Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

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Abstract

Purpose: To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)–based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). Methods and Materials: From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57 years (median, 25 years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75 mg/m2) followed by 13.2 Gy TBI given in 8 twice-daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2 cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15 cGy/min; 56%) or low-dose-rate (LDR; ≤15 cGy/min; 44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. Results: IPS developed in 42 patients (21%) between 4 and 73 days (median, 16 days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29% vs 10%; P <.01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95% confidence interval, 1.2-5.3; P =.01), and this led to inferior 1-year overall survival (60% vs 76%; P =.01) and increased 1-year nonrelapse mortality (28% vs 15%; P =.02). Conclusions: TBI dose rates ≤15 cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.

Original languageEnglish (US)
Pages (from-to)180-189
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2019

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pneumonia
transplantation
leukemias
Whole-Body Irradiation
Cell Transplantation
Pneumonia
Leukemia
dosage
irradiation
Large Deployable Reflector
cells
conditioning
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
pulmonary functions
Particle Accelerators
Survival
mortality
Lung Injury
infectious diseases

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{cfeafbda85d04c1dbc42c17e8d7a4d8d,
title = "Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation",
abstract = "Purpose: To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)–based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). Methods and Materials: From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57 years (median, 25 years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120 mg/kg) with (68{\%}) or without fludarabine (75 mg/m2) followed by 13.2 Gy TBI given in 8 twice-daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2 cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15 cGy/min; 56{\%}) or low-dose-rate (LDR; ≤15 cGy/min; 44{\%}) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. Results: IPS developed in 42 patients (21{\%}) between 4 and 73 days (median, 16 days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29{\%} vs 10{\%}; P <.01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95{\%} confidence interval, 1.2-5.3; P =.01), and this led to inferior 1-year overall survival (60{\%} vs 76{\%}; P =.01) and increased 1-year nonrelapse mortality (28{\%} vs 15{\%}; P =.02). Conclusions: TBI dose rates ≤15 cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.",
author = "Gao, {Robert W.} and Weisdorf, {Daniel J} and {De For}, {Todd E} and Ehler, {Eric D} and Dusenbery, {Kathryn E}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ijrobp.2018.09.002",
language = "English (US)",
volume = "103",
pages = "180--189",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Influence of Total Body Irradiation Dose Rate on Idiopathic Pneumonia Syndrome in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

AU - Gao, Robert W.

AU - Weisdorf, Daniel J

AU - De For, Todd E

AU - Ehler, Eric D

AU - Dusenbery, Kathryn E

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)–based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). Methods and Materials: From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57 years (median, 25 years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75 mg/m2) followed by 13.2 Gy TBI given in 8 twice-daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2 cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15 cGy/min; 56%) or low-dose-rate (LDR; ≤15 cGy/min; 44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. Results: IPS developed in 42 patients (21%) between 4 and 73 days (median, 16 days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29% vs 10%; P <.01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95% confidence interval, 1.2-5.3; P =.01), and this led to inferior 1-year overall survival (60% vs 76%; P =.01) and increased 1-year nonrelapse mortality (28% vs 15%; P =.02). Conclusions: TBI dose rates ≤15 cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.

AB - Purpose: To determine the relationship between dose rate and other factors in the development of idiopathic pneumonia syndrome (IPS) in patients with acute lymphoblastic leukemia or acute myeloid leukemia who are undergoing total body irradiation (TBI)–based myeloablative conditioning for allogeneic hematopoietic cell transplantation (HCT). Methods and Materials: From 2006 to 2016, 202 patients with acute leukemia (111 acute lymphoblastic leukemia, 91 acute myeloid leukemia) ranging in age from 1 to 57 years (median, 25 years) underwent allogeneic HCT at University of Minnesota. Pretransplantation conditioning included cyclophosphamide (120 mg/kg) with (68%) or without fludarabine (75 mg/m2) followed by 13.2 Gy TBI given in 8 twice-daily fractions of 1.65 Gy over 4 days. Dose rate varied based on linear accelerator availability and ranged from 8.7 to 19.2 cGy/min. Patients were stratified by receipt of high-dose-rate (HDR; >15 cGy/min; 56%) or low-dose-rate (LDR; ≤15 cGy/min; 44%) TBI for all 8 fractions. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. Results: IPS developed in 42 patients (21%) between 4 and 73 days (median, 16 days) after transplantation. HDR TBI was associated with a higher rate of IPS compared with LDR TBI (29% vs 10%; P <.01). On multiple regression analysis, HDR remained a significant predictor of IPS (hazard ratio, 2.6; 95% confidence interval, 1.2-5.3; P =.01), and this led to inferior 1-year overall survival (60% vs 76%; P =.01) and increased 1-year nonrelapse mortality (28% vs 15%; P =.02). Conclusions: TBI dose rates ≤15 cGy/min reduce the risk of posttransplantation IPS and improve overall survival. LDR TBI should be strongly considered as an easily implemented parameter to improve the safety of pretransplantation TBI-based conditioning.

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