Robert A. Krance 4, Ngoc-Yen Nguyen 7, Caridad Martinez 4. 1 Baylor College of ... Hospital, Houston, TX; 4 Center for Cell and Gene Therapy,. Baylor College ...
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
histologic findings despite the common practice of endoscopic evaluation. Methods: Thirty-nine patients underwent 49 separate upper and/or lower endoscopies for gastrointestinal symptoms. A pathologist blinded to the patients’ clinical staging reviewed biopsy slides for the following histologic signs of GVHD: number of apoptotic bodies per high powered field (400x), maximum number of apoptotic bodies per gland, and the percent of glands with apoptotic bodies. All patients had clinical GVHD staging documented weekly during the study period. The maximum reported stage of intestinal GVHD was used 7 days prior to or after the date of the procedure for correlative analysis. The average was used for subjects with multiple measurements. To accommodate this averaging, a weighted least squares logistic regression model was used with weights for each subject equal to the number measurements taken. Results: Endoscopies were performed a median of 58 days (range 22 e 202) post-HSCT. Univariate analysis performed on patients with stages 2-4 clinical gut GVHD showed a statistically significant association with all 3 histologic signs of GVHD found in the colon (Table 1). Although this trend was also seen in the stomach, this association did not reach statistical significance. Patients with a higher assigned clinical stage of gut GVHD at the time of endoscopy were found to have more histologic signs indicative of glandular apoptosis (Table 2). This observation was seen in both the colon and stomach. Conclusions: Our study showed good correlation of clinical gut GVHD stage with histologic findings. Future prospective studies will be needed to determine a more accurate GVHD grading system based on developing clinicopathologic criteria.
Table 1 Univariate analysis of patients with stage 2-4 gut GVHD colon (n¼45)
Odds Ratio
pvalue
Number of apoptotic bodies per high powered field Maximum Number of apoptotic bodies per gland Percent of glands w/ apoptotic bodies stomach (n ¼ 38) Number of apoptotic bodies per high powered field Maximum Number of apoptotic bodies per gland Percent of glands w/ apoptotic bodies
1.2 1.5 1.04
0.0073 0.0071 0.0063
1.16 1.39 1.05
0.129 0.202 0.192
Table 2 Histologic findings of the colon and stomach in patients with varying stages of GVHD Stage N Mean (median) value of apoptotic bodies per high powered field
colon
0 1 2 3 4 Stomach 0 1 2 3 4
20 3.5 (4.5) 2 4.7 (0.9) 12 9 (9.8) 9 10.8 (7.8) 2 12 (8.5) 19 1.8 (2.5) 1 6 (-) 11 4.8 (4.4) 5 3.2 (4.4) 2 0 (0)
Mean (median) value of apoptotic bodies per gland
Mean (median) percent of glands w/ apoptotic bodies
1.7 2.2 3.4 4.1 4 1 1 2.1 1.2 0
9.3 31.5 31.1 39.1 45 2.9 20 9.1 24.4 0
(2.2) (2.2) (3) (2.8) (1.4) (1) (-) (2) (.8) (0)
(13.4) (16.3) (28.4) (27.2) (35.4) (6.6) (-) (10.1) (43.1) (0)
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342 Fludarabine, Antithymocyte Globulin and Low Dose Cyclophosphamide As Conditioning Regimen for Allogeneic Stem Cell Transplantation in Children with Severe Aplastic Anemia Mohammed F. Essa 1, Reem Al Sudairy 2, Sameera Al Afghani 3, Mohammad Jarrar Dr. 4, Abdulrahman S. Alsultan 1, 5. 1 Pediatric Haematology/Oncology/SCT, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children’s Hospital, NGHA, Riyadh, Saudi Arabia; 2 Pediatric Haematology/Oncology/SCT, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children’s Hospital, NGHA, Riyadh, Saudi Arabia; 3 King Fahad Specialist Hospital, Dammam, Saudi Arabia; 4 Pediatric Haematology/Oncology/SCT, King Saud bin Abdulaziz University for Health Sciences, King Abdullah Specialized Children’s Hospital, NGHA, Riyadh, Saudi Arabia; 5 King Saud University, Riyadh, Saudi Arabia There is no standard conditioning regimen for children with severe aplastic anemia (SAA) and short telomeres. Here, we summarize our experience in ten patients with SAA and short (n¼6) or undetermined telomeres (n¼4) who have been transplanted with HLA-matched related hematopoietic donor cells. All patients were transplanted using the following conditioning that included fludarabine (35mg/m2) on day -6 to -2, cyclophosphamide (40mg/kg) on day -6 and -5, and rabbit antithymocyte globulin (thymoglobulin) (2.5mg/kg) on day -5 to -2. GVHD prophylaxis was mycophenolate mofetil and cyclosporine. All ten patients (6 females and 4 males) with an average age of 7 (range 0.8-13.3 years) had bone marrow failure as a predominate feature and except for one patient who had short stature, mental retardation and a brain MRI with bilateral encephalomalacia there were no abnormal physical findings, specifically no classical features of DC i.e. nail dystrophy, leukoplakia, and skin pigmentation. All donors had normal physical examination and normal CBC. History of consanguinity was reported in all patients except one. Patients had normal chromosomal fragility test. All ten patients engrafted successfully, median time to neutrophil engraftment was 20 (range, 11-29 days) and platelet engraftment 22 (range, 13-42 days). Median infused nucleated cell dose was 3.2 (range, 1.6-4.4 X108/kg) and CD34 cell dose was 6.6 (range, 1.1-13.1 X106/kg). Median donor chimerism was 94% for myeloid cells and 63% for T cells around 90 days post HSCT. None of our patients had acute GVHD and one patient had mild classic chronic GVHD of the skin that was controlled with topical therapy. Two patients had late graft failure. The first patient had pancytopenia one year post transplant with loss of donor chimerism and underwent successful second transplant using fludarabine, ATG, and melphalan. The second patient had progressive pancytopenia starting six months post transplant despite having full donor chimerism. All patients are alive with median follow-up duration of 917 days (range, 40-1413 days). In conclusion, fludarabine-based conditioning using reduced dose cyclophosphamide (80mg/kg) seems safe and feasible in our SAA patients with shorter telomeres. Larger study is needed to confirm our results and to determine the optimal dose of cyclophosphamide.
343 Hematopoietic Stem Cell Transplantation in Fanconi Anemia: Experience Pediatric Transplant Unit Marcela Estupinan, Mauricio Chaparro. HSCT Unit, Fundacion HOMI Hospital de la Misericordia, Bogota, Colombia
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Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
SUMMARY Introduction: Fanconi anemia is a genetic disease phenotypically heterogeneous, low frequency, characterized by congenital malformations, progressive predisposition to malignancy and bone marrow failure. To describe the results of a cohort of pediatric patients undergoing hematopoietic stem cell transplantation in a pediatric facility. Materials and Methods: Between August 2007 and April 2015 16 patients with Fanconi anemia were taken to transplant. 14 patients for bone marrow failure, 1 patient for diagnosis of ALL and Fanconi Anemia and one patient with myelodysplasia type refractory cytopenia with monosomy 7. The latter two patients were excluded from analysis. 5 patients received identical related donor transplantation and 9 patients underwent to umbilical cord blood transplant. Results: The overall survival for the entire cohort is 50%. By separating the source of the graft, match related donor (MRD) vs alternative donor (AD-UCBT) the probability of survival is significantly higher in patients who received transplants from MRD(60%) vs AD-UCBT (44.5%). Because of the high incidence of primary graft failure changes were made in the preparative regimen and the criteria for selecting the unit of umbilical cord blood. Conclusions: Hematopoietic stem cell transplantation in Fanconi anemia is feasible in our country. Early referral to transplant improves the chance of survival in this population. Increasing doses of cyclophosphamide and optimizing the selection criteria of the unit cord blood allowed increased survival. Keywords: Fanconi anemia, hematopoietic stem cells, cell transplantation.
344 IVIG Prophylaxis in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplant: A Retrospective Analysis of Monthly Intravenous Immunoglobulin Infusion vs. IgG Level Based Dosing Jennifer Foster 1, W. Susan Cheng 2, Stacey Shubert 3, Kathryn Leung 4, Swati Naik 4, Stephen Gottschalk5, Carl Allen 4, Nabil Ahmed 4, Ghadir Sasa 4, Meena Hegde 4, Bilal Omer 4, Ann M. Leen 4, Helen E. Heslop 6, Malcolm K. Brenner 4, Robert A. Krance 4, Ngoc-Yen Nguyen 7, Caridad Martinez 4. 1 Baylor College of Medicine, Texas Children’s Hospital, Houston, TX; 2 Benedictine University, Lisle, IL; 3 Texas Childrens Hospital, Houston, TX; 4 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Methodist Hospital Houston, Houston, TX; 5 Pathology and Immunology, Baylor College of Medicine, Houston, TX; 6 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX; 7 Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Houston, TX Background: After allogeneic hematopoietic stem cell transplant (HSCT) patients have an increased susceptibility to infections, thought to be due in part to hypogammaglobulinemia. Thus, prophylactic administration of intravenous immunoglobulins (IVIG) has been administered to patients after HSCT as standard of care. In 2012 our institution amended our practice of administering IVIG prophylactically every 28 days to administering IVIG to maintain trough IgG levels of >500mg/dL. Objective: This study compares the viral infection rate between dosing IVIG by IgG trough levels versus by routine monthly administration in pediatric patients after HSCT.
Table 1 Viral Infection Rate
BK Virus Ebstein-Barr virus Respiratory Syncytial Virus Human Herpes Virus HHV-6 HHV-7 Adenovirus Cytomegalovirus JC virus Herpes Simplex Virus Parvovirus Parainfluenza Rotavirus Varicella Influenza Norovirus Overall Infection, n (%)
Group 1 n (%)
Group 2 n (%)
23 (46%) 12 (24%) 3 (6%) 17 (34%) 5 (10%)
26 (26%) 36 (36%) 5 (5%) 31 (31%) 1 (1%)
18 15 3 2 2 2 1 1 0 0 47
30 24 1 2 4 5 0 0 4 4 90
(36%) (30%) (6%) (4%) (4%) (4%) (2%) (2%) (0%) (0%) (94%)
(30%) (24%) (1%) (2%) (4%) (5%) (0%) (0%) (4%) (4%) (90%)
P-value 0.014 0.137 0.066 0.71 0.008 0.458 0.430 0.073 0.474 1.000 0.784 0.156 0.156
