pediatric Oncology Group

Purpose One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. Methods Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m2, cyclophosphamide 1,200 mg/m2, and either doxorubicin 75 mg/m2 or dactinomycin 1.25 mg/m2. Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m2/d for 5 days and etoposide 100 mg/m2/d for 5 days. Results Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. Conclusion Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.

scholarly journals Balancing cure and long-term risks in acute lymphoblastic leukemia

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 190-197 ◽  
Author(s):  
Lewis B. Silverman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Late Effects ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Second Malignant Neoplasms ◽  
Current Therapies ◽  
Cure Rates ◽  
Long Term Survivors

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.

scholarly journals TP53 Germline Variations Influence the Predisposition and Prognosis of B-Cell Acute Lymphoblastic Leukemia in Children

2018 ◽  
Vol 36 (6) ◽  
pp. 591-599 ◽  
Author(s):  
Maoxiang Qian ◽  
Xueyuan Cao ◽  
Meenakshi Devidas ◽  
Wenjian Yang ◽  
Cheng Cheng ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Treatment Outcomes ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Loss Of Function ◽  
Childhood All ◽  
Li Fraumeni Syndrome ◽  
Pathogenic Variants ◽  
Second Malignant Neoplasms ◽  
Li Fraumeni

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.

Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols

Blood ◽  
2009 ◽  
Vol 114 (7) ◽  
pp. 1314-1318 ◽  
Author(s):  
Martin Stanulla ◽  
Elke Schaeffeler ◽  
Anja Möricke ◽  
Sally A. Coulthard ◽  
Gunnar Cario ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasm ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Tpmt Activity ◽  
Malignant Neoplasms ◽  
Thiopurine Methyltransferase ◽  
Childhood All ◽  
Increased Risk ◽  
Secondary Malignant Neoplasm

AbstractThiopurine methyltransferase (TPMT)is involved in the metabolism of thiopurines such as 6-mercaptopurine and 6-thioguanine. TPMT activity is significantly altered by genetics, and heterozygous and even more homozygous variant people reveal substiantially decreased TPMT activity. Treatment for childhood acute lymphoblastic leukemia (ALL) regularly includes the use of thiopurine drugs. Importantly, childhood ALL patients with low TPMT activity have been considered to be at increased risk of developing therapy-associated acute myeloid leukemia and brain tumors. In the present study, we genotyped 105 of 129 patients who developed a secondary malignant neoplasm after ALL treatment on 7 consecutive German Berlin-Frankfurt-Münster trials for all functionally relevant TPMT variants. Frequencies of TPMT variants were similarly distributed in secondary malignant neoplasm patients and the overall ALL patient population of 814 patients. Thus, TPMT does not play a major role in the etiology of secondary malignant neoplasm after treatment for childhood ALL, according to Berlin-Frankfurt-Münster strategies.

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