John L. Jefferies3, Thomas D. Ryan 3, Michelle Cash 3,. Seth Joshua Rotz 1, Abigail Pate1, Michael D. Taylor 3, Javier. El-Bietar 1, Kasiani C. Myers 1, Gregory ...
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host disease (GvHD) prophylaxis included cyclosporine with methotrexate/prednisone and mycophenolate. Campath (anti-CD52) was used to reduce graft rejection and GvHD in all patients. Long-term outcomes data was analyzed in patients greater than one year post-transplantation. Three patients were excluded from the study: two patients died early post-transplant and one patient was less than one year after transplantation. Of the remaining 19 patients, long-term organ function evaluations were available for 16 patients with a median follow-up of 5.5 years (range: 1.2-8.4 years). The median left ventricular (LV) shortening fraction (SF) was 37.5% (range: 30-48%) with median LV ejection fraction (EF) 63% (range: 55-78%). The median forced expiratory volume in one second (FEV1) on spirometry for patients able correctly perform the maneuver (n¼13) was 86% (range: 67-119%) of predicted values. The median corrected 24-hour creatinine clearance or nuclear glomerular filtration rate was 97.8 mL/min/1.73m2 (range: 39.0-173.7 mL/min/1.73m2). Endocrine dysfunction was identified in nine patients with four patients having more than one dysfunction; endocrinopathies included short stature (n¼5), Graves’ disease/other hyperthyroidism (n¼4), gonadal failure (n¼2), premature puberty (n¼1), delayed bone age (n¼1), and osteoporosis (n¼1). Three patients were noted to have special learning disability changes post-HSCT: Attention Deficit Hyperactivity Disorder (n¼2) or learning disability not well defined (n¼1). A fourth patient suffered severe brain injury following intractable seizures after transplant resulting in global developmental delay. Longterm organ function after HSCT in patients with CGD is acceptable and encouraging even in the setting of severe lung disease prior to transplantation.
336 Pericardial Effusion Following Hematopoietic Cell Transplantation in Children Is Associated with Increased Risk of Mortality Kelly Cox 1, Rajesh Punn 2, Elizabeth Schnorr3, Sandhya Kharbanda 4. 1 Pediatrics, Stanford University, Palo Alto, CA; 2 1000 Welch Road, Stanford University, Palo Alto, CA; 3 1000 Welch Road, Stanford University, palo Alto, CA; 4 Pediatric Stem Cell Transplantation, Stanford University, Palo Alto, CA Background: Hematopoietic cell transplantation (HCT) is curative for many pediatric malignant and non-malignant disorders. Limited published reports describe cardiac complications of HCT. Pericardial effusion (PEF) has recently been reported to be a significant risk factor for increased morbidity following HCT. The exact incidence, risk factors, and prognostic effect of PEF in HCT patients are not well described. Methods: We performed a retrospective chart review under an IRB approved protocol, of 119 pediatric HCT patients over a 3 year period. Data was collected on variables as shown in the table below. Statistical analysis was performed using Wilcoxon rank-sum non-parametric test, Fisher’s exact test for all categorical risk factors, and Freeman-Halton test for multiple comparisons of categorical risk factors. Results: The overall incidence of PEF was 21%. Time of diagnosis of effusion ranged from 11 days after transplant to 175 days (mean 67, median 63). Overall, patients with PEF had a statistically significant higher likelihood of death when compared to patients without a PEF (p ¼ 0.0071). Risk factors for development of PEF included unrelated donor transplants (p¼0.005) and cord blood as stem cell source (p¼0.005), while HLA mismatching approached significance (p¼0.055).
Age (yrs) Sex
Median Female Male Disease Malignant Non-Malignant Stem Cell Bone Marrow Source Cord Blood Peripheral Blood Stem Cells Donor Autologous Haplo-identical Match-Related Donor Unrelated Donor HLA Matched Mismatched Conditioning Myeloablative Other Acute GVHD Yes No Chronic Yes GVHD No Death Yes No
No Pericardial Effusion
Pericardial Effusion
6 75 19 69 25 57 18 19
9 (80%) (20%) (73%) (27%) (61%) (19%) (20%)
9 (36%) 16 (64%) 15 (60%) 10 (40%) 10 (40%) 13 (52%) 2 (8%)
18 (19%) 1 (1%) 36 (38%) 39 (41%) 48 (63%) 28 (37%) 84 (89%) 10 (11%) 28 (30%) 66 (70%) 18 (19%) 76 (81%) 16 (17%) 78 (83%)
2 (8%) 0 (0%) 3 (12%) 20 (80%) 9 (39%) 14 (61%) 20 (80%) 5 (20%) 12 (48%) 13 (52%) 7 (28%) 18 (72%) 11 (44%) 14 (56%)
Additionally, 8/25 (32%) patients required pericardiocentesis. Interestingly, pericardial fluid testing in 4/8 patients was noted to be positive for either a Herpes virus (HHV6, EBV, CMV) and/or Adenovirus, and three of these patients died. This retrospective chart review demonstrates an increased risk of mortality in children with PEF following HCT. Prospective studies are needed in the field to further elucidate the risk factors for development of hemodynamically significant PEF including viral infections as potential etiologies.
337 Detection of Cardiac Abnormalities in Critically Ill Stem Cell Transplant Recipients Using Structured Echocardiographic Screening Christopher E. Dandoy 1, Zachary Paff 2, Russel Hirsch 3, John L. Jefferies3, Thomas D. Ryan 3, Michelle Cash 3, Seth Joshua Rotz 1, Abigail Pate1, Michael D. Taylor 3, Javier El-Bietar 1, Kasiani C. Myers 1, Gregory Wallace 1, Adam S. Nelson 1, Adam Lane 1, Stella M. Davies 1, Sonata Jodele 1, Ranjit Chima 2. 1 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 2 Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 3 Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH Introduction: We have observed pulmonary hypertension (PH), pericardial effusions and left ventricular systolic dysfunction (LVSD) in multiple cases of critically ill stem cell transplant (SCT) recipients. Notably these findings were in patients diagnosed with transplant associated thrombotic microangiopathy (TA-TMA). Given our observations we implemented structured echocardiographic screening for all SCT recipients needing admission to the pediatric intensive care unit (PICU). Methods: We implemented our screening protocol in January 2012. All SCT recipients admitted to the PICU with TA-TMA, respiratory distress/hypoxia, or shock were screened on admission and every 1-2 weeks thereafter. Echocardiography findings requiring intervention and/or further screening included: elevated right ventricular (RV) pressure, LVSD, and moderate to large pericardial effusion (PEF). Patients with elevated RV pressure were stratified as
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
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Figure. Echocardiography findings of pediatric stem cell transplant patients admitted to the pediatric intensive care unit (PICU) (n¼70). Figure 1.
being “at risk” for, or having PH if their right ventricular (RV) pressure was estimated at 35-49% or >50% of systolic blood pressure, respectively. LVSD was defined as an ejection fraction < 55%. All echocardiograms were compared to data from routine pre-transplant baseline echocardiograms. Results: Over a 2-year period 70 SCT recipients needed PICU admission, the majority having undergone SCT for malignancy or immune deficiency (32 and 23 patients respectively). Almost all had undergone allogeneic transplant from unrelated donors with 66% having TA-TMA. The median PRISM score on PICU admission was 11 (7-14). Echo abnormalities requiring intervention and/or further screening were found in 50% (35/70) of patients. Twenty-four (34%) were noted to have elevated RV pressure; of these, 20% (14/70) were arPH while 14% (10/70) had PH. All patients with PH were treated with pulmonary vasodilators. Depressed LV function was noted in 31% (22/70), 15 (68%) received inotropic support. Moderate to large pericardial effusions were present in 13% (9/70) of patients with two-thirds needing pericardial drain placement. The majority of patients with elevated RV pressure and moderate to large pericardial effusion had TA-TMA. Conclusions: Echo abnormalities are common in critically ill SCT recipients. Utilization of routine echo screening allows for early detection of cardiac complications thereby allowing early intervention in this high-risk cohort.
Background: Left ventricular systolic dysfunction (LVSD) is a known complication of stem cell transplant (SCT) occurring in 10-20% of all patients afterwards. The IL-33/ST2 complex is upregulated in cardiomyocytes and cardiac fibroblasts in response to injury and has been shown to be cardioprotective. However, excessive Soluble Suppression of Tumorigenicity 2 (sST2), released in response to cell damage, blocks the beneficial effects of IL-33 and leads to increased cardiac inflammation and fibrosis. Therefore, sST2 is a strong predictor of acute decompensated heart failure and is known as a novel biomarker of cardiac stress. Methods: We compared peri-SCT sST2 levels in patients that developed LVSD by day +100 to those that did not. Serum sST2 levels were obtained at baseline, then weekly from the start of their preparative regimen through day +21. Echocardiography screening was performed on all SCT patients at baseline and at days +30 and +100. Patients were classified as
338 Early Soluble ST2 Elevation Predicts Future Left Ventricular Systolic Dysfunction after Stem Cell Transplant Christopher E. Dandoy 1, Thomas D. Ryan 2, John L. Jefferies2, Russel Hirsch 2, Adam Lane 1, Ranjit Chima 3, Seth Joshua Rotz 1, Michael D. Taylor 2, Abigail Pate1, Ryan Moore 4, Javier El-Bietar 1, Kasiani C. Myers 1, Gregory Wallace 1, Adam S. Nelson 1, Zachary Paff 3, Stella M. Davies 1, Sonata Jodele 1. 1 Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 2 Heart Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 3 Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; 4 Division of Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH
Figure 2.
