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Late Cardiovascular Morbidity Following Pediatric Allogeneic Hematopoietic Cell Transplantation
S60
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
SESSION H: PEDIATRIC DISORDERS
55 Late Cardiovascular Morbidity Following Pediatric Allogeneic Hematopoietic Cell Transplantation Christine Duncan 1, Ruta Brazauskas 2, Jiaxing Huang 3, Bronwen E. Shaw 4, Navneet S. Majhail 5, Bipin N. Savani 6, Mary E.D. Flowers 7, Minoo Battiwalla 8, Kristen Beebe 9, Andrew C. Dietz 10, Christopher C. Dvorak 11, Roger Giller 12, David A. Jacobsohn 13, Morris Kletzel 14, Paul J. Martin 7, Eneida R. Nemecek 15, Julie-An M. Talano 16, Michael A. Pulsipher 17, K. Scott Baker 7. 1 Department of Pediatric Oncology, Boston Children’s Hospital and DanaFarber Cancer Institute, Boston, MA; 2 Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 3 Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI; 4 Department of Medicine, CIBMTR and Medical College of Wisconsin, Milwaukee, WI; 5 Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; 6 Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; 7 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 8 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; 9 Mayo Clinic Arizonia and Phoenix Children’s Hospital, Phoenix, AZ; 10 Pediatric Heme/Onc/BMT, Children’s Hospital Los Angeles, Los Angeles, CA; 11 Department of Pediatrics, University of California San Francisco Medical Center, San Francisco, CA; 12 Section of Hematology, Oncology and BMT, Department of Pediatrics, Children’s Hospital Colorado, Aurora, CO; 13 Division of Blood and Marrow Transplantation Center for Cancer and Blood Disorders, Children’s National Health System, Washington, DC; 14 Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; 15 Pediatric Blood & Marrow Transplant Program, Department of Pediatrics, Doernbecher Children’s Hospital and Oregon Health & Science University, Portland, OR; 16 Pediatric Hematology/Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI; 17 Children’s Hospital of Los Angeles, Los Angeles, CA Late cardiovascular (CV) complications are a leading cause of treatment-related morbidity and mortality in childhood cancer survivors. However, little is known regarding CV toxicity after hematopoietic cell transplant (HCT) in childhood. We analyzed late CV outcomes of 661 survivors of HCT for hematologic malignancy between 1995 and 2008 at 12 CIBMTR centers. Eligible patients survived disease-free a minimum of two years following allogeneic, myeloablative HCT for ALL, AML, CML, JMML, or MDS. CIBMTR data was supplemented with additional pre- and post-transplant data collection focused on CV late effects and potential risk factors. The median duration of follow-up was 73 months (range <1206 months) from the 2 year post-HCT time point. Overall and disease-free survival at 7 years conditioned on surviving the first 2 years were 94% (95% CI 92-96%) and 89% (95% CI 87-92). Causes of death included relapse (27%), GVHD (42%), new malignancy (13%) and infection (6%). 28 patients (4.2%) had at least one of the primary outcomes including coronary artery disease/myocardial infarction (0.15%), cerebrovascular accident (0.61%), cardiomyopathy (3.3%), and cardiac-related death (0.45%). Amongst patients who survived 2 years disease and CV event free the cumulative incidence of developing any
CV event within the next 5 years was 3% (95% CI 2-4%). Patients who received pre-HCT anthracycline chemotherapy (HR 4.67, p¼ 0.036), cranial radiation (HR 5.58, p<0.0001), or chest radiation (HR 2.18, p¼ 0.0087) were at greater risk for developing one of the primary outcomes. We investigated secondary outcomes of dyslipidemia, diabetes, and obesity. Dyslipidemia was present in 61% of patients at some time post-HCT and 13% at most recent contact. Pre-HCT anthracycline chemotherapy (HR 1.74, p< 0.0001) and chest radiation (HR 1.34, p¼ 0.0371) put survivors at greater risk for dyslipidemia. Diabetes/hyperglycemia was present in 8% of patients post-HCT. Body mass index (BMI) was calculated for patients aged > 2 years prior to the start of the conditioning regimen, at 2 years following HCT, and at most recent follow-up. Patients were classified as underweight, normal weight or overweight/obese based on CDC definitions. Overweight/ obese status was present in 63% of patients assessed prior to HCT conditioning (n¼389), 65% of patients at 2 years (n¼501), and 52% of patients at most recent evaluation (n¼622). This is compared to the 32% overweight/obese status in CDC reports of 2-19 year old healthy children. In conclusion, serious late CV complications are uncommon, but important toxicities following HCT for hematologic malignancy in childhood. However, the high incidence of dyslipidemias, diabetes and obesity is concerning and may increase the risk of CV disease over time. Addition follow-up and prospective studies of other potential risk-factors for late CV toxicity are needed.
56 The Impact of Neutrophil Engraftment on the Survival of Intubated Pediatric HCT Patients: A Pediatric Acute Lung Injury and Sepsis Network Study Jerelyn R. Moffet 1, Kris Michael Mahadeo 2, Julie Fitzgerald 3, Shira Gertz4, Mark Hall 5, Ashley Loomis Loomis 6, Jennifer McArthur 7, Mara Nitu8, Robert Tamburro 9, Christine Duncan 10, Courtney Rowan8. 1 Pediatric BMT Program, Duke University Medical Center, Durham, NC; 2 Pediatric Hematology, Oncology and Blood and Marrow Cell Transplantation, Children’s Hospital at Montefiore, Bronx, NY; 3 Children’s Hospital of Philadelphia, Philadelphia, PA; 4 Hackensack University Medical Center, Hackensack, NJ; 5 Intensive Care Unit, Nationwide Children’s Hospital, Columbus, OH; 6 Pediatric Critical Care, University of Minnesota, Minneapolis, MN; 7 Pediatric Critical Care, Medical College of Wisconsin, Milwaukee, WI; 8 Indiana University, Indianapolis, IN; 9 National Institutes of Health, Rockville, MD; 10 Department of Pediatric Oncology, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston, MA Objective: We investigated the role of neutrophil engraftment on survival of pediatric patients who received invasive ventilation for acute respiratory failure following hematopoietic cell transplant (HCT). Methods: This is a retrospective cohort study of allogeneic HCT recipients intubated for acute respiratory failure between January 1, 2009 and December 31, 2014. Patients were less 21 years at the time of HCT. All indications for HCT, stem cell source, donor type, and conditioning regimens were included. Institutions contributed the most recent, consecutive 25 patients who received mechanical ventilation during the study period. Patients intubated for surgical procedures were excluded. Results: 128 children from 12 centers were intubated within the first 60 days after HCT (median of 21 days;range 0-59). Acute respiratory failure was the primary indication for ICU admission occurring in 86.7% of patients. 41% of patients (n¼53) had not achieved neutrophil engraftment at the time
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
SESSION H: PEDIATRIC DISORDERS
55 Late Cardiovascular Morbidity Following Pediatric Allogeneic Hematopoietic Cell Transplantation Christine Duncan 1, Ruta Brazauskas 2, Jiaxing Huang 3, Bronwen E. Shaw 4, Navneet S. Majhail 5, Bipin N. Savani 6, Mary E.D. Flowers 7, Minoo Battiwalla 8, Kristen Beebe 9, Andrew C. Dietz 10, Christopher C. Dvorak 11, Roger Giller 12, David A. Jacobsohn 13, Morris Kletzel 14, Paul J. Martin 7, Eneida R. Nemecek 15, Julie-An M. Talano 16, Michael A. Pulsipher 17, K. Scott Baker 7. 1 Department of Pediatric Oncology, Boston Children’s Hospital and DanaFarber Cancer Institute, Boston, MA; 2 Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 3 Department of Medicine, CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI; 4 Department of Medicine, CIBMTR and Medical College of Wisconsin, Milwaukee, WI; 5 Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; 6 Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; 7 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 8 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; 9 Mayo Clinic Arizonia and Phoenix Children’s Hospital, Phoenix, AZ; 10 Pediatric Heme/Onc/BMT, Children’s Hospital Los Angeles, Los Angeles, CA; 11 Department of Pediatrics, University of California San Francisco Medical Center, San Francisco, CA; 12 Section of Hematology, Oncology and BMT, Department of Pediatrics, Children’s Hospital Colorado, Aurora, CO; 13 Division of Blood and Marrow Transplantation Center for Cancer and Blood Disorders, Children’s National Health System, Washington, DC; 14 Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; 15 Pediatric Blood & Marrow Transplant Program, Department of Pediatrics, Doernbecher Children’s Hospital and Oregon Health & Science University, Portland, OR; 16 Pediatric Hematology/Oncology and BMT, Medical College of Wisconsin, Milwaukee, WI; 17 Children’s Hospital of Los Angeles, Los Angeles, CA Late cardiovascular (CV) complications are a leading cause of treatment-related morbidity and mortality in childhood cancer survivors. However, little is known regarding CV toxicity after hematopoietic cell transplant (HCT) in childhood. We analyzed late CV outcomes of 661 survivors of HCT for hematologic malignancy between 1995 and 2008 at 12 CIBMTR centers. Eligible patients survived disease-free a minimum of two years following allogeneic, myeloablative HCT for ALL, AML, CML, JMML, or MDS. CIBMTR data was supplemented with additional pre- and post-transplant data collection focused on CV late effects and potential risk factors. The median duration of follow-up was 73 months (range <1206 months) from the 2 year post-HCT time point. Overall and disease-free survival at 7 years conditioned on surviving the first 2 years were 94% (95% CI 92-96%) and 89% (95% CI 87-92). Causes of death included relapse (27%), GVHD (42%), new malignancy (13%) and infection (6%). 28 patients (4.2%) had at least one of the primary outcomes including coronary artery disease/myocardial infarction (0.15%), cerebrovascular accident (0.61%), cardiomyopathy (3.3%), and cardiac-related death (0.45%). Amongst patients who survived 2 years disease and CV event free the cumulative incidence of developing any
CV event within the next 5 years was 3% (95% CI 2-4%). Patients who received pre-HCT anthracycline chemotherapy (HR 4.67, p¼ 0.036), cranial radiation (HR 5.58, p<0.0001), or chest radiation (HR 2.18, p¼ 0.0087) were at greater risk for developing one of the primary outcomes. We investigated secondary outcomes of dyslipidemia, diabetes, and obesity. Dyslipidemia was present in 61% of patients at some time post-HCT and 13% at most recent contact. Pre-HCT anthracycline chemotherapy (HR 1.74, p< 0.0001) and chest radiation (HR 1.34, p¼ 0.0371) put survivors at greater risk for dyslipidemia. Diabetes/hyperglycemia was present in 8% of patients post-HCT. Body mass index (BMI) was calculated for patients aged > 2 years prior to the start of the conditioning regimen, at 2 years following HCT, and at most recent follow-up. Patients were classified as underweight, normal weight or overweight/obese based on CDC definitions. Overweight/ obese status was present in 63% of patients assessed prior to HCT conditioning (n¼389), 65% of patients at 2 years (n¼501), and 52% of patients at most recent evaluation (n¼622). This is compared to the 32% overweight/obese status in CDC reports of 2-19 year old healthy children. In conclusion, serious late CV complications are uncommon, but important toxicities following HCT for hematologic malignancy in childhood. However, the high incidence of dyslipidemias, diabetes and obesity is concerning and may increase the risk of CV disease over time. Addition follow-up and prospective studies of other potential risk-factors for late CV toxicity are needed.
56 The Impact of Neutrophil Engraftment on the Survival of Intubated Pediatric HCT Patients: A Pediatric Acute Lung Injury and Sepsis Network Study Jerelyn R. Moffet 1, Kris Michael Mahadeo 2, Julie Fitzgerald 3, Shira Gertz4, Mark Hall 5, Ashley Loomis Loomis 6, Jennifer McArthur 7, Mara Nitu8, Robert Tamburro 9, Christine Duncan 10, Courtney Rowan8. 1 Pediatric BMT Program, Duke University Medical Center, Durham, NC; 2 Pediatric Hematology, Oncology and Blood and Marrow Cell Transplantation, Children’s Hospital at Montefiore, Bronx, NY; 3 Children’s Hospital of Philadelphia, Philadelphia, PA; 4 Hackensack University Medical Center, Hackensack, NJ; 5 Intensive Care Unit, Nationwide Children’s Hospital, Columbus, OH; 6 Pediatric Critical Care, University of Minnesota, Minneapolis, MN; 7 Pediatric Critical Care, Medical College of Wisconsin, Milwaukee, WI; 8 Indiana University, Indianapolis, IN; 9 National Institutes of Health, Rockville, MD; 10 Department of Pediatric Oncology, Boston Children’s Hospital and Dana-Farber Cancer Institute, Boston, MA Objective: We investigated the role of neutrophil engraftment on survival of pediatric patients who received invasive ventilation for acute respiratory failure following hematopoietic cell transplant (HCT). Methods: This is a retrospective cohort study of allogeneic HCT recipients intubated for acute respiratory failure between January 1, 2009 and December 31, 2014. Patients were less 21 years at the time of HCT. All indications for HCT, stem cell source, donor type, and conditioning regimens were included. Institutions contributed the most recent, consecutive 25 patients who received mechanical ventilation during the study period. Patients intubated for surgical procedures were excluded. Results: 128 children from 12 centers were intubated within the first 60 days after HCT (median of 21 days;range 0-59). Acute respiratory failure was the primary indication for ICU admission occurring in 86.7% of patients. 41% of patients (n¼53) had not achieved neutrophil engraftment at the time