Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Melissa Gabriel; Bronwen E Shaw; Ruta Brazauskas; Min Chen; David A Margolis; Henrik Sengelov; Ann Dahlberg; Ibrahim A Ahmed; David Delgado; Hillard M Lazarus; Brenda Gibson; Kasiani C Myers; Rammurti T Kamble; Aly Abdel-Mageed; Chi-Kong Li; Mary E D Flowers; Minoo Battiwalla; Bipin N Savani; Navneet Majhail; Peter J Shaw

doi:10.1016/j.bbmt.2017.04.004

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Melissa Gabriel, Bronwen E Shaw, Ruta Brazauskas, Min Chen, David A Margolis, Henrik Sengelov, Ann Dahlberg, Ibrahim A Ahmed, David Delgado, Hillard M Lazarus, Brenda Gibson, Kasiani C Myers, Rammurti T Kamble, Aly Abdel-Mageed, Chi-Kong Li, Mary E D Flowers, Minoo Battiwalla, Bipin N Savani, Navneet Majhail, Peter J Shaw

Department of Clinical Medicine

1 Citation (Scopus)

Abstract

Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.

Original language	English
Journal	Biology of Blood and Marrow Transplantation
Volume	23
Issue number	8
Pages (from-to)	1320-1326
ISSN	1083-8791
DOIs	https://doi.org/10.1016/j.bbmt.2017.04.004
Publication status	Published - Aug 2017

Keywords

Adolescent
Adult
Allografts
Central Nervous System Neoplasms/mortality
Child
Child, Preschool
Female
Hematologic Neoplasms/mortality
Hematopoietic Stem Cell Transplantation
Humans
Incidence
Infant
Leukemia, Myeloid, Acute/mortality
Male
Neoplasms, Second Primary/mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality
Unrelated Donors

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Gabriel, M., Shaw, B. E., Brazauskas, R., Chen, M., Margolis, D. A., Sengelov, H., Dahlberg, A., Ahmed, I. A., Delgado, D., Lazarus, H. M., Gibson, B., Myers, K. C., Kamble, R. T., Abdel-Mageed, A., Li, C-K., Flowers, M. E. D., Battiwalla, M., Savani, B. N., Majhail, N., & Shaw, P. J. (2017). Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR). Biology of Blood and Marrow Transplantation, 23(8), 1320-1326. https://doi.org/10.1016/j.bbmt.2017.04.004

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant : A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR). / Gabriel, Melissa; Shaw, Bronwen E; Brazauskas, Ruta et al.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 8, 08.2017, p. 1320-1326.

Research output: Contribution to journal › Journal article › Research › peer-review

Gabriel, M, Shaw, BE, Brazauskas, R, Chen, M, Margolis, DA, Sengelov, H, Dahlberg, A, Ahmed, IA, Delgado, D, Lazarus, HM, Gibson, B, Myers, KC, Kamble, RT, Abdel-Mageed, A, Li, C-K, Flowers, MED, Battiwalla, M, Savani, BN, Majhail, N & Shaw, PJ 2017, 'Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)', Biology of Blood and Marrow Transplantation, vol. 23, no. 8, pp. 1320-1326. https://doi.org/10.1016/j.bbmt.2017.04.004

Gabriel M, Shaw BE, Brazauskas R, Chen M, Margolis DA, Sengelov H et al. Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR). Biology of Blood and Marrow Transplantation. 2017 Aug;23(8):1320-1326. doi: 10.1016/j.bbmt.2017.04.004

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title = "Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)",

abstract = "Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.",

keywords = "Adolescent, Adult, Allografts, Central Nervous System Neoplasms/mortality, Child, Child, Preschool, Female, Hematologic Neoplasms/mortality, Hematopoietic Stem Cell Transplantation, Humans, Incidence, Infant, Leukemia, Myeloid, Acute/mortality, Male, Neoplasms, Second Primary/mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality, Unrelated Donors",

author = "Melissa Gabriel and Shaw, {Bronwen E} and Ruta Brazauskas and Min Chen and Margolis, {David A} and Henrik Sengelov and Ann Dahlberg and Ahmed, {Ibrahim A} and David Delgado and Lazarus, {Hillard M} and Brenda Gibson and Myers, {Kasiani C} and Kamble, {Rammurti T} and Aly Abdel-Mageed and Chi-Kong Li and Flowers, {Mary E D} and Minoo Battiwalla and Savani, {Bipin N} and Navneet Majhail and Shaw, {Peter J}",

year = "2017",

month = aug,

doi = "10.1016/j.bbmt.2017.04.004",

language = "English",

volume = "23",

pages = "1320--1326",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

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number = "8",

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TY - JOUR

T1 - Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant

T2 - A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)

AU - Gabriel, Melissa

AU - Shaw, Bronwen E

AU - Brazauskas, Ruta

AU - Chen, Min

AU - Margolis, David A

AU - Sengelov, Henrik

AU - Dahlberg, Ann

AU - Ahmed, Ibrahim A

AU - Delgado, David

AU - Lazarus, Hillard M

AU - Gibson, Brenda

AU - Myers, Kasiani C

AU - Kamble, Rammurti T

AU - Abdel-Mageed, Aly

AU - Li, Chi-Kong

AU - Flowers, Mary E D

AU - Battiwalla, Minoo

AU - Savani, Bipin N

AU - Majhail, Navneet

AU - Shaw, Peter J

PY - 2017/8

Y1 - 2017/8

N2 - Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.

AB - Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients of allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research between 1976 and 2008. A case control design was used. There were no CNS tumors in the nonmalignant cohort (n = 4543) or in those undergoing HCT for solid tumors (n = 26). There were 59 CNS tumors in 8720 patients transplanted for hematologic malignancies. In comparison with the general population, pediatric HCT recipients with hematologic malignancies had a 33 times higher than expected rate of CNS tumors (95% confidence interval, 22.98 to 45.77; P < .0001). The cumulative incidence of subsequent CNS tumors was 1.29% (95% confidence interval .87 to 1.87) at 20 years after HCT. Significant risk factors in the entire cohort were having an unrelated donor (HR, 3.35; P = .0002) and CNS disease before HCT for both acute lymphoblastic leukemia (HR, 8.21; P = .0003) and acute myeloid leukemia (HR, 6.21; P = .0174). Analysis of the matched cohort showed having an unrelated donor transplant (HR, 4.79; P = .0037), CNS disease before HCT (HR, 7.67; P = .0064), and radiotherapy exposure before conditioning (HR, 3.7; P = .0234) to be significant risk factors. Chronic graft-versus-host disease was associated with a lower risk (HR, .29; P = .0143). Survivors of HCT for nonmalignant diseases did not show an increased incidence of CNS tumors, whereas survivors of hematologic malignancies have a markedly increased incidence of CNS tumors that warrants lifelong surveillance.

KW - Adolescent

KW - Adult

KW - Allografts

KW - Central Nervous System Neoplasms/mortality

KW - Child

KW - Child, Preschool

KW - Female

KW - Hematologic Neoplasms/mortality

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Incidence

KW - Infant

KW - Leukemia, Myeloid, Acute/mortality

KW - Male

KW - Neoplasms, Second Primary/mortality

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality

KW - Unrelated Donors

U2 - 10.1016/j.bbmt.2017.04.004

DO - 10.1016/j.bbmt.2017.04.004

M3 - Journal article

C2 - 28411175

SN - 1083-8791

VL - 23

SP - 1320

EP - 1326

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 8

ER -

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant: A Study from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Abstract

Keywords

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