bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residual Lymphocytes in GM-CSF and IL-15 Differentiated Monocyte-Derived Dendritic Cells Enables Cytotoxic T Lymphocyte Responses.
Authors: Hardy Melinda Y. , Kassianos Andrew J. , Wilkinson Ray , Vulink Annelie , Hart Derek N.J. , Radford Kristen J. 
Published: October 2019

Abstract
We investigated the capacity of IL-15 to differentiate human dendritic cells (DC) from monocytes in the presence of GM-CSF (IL-15 MoDC) and compared them with MoDC differentiated in IL-4 and GM-CSF (IL-4 MoDC) as used in many immunotherapy protocols. IL-15 MoDC expressed higher levels of CD40 and HLA-DR and importantly, induced MART-1 specific cytotoxic T lymphocyte (CTL) responses with superior lytic capacity, when compared to IL-4 MoDC. In response to activation, IL-15 MoDC secreted high levels of IFN-γbut low or no IL-12, whereas IL-4 MoDC secreted high IL-12 but low or no IFN-γ. Using an IFN-γ blocking antibody, we demonstrated that IFN-γ production by the IL-15 MoDC did not account for the superior CTL responses induced. Despite immunoselecting monocytes to greater than 97% purity prior to DC differentiation, we noticed a small population (1–2%) of CD56+ and CD3+ lymphocytes in the IL-15 MoDC preparations that were less prominent in IL-4 MoDC differentiated from the same monocytes. Removal of the residual lymphocytes from monocytes prior to differentiation into IL-15 MoDC diminished their capacity to induce CTL but did not affect the expression of HLA-DR or CD40. These data suggest that IL-15-dependent cross-talk between the small lymphoid populations present and DC, during DC differentiation from monocytes results in superior CTL priming that is independent of IL-12 and IFN-γ. Based on these results, appropriately manufactured IL-15 MoDC preparations containing defined numbers of lymphoid cells should be considered for immunotherapy.
Utilization of ‘Rainy Day’ Autologous Peripheral Blood Stem Cells.
Authors: Wall Dominic , Yallouridis Alexander , Gambell Peter , David Ritchie , Miles Prince 
Published: October 2019

Abstract
High-Dose myeloablative therapy in conjunction with Autologous Peripheral Blood Stem Cell (APBSC) transplantation is an effective first line treatment in patients with haematological malignancies including Multiple Myeloma (MM) and Non-Hodgkin Lymphoma (NHL). With sufficient resources, APBSC’s can be harvested in patients during remission or consolidation treatment for subsequent transplantation if required (‘Rainy Day’ Collection). We investigated the eventual transplantation of ‘Rainy Day’ collections at our centre to assess the utilization of this strategy. We defined ‘Rainy Day’ collections as those that were not intended to be used as part of initial therapy and in general, patients were not planned to be transplanted within the 12 months following harvest. For collections that were transplanted within 12 months following harvest, ‘Rainy Day’ collections were differentiated based on the utilization intent at time of collection. Any collections infused within 3 months following harvest were excluded from the analysis. Over a 6 year period, we collected APBSC’s from 365 patients with the intent of ‘Rainy Day’ storage. Primary disease indications included NHL (45%, n=166), MM (12%, n=44), Acute Myeloid Leukaemia (AML) (8%, n=29) and Chronic Myeloid Leukaemia (CML) (7%, n=25). To date, 23% (n=84) of these ‘Rainy Day’ collections have been subsequently infused. NHL has been the most common disease requiring Rainy Day collections and has resulted in 41 subsequent transplants (24% utilization) with a median time between collection and infusion of 1.74 years (SD =1.60). Mean days until platelets > 20x109/L=15 (SD=7.0) and days until ANC > 0.5x106/L=10 (SD=1.7). Follicular Non-Hodgkin Lymphoma (fNHL) has accounted for the majority of NHL transplants (37%, 5/15), with 5 of 15 patients exhibiting transformation of fNHL into Diffuse Large B-Cell Lymphoma and an average time between collection and infusion of 2.07 years (SD 2.01). Peripheral T-Cell Lymphoma (T-NHL) has contributed to 15% (n=6/41) of transplanted NHL ‘Rainy Day’ collections with a mean time between collection and infusion being shorter at 1.53 years (SD=0.97). 23% of MM patients (n=44/202) have had APBSC’s collected for potential ‘Rainy Day’ utilization compared with 53% of NHL (n=166/309), 86% of AML (n=29/34) and 100% of CML (25/25). MM has shown to have the highest ‘Rainy Day’ APBSC utilisation with 55% (n=23/44) of patients resulting in transplantation. The average time between collection and infusion has been 2.79 years (SD=1.65) with mean days until platelets > 20x109/L=14 (SD =6.9) and days until ANC > 0.5x106/L=10 (SD=1.7). We conclude that it is clinically feasible and safe to perform ‘Rainy Day’ collections although more stringent criteria would result in a more efficient use of this resource intensive strategy.
Multivariate Analysis of Factors Influencing Stomatitis in Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Ohbayashi Yumiko , Imataki Osamu , Ohnishi Hiroaki , Miyake Minoru , Iwasaki Akinori , Ogawa Takaaki , Kitanaka Akira , Kubota Yoshitsugu , Tanaka Terukazu , Ishida Toshihiko , Nagahata Shunichiro 
Published: October 2019

Abstract
Purpose: Stomatitis in allogenic hematopoietic stem cell transplant (HSCT) recipients sometimes causes serious complications. Stomatitis causes disturbances in oral functioning thus diminishing quality of life (QOL) in transplant patients; these include such simple tasks such as feeding, swallowing and speaking. However, given this serious complication, little information is available regarding the prophylactic effect of oral intervention in hematopoietic stem cell transplantation (HSCT).
Methods: We retrospectively analyzed the incidence and severity of stomatitis after allogeneic HSCT with or without oral intervention among 96 consecutive patients in our hospital between January 1988 and March 2006. Inclusion criteria were
conditioning regarding both conventional (CST) and reduced-intensity regimens (RIST), donor source that included both bone marrow and peripheral blood omitting cord blood, HLA disparity eligible to one or two locus mismatched related or unrelated donor.
We used a combination following two strategies; one is cryotherapy which has applied since 2003, and another is oral health care which has been used since 2004. The incidence and severity of stomatitis was evaluated during the start of chemotherapy until day 100 after transplantation. Stomatitis was evaluated according to NCI CTCAE v3.0. ‘Cryotherapy’ is defined as the use of cold to treat an injury. Generally, an ice tip is used to make the mucosa cold. ‘Oral health care’ is defined as a prevention or treatment, including that administered by oneself, encompassing any of the immunologic, sensory, neuromuscular and structural functions of the mouth and craniofacial complex.
Results: The mean age was 42.7 years. Among 96 patients, 41 patients were treated by CST and 55 by RIST. The incidence of stomatitis was 30.9% (17/55) in RIST, which was significantly lower than the 90.2% (37/41) in CST (P < 0.001). Among these 96 patients, severe stomatitis (grade 3 to 4) was observed in 19 (46.3%) CST cases and in 6 (10.9%) RIST cases (P<0.001). The occurrence of stomatitis apparently decreased after oral health care was started. The incidence of overall grade was from 71.1% to 25.6%, and severe grade was from39.6% to 9.3%, at one year. Multiple logistic analysis revealed that both the conditioning regimen as well as the oral health care were independent risk factors for the incidence of stomatitis.
Conclusion: We concluded that although cryotherapy could not prevent oral stomatitis in patients who had undergone CST or RIST, the oral health care improved tissue damage due to an overall upgrade in oral hygiene during chemotherapy.
Thymoglobulin ® Rabbit Anti-Thymocyte Globulins (r-ATG) Induces Faster Platelet Recovery and Does Not Suppress Granulocyte Engraftment in a Non-Myeloablative Stem Cell Transplantation Setting.
Authors: Shapira Michael Y. , Resnick Igor B. , Gesundeheidt Benjamin , Bitan Menachem , Ackerstein Aliza , Samuel Simcha , Drey Liliane , Verkholevsky Yuri , Slavin Shimon , Or Reuven 
Published: October 2019

Abstract
Introduction: The role of anti thymocyte globulin in GVHD prevention is well established, but it is also known that anti thymocyte globulin induces leucopenia and thrombocytopenia and as such might theoretically delay engraftment. Additionally, fast platelet engraftment is a marker for good hematopoietic stem cell graft function. We have prospectively compared the effect of Thymoglobulin on engraftment of granulocytes and platelets following a single non-myeloablative conditioning protocol in a randomized study.
Methods: 28 consecutive patients undergoing SCT were conditioned with the NST protocol (I.V.fludarabine 30mg/m2/day (days −10 to −5) and I.V. busulfex (3.2 mg\kg on days −6 and −5), with or without I.V. Thymoglobulin according to randomization (days −4 to −1). Thymoglobulin dosing schedule: a cumulative dose of 7.5 mg/kg r-ATG was given with the following program 0.5 mg/kg day −4, 2.0 mg/kg day −3, 2.5 mg/kg day −2, 2.5 mg/kg day −1. Patients were followed for engraftment of leukocytes and platelets.
Results: only one patient rejected the graft (conditioned without Thymoglobulin, NS). In 4 patients underlying disease progression prevented engraftment of either ANC or platelets (2 per group). The median time to ANC engraftment was similar between the groups, 15±2.8 and 14±2.9 days for the Thymoglobulin and control groups respectively (figure 1, p=0.21). However, the median time for platelet engraftment was significantly shorter in patients receiving Thymoglobulin as part of the conditioning. Platelet recovery occurred 9.5±1.2 and 11±2.5 days for the Thymoglobulin and control groups respectively (figure 2, p=0.018).
Conclusions: in the non-myeloablative setting, Thymoglobulin induces faster platelet recovery and does not delay ANC engraftment.
Figure Figure Figure Figure
Clinical Analysis of Late-Onset Nephrotic Syndrome after Allogenic Hematopoietic Stem Cell Transplantation.
Authors: Luo Xiaodan , Liu Qifa , Ning Juan , Wei Yongqiang , Fan Zhiping , Zhang Yu , Sun Jing 
Published: October 2019

Abstract
Objective: To investigate the morbidity, pathology, pathogenesis and treatment of late-onset nephrotic syndrome (NS) after allogenic hematopoietic stem cell transplantation (allo-HSCT).
Methods: Late-onset NS was investigated in 167 patients with hematopoietic malignancies who survived more than 3 months after allo-HSCT from February 2001 to August 2006. Kidney biopsy and detection of serum levels of immunoglobulin (Ig), autoantibody, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were performed in patients with late-onset NS. Pathology of kidney was studied by light microscopy, immunofluorescence and transmission electron microscopy. Associations between the onset of NS with conditioning regimens, human leucocyte antigen (HLA) matching, chronic graft versus host disease (cGVHD) and cytomegalovirus infection were analyzed. Statistical analysis was performed with SPSS/PC version 13.0.
Results: Five patients were identified as late-onset NS after allo-HSCT in167 allo-HSCT patients, including 4 patients with membranous glomerulonephritis (MGN) and 1 patient with minimal change disease (MCD). The immunofluorescence of glomerular lesions revealed that the Ig of immune complex deposition were IgG in 3 patients, IgM in 1 patient and IgG/IgM double-positive in 1 patient. Electron-dense deposit can be found on epithelium and basement membrane under the transmission electron microscope. Serum levels of IFN-γ and TNF-α were markedly increased in NS patients as compared with patients without NS. Serum antinuclear antibody was positive in 2 patients and serum IgG and IgM were in high level in 2 patients, respectively. Glucocorticoid combined with cyclophosphamide (CTX) was fundamentally effective in treatment for late-onset NS. One patient got complete response, 3 got partial response and 1 was stable after the treatment. The associations of the onset of late-onset NS post-HSCT with conditioning regiments, HLA-matching, cGVHD and CMV infection had no statistical significance.
Conclusions: Glomerular histology of late-onset NS after allo-HSCT was comprised mainly of MGN and secondary MCD. The pathogenesis of late-onset NS may be related to the abnormality of humoral immunity. Glucocorticoid combined with CTX was a fundamentally effective treatment.
Chemokine Receptor Gene Polymorphisms and Severity of Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation from Sibling Donors.
Authors: Pullarkat Vinod , Sun Jiyao , Hong Fangxin , Nakamura Ryotaro , Cao Lan-Feng , Palmer Joycelynn , Forman Stephen J. , Senitzer David 
Published: October 2019

Abstract
Background: Single nucleotide polymorphisms (SNPs) and other genetic variations in various genes involved in the immune response have been variably associated with acute graft-versus-host-disease (GVHD). The interaction of chemokines with their receptors is crucial for organ-specific recruitment of immune cells. Trafficking of recipient antigen presenting cells as well as donor lymphocytes between lymph nodes and target tissues are especially important events in acute GVHD pathogenesis. In this pilot, retrospective study, we sought to examine the role of recipient and donor chemokine receptor gene polymorphisms in determining the incidence of severe acute GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) from matched sibling donors.
Methods: Patient and donor samples were genotyped for the following chemokine receptor polymorphisms: CCR5 -59029 A/G, CCR2 190 A/G (V64I), CX3CR1 745 A/G (V249I) and CX3CR1 839 C/T (T280M) and CCR5Δ32. Due to the extreme rarity of homozygosity for the Δ32 deletion in CCR5, the CCR5Δ32 homozygotes and heterozygotes were grouped together for analysis. The relationship between polymorphism genotypes and acute GVHD outcomes (Grade 0 vs Grades III/IV) were evaluated.
Results: A total of 103 donor-recipient pairs were analyzed which included 58 recipients who experienced severe acute GVHD (Grades III/IV) and 45 recipients who did not develop acute GVHD (Grade 0). Compared to the wild type CCR5 allele, the presence of the CCR5Δ32 allele in the donor conferred an increased risk for severe acute GVHD (P=0.04). The odds ratio is estimated to be 6.16 (95% CI [0.73, 52.05]). Presence of CCR5Δ32 in the recipient was not associated with increased acute GVHD risk (P=0.14). For the CCR5 -59029 A/G polymorphism, there was the suggestion of a decreased trend for developing severe acute GVHD if the donor had the A/A genotype (P=0.09). A trend for an association with the incidence of severe acute GVHD was observed for the CCR2 V64I polymorphism in the recipient. (P= 0.08). Donor genotype for this polymorphism was not associated with severe GVHD (P=0.17). A trend towards increased incidence of severe GVHD was observed for the 745 A/G (V249I) polymorphism (P=0.1). No significant effect was observed for the CX3CR1 839 C/T (T280M) polymorphism in this study.
Conclusions: CCR5Δ32 polymorphism in the donor was associated with severe acute GVHD in this study. This and other functional chemokine receptor polymorphisms are potential candidates for evaluation in large prospective studies in future to precisely determine their association with acute GVHD.
Day 15 Dendritic Cell Recovery Predicts Overall Survivial after Autologous Stem Cell Transplantation in Non-Hodgkin’s Lymphoma.
Authors: Siddiqui Mustaqeem A. , Markovic Svetomir N. , Nevala Wendy K. , Morice William , Inwards David J. , Ansell Stephen M. , Micallef Ivana N. , Johnston Patrick B. , Porrata Luis 
Published: October 2019

Abstract
The peripheral blood absolute lymphocyte count (ALC) on day 15 after autologous stem cell transplantation (ASCT) has been shown to be an independent predictor for overall survival (OS) for many malignancies including acute myelogenous leukemia (AML), breast cancer, multiple myeloma (MM), primary systemic amyloidosis, and Hodgkin’s and non-Hodgkin’s lymphoma (NHL). A recent report (Dean et al. BMT2005; 36, 1049–1052) suggested that infused autograft dendritic cells (DC) affect survival post-ASCT in NHL. Thus, DC recovery at day 15 post-ASCT was assessed and correlated with OS. Preliminary data from an ongoing prospective study of 28 NHL patients post-ASCT are reported. Absolute DC at day 15 was analyzed by four color flow cytometry using antibodies to CD3, CD14, CD16, and CD19. In this approach lymphocytes and DCs were initially gated by their similar forward and side light scatter characteristics; DCs were then identified as cells in this gate that lacked staining for the lymphocyte antigens CD3, CD16, and CD19 and the monocyte antigen CD14. The percentage of antigen negative cells cells in the lymphocyte gate was then multiplied by the coincident peripheral blood absolute lymphocyte to determine the absolute DC count. Survival was then analyzed using the Kaplan-Meier method. With a median follow-up of 18 months, patients recovering a DC of 10 cells/μl or above experienced superior median OS versus those who did not (not reached vs 21 months, p < 0.02, Figure 1). This study shows that an immunocompetent immune system at day 15 (not only ALC recovery, but also DC recovery) correlates with survival in NHL patients undergoing ASCT.
Figure Figure
Predicting Response to Therapy for Graft-vs-Host Disease (GvHD) with a Rapid Immune Function Assay.
Authors: Anaissie Elias J. , Diaz Jose A. , Grazziutti Monica L. , Miceli Marisa H. , Fox-Cottler Michele , Barlogie Bart , van Rhee Frits 
Published: October 2019

Abstract
Background: GvHD following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases morbidity and mortality and is difficult to predict for. We explored the use of a novel immune function assay to determine whether an immunologic response to changes in immunosuppressive therapy for GvHD could predict clinical response.
Methods: The FDA-approved Cylex ® Immune Cell Function assay (ICF) measures the response of whole blood CD4+ lymphocytes to stimulation with phytohemagglutinin (PHA) with as read-out ATP production. The assay is quick and results are available on the same day. Use of this test in solid-organ transplant recipients demonstrated its utility in monitoring changes in immunosuppressive therapy. A retrospective analysis of the ICF assay results from allo-HSCT patients treated at our center for acute or chronic GvHD was conducted.
Results: 13 GvHD events (11 chronic, 2 acute) occurring in 8 patients between 35 and 2118 days post-transplant (682 +/− 556 d) were analyzed. At diagnosis of GvHD, the average ICF value was 425 +/− 111 ng/mL ATP. Same day white blood cell (WBC) and absolute neutrophil count (ANC) values were 10.6 +/− 3.2 x 103 cells/μL and 9.2 +/− 3.3 x 103 cells/μL, respectively. Treatment for GvHD consisted of increasing calcineurin inhibitor dose and addition of prednisone and/or other immunosuppressants. Ten GvHD events responded to therapy within 10 +/−7 days with a corresponding significant decrease of ICF values from 430 +/− 109 ng/mL to 239 +/− 130 ng/mL (p=0.002) and a decrease of WBC from 11.2 to 8.0 x103 cells/μL (p=0.027). ANC and C - reactive protein values were not statistically different (p=0.09 and p>0.5 respectively). In contrast, no significant decrease in the ICF values before and after therapy (406 to 465 ng/mL ATP) was observed for the 3 GvHD events that failed to respond to therapy.
Conclusion: These preliminary data suggest that the ICF assay is a good predictor of response of GvHD to immunosuppressive therapy and could be used to intensify immunosuppression early in non-responders.
Risk Factors for Response after Initial Therapy for Acute Graft-Versus-Host-Disease (aGVHD).
Authors: Westin Jason R. , Saliba Rima M. , de Lima Marcos , Alousi Amin , Hosing Chitra , Qazilbash Muzaffar H. , Khouri Issa F. , Shpall Elizabeth J. , Champlin Richard , Couriel Daniel R. 
Published: October 2019

Abstract
Introduction: Acute GVHD remains the most important early complication and limitation to allogeneic hematopoietic stem cell transplantation (HSCT). Although far from optimal, corticosteroids remain initial standard therapy with an overall response rate of 50%. Steroid resistant patients have a dismal prognosis, with mortality rates reaching 90%.
Objective: To identify the subgroup of patients that would not benefit from initial therapy with corticosteroids. Thus, accrual of these patients into clinical studies would be mandatory.
Methods: Retrospective evaluation of all (N= 287) patients who developed biopsy proven aGVHD after allogeneic HSCT at the University of Texas M. D. Anderson Cancer Center from 1998 through 2002. All patients received initial therapy for aGVHD with methylprednisolone. Prognostic factors for response (CR/PR) to initial therapy with corticosteroids were evaluated using logistic regression analysis including age, gender, donor/patient sex mismatch (F/M), donor type, cell type, intensity of conditioning regimen, diagnosis, disease status at transplant, number of prior chemotherapy regimens, number of prior autologous HSCT, CD34+ cell dose infused, time of onset of aGVHD and grade at initiation of first line therapy.
Results: At the time of first line therapy, 89/287 patients (31%) had grade I aGVHD, 141 (49%) had grade II, and 57 (20%) had grade III–IV. Overall response to first line therapy was 56% and was comparable between patients with grade I and II aGVHD. Grade III–IV aGVHD (CR/PR 39% vs. 60%, p=0.003) and hyperacute GVHD (occurring by day +14) (CR/PR 42% vs. 61%, p=0.007) were the most significant prognostic factors for failure. Sex mismatch was associated with significantly lower response rate in patients with grade III–IV (CR/PR 12% vs. 49%, p=0.02) but not in patients with grade I–II (CR/PR 61% vs. 60%, p=0.9). Failure to respond to first line therapy was the most significant predictor of non-relapse mortality at one and two years after initiation of first line therapy (p<0.001) for all GVHD grades.
Conclusions: Hyperacute GVHD and sex mismatch are significant predictors of response to first line therapy. Response to first line therapy has a strong and independent effect on survival. These factors should be integrated in prognostic scoring systems of aGVHD, which would allow identification of patients who would not benefit from standard therapeutic approaches.
Response To First Line Therapy Overall (N=287) n %CR/PR p value CR: complete remission, PR: partial remission Grade at First Line I 89 65% Reference II 141 57% 0.2 III/IV 57 39% 0.003 Grade I/II (N=230) Grade III/IV(N=57) n, %CR/PR p value n, %CR/PR p value Hyperacute GVHD Yes 73 42% 60, 48% 13, 15% No 214 61% 0.007 170, 65% 0.03 44, 45% 0.05 Donor/Patient sex mismatch Yes 73 51% 57, 61% 16, 12% No 214 58% 0.3 173, 60% 0.9 41, 49% 0.02