Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

Kjeld Schmiegelow, Mette Frandsen Levinsen, Andishe Attarbaschi, Andre Baruchel, Meenakshi Devidas, Gabriele Escherich, Brenda Gibson, Christiane Heydrich, Keizo Horibe, Yasushi Ishida, Der Cherng Liang, Franco Locatelli, Gérard Michel, Rob Pieters, Caroline Piette, Ching Hon Pui, Susana Raimondi, Lewis Silverman, Martin Stanulla, Batia Stark & 2 others Naomi Winick, Maria Grazia Valsecchi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2469-2476
Number of pages8
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume31
Issue number19
DOIs
StatePublished - Jul 1 2013

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Second Primary Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Brain Neoplasms
Neoplasms
Survival Rate
Topoisomerase II Inhibitors
Cranial Irradiation
Therapeutics
6-Mercaptopurine
Polyploidy
Survival
Basal Cell Carcinoma
Myelodysplastic Syndromes
Parotid Gland
Stem Cell Transplantation
Meningioma
Hodgkin Disease
Karyotype
Thyroid Neoplasms
Acute Myeloid Leukemia

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia. / Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 31, No. 19, 01.07.2013, p. 2469-2476.

Research output: Contribution to journalArticle

Schmiegelow, K, Levinsen, MF, Attarbaschi, A, Baruchel, A, Devidas, M, Escherich, G, Gibson, B, Heydrich, C, Horibe, K, Ishida, Y, Liang, DC, Locatelli, F, Michel, G, Pieters, R, Piette, C, Pui, CH, Raimondi, S, Silverman, L, Stanulla, M, Stark, B, Winick, N & Valsecchi, MG 2013, 'Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 31, no. 19, pp. 2469-2476. https://doi.org/10.1200/JCO.2012.47.0500
Schmiegelow, Kjeld ; Levinsen, Mette Frandsen ; Attarbaschi, Andishe ; Baruchel, Andre ; Devidas, Meenakshi ; Escherich, Gabriele ; Gibson, Brenda ; Heydrich, Christiane ; Horibe, Keizo ; Ishida, Yasushi ; Liang, Der Cherng ; Locatelli, Franco ; Michel, Gérard ; Pieters, Rob ; Piette, Caroline ; Pui, Ching Hon ; Raimondi, Susana ; Silverman, Lewis ; Stanulla, Martin ; Stark, Batia ; Winick, Naomi ; Valsecchi, Maria Grazia. / Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013 ; Vol. 31, No. 19. pp. 2469-2476.
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AU - Schmiegelow, Kjeld

AU - Levinsen, Mette Frandsen

AU - Attarbaschi, Andishe

AU - Baruchel, Andre

AU - Devidas, Meenakshi

AU - Escherich, Gabriele

AU - Gibson, Brenda

AU - Heydrich, Christiane

AU - Horibe, Keizo

AU - Ishida, Yasushi

AU - Liang, Der Cherng

AU - Locatelli, Franco

AU - Michel, Gérard

AU - Pieters, Rob

AU - Piette, Caroline

AU - Pui, Ching Hon

AU - Raimondi, Susana

AU - Silverman, Lewis

AU - Stanulla, Martin

AU - Stark, Batia

AU - Winick, Naomi

AU - Valsecchi, Maria Grazia

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N2 - 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.

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