bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-Thaw Colony Forming Unit (CFU) Counts and Yield Are the Most Important Predictors of Engraftment and Survival Following Unrelated Donor Cord Blood Transplantation (CBT): A COBLT Study Report.
Authors: Wall Donna A. , Wagner Elizabeth L. , Carter Shelly L. , Mendizabal Adam M. , Cairo Mitchell S. , Kernan Nancy A. , Laughlin Mary , Kurtzberg Joanne 
Published: October 2019

Abstract
Total nucleated cell count (TNC), CD34 and CFU content of cryopreserved cord blood units (CBUs) are measurements of hematopoietic potential previously demonstrated to be predictive of engraftment and/or survival post-transplant. Pre-cryopreservation measurements do not capture downstream events in cord blood banking that could impact CBT outcome: freezing, long-term storage, shipment to the transplant center and thawing. We hypothesized post-thaw enumeration of these measures would be more predictive of outcome. These tests were routinely performed at two of the COBLT transplant centers, at the time of CBU thaw. We examined the correlation of these laboratory measures pre-cryopreservation and post-thaw with engraftment and survival of 153 patients with leukemia and metabolic disorders undergoing myeloablative transplantation. The median age of recipients was 4.4 years (range 0.1 – 17.9) and weight 19.1 kg (range 3.9 – 118.4).
Pre-cryopreservation Thaw Yield Median (range) Median (range) Median (range) TNC/kg x 107/kg 6.9 (1.5 – 50.4) 5.7 (1.1 – 31.6) 80.9% (43.0 – 98.9) CD34/kg x 105/kg 2.3 (0.1 – 20.1) 2.0 (0.2 – 15.5) 72.6% (16.1 – 99.6) CFU/kg x 104/kg 20.2 (1.7 – 169.7) 3.0 (0.0 – 31.1) 17.7% (0.0 – 82.7) Trypan blue viability 99 (91 – 100) 98 (83 – 100) —
Overall 114/153 engrafted by day +42 with a median day to engraftment of 29 days. In multivariate analysis, post-thaw CFU count and yield were the highest correlates with engraftment (p<0.0001 and p<0.02, respectively) and survival (p=0.05 and p=0.02, respectively). If the CFU yield was 50–100% of pre-cryopreservation CFU then the probability of engraftment by day +42 was 93%. However, engraftment by day +42 fell to 63% when the yield was <5% (16% of CBUs). Survival at 2 years was poorer if CFU yield was less than 5% compared to >5% (38% vs. 65%, p =0.05). Importantly, post-thaw yield of TNC and trypan blue viability did not correlate with engraftment. Total hematopoietic content of units (TNC, CD34, and CFU) was strongly predictive of engraftment. However, independently, low CFU counts and poor yield of CFU at time of CBU thaw is a harbinger of poor/nonengraftment and is evidence of deterioration of the product between time of processing and infusion. Low CFU count or poor yield of CFU post-thaw may be used clinically to predict engraftment in patients undergoing CBT. These findings illustrate the need for the development of product release testing criteria for CBUs and should be a priority for the cord blood community.
Unrelated Bone Marrow Transplantation for Adult T Cell Leukemia/Lymphoma: A Study from the Japan Marrow Donor Program.
Authors: Kato Koji , Kanda Yoshinobu , Eto Tetsuya , Muta Tsuyoshi , Gondo Hisashi , Utsunomiya Atae , Taniguchi Shuichi , Shibuya Tsunefumi , Morishima Yasuo , Kato Shunichi , Kodera Yoshihisa , Harada Mine 
Published: October 2019

Abstract
Adult T cell leukemia/lymphoma(ATLL) is known to be a very poor prognosis, and intensified chemotherapy has not yet improved this prognosis. Some successful cases of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched siblings have been reported and allo-HSCT has been suggested as improving the prognosis of ATLL. However, HLA-matched related donor is seldom available and about two-thirds of siblings of patients with ATLL are HTLV-1 carriers. Although most of ATLL patients require an unrelated donor to benefit from allo-HSCT, there is little information about the outcome of unrelated bone marrow transplantation(UBMT) for ATLL. To elucidate the feasibility and efficacy of UBMT from HTLV-1 seronegative donor, we retrospectively analyzed the data of 33 patients who were ATLL and underwent UBMT through the Japan Marrow Donor Program. Median age of patients at transplantation was 51 years(range,24–59). The conditioning regimens of 27 patients had myeloablative intensity and 6 had reduced intensity. At transplantation, 12 patients were in complete remission, 3 were partial remission and 14 were no remission. A total of 14 patients died after allo-HSCT, and 9 of those 14 patients were lost within 100 days after HSCT due to treatment related adverse events. The overall survival(OS), progression-free survival(PFS), cumulative incidences of disease progression, and nonprogression mortality at 2 years after UBMT were 49.7%, 42.6%, 24.5%, and 32.9%, respectively. Multivariate analysis demonstrated that recipient age(P=.044) and disease status at transplantation(P=.059) were independent prognostic factors for OS and PFS. These results suggest that UBMT could be considered as a treatment option for ATLL patients without an HLA-matched related donor. Further study is required to determine the indication of nonmyeloablative conditioning based on patient’s age or disease status, because myeloablative conditioning had high incidence of treatment related mortality.
Allogeneic Stem Cell Transplantation from Unrelated Donors within the Seventh Decade of Life.
Authors: Dahlke Joachim , Zabelina Tatjana , Ayuk Francis , Panse Jens , Schieder Heike , Renges Helmut , Atanackovic Djorde , Wolschke Christine , Zander Axel R. , Kroeger Nicolaus 
Published: October 2019

Abstract
We analyzed the outcome of 28 patients who were treated within prospective treatment protocols to investigate the feasibility of unrelated stem cell transplantation for patients with haematological malignancies within the seventh decade of life. Twenty-eight patients with a median age of 62 years (range 60–70) were enrolled. Twenty-six received a dose-reduced conditioning regimen while two patients were transplanted after standard conditioning regimen, and eight of the patients had received at least one prior high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. Diagnoses were leukaemia (AML: n=10; ALL: n=1; CML: n=2), MDS (n=5), myelofibrosis (n=3), multiple myeloma (n=6) or non-Hodgkin’s lymphoma (n=1). No primary graft-failure was observed, and the median number of days to leucocyte and platelet engraftment was 18 days and 23 days, respectively. Acute GvHD grade II–IV was seen in 35% of the patients, chronic GvHD was seen in 56% of the patients. The one-year cumulative incidence of treatment-related mortality was 25%. The four-year estimated overall- and disease-free survival was 49% and 40%, respectively. Unrelated stem cell transplantation in patients within the seventh decade of life is a feasible treatment option and may induce long-term disease-free survival.
Autologous Stem Cell Transplantation (ABMT) for Recurrent Hodgkin’s Disease from 1990–2005: Factors Contributing to Post-Transplant Relapse.
Authors: Bolwell Brian , Pohlman Brad , Kalaycio Matt , Andresen Steve , Kuczkowski Elizabeth , Brown Stacey , Bates Jennifer , Rybicki Lisa , Curtis Julie , Bell Kimberly , Sobecks Ronald M. 
Published: October 2019

Abstract
Long-term results of conventional therapy of Hodgkin’s disease (HD) has demonstrated the importance of long-term and ongoing follow-up given the potential for later complications after curative therapy. While many transplant series report follow-up of several years after ABMT, few report a 15-year experience from a single institution. This report examines the outcomes of 220 patients receiving high-dose chemotherapy and autologous stem cell transplant (ABMT) at The Cleveland Clinic Foundation from January 1990 through June 2005. Median age was 33 years (range, 14–70 years); median time from diagnosis to transplant was 19 months; 47% received prior radiation therapy; 82% had nodular sclerosis histologic subtype; number of courses of prior chemotherapy were: 1 (16%), 2 (66%), 3 (14%), 4 or more (4%). All patients received salvage therapy prior to transplant: 29% were in a complete remission (CR), 55% in a partial remission (PR), and 16% refractory. All patients received a chemotherapy-only preparative regimen, most commonly Bu/Cy/VP (73%), followed by CBV (17%). 78% received peripheral stem cells alone; 22% received either autologous bone marrow or a combination of bone marrow plus peripheral stem cells. At the present time 60% of patients are alive. Of the 88 patients who died, the most common cause of death is relapse (69% of deaths). Secondary malignancy occurred in 11 patients (5%); 9 of these cases were secondary AML/MDS and 5 of these patients with secondary malignancies have died. 44% of the entire cohort has relapsed, at a median of 9 months post-transplant (range, 1.4–76 months). 10-year overall survival is 47%. A multivariable analysis showed that the two significant variables that correlated with post-BMT relapse were the number of prior chemotherapies (p = 0.011), and patients treated in remission vs. those not in remission (p = 0.002). Of patients receiving 2 or more prior courses of chemotherapy, 60% have relapsed 8 years post-transplant, compared to 40% of those receiving one course of prior chemotherapy. The risk of relapse by the number of prior chemotherapy courses is shown graphically below:
Figure Figure
In conclusion, this very large series of ABMT for recurrent HD with long-term follow-up demonstrates the importance of timely autografting in relapsed HD patients. The optimal time to proceed with ABMT is after failing one, and only one, course of chemotherapy. Delaying transplant for unrealistic long-term salvage with other courses of traditional chemotherapy will negatively affect the outcome of subsequent ABMT.
Prognostic Value of FDG-PET in Lymphoma Patients Undergoing Autologous Stem Cell Transplantation.
Authors: Svoboda Jakub , Elstrom Rebecca , Chong Elise A. , Andreadis Charalambos , Berkowitz Arnold , Luger Selina M. , Porter David L. , Nasta Sunita , Downs Lisa H. , Siegel Donald L. , Glatstein Eli , Alavi Abass , Stadtmauer Edward A. , Schuster Stephen J. 
Published: October 2019

Abstract
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients (pts) with relapsed or primary refractory lymphoma that is responding to salvage chemotherapy. Limitations of ASCT include significant morbidity, cost, restriction of further treatment options, and frequent relapse of lymphoma. To define the ability of FDG-PET to predict clinical outcome after ASCT, we conducted a retrospective analysis of lymphoma pts in our institution who received salvage chemotherapy followed by ASCT for relapsed or primary refractory lymphoma between 1999 and 2005. We identified 47 lymphoma pts (19 with diffuse large B-cell, 18 with Hodgkin, 4 with mantle cell, 3 with follicular and 3 with other lymphomas) who had an FDG-PET scan after at least two cycles of salvage chemotherapy and prior to ASCT. Three pts were excluded from the analysis because their FDG-PET scan results were non-conclusive. The remaining 44 pts (median age 44 yrs, range: 19–65) were categorized into FDG-PET scan negative (26 pts) and positive (18 pts) groups. Each group was evaluated for event-free survival (EFS), which was defined as the interval between the date of the transplant to the date of relapse after complete remission (CR) or the date of progression for pts without CR or the date of death from any cause without a documented relapse. The overall median follow-up was 14 mo (range: 2–58). There were no statistically significant differences in the distribution of lymphoma subtypes between the two groups. In the FDG-PET negative group, the median EFS was 18 mo (range: 3–58) with 14 pts (54%) remaining in CR. In the FDG-PET positive group, the median EFS was 5 mo (range: 1.5–19) with only 1 pt (6%) remaining in CR. Comparison between the two groups confirmed that the difference in the median EFS was highly statistically significant (p<0.001). Additional data to determine the correlation of the FDG-PET with conventional CT scans will be presented. Our study suggests that a positive FDG-PET scan after salvage chemotherapy and prior to ASCT indicates an extremely poor chance of achieving a prolonged remission after ASCT. Clinical trials of new approaches should be investigated for pts with relapsed or primary refractory lymphoma that remains detectable by FDG-PET after salvage chemotherapy.
Figure Figure
Allogeneic or Autologous Stem Cell Transplantation (SCT) for the Treatment of Pediatric Patients with Non-Hodgkins Lymphoma (NHL).
Authors: Ricafort Rosanna , Trippett Tanya , Kernan Nancy A. , Small Trudy N. , Prockop Susan , Scaradavou Andromachi , Keating Anna , O’Reilly Richard J. , Boulad Farid 
Published: October 2019

Abstract
Thirty six patients (pts) with NHL, aged 3.5–20.9 years (median 14.7 years) received an allo-SCT (n=21) or auto-SCT (n=15) at our institution between 12/82 and 12/04. Pathologic NHL classification included: lymphoblastic (n=12), Burkitt’s (n=5), Large Cell (n=17) including ki-1 + (n=11), peripheral NHL (n=1), and undifferentiated NHL (n=1). Disease status at SCT was: first remission (CR1) (n=1), CR2 (n=15), CR3 (n=5), partial remission (n=7), relapse (Rel) or refractory (Ref) (n=8). Cytoreductive regimens were total body irradiation (TBI)-based for all but 3 pts in each of the allo-SCT and auto-SCT group. For the allo-SCT pts, donors were: matched related (n=15), mismatched related (n=1), and unrelated (n=5); graft-versus-host disease (GvHD) prophylaxis included T-cell depletion (TCD) (n=10) or post-BMT immunosuppression (n=11). Only one pt received a non-myeloablative allo-SCT. With one pt in the allo-SCT group lost to follow-up, 35 of 36 pts in the entire cohort were evaluable. The median follow up of the entire group was 21.5 months; it was 34 months and 20 months respectively for the allo-SCT and the auto-SCT groups. The overall survival (OS) and disease-free survival (DFS) were 56% and 54%, respectively. Ten of the 11 pts with ki-1 positive NHL are alive, disease-free after either allo-SCT (n=4) or auto-SCT (n=7) with a median follow-up of 26 months. The DFS for those patients transplanted in CR was 60% compared to 49% for those transplanted in either PR or Rel/Ref disease. Of the eight pts transplanted with progressive disease, 2 are alive, disease-free at 110 and 115 months; both pts post allo-SCT. For the allo-SCT group, the DFS was 52%. Seven pts relapsed, 4 of whom had Rel/Ref disease at the time of SCT. Four pts died of SCT-related complications. Five pts developed Grade II–IV aGvHD. For the auto-SCT group, the DFS was 53%. Two pts relapsed, and 2 pts died of toxicity. In summary, both allo-SCT and auto-SCT offer the prospect of durable disease-free survival for a significant proportion of pediatric patients with NHL after a first relapse or disease progression. In particular, those pts with ki-1-positive NHL had the most favorable outcome. As expected, pts transplanted in minimal residual disease achieved superior DFS.
Results N CR/PR Rel/Ref Relapse TRM DFS Allo-SCT 21 11/4 6 33% 20% 52% Auto-SCT 15 10/3 2 13% 13% 53%
Measurement of ZAP-70 Expression in CLL Using an Optimized Flow Cytometric Assay for ZAP-70 Protein Levels in Whole Blood Samples.
Authors: Shankey T. Vincent , Cobb Jeffrey , Scibelli Paul , Smith Cecilia , Mills Rhonda , Forman Meryl 
Published: October 2019

Abstract
ZAP-70 protein plays a critical role in the initiation of T-cell signaling through the TCR, and also regulates B cell differentiation. Studies aimed at understanding the relationship of maturation to disease course in the B-cell form of Chronic Lymphocytic Leukemia (B-CLL) have demonstrated a correlation of disease progression with IgVH configuration (germ line vs mutated). Flow cytometry-based assays for ZAP-70 expression in CLL patient samples have been previously reported, and generally show poor separation of ZAP-70 levels in samples considered as positive from negative, making interpretation of these data difficult, and reducing the likely agreement between laboratories. Using a unique fixation and permeabilization technique in conjunction with an optimal ZAP-70-PE antibody conjugate, we have developed a whole blood assay for the measurement of ZAP-70 protein expression which results in a significantly increased S/N of 18–24 (normal blood T-cells to B-cells) compared to previously reported flow cytometric assays (S/N of 3 to 8). Based on these data, we have developed a 5 antibody/4 color whole blood assay (CD5-FITC, ZAP-70-PE, CD19-PE-Cy5, CD3+CD56-PECy7) which includes surface labeling before fixation and ZAP-70 labeling after permeabilization. Critical assay details including pre and post staining stability, instrument standardization, gating strategies and data interpretation will be presented and discussed. Using this optimized assay, we have undertaken a multi-institutional study to determine the inter-laboratory variability of ZAP-70 measurements using normal donors, and an assessment of the ability of this assay to increase the separation of B-CLL ZAP-70 positive from negative populations. Finally, we have developed a method to index differential ZAP-70 expression using internal controls, which obviates the use of quadrant analysis techniques.
Hemostatic Factors Regulate Immune Surveillance and Contribute to the Rapid Clearance of Bacterial Pathogens In Vivo.
Authors: Flick Matthew J. , Du Xinli , Talmage Kathryn E. , LaJeunesse Christine M. , Witte David P. , Palumbo Joseph S. , Degen Jay L. 
Published: October 2019

Abstract
The local activation of coagulation system proteases and secondary deposition of fibrin may constitute important “danger” or “damage” signals that promote leukocyte activation events at sites of infection or injury. Consistent with this general hypothesis, we previously showed that mice expressing a mutant form of fibrinogen lacking the leukocyte integrin receptor αMβ2-binding motif displayed compromised clearance of bacteria in a model of S. aureus-induced peritonitis. Here, we show that mice with a complete genetic deficiency in fibrinogen (Fib−/−) show an even more profound sensitivity to S. aureus peritonitis. Fib−/− mice were found to succumb to bacterial doses that were rarely fatal in wildtype mice following intraperitoneal injection of wildtype S. aureus. This profound difference in survival profile was also seen when mice were challenged with S. aureus lacking either the bacterial fibrinogen-receptor (ClfA) or the bacterial prothrombin activator, coagulase. These results indicate that efficient bacterial clearance in control animals is related to host leukocyte engagement of fibrin(ogen) as opposed to bacterial engagement of this hemostatic factor. Following intraperitoneal inoculation with one billion CFU of S. aureus, control mice successful cleared >99% of the bacteria within 1 hour, whereas the number of bacteria retrieved within peritoneal lavage fluid of Fib−/− mice remained similar to the original input CFU. Microscopy studies and bacterial fate studies revealed that the rapid loss of viable bacteria in control animals was not due to either fibrinogen-dependent dissemination to other tissues nor the simple association of live bacteria with peritoneal surfaces. Neutrophils and macrophages appear to participate in early bacterial clearance in animals of both genotypes, but these cells appear to be overwhelmed and engorged with microbes in Fib-/− mice. Leukocyte composition and trafficking into the peritoneal cavity was not appreciably altered in fibrin(ogen)-deficient mice. Furthermore, B cells, T cells, mast cells and complement factors C3 and C5 were not found to be major factors in the fibrinogen-dependent bacterial clearance. Taken together, the available data indicate that a failure to fully implement leukocyte-mediated antimicrobial mechanisms is the primary impediment to bacterial clearance in Fib−/− mice. The findings are consistent with the hypothesis that leukocyte engagement of provisional fibrin matrices within challenged tissues is a critical parameter in leukocyte “target recognition” in vivo.
Fibrinogen Hershey IV: A Novel Dysfibrinogen with a γ V411I Mutation in the Integrin αIibβ3 Binding Site.
Authors: Flood Veronica H. , Al-Mondhiry Hamid A. , Bakke Antony C. , Farrell David H. 
Published: October 2019

Abstract
The C-terminal segment of the fibrinogen γ chain plays a crucial role in platelet aggregation via its interaction with the platelet receptor αIIbβ3. It is well established that the last four amino acids of the γ chain (408 to 411) are critical for this function, as mutations or deletions of this region abrogate fibrinogen’s ability to bind αIIbβ3. We describe here the first naturally occurring fibrinogen mutation affecting the C-terminal region of the γ chain and investigate its effects on platelet interactions. The proband, a 49-year-old woman, was diagnosed with dysfibrinogenemia based on a prolonged thrombin time and low fibrinogen activity (55 mg/dL). Her bleeding history was significant for menorrhagia and one episode of post-operative hemorrhage. DNA sequencing of the fibrinogen genes demonstrated heterozygosity for two mutations, γ R275C and γ V411I. The latter γ V411I mutation represents a novel mutation affecting the C-terminal amino acid of the γ chain. We hypothesized that this mutation would decrease fibrinogen’s affinity for the platelet receptor αIIbβ3. In order to isolate the effects of this mutation on fibrinogen-platelet binding, γ 400-411 dodecapeptides were synthesized to mimic the C-terminal γ chain sequence. One peptide contained the wild-type sequence ending in valine (γ 400-V411), and the second peptide incorporated the isoleucine mutation (γ 400-I411). Previous studies have demonstrated that the wild type γ 400-V411 dodecapeptide inhibits platelet aggregation by competing for fibrinogen binding to αIIbβ3. We performed platelet aggregation studies comparing inhibition of aggregation with the wild-type γ 400-V411 and the mutant γ 400-I411 peptides. Washed platelets were obtained from a normal donor, and platelet aggregation monitored using the agonist ADP. The IC50 for the initial rate of aggregation with the γ 400-I411 peptide was 214 μM, compared to 133 μM with the wild-type peptide. We then examined the extent of aggregation in the presence of either wild-type or mutant peptide. Consistent with the previous results, total aggregation was lower with the wild-type peptide compared to the mutant peptide. The IC50 for the γ 400-I411 peptide was 450 μM compared to 250 μM with the γ 400-V411 peptide. Overall, these findings suggest that the γ I411 mutation results in a decreased ability to bind platelets. In the heterozygous state, however, the available amount of wild-type fibrinogen may be sufficient to support platelet aggregation. The bleeding diathesis observed for the proband could therefore reflect other factors, especially the γ R275C mutation.