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Dendritic Cells Recovery after Umbilical Cord Blood Transplant Is Superior to Related Donor Transplant and Predicts Better Survival
S156
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Table 1 Patient demographics (n¼81) Patient characteristics
Table DC and pDC recovery after transplant based on stem cell source
Mobilization regimen G-CSF + plerixafor (N¼65) %
Age at BMT (yrs) Gender (M/F) KPS ( 80) NHL histology DLBCL MCL Status at BMT CR1 CR2 CR3 Conditioning regimen BuCy CBV
p-value G-CSF alone (N¼16) %
62 (34-77) 71/29 60
53 (43-74) 75/25 88
54 46
56 44
61 34 6
50 38 12
62 38
25 75
0.03 NS 0.04 NS
NS
0.01
196 Dendritic Cells Recovery after Umbilical Cord Blood Transplant Is Superior to Related Donor Transplant and Predicts Better Survival Waseem Touma 1, Qing Cao 2, Claudio G. Brunstein 3, Michael R. Verneris 4, Jeffrey S. Miller 5, Veronika Bachanova 6. 1 Hematology Oncology and Transplant, Internal Medicine Department, University of Minnesota, Minneapolis, MN; 2 Biostatistics and Bioinformatics, University of Minnesota, Minneapolis, MN; 3 Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN; 4 Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN; 5 Masonic Cancer Center, University of Minnesota, Minneapolis, MN; 6 University of Minnesota Medical Center, Minneapolis, MN Background: Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery on HCT outcomes. Methods: In landmark analysis, we studied patients with hematologic malignancies who were alive and in remission at 3 months after umbilical cord blood (UCB) and matched related donor (MRD) allo-HCT and have blood samples collected in a prospective immune reconstitution-monitoring protocol between 2006-2010. Peripheral blood was collected and analyzed for circulating DCs (HLA-DR+/lineage negative), mDCs (CD123-/CD11c+), and pDCs (CD123+/ CD11c-) pre-HCT and at 3, 12 months post HCT. DC reconstitution kinetics were compared between donor sources, and absolute number of DCs at 3 months were correlated with HCT outcomes. Results: Eighty-one patients (42 UCB and 39 MRD) with a 3-month blood sample were included in the analysis. Median age was 51 years (20-71). Most patients had acute leukemia (50%) or lymphoma (27%) and received reduced-intensity conditioning (61.0%) with cyclophosphamide, fludarabine, and total body radiation. Nearly all UCB grafts were composed of 2 units (93%). UCB recipients had higher total DC and pDC counts compared to MRD recipients at 3 and 12 months posttransplant (Table). Levels of mDC did not significantly differ. Overall survival (OS) and progression-free survival (PFS) at 2 years for UCB recipients with pDChigh (>median count of 4.7
Median cells/mm3 (range)
3 months
12 months
DCs
pDC
DCs
pDC
MRD UCB P
7.3 (0-180) 14.5 (0.2-65) 0.07
1.8 (0-88) 4.7 (0-35) 0.02
8.6 (0.4-37) 20.5 (1-48) 0.04
2.9 (0.2-10) 8.2 (0.3-20) <0.01
cell/mm3) and pDClow (<4.7 cell/mm3) counts at 3 months were 100% and 81% (p¼0.04) and 86% and 62% (p¼0.07), respectively. Relapse rates after UCB HCT in pDChigh vs. pDClow groups were 33% and 50% (p¼0.27). Levels of pDC at 3 months did not affect OS, PFS, relapse, or transplant-related mortality after MRD HCT. Low levels of pDC at 3 months correlated with higher incidence of acute grade II-IV graftversus-host disease (GVHD) in UCB recipients (pDClow 67% vs pDChigh 29%, p¼0.03) and MRD recipients (70% vs 11%, p<0.01), but was not associated with development of chronic GVHD. Conclusion: We found that total DC and pDC reconstitution after HCT is superior among UCB than MRD recipients. While pDC reconstitution is associated with less acute GVHD in both UCB and MRD HCT, our data suggest that UCB recipients with high levels of circulating pDCs exhibit a survival advantage at 2 years. These results warrant further investigations.
197 Adoptively-Transferred Epstein-Barr Virus (EBV)-Specific T Cells to Prevent or Treat EBV-Related Lymphoproliferative Disease in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients - a Single Center Experience Spanning 22 Years Ifigeneia Tzannou 1, Bilal Omer 2, Anastasia Papadopoulou 1, Ulrike Gerdemann 1, Adrian P. Gee 1, Bambi Grilley 1, Malcolm K. Brenner 1, Catherine M. Bollard 1, Ann M. Leen 2, Cliona M. Rooney 1, Helen E. Heslop 1, Colton Smith 3. 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX; 2 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Methodist Hospital Houston, Houston, TX; 3 St Jude Children’s Research Hospital, Memphis, TN EBV reactivation post-allogeneic HSCT can lead to the outgrowth of EBV-infected B cells and the development of post-transplant lymphoproliferative disease (EBV-PTLD). Since 1993 our group has investigated the use of adoptivelytransferred in vitro expanded EBV-specific T cells in HSCT patients as a means to prevent or treat these lymphomas and in a series of Phase I and II clinical trials we have assessed their safety and clinical benefits. The T cell products infused were generated using 3 different manufacturing methodologies - (i) EBV-transformed lymphoblastoid cell lines (EBVLCLs), (ii) plasmid-nucleofected dendritic cells and (iii) direct stimulation of PBMCs using overlapping peptide libraries. They were administered to either prevent (n¼162) or treat (n¼47) EBV reactivation/disease in allogeneic HSCT recipients ranging in age from 6 months to 63 years. Two hundred and nine patients have been infused with virus-specific T cells (VSTs) generated from the stem cell donor (n¼198) or a third party donor (n¼11) at doses
Abstracts / Biol Blood Marrow Transplant 22 (2016) S19eS481
Table 1 Patient demographics (n¼81) Patient characteristics
Table DC and pDC recovery after transplant based on stem cell source
Mobilization regimen G-CSF + plerixafor (N¼65) %
Age at BMT (yrs) Gender (M/F) KPS ( 80) NHL histology DLBCL MCL Status at BMT CR1 CR2 CR3 Conditioning regimen BuCy CBV
p-value G-CSF alone (N¼16) %
62 (34-77) 71/29 60
53 (43-74) 75/25 88
54 46
56 44
61 34 6
50 38 12
62 38
25 75
0.03 NS 0.04 NS
NS
0.01
196 Dendritic Cells Recovery after Umbilical Cord Blood Transplant Is Superior to Related Donor Transplant and Predicts Better Survival Waseem Touma 1, Qing Cao 2, Claudio G. Brunstein 3, Michael R. Verneris 4, Jeffrey S. Miller 5, Veronika Bachanova 6. 1 Hematology Oncology and Transplant, Internal Medicine Department, University of Minnesota, Minneapolis, MN; 2 Biostatistics and Bioinformatics, University of Minnesota, Minneapolis, MN; 3 Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN; 4 Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, MN; 5 Masonic Cancer Center, University of Minnesota, Minneapolis, MN; 6 University of Minnesota Medical Center, Minneapolis, MN Background: Dendritic cells (DCs) orchestrate immune responses after allogeneic hematopoietic cell transplantation (HCT). We studied the association of donor-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) recovery on HCT outcomes. Methods: In landmark analysis, we studied patients with hematologic malignancies who were alive and in remission at 3 months after umbilical cord blood (UCB) and matched related donor (MRD) allo-HCT and have blood samples collected in a prospective immune reconstitution-monitoring protocol between 2006-2010. Peripheral blood was collected and analyzed for circulating DCs (HLA-DR+/lineage negative), mDCs (CD123-/CD11c+), and pDCs (CD123+/ CD11c-) pre-HCT and at 3, 12 months post HCT. DC reconstitution kinetics were compared between donor sources, and absolute number of DCs at 3 months were correlated with HCT outcomes. Results: Eighty-one patients (42 UCB and 39 MRD) with a 3-month blood sample were included in the analysis. Median age was 51 years (20-71). Most patients had acute leukemia (50%) or lymphoma (27%) and received reduced-intensity conditioning (61.0%) with cyclophosphamide, fludarabine, and total body radiation. Nearly all UCB grafts were composed of 2 units (93%). UCB recipients had higher total DC and pDC counts compared to MRD recipients at 3 and 12 months posttransplant (Table). Levels of mDC did not significantly differ. Overall survival (OS) and progression-free survival (PFS) at 2 years for UCB recipients with pDChigh (>median count of 4.7
Median cells/mm3 (range)
3 months
12 months
DCs
pDC
DCs
pDC
MRD UCB P
7.3 (0-180) 14.5 (0.2-65) 0.07
1.8 (0-88) 4.7 (0-35) 0.02
8.6 (0.4-37) 20.5 (1-48) 0.04
2.9 (0.2-10) 8.2 (0.3-20) <0.01
cell/mm3) and pDClow (<4.7 cell/mm3) counts at 3 months were 100% and 81% (p¼0.04) and 86% and 62% (p¼0.07), respectively. Relapse rates after UCB HCT in pDChigh vs. pDClow groups were 33% and 50% (p¼0.27). Levels of pDC at 3 months did not affect OS, PFS, relapse, or transplant-related mortality after MRD HCT. Low levels of pDC at 3 months correlated with higher incidence of acute grade II-IV graftversus-host disease (GVHD) in UCB recipients (pDClow 67% vs pDChigh 29%, p¼0.03) and MRD recipients (70% vs 11%, p<0.01), but was not associated with development of chronic GVHD. Conclusion: We found that total DC and pDC reconstitution after HCT is superior among UCB than MRD recipients. While pDC reconstitution is associated with less acute GVHD in both UCB and MRD HCT, our data suggest that UCB recipients with high levels of circulating pDCs exhibit a survival advantage at 2 years. These results warrant further investigations.
197 Adoptively-Transferred Epstein-Barr Virus (EBV)-Specific T Cells to Prevent or Treat EBV-Related Lymphoproliferative Disease in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Recipients - a Single Center Experience Spanning 22 Years Ifigeneia Tzannou 1, Bilal Omer 2, Anastasia Papadopoulou 1, Ulrike Gerdemann 1, Adrian P. Gee 1, Bambi Grilley 1, Malcolm K. Brenner 1, Catherine M. Bollard 1, Ann M. Leen 2, Cliona M. Rooney 1, Helen E. Heslop 1, Colton Smith 3. 1 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX; 2 Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital Cancer Center, Methodist Hospital Houston, Houston, TX; 3 St Jude Children’s Research Hospital, Memphis, TN EBV reactivation post-allogeneic HSCT can lead to the outgrowth of EBV-infected B cells and the development of post-transplant lymphoproliferative disease (EBV-PTLD). Since 1993 our group has investigated the use of adoptivelytransferred in vitro expanded EBV-specific T cells in HSCT patients as a means to prevent or treat these lymphomas and in a series of Phase I and II clinical trials we have assessed their safety and clinical benefits. The T cell products infused were generated using 3 different manufacturing methodologies - (i) EBV-transformed lymphoblastoid cell lines (EBVLCLs), (ii) plasmid-nucleofected dendritic cells and (iii) direct stimulation of PBMCs using overlapping peptide libraries. They were administered to either prevent (n¼162) or treat (n¼47) EBV reactivation/disease in allogeneic HSCT recipients ranging in age from 6 months to 63 years. Two hundred and nine patients have been infused with virus-specific T cells (VSTs) generated from the stem cell donor (n¼198) or a third party donor (n¼11) at doses