bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Donor Epstein-Barr Virus (EBV) Seropositivity Affect Recipient's Risk of Graft Versus Host Disease (GVHD) in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)?
Authors: Atilla Erden , Kaplan Esmanur , Ataca Atilla Pinar , Toprak Selami Kocak , Topcuoglu Pervin , Akan Hamdi 
Published: November 2019

Abstract
Introduction:
EBV seropositivity in general population is 80%. Reactivation of latent infection in pre-transplant seropositive patients causes post-transplant lenfoproliferative disease (PTLD) following Allo-HSCT. The effect of donor EBV positivity on recipient's risk of graft versus host disease is not clear. Our aim is to present EBV seroprevalence and PTLD incidence as well as demonstrating the relation of EBV seropositivity with GVHD.
Patients and Methods:
A total of 364 allogeneic stem cell transplant recipients and donors were evaluated retrospectively from 2006 to 2015. During Allo-HSCT preparation procedures all recipients and donors were serologically tested. EBV specific IgG (VCA-IgG, EBNAIgG, EA-IgG) and IgM (VCA-IgM) antibodies were determined by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). All patients were followed for reactivation.
Results:
EBV IgG positivity was detected in 338 of recipients (92.8%) and 283 of donors (77.7%). There was no statistically difference detected between related or unrelated transplants. The mean age was 37 (range 16-67). 217 recipients were male (60%). 295 (81%) patients were transplanted for malign hematological diseases. The majority of patients were grafted from full-matched related donors (258, 71%). The most common source of stem cell was peripheral blood in 299 patients (82%) followed by bone-marrow in 56 patients (15%), bone-marrow plus peripheral blood in 9 patients (3%). 273 (75%) patients received myeloablative conditioning regimen. All patients received prophylactic acyclovir (in related transplants 400mg 3 times daily, in un-related transplants 800mg 3 times daily) starting from conditioning and up to three months posttranplant period. One pretransplant seropositive 26 year-old aplastic anemia patient had PTLD with EBV IgM positivity within 3 months posttransplant. He received 4 cycles of rituximab and prednisolone and achieved complete response. Three patients had EBV IgM positivity in posttransplant 4, 9 and 24th months with symptoms of infectious mononucleosis. The seropositivity resolved without treatment. Acute GVHD developed in 223 patients (61%) whereas chronic GVHD was detected in 285 (78%) of patients. The incidence of acute GVHD was similar when donor was EBV seropositive compared to seronegative (78% vs 22%, p=0.72). Chronic GVHD incidence was similar between donor EBV seropositive group compared to seronegative group (80% vs 20%, P=0.199).
Conclusion:
EBV seropositivity is common detected in 92.8% of our allo-HSCT recipient cohort. Donor EBV status did not have an effect on developing acute or chronic GVHD.

Disclosures
No relevant conflicts of interest to declare.
Zoledronic Acid Boosts γδ T-Cell Activity in Children Receiving αβ+ T and CD19+ CELL-Depleted Grafts from a Haplo-Identical DONOR
Authors: Barbarito Giulia , Airoldi Irma , Zorzoli Alessia , Bertaina Alice , Petretto Andrea , Inglese Elvira , Lavarello Chiara , Brescia Letizia Pomponia , De Angelis Biagio , Tripodi Gino , Merli Pietro , Moretta Lorenzo , Locatelli Franco 
Published: November 2019

Abstract
A new method of graft manipulation based on physical removal of αβ+ T cells and CD19+ B cells, leaving mature NK cells and γδ T cells in the graft, has been recently developed for HLA-haploidentical HSCT. We demonstrated that γδ T cells collected from transplanted patients are endowed with capacity of killing leukemia cells after ex vivo treatment with zoledronic acid (ZOL). Thus, we hypothesized that infusion of ZOL in patients receiving this type of graft, may boost γδ T cell cytotoxic activity against leukemia cells.
Thirty-three patients were treated with ZOL every 28 days at least twice. γδ T cells before and after ZOL treatments were studied till at least 7 months after HSCT by high-resolution mass spectrometry, flow-cytometry, and degranulation assay.
Proteomic analysis of γd T cells purified from patients showed that, starting from the first infusion, ZOL caused up-regulation of proteins involved in activation processes and immune response, paralleled by down-regulation of proteins involved in proliferation. These findings are consistent with an induction of Vδ2 cell differentiation, paralleled by increased cytotoxicity of both Vδ1 and Vδ2 cells against primary leukemia blasts. Furthermore, a proteomic signature was identified for each individual ZOL treatment. Patients given 3 or more ZOL infusions had a better probability of survival in comparison to those given 1 or 2 treatments.
In conclusion,ZOL influences Vδ2 cell activity, determines a specific proteomic signature and enhances anti-leukemia activity, this potentially resulting into an increased anti-tumor effect.

Disclosures
No relevant conflicts of interest to declare.
Busulfan-Cyclophosphamide Worsens Peripheral Gvhd While Fludarabine-Busulfan Results in Wide Bone Marrow Involvement in a Murine Model of Acute Gvhd
Authors: He Xin , Xu Xiaojun , Ye Yongbin , Liu Qifa 
Published: November 2019

Abstract
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and A proper conditioning regimen is vital to stop the development of aGVHD. To provide a platform for the study of aGVHD and evaluate the impact of different conditioning regimens, we established a murine aGVHD model that simulates the clinical situation and can be conditioned with Busulfan-Cyclophosphamide (BU-Cy) and Fludarabine-BU (Flu-BU). In our study, BALB/c mice were conditioned with BU-Cy or Flu-BU and transplanted with 2×107 bone marrow cells and 2×107splenocytes from either allogeneic (C57BL/6) or syngeneic (BALB/c) donors. The allogeneic recipients conditioned with BU-Cy had shorter survival (P<0.05) and more severe hepatic and intestinal clinical manifestations and pathological changes associated with increased INF-γ expression and diminished IL-4 expression in serum compared to allogeneic recipients conditioned with Flu-BU. Meanwhile increased donor-derived T-cell infiltration and impaired bone marrow B-cell development could be seen in the aGVHD mice conditioned with Flu-BU. Our study showed that the conditioning regimen with BU-Cy resulted in more severe peripheral aGVHD, while the Flu-BU regimen was associated with aGVHD with wide bone marrow involvement.

Disclosures
No relevant conflicts of interest to declare.
Late Reversal of Dominance after Dual Cord Blood Transplantation
Authors: Berg Mary , Gutman Jonathan A , Vinson Leslie , Draper Nicole 
Published: November 2019

Abstract
Background: Most adult patients are transplanted with two cord units to enhance engraftment after stem cell transplantation. Previous reports have demonstrated that one cord blood unit becomes dominant in the recipient and the other unit regresses. Complete chimerism with the dominant unit is achieved in >90% of patients by day +100 after transplantation. We report a case of a patient who initially demonstrated engraftment with one cord blood unit, but months later was found to be engrafted with the other unit.
A 30 year old man underwent dual cord blood transplantation for Acute Myeloid Leukemia in June 2015. The cords had identical HLA types and were both 6/10 match to the patient. During his recovery, he experienced engraftment syndrome, mild sinusoidal obstruction syndrome, Enterococcus bacteremia, and prolonged count recovery. A bone marrow biopsy done on day +77 demonstrated no evidence of disease; chimerism studies demonstrated 95% donor cells (CD3: 44% cord 1, 56% cord 2; CD33: 100% cord 2; CD56: 16% cord 1, 84% cord 2, see table). He was noted to have converted his blood type from his original O-Positive to B-Positive. He returned to his home and was not seen at our institution for several months. When he returned for follow-up on day +244, he was found to have a blood type of A-Negative. Testing with a new specimen confirmed this finding. Chimerism studies were performed to evaluate the status of the two donors in his peripheral blood on day +306.
Methods: A PCR-based STR assay was done on peripheral blood or bone marrow using the PromegaPowerPlex 16 HS System. The WBC populations were manipulated to create sub-populations enriched for CD3, CD33, and CD56, respectively.
Results: No significant recipient DNA was found in any of the specimens. On day +29, Cord 1 dominated in the CD56 cell population, but Cord 2 dominated in the CD3 and CD33 populations. On day +77, Cord 2 dominated in all cell populations, but Cord 1 still represented nearly half (44%) of CD3 cells. On day +306, Cord 1 dominated all cell populations.
Conclusion: The change in the patient's blood type is consistent with reversal of the dominance of the cord blood units received by this patient. Only one other case of this sort of reversal has been reported. This is not consistent with previously published data that the cord unit with higher CD3 chimerism as early as day +14 becomes the long-term engrafting unit.
Table Table.

Disclosures
No relevant conflicts of interest to declare.
An Innovative in Vitro Potency Assay Designed to Predict the Fate of Chimeric Antigen Receptors Modified T Cell Therapy Post Infusion in ALL
Authors: Wang Junxia , Dudley Mark , Choquette Therese , Jeschke Margit , Rutjens Erik , Kassim Sadik 
Published: November 2019

Abstract
Background: Chimeric antigen receptors modified T cells (CARTs) are T cells engineered to express tumor CARs that consist of T cell activation domains coupled to anti-tumor antigen single-chain variable fragments. Upon binding of tumor antigen to anti-tumor antigen antibody fragments on CART cells, the intracellular T-cell receptor CD3-zeta chain signaling domain induces T cell activation. The activated T cells undergo proliferation, cytokines release and tumor cells killing in an antigen-dependent manner. A number of CART-cell immunotherapies are now advancing to pivotal trials, however, little is known about how to characterize these cellular products before administration; one such gap relates to cell therapy product potency. Methods: Within this context, we developed a novel potency assay that quantifies the in vitro proliferative capacity of CART cell therapy products. We tested this assay using CART cell therapy products from patients with pediatric acute lymphoblastic leukemia (pedALL) and diffuse large B cell lymphoma (DLBCL). Results: In 40 CART products from pedALL patients evaluated for proliferation, and 37 products demonstrated significant (20% higher than background) proliferation. Overall, in vitro proliferation was correlated the expansion of the cell product in the patient after infusion. 23 CART products from DLBCL patients were analyzed, and 20 demonstrated significant specific in vitro proliferation. A strong correlation between in vitro proliferation and cell growth has been observed for the DLBCL patient samples. Conclusions: These data suggest that in vitro proliferation is a highly informative potency assay that may help predict product efficacy and safety of CAR T cell therapies.

Disclosures
Wang: Novartis: Employment. Dudley:Novartis: Employment. Choquette:Novartis: Employment. Jeschke:Novartis: Employment. Rutjens:Novartis: Employment. Kassim:Novartis: Employment.
HLA-Mismatched Stem Cell Microtransplantation Compared to Matched-Sibling Donor Transplantation for Acute Myeloid Leukemia in First Complete Remission
Authors: Liu Limin , Qiu Huiying , Tang XiaoWen , Han Yue , Miao Miao , Fu Chengcheng , Jin Zhengming , Zhu Mingqing , Wu Depei 
Published: November 2019

Abstract
HLA-mismatched stem cell microtransplantation is a new transplantation which has been reported in recent years. We treated 41 patients with intermediate- or high-risk acute myelogenous leukemia (AML) in first complete remission (CR1) undergoing HLA-mismatched stem cell microtransplantation and compared with 56 patients undergoing HLA-matched sibling donor (MSD) transplantation at the same period in our center from July 2012 to August 2015. The estimated leukemia-free survival (LFS) at 2-year was 65.6% ± 9.5% in the MSD group and 27.6% ± 14.0% in the microtransplantation group (P = 0.011). The estimated overall survival (OS) at 2-year was 73.6% ± 8.6% in the MSD group and 46.2% ± 15.6% in the microtransplantation group (P = 0.056). The cumulative incidences of relapse were 22.5% and 58.7% among MSD and microtransplantation groups (P = 0.011). The cumulative incidence of nonrelapse mortality was 7.8% in MSD group, and no nonrelapse mortality in microtransplantation group (P = 0.265). Hematopoietic recovery time was shorter in the microtransplantation group than MSD group (P < 0.05). The infection rate of MSD group was higher than in the microtransplantation group (91.1% vs 75.6%, P = 0.037). The preliminary results suggest that LFS of microtransplantation is inferior to MSD transplantation and a trend toward the OS of microtransplantation was lower than MSD transplantation for intermediate- or high-risk AML in CR1.

Disclosures
No relevant conflicts of interest to declare.
A Comparison Study Between Allogeneic and Autologous Hematopoietic Stem Cell Transplant for High-Risk Peripheral T-Cell Lymphomas (PTCL)
Authors: Huang Haiwen , Wang Qiangli , Jin Zhengming , Tang XiaoWen , Qiu Huiying , Fu Chengcheng , Han Yue , Miao Miao , Chang Huirong , Sun Aining , Wu Depei 
Published: November 2019

Abstract
Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL).
Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively.
Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (13-55) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 with ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 with angioimmunoblastic T-cell lymphoma (AITL). Twenty-one (21/60) received allo-HSCT and thirty-nine patients (39/60) received auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients were partial remission (PR) and 18/60 patients were not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients received auto-HSCT. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients received auto-HSCT. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS for auto-HSCT and allo-HSCT were 61% and 60% (P = 0.724). The 5-year OS for auto-HSCT and allo-HSCT were 62% and 61% (P = 0.724). There were no statistically significant differences between the auto-HSCT and allo-HSCT. And the cumulative TRM of allo-HSCT and auto-HSCT were 16.5% and 0 (P=0.250) within 5-years after transplantation. At the end of the last follow-up, 7 patients relapsed in auto-HSCT group and 2 patients relapsed in allo-HSCT group, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively.
Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. The effect of allo-HSCT may be better for NR patients.

Disclosures
No relevant conflicts of interest to declare.
Evolving Criteria for Donor Selection for Transplants in Acute Myeloid Leukemia
Authors: Wang Yu , Liu qi-Fa , Wu de-Pei , Huang Xiao-jun 
Published: November 2019

Abstract
Background The best donor for a haematopoietic cell transplant in a person with acute myeloid leukaemia (AML) in 1st remission is controversial. Prior data indicate similar outcomes after transplants from HLA-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors.
Methods We analyzed data from persons with intermediate- or high-risk AML in 1st complete remission (CR1) treated in a prospective, multi-centre study.
Results 602 consecutive subjects received a transplant from an HLA-haplotype-matched relative (N=328) or an HLA-identical sibling (N=274). 4 year leukaemia-free survivals were 78% (95% confidence interval [CI], 73, 83%) and 80% (75, 85%; P=0.39). In multivariate analyses younger donor/recipient age (donor<30y-receipient<30y) was associated with less transplant-related-mortality (TRM) (hazard ratio [HR)=0.25; [0.06, 1.00]; P=0.05) whereas female-to-male transplants (HR=1.93; [1.10, 3.38; P=0.02) and donor-recipient ABO major-mismatch transplants (HR=1.95 [1.12, 3.38; P=0.02) were correlated with higher TRM. A risk score was generated based on donor/recipient age, gender and ABO-incompatibility. The scoring system predicted TRM and survival. TRMs were 5% (3, 7%), 15% (10, 20%) and 20% (4, 36%) for subjects with scores of 0-1, 2 and 3 (trend comparison P<0.001). 4 year survivals were 85% (81, 89%), 77% (71, 83%), and 75% (59, 91%; trend comparison P=0.04).
Conclusions In contrast to the lack of impact of HLA-disparity on transplant outcomes, selection of the best donor needs to consider D/R age, sex and ABO-incompatibility combined together. Our data suggest choosing young, male, ABO match/minor-mismatch donors is reasonable. Transplants from older female-to-male and from ABO major-mismatched donors should probably be avoided.

Disclosures
No relevant conflicts of interest to declare.
UCBT Using Myeloablative Conditioning Regimen without ATG Has Similar Survival but Better Life Quality Compared with Upbsct for Adults with Primary Acute Leukemia-a Multicenter Study in China
Authors: Tong Juan , Xuan Li , Sun Yanling , Zheng Changcheng , Liu Huilan , Zhu Xiaoyu , Tang Baolin , Liu Qifa , Lin Dongjun , Sun Zimin 
Published: November 2019

Abstract
Objective
Data regarding the outcome of unrelated cord-blood transplantation (UCBT) with myeloablative conditioning regimen without ATG comparing with unrelated peripheral blood stem cell transplantation (UPBSCT) for adults with primary acute leukemia.
Methods
From Jan 2010 to Dec 2014, 175 consecutive adult patients with primary acute leukemia (AL), who had no HLA-compatible related donors who were eligible for a single UCBT (79 patients) or UPBSCT (96 patients). The two groups all received a TBI/CY2 and BU/CY2 based myeloablative conditioning regimen which plus fludarabine (FLU), etoposide (VP-16) or cytarabine (Ara-c). The GVHD prophylaxis regimens of UCBT were cyclosporine A (CsA) and mycophenolate mofetil (MMF) and UPBSCT were CsA, Methotrexate (MTX) and antithymocyte globulin (ATG).
Results
There was no significant difference for the patients characteristics between the UCBT and UPBSCT group except for UCBT patients were younger. Although the UCBT patients received lower doses of nucleated and CD34 positive cells and more patients were HLA mismatched, the two groups acquired the similar percentage of hematopoiesis engraftment rate (97.4% vs 100%, p=0.497) but the granulocyte and platelet recovery was slower in UCBT group. The incidence of bacterial or invasive fungal infection in the UCBT group and the UPBSCT group had no significant difference (46.8% vs 52.6%, P=0.572) may be attributed to the omission of ATG in UCBT group. TRM by three years was 21.0% and 16.9% in the UCBT and UPBSCT cohorts (P=0.46). The 3-year cumulative incidence of relapse was similar between the UCBT group and the UPBSCT group (26.3% vs 27.1%, P=0.75). The grade II to IV acute graft-versus-host disease (aGVHD) and severe aGVHD (grades III and IV) incidence was similar between the two groups (24.7% vs 33.0%, P=0.40), (13.3% vs 8.7%, P=0.28)]. Compared with the UPBSCT cohort, the UCBT cohort had a significantly lower rate of chronic graft-versus-host disease (cGVHD) (20.7% vs 44.0%, p=0.003) or extensive cGVHD (5.6% versus 17.5%, P=0.04). The overall survival (63.2% vs 64.1%, P=0.996) and leukemia free survival (57.5% vs 59.8%, P=0.824) had no significant difference between the two groups. The performance status observed in patients surviving 3 years was measured using the Karnofsky performance score. The UCBT recipients had obviously higher activity scores than UPBSCT recipients (94.5% vs 83.5%, p=0.03).
Conclusion
When use intensive myeloablative conditioning regimen without ATG, UCBT can reach similar survival with UPBSCT and may have better life quality. Primary acute leukemia patients who lack an HLA-matched sibling donor can select UCBT or the UPBSCT of equal status.

Disclosures
No relevant conflicts of interest to declare.
Impact of Disease Status on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation with Refractory and Relapsed Acute Lymphoblastic Leukemia
Authors: Cao Jing , Zhu Xiaoming , Sun Aining , Qiu Huiying , Jin Zhengming , Miao Miao , Wu Depei , Tang XiaoWen 
Published: November 2019

Abstract
Objective: To evaluate the impact of disease status on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of patients with refractory and relapsed acute lymphoblastic leukemia(ALL).
Methods: 52 patients with refractory and relapsed ALL, including 19 cases in advanced stage (nonremission, NR) and 33 cases in more than or equal to second complete remission(≥CR2), received allo-HSCT after myeloablative conditioning regimen in our department.
Results: 51 patients engrafted successfully. The transplantation-related mortality (TRM) rate of NR and ≥CR2 was 10.5% vs 12.1% (P=0.815). The incidence of aGVHD was 52.6% vs 57.6% (P=0.730), including 42.1% vs 33.3% (P=0.527) with mild (grade I-II) and 10.5% vs 24.3% (P=0.399) with severe (grade III-IV) aGVHD. The incidence of cGVHD was similar also(41.6% vs 57.9% ,P=0.660). With a median follow-up of 12(1.8-44.5) months, the cumulative relapse rate of NR and ≥CR2 was 47% vs 34.3% (P=0.425) respectively. The estimated 2 year overall survival (OS) and 2 year leukemia-free survival (LFS) rate were 42.6% vs 45.7% (P=0.487) and 46.3% vs 46.2% (P=0.571) respectively. Multivariate Analysis results showed that cGVHD was independent favorable risk factor for OS and LFS of R/R ALL. For relapsed patients, OS was significantly better with first CR duration>6 month and time to transplant≤2 months.
Conclusion: AlIo-HSCT is an effective salvage treatment option for patients with refractory and relapsed ALL. Our retrospective analysis showed that R/R ALL with different status prior transplant had similar outcome post transplantation.

Disclosures
No relevant conflicts of interest to declare.