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Impact of Early Bloodstream Infection (BSI) By Vancomycin-Resistant Enterococci (VRE) on Long-Term Transplant Outcomes
Abstracts / Biol Blood Marrow Transplant 23 (2017) S18–S391
reliable identification of clinically relevant bacteria. We found that the oral bacterial species changed from Streptococcus sp, Prevotella sp, or Veillonella sp to CNS or Candida sp after HSCT. Our results suggest that oral microbial substitution possibly underlies high-grade OM after HSCT.
233 Impact of Early Bloodstream Infection (BSI) By Vancomycin-Resistant Enterococci (VRE) on Long-Term Transplant Outcomes Genovefa A. Papanicolaou 1, Celalettin Ustun 2, Jo-Anne H. Young 3, Min Chen 4, Soyong Kim 4,5, Kwang Woo Ahn 4,6, Jeffery J. Auletta 7, Caroline A. Lindemans 8, Krishna V. Komanduri 9, Marcie L. Riches 10. 1 Memorial Sloan Kettering Cancer Center, New York, NY; 2 Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN; 3 Division of Infectious Disease, Department of Medicine, University of Minnesota, Minneapolis, MN; 4 CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 5 Division of Biostatisitcs, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 6 Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 7 Hematology, Oncology and Bone Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH; 8 Pediatric Blood and Bone Marrow Transplantation Program, Wilhelmina Children’s Hospital, Utrecht, Netherlands; 9 Adult Stem Cell Transplant Program, Sylvester Comprehensive Cancer Center, Miami, FL, University of Miami, Miami, FL; 10 University of North Carolina Hospitals Bone Marrow and Stem Cell Transplant Clinic, North Carolina Cancer Hospital, Chapel Hill, NC Background: Despite evolution of transplant supportive care practices to improve post-transplant outcomes, early bloodstream infection (BSI) by vancomycin-resistant enterococci (VRE) associates with poor outcomes following allogeneic hematopoietic cell transplantation (alloHCT). We sought to examine the association between VRE BSI and other BSI on overall survival (OS), relapse, non-relapse mortality (NRM), and disease-free survival (DFS) following alloHCT. Methods: Patients receiving alloHCT for AML, ALL and MDS from 2008-12 were identified using the CIBMTR database and were retrospectively analyzed. BSI between 10 days before (D-10) and 100 days after (D100) transplant were analyzed as three mutually exclusive groups: VRE-BSI, Other-BSI, and no BSI (Controls). Univariate outcomes for OS, DFS, NRM, and relapse were compared among the three groups. Cox models examined the impact of VRE-BSI on survival and other transplant outcomes. Results: Median age was 47 years (range < 1-79). Of 7128 patients, 59% (4205) received peripheral blood (PB), 15% (1069) bone marrow (BM) and 26% (1853) cord blood (UCB) allograft, after myeloablative (74%, 5274) or RIC/NMA (26%, 1853) conditioning. By D100, 2656 (37%) patients had experienced either VRE (258, 3.6%) or other (2398, 33.6%) BSI. Median time to first BSI was 11 days post-HCT. Patients with VRE-BSI had more advanced leukemia, received more UCB allografts, and had more delayed engraftment. VRE BSI had lower OS and DFS, mainly due to higher NRM compared to other BSI or controls (Table 1). Risk of death for VRE BSI was 2.9-fold greater than for controls and 2-fold greater than other BSI. In multivariable analyses, variables associated with increased risk of death were: older age at transplant, more advanced disease stage, comorbidity index ≥3, CMV seropositivity, use of alternative donor (mismatched unrelated,
S183
Table 1 Impact of VRE on Transplant outcomes
Variables OS No BSI VRE BSI Other BSI DFS No BSI VRE BSI Other BSI Relapse No BSI VRE BSI Other BSI NRM No BSI VRE BSI Other BSI
99% CI
99% CI
Overall
Lower Limit
Upper Limit
P-value
N
RR
4472 258 2398
1.00 2.86 1.43
2.23 1.29
3.66 1.59
<.0001 <.0001
4386 247 2348
1.00 2.33 1.28
1.85 1.16
2.94 1.41
<.0001 <.0001
4386 247 2348
1.00 1.07 .98
.74 .87
1.56 1.11
.6265 .7507
4399 247 2352
1.00 4.73 1.79
3.60 1.56
6.21 2.05
<.0001 <.0001
P-value
<.0001
<.0001
.8460
<.0001
UCB, or other donor), lower performance score, longer time from diagnosis to transplant, diagnosis of acute leukemia, and allogeneic HCT before 2010. Conclusion: Despite low incidence (<5%), VRE BSI has greater negative impact than other BSI on HCT outcomes. Therefore, optimizing VRE prevention and treatment strategies are critical to improving transplant outcomes.
234 HIV-Specific T CELLS Expanded from HIV+ and HIV-Naive Donors Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic HSCT Shabnum Patel 1, Sharon Lam 1, Conrad Russell Y. Cruz 2, Julia A.M. Sung 3, David A. Margolis 3, Richard F. Ambinder 4, Elizabeth J. Shpall 5, Catherine M. Bollard 6. 1 Children’s National Medical Center, Washington, DC; 2 Children’s National Health System, Washington, DC; 3 Genetic Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC; 4 Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; 5 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 6 Center for Cancer and Immunology Research, Children’s National Medical Center, Washington, DC The efficacy of HIV-specific T-cell therapy has been relatively modest likely due to the restricted specificity of the adoptively transferred CD8+ T cell clones. We hypothesized that ex vivo expanded, broadly HIV-specific CD8+ and CD4+ T cells (HXTCs) could be expanded from patients on antiretrovirals (ARVs), as well as HIV negative adult and cord blood (dHXTCs) donors using a non-HLA restricted approach for the treatment of HIV+ individuals after autologous or allogeneic HSCT. We expanded autologous HXTCs from HIV+ subjects under NCT02208167. To extend this approach to the allogeneic HSCT setting, we expanded dHXTCs from HIV naive adult and cord blood donors (n = 16). IFNγ ELISPOT showed dHXTCs were specific against Gag (mean = 331.25SFC/105 cells) and Nef (mean = 242.63SFC/10 5 cells) vs irrelevant antigen (mean = 13SFC/105cells). dHXTCs produced pro-inflammatory responses (P < .05) to gag/nef stimulation, as determined by levels of TNF-α, IL-2, IL-6, IL-8, and perforin. Importantly, dHXTCs derived from both adult (P = .0004) and cord blood (P = .0003) were able to suppress HIV replication more than
reliable identification of clinically relevant bacteria. We found that the oral bacterial species changed from Streptococcus sp, Prevotella sp, or Veillonella sp to CNS or Candida sp after HSCT. Our results suggest that oral microbial substitution possibly underlies high-grade OM after HSCT.
233 Impact of Early Bloodstream Infection (BSI) By Vancomycin-Resistant Enterococci (VRE) on Long-Term Transplant Outcomes Genovefa A. Papanicolaou 1, Celalettin Ustun 2, Jo-Anne H. Young 3, Min Chen 4, Soyong Kim 4,5, Kwang Woo Ahn 4,6, Jeffery J. Auletta 7, Caroline A. Lindemans 8, Krishna V. Komanduri 9, Marcie L. Riches 10. 1 Memorial Sloan Kettering Cancer Center, New York, NY; 2 Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN; 3 Division of Infectious Disease, Department of Medicine, University of Minnesota, Minneapolis, MN; 4 CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 5 Division of Biostatisitcs, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 6 Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI; 7 Hematology, Oncology and Bone Marrow Transplant, Nationwide Children’s Hospital, Columbus, OH; 8 Pediatric Blood and Bone Marrow Transplantation Program, Wilhelmina Children’s Hospital, Utrecht, Netherlands; 9 Adult Stem Cell Transplant Program, Sylvester Comprehensive Cancer Center, Miami, FL, University of Miami, Miami, FL; 10 University of North Carolina Hospitals Bone Marrow and Stem Cell Transplant Clinic, North Carolina Cancer Hospital, Chapel Hill, NC Background: Despite evolution of transplant supportive care practices to improve post-transplant outcomes, early bloodstream infection (BSI) by vancomycin-resistant enterococci (VRE) associates with poor outcomes following allogeneic hematopoietic cell transplantation (alloHCT). We sought to examine the association between VRE BSI and other BSI on overall survival (OS), relapse, non-relapse mortality (NRM), and disease-free survival (DFS) following alloHCT. Methods: Patients receiving alloHCT for AML, ALL and MDS from 2008-12 were identified using the CIBMTR database and were retrospectively analyzed. BSI between 10 days before (D-10) and 100 days after (D100) transplant were analyzed as three mutually exclusive groups: VRE-BSI, Other-BSI, and no BSI (Controls). Univariate outcomes for OS, DFS, NRM, and relapse were compared among the three groups. Cox models examined the impact of VRE-BSI on survival and other transplant outcomes. Results: Median age was 47 years (range < 1-79). Of 7128 patients, 59% (4205) received peripheral blood (PB), 15% (1069) bone marrow (BM) and 26% (1853) cord blood (UCB) allograft, after myeloablative (74%, 5274) or RIC/NMA (26%, 1853) conditioning. By D100, 2656 (37%) patients had experienced either VRE (258, 3.6%) or other (2398, 33.6%) BSI. Median time to first BSI was 11 days post-HCT. Patients with VRE-BSI had more advanced leukemia, received more UCB allografts, and had more delayed engraftment. VRE BSI had lower OS and DFS, mainly due to higher NRM compared to other BSI or controls (Table 1). Risk of death for VRE BSI was 2.9-fold greater than for controls and 2-fold greater than other BSI. In multivariable analyses, variables associated with increased risk of death were: older age at transplant, more advanced disease stage, comorbidity index ≥3, CMV seropositivity, use of alternative donor (mismatched unrelated,
S183
Table 1 Impact of VRE on Transplant outcomes
Variables OS No BSI VRE BSI Other BSI DFS No BSI VRE BSI Other BSI Relapse No BSI VRE BSI Other BSI NRM No BSI VRE BSI Other BSI
99% CI
99% CI
Overall
Lower Limit
Upper Limit
P-value
N
RR
4472 258 2398
1.00 2.86 1.43
2.23 1.29
3.66 1.59
<.0001 <.0001
4386 247 2348
1.00 2.33 1.28
1.85 1.16
2.94 1.41
<.0001 <.0001
4386 247 2348
1.00 1.07 .98
.74 .87
1.56 1.11
.6265 .7507
4399 247 2352
1.00 4.73 1.79
3.60 1.56
6.21 2.05
<.0001 <.0001
P-value
<.0001
<.0001
.8460
<.0001
UCB, or other donor), lower performance score, longer time from diagnosis to transplant, diagnosis of acute leukemia, and allogeneic HCT before 2010. Conclusion: Despite low incidence (<5%), VRE BSI has greater negative impact than other BSI on HCT outcomes. Therefore, optimizing VRE prevention and treatment strategies are critical to improving transplant outcomes.
234 HIV-Specific T CELLS Expanded from HIV+ and HIV-Naive Donors Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic HSCT Shabnum Patel 1, Sharon Lam 1, Conrad Russell Y. Cruz 2, Julia A.M. Sung 3, David A. Margolis 3, Richard F. Ambinder 4, Elizabeth J. Shpall 5, Catherine M. Bollard 6. 1 Children’s National Medical Center, Washington, DC; 2 Children’s National Health System, Washington, DC; 3 Genetic Medicine, University of North Carolina-Chapel Hill, Chapel Hill, NC; 4 Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD; 5 Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 6 Center for Cancer and Immunology Research, Children’s National Medical Center, Washington, DC The efficacy of HIV-specific T-cell therapy has been relatively modest likely due to the restricted specificity of the adoptively transferred CD8+ T cell clones. We hypothesized that ex vivo expanded, broadly HIV-specific CD8+ and CD4+ T cells (HXTCs) could be expanded from patients on antiretrovirals (ARVs), as well as HIV negative adult and cord blood (dHXTCs) donors using a non-HLA restricted approach for the treatment of HIV+ individuals after autologous or allogeneic HSCT. We expanded autologous HXTCs from HIV+ subjects under NCT02208167. To extend this approach to the allogeneic HSCT setting, we expanded dHXTCs from HIV naive adult and cord blood donors (n = 16). IFNγ ELISPOT showed dHXTCs were specific against Gag (mean = 331.25SFC/105 cells) and Nef (mean = 242.63SFC/10 5 cells) vs irrelevant antigen (mean = 13SFC/105cells). dHXTCs produced pro-inflammatory responses (P < .05) to gag/nef stimulation, as determined by levels of TNF-α, IL-2, IL-6, IL-8, and perforin. Importantly, dHXTCs derived from both adult (P = .0004) and cord blood (P = .0003) were able to suppress HIV replication more than