Hematologic Cancer

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MO_44_2517 - Determinants of Idiopathic Pneumonia Syndrome in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Transplantation with Total Body Irradiation-Based Myeloablative Conditioning

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Determinants of Idiopathic Pneumonia Syndrome in Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Transplantation with Total Body Irradiation-Based Myeloablative Conditioning
R. W. Gao, D. J. Weisdorf, T. E. DeFor, E. Ehler, and K. E. Dusenbery; University of Minnesota Medical School, Minneapolis, MN

Purpose/Objective(s): The purpose of this study was to determine the radiation parameters associated with the development of idiopathic pneumonia syndrome (IPS) in acute lymphoblastic leukemia (ALL) patients undergoing total body irradiation (TBI)-based myeloablative conditioning for allogeneic hematopoietic stem cell transplantation (HSCT).

Materials/Methods: From 2006 to 2016, 148 ALL patients ranging in age from <1 to 55 years (median: 16) underwent allogeneic HSCT at a single institution. Conditioning included cyclophosphamide (120 mg/kg) on days -6 and -5 with or without (n=42) fludarabine (75 mg/m2) on day -5 followed by TBI (13.2 Gy in 8 twice daily fractions at least 6 hours apart) on days -4 to -1. Stem cells were infused on day 0. Donors were matched sibling (n=43), single cord blood (n=45), or double cord blood (n=60). All patients received graft-versus-host disease (GVHD) prophylaxis. TBI was delivered via linac with right and left lateral fields prescribed to midplane at mid-pelvis with low (6 MV) or high (18 or 25 MV) energy photon beams. Compensators were used to keep the dose along the axis of the patient within 10% of the prescription dose and, depending on lung thickness, a lung compensator was used on 44 patients. Due to variation in available dose rates on different linac machines, patients were treated with either low dose rate TBI (median 10.62 cGy/min, range 9.3-14.97) for all 8 fractions (n=52), high dose rate TBI (median 16.81 cGy/min, range 15.27-19.23) for all fractions (n=50) or mixed dose rates (median 13.89 cGy/min, range 8.67-17.98) (n=46). IPS was defined as pulmonary toxicity based on clinical symptoms, radiographic evidence, and/or pulmonary function tests without evidence of infection at the time of the event. Radiation parameters considered in a risk factor analysis were dose rate, lung thickness, presence of a lung compensator, and average time interval between TBI fractions. Regression analysis was stratified by donor types and their associated conditioning and GVHD prophylaxis.

Results: IPS developed in a total of 49 patients (33%). On univariate analysis, significant predictors of IPS included the associated factors of double cord blood donor (P<.01), use of fludarabine conditioning (P<.01), and exclusion of methotrexate in GVHD prophylaxis (P<.01). IPS incidence was lowest in patients treated with low dose rate TBI (19/70 = 27%) compared to those treated with high dose rate TBI (30/78 = 38%) and mixed dose rates (16/46 = 35%) (P=.08). In a multivariate regression analysis, no factors were independently significant predictors of IPS. There was a trend towards increased risk of IPS in patients treated with high dose rates (HR 1.7; CI 0.9-3.3; P=.14) and patients treated with mixed dose rates (HR 1.4; CI 0.7-2.9; P=.38) compared to those treated with low dose rates.

Conclusion: In ALL patients receiving TBI-based myeloablative conditioning for HSCT, using dose rates of 10-11 cGy/min may reduce the risk of IPS.

Author Disclosure: R.W. Gao: None. D.J. Weisdorf: None. T.E. DeFor: None. E. Ehler: Employee; University of Minnesota. K.E. Dusenbery: None.

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