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Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

ABSTRACT: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events.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.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/m(2) per week and mercaptopurine of at least 75 mg/m(2) 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).SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts.

SUBMITTER: Schmiegelow K

PROVIDER: S-EPMC3807139 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

Schmiegelow Kjeld K Levinsen Mette Frandsen MF Attarbaschi Andishe A Baruchel Andre A Devidas Meenakshi M Escherich Gabriele G Gibson Brenda B Heydrich Christiane C Horibe Keizo K Ishida Yasushi Y Liang Der-Cherng DC Locatelli Franco F Michel Gérard G Pieters Rob R Piette Caroline C Pui Ching-Hon CH Raimondi Susana S Silverman Lewis L Stanulla Martin M Stark Batia B Winick Naomi N Valsecchi Maria Grazia MG

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130520 19

<h4>Purpose</h4>Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events.<h4>Patients and methods</h4>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.<h4>Results</h4>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 ...[more]

PMID: 23690411

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Project description:Comprehensive studies on neutropenia and infection-related complications in patients with acute lymphoblastic leukemia (ALL) are lacking.We evaluated infection-related complications that were grade??3 on National Cancer Institute's Common Terminology Criteria for Adverse Events (version 3.0) and their risk factors in 409 children with newly diagnosed ALL throughout the treatment period.Of the 2420 infection episodes, febrile neutropenia and clinically or microbiologically documented infection were seen in 1107 and 1313 episodes, respectively. Among documented infection episodes, upper respiratory tract was the most common site (n?=?389), followed by ear (n?=?151), bloodstream (n?=?147), and gastrointestinal tract (n?=?145) infections. These episodes were more common during intensified therapy phases such as remission induction and reinduction, but respiratory and ear infections, presumably viral in origin, also occurred during continuation phases. The 3-year cumulative incidence of infection-related death was low (1.0±0.9%, n?=?4), including 2 from Bacillus cereus bacteremia. There was no fungal infection-related mortality. Age 1-9.9 years at diagnosis was associated with febrile neutropenia (P?=?0.002) during induction and febrile neutropenia and documented infection (both P?<?0.001) during later continuation. White race was associated with documented infection (P?=?0.034) during induction. Compared with low-risk patients, standard- and high-risk patients received more intensive therapy during early continuation and had higher incidences of febrile neutropenia (P?<?0.001) and documented infections (P?=?0.043). Furthermore, poor neutrophil surge after dexamethasone pulses during continuation, which can reflect the poor bone marrow reserve, was associated with infections (P?<?0.001).The incidence of infection-related death was low. However, young age, white race, intensive chemotherapy, and lack of neutrophil surge after dexamethasone treatment were associated with infection-related complications. Close monitoring for prompt administration of antibiotics and modification of chemotherapy should be considered in these patients.

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Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

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Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

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