More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling

on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group

Research output: Contribution to journalArticle

Abstract

Detection of minimal residual disease (MRD) pre– and post–hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD1 patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n 5 191), unrelated (n 5 259), mismatched (n 5 56), and cord blood (n 5 110) grafts given after myeloablative conditioning. Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease. We derived a risk score with an MRD cohort from Europe, North America, and Australia using negative predictive characteristics (late disease status, non–total body irradiation regimen, and MRD [high, very high]) defining good, intermediate, and poor risk groups with 2-year cumulative incidences of relapse of 21%, 38%, and 47%, respectively. We validated the score in a second, more contemporaneous cohort and noted 2-year cumulative incidences of relapse of 13%, 26%, and 47% (P, .001) for the defined risk groups.

Original languageEnglish (US)
Pages (from-to)3393-3405
Number of pages13
JournalBlood Advances
Volume3
Issue number21
DOIs
StatePublished - Nov 12 2019

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Residual Neoplasm
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Recurrence
Incidence
Cell Transplantation
Graft vs Host Disease
North America
Fetal Blood
Siblings
Databases
Transplants

ASJC Scopus subject areas

  • Hematology

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on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group (2019). More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling. Blood Advances, 3(21), 3393-3405. https://doi.org/10.1182/bloodadvances.2019000449

More precisely defining risk peri-HCT in pediatric ALL : Pre- vs post-MRD measures, serial positivity, and risk modeling. / on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group.

In: Blood Advances, Vol. 3, No. 21, 12.11.2019, p. 3393-3405.

Research output: Contribution to journalArticle

on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group 2019, 'More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling', Blood Advances, vol. 3, no. 21, pp. 3393-3405. https://doi.org/10.1182/bloodadvances.2019000449
on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group. More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling. Blood Advances. 2019 Nov 12;3(21):3393-3405. https://doi.org/10.1182/bloodadvances.2019000449
on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation, and the Westhafen Intercontinental Group. / More precisely defining risk peri-HCT in pediatric ALL : Pre- vs post-MRD measures, serial positivity, and risk modeling. In: Blood Advances. 2019 ; Vol. 3, No. 21. pp. 3393-3405.
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abstract = "Detection of minimal residual disease (MRD) pre– and post–hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD1 patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n 5 191), unrelated (n 5 259), mismatched (n 5 56), and cord blood (n 5 110) grafts given after myeloablative conditioning. Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease. We derived a risk score with an MRD cohort from Europe, North America, and Australia using negative predictive characteristics (late disease status, non–total body irradiation regimen, and MRD [high, very high]) defining good, intermediate, and poor risk groups with 2-year cumulative incidences of relapse of 21{\%}, 38{\%}, and 47{\%}, respectively. We validated the score in a second, more contemporaneous cohort and noted 2-year cumulative incidences of relapse of 13{\%}, 26{\%}, and 47{\%} (P, .001) for the defined risk groups.",
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AU - on behalf of the Children’s Oncology Group, the Pediatric Blood & Marrow Transplant Consortium, the Australian Transplantation Group, the International Berlin-Frankfurt-Münster Study Group, the Pediatric Diseases Working Party of the European Society for

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AU - Dalle, Jean Hugues

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