Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983

Bhatia, Smita; Sather, Harland N.; Pabustan, Olga B.; Trigg, Michael E.; Gaynon, Paul S.; Robison, Leslie L.

doi:10.1182/blood.v99.12.4257

Cited by 174 publications

(147 citation statements)

References 56 publications

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“…In total 230 SMNs (0.99%) were reported among 23,051 children treated for ALL (Table I). This percentage (0.99%) is similar to the 1.18% and 2.5% cumulative risk of SMN at 10 years and 15 years, respectively, reported by Bhatia and Neglia [3,4]. The most common SMNs observed in this review were CNS tumors (31.7%) followed by AML/MDS (16.5%), thyroid cancer (10%), lymphomas (8.2%), and skin cancer (7.8%).…”

Section: Discussionsupporting

confidence: 84%

“…Other studies have shown that radiation to the craniospinal axis, CNS involvement, front-line therapy with epipodophyllotoxins, female sex, and relapse of primary disease may be similarly associated with increased risk of SMN in children previously treated for ALL [4,5]. Although the increased risk in relapsed patients may reflect more intensive chemotherapy and radiation therapy utilization, the increased risk reported for females remains unexplained.…”

Section: Discussionmentioning

confidence: 99%

“…Among these 230 SMNs reviewed, only 1 case of PNET of bone was reported [5]. The predominance of CNS tumors in this group of patients has been partly attributed to the use of cranial or craniospinal radiation therapy and it appears to be dose related [4,5,14,18]. The overall cumulative risk of a SMN 15 years after diagnosis of ALL is three times higher when cranial irradiation is administered (3.5% vs. 1.2%) [5].…”

Section: Discussionmentioning

confidence: 99%

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Second malignant neoplasms in childhood acute lymphoblastic leukemia: Primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm

et al. 2004

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About 80% of children treated for acute lymphoblastic leukemia (ALL) will be long-term survivors. Second malignant neoplasm (SMNs) are a devastating sequelae observed on these children, with an estimated cumulative risk of 2-3.3% fifteen years after diagnosis. Primitive neuroectodermal tumor of bone (PNET) is rarely observed as a SMN following treatment of childhood ALL. The authors described the occurrence of a chest wall PNET of the bone at the site of a central line placement associated with both germ-line and tumor cell p53 mutation in a 8-year-old boy 1 year after completing therapy for standard risk ALL. A review of the literature of 25,051 children treated for ALL discovered 230 SMNs (0.99%), and only one case of PNET of the bone was noted among this group. The occurrence of a SMN in children treated for ALL is a rare event. Such an occurrence, in particular the development of an unusual SMN, should be evaluated for a germline p53 mutation. Am.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Second malignant neoplasms in childhood acute lymphoblastic leukemia: Primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm

et al. 2004

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“…Nonetheless, the rate of second neoplasm observed by our group in patients undergoing autologous transplantation for haematologic malignancies (1.25%) 45 is similar to data reported by other groups utilizing chemotherapy protocols for these diseases. 46,47 We conclude that our results, and those reported elsewhere, indicate that auto-HSCT is a treatment option in children with ALL after late marrow relapse and after extramedullary relapse. Improvements in the diverse approaches and additional comparative clinical studies might help to define subsets of patients who may experience a better response to a defined transplantation procedure.…”

Section: Discussionsupporting

confidence: 63%

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983–1998

Badell

Muñoz

Ortega

et al. 2005

Bone Marrow Transplant

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Summary:We present a retrospective study of long-term outcome and predictive factors of survival and relapse in 219 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. They received allogeneic (allo) or autologous (auto) haemopoietic cell transplantation (HCT) depending on the availability of a matched sibling donor. The probability of event-free survival (EFS) for the total patient group was 0.35 þ 0.03 at 14 years. No significant differences were observed for EFS between allo-and auto-HCT: 0.39 þ 0.05 vs 0.32 þ 0.04 (P ¼ 0.43). A better EFS was seen in patients with a late relapse (LR) (P ¼ 0.06 and 0.02, for allogeneic and autologous respectively). Significantly better EFS was observed in allo-HCT patients under 10 years of age and in auto-HCT patients with leukocytes at diagnosis below 25 Â 109/l and late relapse. Predictive factors of failure in both groups were early relapse (ER), medullary relapse and age over 10 years. The probability of relapse (RP) for the total group of patients was 0.57 þ 0.03, and it was significantly higher in auto-HCT patients: 0.65 þ 0.04 vs 0.42 þ 0.06 (P ¼ 0.002). Factors predictive for relapse were medullary and early relapse, auto-HCT and WBC 425 Â 109/l at diagnosis. The intensive chemotherapy regimen presently used for childhood lymphoblastic leukaemia allows a prolonged disease-free survival in more than 70% of patients. 1 Relapse is observed in approximately 20-25% of patients, mostly within the first 5 years after diagnosis. 2,3 Optimal therapy for relapsed patients remains controversial in some areas. 4 With the use of intensive chemotherapy, 80-95% of patients achieved a complete second remission. However, less than 5% of the patients with an early relapse (during therapy or within 30 months of diagnosis) and 25-40% of those with a late relapse (after 6 months of completion of therapy or as of 30 months since diagnosis) are long-term survivors. 5-7 Allogeneic haemopoietic cell transplantation (allo-HCT) from a matched sibling donor has been shown to be superior to chemotherapy, especially for patients with an early relapse; 8-13 for late isolated extramedullary relapse, chemotherapy alone may play a role. 14,15 However, the lack of a compatible matched sibling donor limits the use of this treatment. The safety and efficacy of autologous HCT (auto-HCT) in children with acute lymphoblastic leukaemia (ALL) has been previously reported. [16][17][18][19][20][21][22] Comparison studies of auto-and allo-HCT have suggested different failure patterns, but comparable survival rates. Auto-HCT offers the advantages of an accelerated immunological recovery and the absence of graft-versus-host disease (GVHD) compared with allo-HCT. By contrast, a higher relapse rate is observed in patients receiving an autologous transplant. [23][24] However, the heterogeneity of populations used for comparison (stage of disease, risk factors, prior therapy, conditioning regimens) makes it difficult to reach any conclusions which may be useful in therapeutic decision-ma...

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“…The risk of a second cancer has been found to be highest in children who received irradiation therapy or suffered a relapse, and this risk persists for up to 30 years after treatment (Kimball Dalton et al, 1998;Lonig et al, 2000;Bhatia et al, 2002).…”

Section: Time Since Diagnosis Relative Survival (%)mentioning

confidence: 99%

Childhood leukaemia: long-term excess mortality and the proportion ‘cured’

et al. 2008

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Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion 'cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971 -2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11 -14) to 19 years (95% CI: 14 -26) for lymphoid leukaemia (average annual increase of 0.3 years; Po0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment.

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Low incidence of second neoplasms among children diagnosed with acute lymphoblastic leukemia after 1983

Cited by 174 publications

References 56 publications

Second malignant neoplasms in childhood acute lymphoblastic leukemia: Primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm

Second malignant neoplasms in childhood acute lymphoblastic leukemia: Primitive neuroectodermal tumor of the chest wall with germline p53 mutation as a second malignant neoplasm

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983–1998

Childhood leukaemia: long-term excess mortality and the proportion ‘cured’

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