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Healthcare Utilization and Cost Associated with Cytomegalovirus Infection Among Pediatric Allogeneic Hematopoietic Cell Transplant Recipients.
Abstracts / Biol Blood Marrow Transplant 25 (2019) S290 S442
expressed markers for both central and effector memory phenotype (3.5§0.6% CD45RO+CD62L+ and 48.1§1.9% + CD45RO CD62L ), with minimal expression of PD-1, Tim-3, Lag-3, and CTLA-4. Notably, both CD4+ and CD8+ subsets were polyfunctional comprising ZIKV-directed T-cell populations, which secreted multiple cytokines (16.7§0.6% CD4+IFN-g +TNFa+ and 7.4§0.4% CD8+IFN-g +TNF-a+) as measured by intracellular cytokine staining. Moreover, multiplex cytokine assay demonstrated specific production of IFN-g (928.7§239.8 pg/mL), TNF-a (1495.5§453.3 pg/mL), IL-2 (38.2§8.4 pg/mL), and GMCSF (67.0§22.2 pg/mL) in response to ZIKV antigens. Importantly, ZIKV-specific T-cells selectively killed autologous monocytes infected with ZIKV confirming functionality of this unique T cell therapeutic. Epitope mapping using peptide arrays in IFN-g ELISpot identified several novel HLA class I or class II-restricted epitopes within NS1, which is essential for viral replication and immune evasion. Conclusions: Our findings demonstrate that it is feasible to generate potent ZIKV-specific T-cells from a variety of cell sources including virus na€ıve donors for future clinical use in an “off the shelf’ setting.
Figure 1. Specificity of ZIKV-specific T-cells against ZIKV antigens
521 Healthcare Utilization and Cost Associated with Cytomegalovirus Infection Among Pediatric Allogeneic Hematopoietic Cell Transplant Recipients. Sonal Rastogi MPH1, Angela Ricci MD2, Zhezhen Jin PhD3, Prakash Satwani MD2. 1 Columbia university, New York, NY; 2 Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, NY; 3 Biostatistics, Columbia University, New York, NY Understanding the cost and healthcare utilization associated with cytomegalovirus (CMV) treatment is particularly important as new alternative agents for CMV prevention and treatment such as letermovir and anti-CMV cytotoxic T lymphocytes
S349
become available. Literature on the impact of CMV-related hospitalization in allogeneic hematopoietic cell transplant (alloHCT) pediatric patients is limited. We hypothesized that CMV infections post-alloHCT will result in increased length of stay (LOS) in hospital and higher healthcare costs. The aim of this study was to determine healthcare utilization and outcomes of CMV-related hospitalization in alloHCT patients using a single-center clinical database. This was a retrospective study of 240 children ages 3 months to 21 years old who were transplanted between 2005 and 2016. Impact of CMV-related length of stay and total healthcare costs were quantified. Factors associated with prolonged CMV viremia (>25 days) were also examined. The median age of patients was 9.5 years old. In at risk CMV patients, the incidence of CMV viremia was 38%, the median time to onset was 33 days (range 0-292 days), and the median time to resolution was 25 days (range 3-148 days). The median LOS in the first year post-alloHCT for patients with viremia was higher compared to those without viremia (101 days [range 25-319 days] vs 72 days [range 26-354 days], p<0.001). The median cost of transplant admission also significantly differed between patients with and without CMV viremia ($183,308 [range 13,126-1,471,698] vs $149,661 [range 63,025-1,149,261], p=0.015). In the regression analyses, the unadjusted association between CMV infection and LOS was 27.4 days (p=0.003). In multivariable analysis, patients with CMV infection had an average of 23.3 days (p=0.004) longer LOS compared to patients without infection [Table] and added hospital costs of US$45,443 (p=0.162) compared to patients without CMV infection. In multivariable analysis, alemtuzumab was associated with CMV viremia >25 days (p=0.027). In conclusion, CMV viremia is associated with prolonged LOS and higher healthcare costs and indicates a need for improved and cost-effective CMV prevention strategies. Further study into patient outcomes and costs in alloHCT pediatric populations is needed.
Multivariable linear regression analysis of the association between CMV infection and length of hospitalization, only risk factors with p<0.1on univariable analysis included. Length of stay Days (SE) P-value CMV infection Negative 1 Positive 23.3 (7.90) 0.004 Age at transplant -0.514 (0.599) 0.39 Transplant type Related 1 Unrelated 6.34 (8.91) 0.48 Cell source Cord Blood 1 Unmanipulated PBSC -32.3 (12.2) 0.009 Bone marrow -26.7 (10.5) 0.012 Other sources -20.3 (11.9) 0.09 HLA Match Mismatch 1 Full match -22.6 (8.03) 0.005 aGVHD 45.4 (7.37) <0.001
522 High Dose Cidofovir and IVIG Combination Treatment for BK Virus Hemorrhagic Cystitis, a Case Series in Three Post Allogeneic Transplant Patients Sami Brake MD. Adult bone marrow transplant, spectrum Health, grand rapids, MI Introduction: BK polyomavirus (BKPyV) is a common cause of hemorrhagic cystitis during the early post engraftment phase.
expressed markers for both central and effector memory phenotype (3.5§0.6% CD45RO+CD62L+ and 48.1§1.9% + CD45RO CD62L ), with minimal expression of PD-1, Tim-3, Lag-3, and CTLA-4. Notably, both CD4+ and CD8+ subsets were polyfunctional comprising ZIKV-directed T-cell populations, which secreted multiple cytokines (16.7§0.6% CD4+IFN-g +TNFa+ and 7.4§0.4% CD8+IFN-g +TNF-a+) as measured by intracellular cytokine staining. Moreover, multiplex cytokine assay demonstrated specific production of IFN-g (928.7§239.8 pg/mL), TNF-a (1495.5§453.3 pg/mL), IL-2 (38.2§8.4 pg/mL), and GMCSF (67.0§22.2 pg/mL) in response to ZIKV antigens. Importantly, ZIKV-specific T-cells selectively killed autologous monocytes infected with ZIKV confirming functionality of this unique T cell therapeutic. Epitope mapping using peptide arrays in IFN-g ELISpot identified several novel HLA class I or class II-restricted epitopes within NS1, which is essential for viral replication and immune evasion. Conclusions: Our findings demonstrate that it is feasible to generate potent ZIKV-specific T-cells from a variety of cell sources including virus na€ıve donors for future clinical use in an “off the shelf’ setting.
Figure 1. Specificity of ZIKV-specific T-cells against ZIKV antigens
521 Healthcare Utilization and Cost Associated with Cytomegalovirus Infection Among Pediatric Allogeneic Hematopoietic Cell Transplant Recipients. Sonal Rastogi MPH1, Angela Ricci MD2, Zhezhen Jin PhD3, Prakash Satwani MD2. 1 Columbia university, New York, NY; 2 Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, NY; 3 Biostatistics, Columbia University, New York, NY Understanding the cost and healthcare utilization associated with cytomegalovirus (CMV) treatment is particularly important as new alternative agents for CMV prevention and treatment such as letermovir and anti-CMV cytotoxic T lymphocytes
S349
become available. Literature on the impact of CMV-related hospitalization in allogeneic hematopoietic cell transplant (alloHCT) pediatric patients is limited. We hypothesized that CMV infections post-alloHCT will result in increased length of stay (LOS) in hospital and higher healthcare costs. The aim of this study was to determine healthcare utilization and outcomes of CMV-related hospitalization in alloHCT patients using a single-center clinical database. This was a retrospective study of 240 children ages 3 months to 21 years old who were transplanted between 2005 and 2016. Impact of CMV-related length of stay and total healthcare costs were quantified. Factors associated with prolonged CMV viremia (>25 days) were also examined. The median age of patients was 9.5 years old. In at risk CMV patients, the incidence of CMV viremia was 38%, the median time to onset was 33 days (range 0-292 days), and the median time to resolution was 25 days (range 3-148 days). The median LOS in the first year post-alloHCT for patients with viremia was higher compared to those without viremia (101 days [range 25-319 days] vs 72 days [range 26-354 days], p<0.001). The median cost of transplant admission also significantly differed between patients with and without CMV viremia ($183,308 [range 13,126-1,471,698] vs $149,661 [range 63,025-1,149,261], p=0.015). In the regression analyses, the unadjusted association between CMV infection and LOS was 27.4 days (p=0.003). In multivariable analysis, patients with CMV infection had an average of 23.3 days (p=0.004) longer LOS compared to patients without infection [Table] and added hospital costs of US$45,443 (p=0.162) compared to patients without CMV infection. In multivariable analysis, alemtuzumab was associated with CMV viremia >25 days (p=0.027). In conclusion, CMV viremia is associated with prolonged LOS and higher healthcare costs and indicates a need for improved and cost-effective CMV prevention strategies. Further study into patient outcomes and costs in alloHCT pediatric populations is needed.
Multivariable linear regression analysis of the association between CMV infection and length of hospitalization, only risk factors with p<0.1on univariable analysis included. Length of stay Days (SE) P-value CMV infection Negative 1 Positive 23.3 (7.90) 0.004 Age at transplant -0.514 (0.599) 0.39 Transplant type Related 1 Unrelated 6.34 (8.91) 0.48 Cell source Cord Blood 1 Unmanipulated PBSC -32.3 (12.2) 0.009 Bone marrow -26.7 (10.5) 0.012 Other sources -20.3 (11.9) 0.09 HLA Match Mismatch 1 Full match -22.6 (8.03) 0.005 aGVHD 45.4 (7.37) <0.001
522 High Dose Cidofovir and IVIG Combination Treatment for BK Virus Hemorrhagic Cystitis, a Case Series in Three Post Allogeneic Transplant Patients Sami Brake MD. Adult bone marrow transplant, spectrum Health, grand rapids, MI Introduction: BK polyomavirus (BKPyV) is a common cause of hemorrhagic cystitis during the early post engraftment phase.