Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

K. 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; Naomi Winick; Maria Grazia Valsecchi

doi:10.1200/JCO.2012.47.0500

Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

K. 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 StarkNaomi Winick, Maria Grazia Valsecchi

Department of Clinical Medicine

79 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Journal of Clinical Oncology
Volume	31
Issue number	19
Pages (from-to)	2469-2476
Number of pages	8
ISSN	0732-183X
DOIs	https://doi.org/10.1200/JCO.2012.47.0500
Publication status	Published - 1 Jul 2013

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Schmiegelow, K., Levinsen, M. F., Attarbaschi, A., Baruchel, A., Devidas, M., Escherich, G., Gibson, B., Heydrich, C., Horibe, K., Ishida, Y., Liang, D-C., Locatelli, F., Michel, G., Pieters, R., Piette, C., Pui, C-H., Raimondi, S., Silverman, L., Stanulla, M., ... Valsecchi, M. G. (2013). Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology, 31(19), 2469-2476. https://doi.org/10.1200/JCO.2012.47.0500

Schmiegelow, K, Levinsen, MF, Attarbaschi, A, Baruchel, A, Devidas, M, Escherich, G, Gibson, B, Heydrich, C, Horibe, K, Ishida, Y, Liang, D-C, Locatelli, F, Michel, G, Pieters, R, Piette, C, Pui, C-H, 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, vol. 31, no. 19, pp. 2469-2476. https://doi.org/10.1200/JCO.2012.47.0500

@article{af2ab7d4af494b2b85685e9d73a4300b,

title = "Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia",

abstract = "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.",

author = "K. Schmiegelow and Levinsen, {Mette Frandsen} and Andishe Attarbaschi and Andre Baruchel and Meenakshi Devidas and Gabriele Escherich and Brenda Gibson and Christiane Heydrich and Keizo Horibe and Yasushi Ishida and Der-Cherng Liang and Franco Locatelli and G{\'e}rard Michel and Rob Pieters and Caroline Piette and Ching-Hon Pui and Susana Raimondi and Lewis Silverman and Martin Stanulla and Batia Stark and Naomi Winick and Valsecchi, {Maria Grazia}",

year = "2013",

month = jul,

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doi = "10.1200/JCO.2012.47.0500",

language = "English",

volume = "31",

pages = "2469--2476",

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TY - JOUR

T1 - Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

AU - Schmiegelow, K.

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

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.2012.47.0500

DO - 10.1200/JCO.2012.47.0500

M3 - Journal article

SN - 0732-183X

VL - 31

SP - 2469

EP - 2476

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 19

ER -

Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

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