bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LTB4 Receptor Is Involved Not Only in the Downstream Pathway of rh-GCSF Mobilization but in the LTB4 Mobilization Pathway in C57BL/6 Mice.
Authors: Mun Yeung-Chul , Lee Seung-Eun , Lee Kyoung-Eun , Yoo Eun-Sun , Lee Sang Min , Kong Jee Hyun , Ahn Jee-Young , Bae Yun-Kyung , Lee Soon-Nam , Kim Jae-Hong , Seong Chu-Myong 
Published: October 2019

Abstract
Though we were able to shorten the CD34+ cell mobilization by 24~48h by using continuous intravenous rhG-CSF rather than SQ rhG-CSF, it still will take several days when used normal individuals (Lee et al, BMT2005, 36:1027–1031). Previously we had reported that LT(Leukotriene)B4 was able to mobilize HSC in the murine model within 4 hours without significant side effects(ASH 2005). However, because there are possibilities of similar mechanisms during the HSC mobilization, which are shared by rhG-CSF or LTB4, in this study, we investigated the role of LTB4 receptors by rhG-CSF during HSC mobilization. LTB4APA and U75302, which are LTB4 receptor antagonists were given to C57BL/6 mice at different dose levels(0.5μg, 1μg, 2μg or PBS with equal volume in control arm) followed by rhG-CSF(5μg, IV) 2 hours later. 24 hours after the rhG-CSF injection, peripheral blood samples were obtained via cardiac puncture. The samples were analyzed for TNC using a trypan blue stain and FACS analysis were performed using Sca-1, Lin, CD45R(B220), CD116, Gr-1, TER119. The number of WBC and HSC were decreased in the rhG-CSF mobilized mice, in which LTB4 receptor antagonists were given. In those with up to 1μg of LTB4APA or U75302, there were tendencies of the blocking of the mobilization in the dose dependent manner. However, beyond 1μg of LTB4 receptor antagonists, the blocking effects plateaued. Interestingly, the blocking effects on mobilization by LTB4 receptor antagonists were more dramatic by the rh-GCSF than by the LTB4. Through our data, one can conclude that the LTB4 receptor is involved not only in the downstream pathway of rh-GCSF mobilization, but in the LTB4 mobilization pathway in C57BL/6 mice. Currently, hematopoietic stem cells mobilization is being tested to see the effects of rh-GCSF on LTB4 K/O mice. It is necessary to have insight into understandings more precise mechanisms on rhG-CSF and LTB4 mobilization for developing efficient protocols in the clinic.
Development of a Potency Assay for Umbilical Cord Blood.
Authors: Reems Jo Anna , Hall Karen M. , Gebru Luluday H. , Rich Ivan N. 
Published: October 2019

Abstract
Total nucleated cell counts, cell viability, CD34 cell numbers and the colony-forming cell (CFC) assay constitute the main parameters used to characterize the quantity and quality of progenitors present in a unit of umbilical cord blood (UCB) prior to transplantation. Of these parameters, only the CFC assay provides information about the functional potential of progenitors. However, technical difficulties associated with the CFC assay have made it difficult to standardize this method among various UCB banks. Consequently, we are focusing on the development of a novel assay that relies on determining the growth potential of progenitors in response to cytokines by measuring intracellular ATP levels (HALO SPC-QC, Hemogenix). This assay is based on the principle that cytokine stimulated proliferation responses by hematopoietic progenitors are proportional to the production of intracellular ATP. To perform the HALO assay, cells obtained from leukocyte enriched UCB units are added to cytokine impregnated methylcellulose media and deposited in replicates of 6 into 96-well plates. After 7 days of culture, cells are lyzed to release ATP, which drives a luciferin/luciferase reaction producing bioluminescence. ATP levels for each well are measured in a plate luminometer and the assay is standardized using an ATP control. Since proliferation, not differentiation is measured, the assay is completed in 7 days rather than the 10–14 days required for CFC assays. For mononuclear cells or erythrocyte-depleted cord blood, ATP levels for cell concentrations as low as 750 cells/well can be detected. An intra-laboratory study comparing total mean ATP (μM) production/well (6 replicates) to the CFC counts from mononuclear cells from UCB, showed a correlation coefficient of 0.99 (n=6). An inter-laboratory study using aliquots from the same UCB to compare the HALO and CFC assays at 2 geographically separate sites revealed correlation coefficients of 0.90 and 0.34 (n=10), respectively. Together these data indicate that the HALO assay is capable of measuring the clonogenic potential of UCB progenitors. These data also demonstrate that highly reproducible results can be achieved by different testing sites when measuring ATP production from proliferating progenitors. Thus, we suggest that the HALO method may be more conducive to standardization among UCB banks. We also propose that the HALO assay may be better than the CFC assay for accurately and precisely measuring the potency of an umbilical cord blood unit prior to transplantation.
Durable Engraftment with Minimal Toxicities after Allogeneic Hematopoietic Stem Cell Transplantation with a Reduced-Intensity Regimen Incorporating Fludarabine and 8 mg/kg Busulfan.
Authors: Uchida Naoyuki , Fukuda Takahiro , Wake Atsushi , Kim Sung-Won , Masuoka Kazuhiro , Mori Shin-ichiro , Miyakoshi Shigesaburo , Tanosaki Ryuji , Takaue Yoichi , Taniguchi Shuichi 
Published: October 2019

Abstract
Background: The optimal regimen for allogeneic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) needs to be established. Therefore, we retrospectively reviewed data of 84 patients who underwent RIST using 180 mg/sqm fludarabine and 8 mg/kg busulfan (Flu/Bu8). All patients received mobilized blood stem cells from a related donor between Nov. 2000 and Jun. 2005.
Patients and Methods: The median age of the patients was 53 years (range, 25–65). The diagnosis included 42 AML/MDS, 34 lymphoma and 8 others. Sixty-nine patients (82%) had high-risk diseases, including 56 (81%) in non-remission status before RIST. All were serologically 6/6 matched pairs, except for one who had a 5/6 match. For GVHD prophylaxis, 61 used cyclosporine A (CSP) alone, 21 used CSP + methotrexate (MTX), and 2 used some other compounds.
Results: The engraftment kinetics were remarkable since all of the patients successfully engrafted at a median of 11 days (5–24 days), with no late graft rejection. Toxicities of grade 2 or 3 according to CTCAE v.3 were observed at minimal frequencies, i.e. 38 mucosal, 35 hepatic, 13 GI tract, 12 renal, 2 cardiac, 1 pulmonary, 19 febrile neutropenia, and 9 documented infections, and there were no grade 4 toxicities. The administration of MTX increased the incidence and severity of stomatitis (P=0.05). The cumulative incidences of grade II–IV and III–IV acute GVHD were, respectively, 50% and 29%, and 76% experienced chronic GVHD. Seventy-three patients (87%), including 38 of the 56 patients who were not in CR at the time of transplant, achieved partial or complete remission. The median follow-up of surviving patients was 1349 days (34–1981 days), and the day-100 mortality was 11% (disease progression 6% and non-relapse mortality [NRM] 5%). The 5-year overall and progression-free survival rates were 36% and 30%, respectively. Among 46 total deaths, 27 were from disease progression and 19 were from NRM primarily related to GVHD. The patients in remission at transplant showed better overall survival than those who were not in remission (85 % vs 34 % at 5 years post-transplant, respectively, P<0.05). The 5-year overall survival was 85 % for those in remission at transplant and 34 % for the remaining patients (P<0.05). Multivariate analyses showed that age older than 52 years and non-CR status at transplant were associated with an increased risk for mortality after RIST.
Conclusions: Our study showed that RIST with this Flu/Bu8 regimen is feasible with durable engraftment and low early mortality. The clinical response rate is adequate for those who stayed in remission at transplantation, but otherwise a novel approach to prevent disease progression should be developed.
Pharmacokinetics and Tolerability of Intravenous Busulfan in Hematopoietic Stem Cell Transplantation.
Authors: Yoon Sung-Soo , Cho Yo-Han , Lim Hyun-Ae , Kim Inho , Bang Soo-Mee , Lee Jong Seok , Park Seonyang , Kim Byoung KooK 
Published: October 2019

Abstract
Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean SCT patients. IV busulfan was administered at 0.8 mg/kg every 6 hours for a total of 16 doses (days -7 to -4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 hours for 2 days (days -3 and -2). The median AUCinf values (at the 1st dose) and AUCss (at the steady state) were 1060.4 mM·min (range: 511.1– 1812.7) and 1092.5 mM·min (range: 539.7 – 1560.8), respectively. All patients had an AUCinf of < 1500 mM·min at the 1st dose, and 13 of the 16 (81.3 %) maintained AUCss levels between 800 and 1500mM·min. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable to those observed in other study. Thirteen of 16 patients achieved successful engraftments but 4 patients (25%) developed hepatic VOD (2 of which were fatal). Although there was no apparent correlation between AUC and hepatic VOD development, 3 out of 4 patients with VOD had advanced disease at the time of SCT. Notably, patients who had uncontrolled diseases (CML blast crisis, ALL 2nd relapse) succumbed to VOD and those who survived VOD had less advanced disease (CML CP, ALL in 2nd CR) at the time of SCT. In conclusion, pharmacokinetics of IV busulfan in our SCT patients appeared comparable to those observed in other studies, however, hepatic VOD was still a major morbidity, especially in patients with advanced disease, warranting consideration of other parameters in addition to pharmacokinetic monitoring of IV busulfan to decrease VOD in high risk patient populations.
Hepatic veno-occlusive disease cases (n=4) sex/age disease state AUCinf AUCss Outcome Comment F/41 CML blast crisis 511.0 539.7 death unrelated donor F/49 CML chronic phase 739.4 991.0 recovered F/39 ALL 2nd CR 1472.1 1465.6 recovered M/17 ALL 2nd relapse 1302.7 1560.8 death pseudomonas sepsis
Respiratory Syncytial Virus Infection Outbreak and Successful Treatment with IVIG and Oral Ribavirin among Pediatric Patients with Oncologic Diseases and/or BMT.
Authors: Anak Sema S. , Atay Didem , Garipardic Mesut , Ozalp Beril , Yani Diana , Agaaoglu Leyla , Ozturk Gulyuz , Unuvar Aysegul , Karakas Zeynep , Devecioglu Omer 
Published: October 2019

Abstract
Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy together with or without autologous/allogeneic stem cell transplantation (APBSCT), but there have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Between February 20 – April 15, 2006, among 15 pediatric patients hospitalized for various oncologic diseases and post-BMT problems, 7 patients developed progressive cough and/or dyspnea. A survey of respiratory viruses was done using direct immunofluorescent antibody assay. Three patients (two high-risk patients with acute lymphoblastic leukemia receiving induction or consolidation chemotherapy, one under treatment for chronic GvHD postBMT) were found positive for RSV (20%). The remaining patients with respiratory symptoms were followed-up for RSV infection, but remained negative during all surveys. Three patients and the sister of the boy with hyper-IgM syndrome, who was also transplanted for hyper-IgM syndrome and under treatment for chronic GvHD and pneumonia, in the same room with her brother, were all treated with IVIG and specific antiviral therapy, oral Ribavirin (20–25 mg/kg/day in three doses). All patients recovered fully, although two were retreated due to recurrent RSV positivity and respiratory symptoms within two weeks. In striking contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in postBMT period, is very low and can easily be treated with IVIG and oral Ribavirin, used effectively because of unavailability of other forms (iv or nebulized forms) in our country, if diagnosed and treated early enough. It is even possible to give the scheduled anti-neoplastic therapy for not being delayed.
Analysis T Cell Receptor Excision Circles (TRECs) in Patients with Graft-Versus-Host Disease (GVHD) after Allogeneic Stem Cell Transplantation.
Authors: Du Xin , Li Yangqiu , Weng Jianyu , Lu Zesheng , Guo Rong , Chen Shaohua , Yang Lijian , Geng Suxia , Huang Zhilun 
Published: October 2019

Abstract
The thymic-dependent pathway that involves generation of new naive T cells from donor-derived precursor cells accounts for the more durable reconstitution of the T-cell compartment and generates a more diverse TCR repertoire. Thymic function and production of recent thymic emigrants (RTEs) may be directly evaluated through the quantification, by real-time polymerase chain reaction (PCR), of the T-cell receptor excision circles (TRECs). Following hematopoietic stem cell transplant (HSCT), there is a prolonged period of profound immune deficiency, which continues for years after HSCT. The factors that inhibit thymic function may include age, graft-versus-host disease (GVHD), and direct thymic damage from chemoradiotherapy. GVHD after HSCT also leads to thymic insufficiency, possibly by direct attack on the thymic stroma by allogeneic effector cells. The aim of our study is to analysis T cell receptor excision circles (TRECs) in patients with GVHD after allogeneic stem cell transplantation. We used real-time polymerase chain reaction (PCR) to quantify SjTRECs in 12 patients with GVHD(9 males, 3 females; median age 32 years old), who underwent HLA-matching sibling BMT and/or peripheral blood stem cell transplantation (PBSCT) at our department. Quantitative detection of sjTRECs in DNA of peripheral blood mononuclear cells from 13 normal individualals. The median value of sjTRECs copies P1 000 PBMCs was 4.37±3.64 in normal indiviuals. However, the decreased levels of TRECs were most profound in the group of patients with active chronic GVHD at the time of study. it was 0.26±0.22 copies P1 000 PBMCs in 12 patients with GVHD (P < 0. 00007). We conclude that measurement of sjTREC may provide an important tool for predicting thymus-dependent T-cell reconstitution in GVHD patients after transplantation.
Puvatherapy in the Management of Graft-Versus-Host Disease: Brazilian Experience.
Authors: Bouzas Luis Fernando , Silva Marcia M. , Lerner Decio , de Cassia B. Tavares Rita , Azevedo Alexandre M. , Filgueira Absalom L. 
Published: October 2019

Abstract
Background: Graft-versus-host disease (GVHD) is a frequent late complication of allogeneic hematopoietic stem cell transplantation(HSCT) and remains a difficult problem to treat and manage. Therapy with 8-methoxypsoralen (8-MOP) and ultraviolet A to control drug resistant chronic graft-versus-host disease(c-GVHD) was based on the induction of functional changes in the effectors of the disease (T lymphocytes and cytokines). The potentially beneficial effect of phototherapy for treatment of cutaneous manifestations of GVHD led us to investigate retrospectively the effect of this therapy in a larger series of patients.
Methods: From May 1991 to April 2005, 43 patients post-bone marrow transplanted for malignant and non-malignant diseases, with c-GVHD were treated with PUVA. Extensive c-GVHD was diagnosed in 39 patients and 4 patients had limited disease. PUVA was administered three times a week with no oral mucosa direct exposure. 8-MOP dose was 0.6mg/Kg given two hours before UVA irradiation and initial dose was based on skin type(Fitzpatrick).
Results: From forty-three patients with resistant chronic graft-versus-host disease who were submitted to PUVAtherapy, three patients had began recently the treatment (less than 20 sessions) and were considered early to evaluated. Seven could not be evaluated because they had abandoned the treatment before complete 20 sessions. Early side effects were: nauseas, vomiting and gastric intolerance in 4 patients, burning in 6, photophobia in 2 and chronic effects were lentigo-PUVA in 1, guttate leukoderma in 1 and basal cell carcinoma in 1 patient. Immunosuppressive therapy was reduced in 7 patients and discontinued in 18 post-PUVAtherapy. Overall 25 patients(75,6%) responded to PUVA. Fifteen patients had complete response and 10 a partial response during PUVA treatment. Six patients(54,5%) from eleven had died from GVHD progression, during PUVAtherapy. The Kaplan-Meier estimate of survival at 3 years after the start of PUVAtherapy was 76%.
Conclusion: PUVAtherapy was effective for tegumental c-GVHD resistant to immunosuppression, improving the quality of life of these patients. Evidence of systemic effect of PUVAtherapy could be observed by oral lesions healed in all patients without direct exposure.
Predicting Risk of Infection and Graft vs. Host Disease (GvHD), and Response to Immunosuppression (ISP) in Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Patients (pts) Using the Cylex®ImmuKnow® Assay: A Pilot Study.
Authors: Anaissie Elias J. , Diaz Jose A. , Grazziutti Monica L. , Miceli Marisa H. , Fox-Cottler Michele , Barlogie Bart 
Published: October 2019

Abstract
Background: GvHD, intensity of ISP and infection are major causes of toxicity post-HSCT. Yet, no method reliably predicts these complications. A functional assay for immunity, which predicts risk of GvHD and infection and allows tailoring ISP and infection prophylaxis, is needed. The ImmuKnow is an assay of global T-cell function that measures increased ATP production after stimulating CD4+ T-helper cells and has been shown useful for managing ISP therapies in solid-organ transplantation. We hypothesized that ImmuKnow could assist in predicting risk of GvHD and infection and response to ISP post-HSCT.
Patients and Methods: Between January 2003 and May 2006, 34 adult allogeneic HSCT pts [mean age 47 years (range 22–71); 53% females; acute myelogenous leukemia, 8 pts; myeloma, 6 pts;] underwent blood sampling for determining ImmuKnow at various times post-HSCT (238 assays, mean of 7/pt). Results were correlated with clinical course (infection, stable, GvHD, response to ISP).
Results: During the testing period, GvHD was documented in 16 pts [(acute, n=7 pts; chronic, n=9 pts] and 53 infections occurred [CMV viremia (n=20); bacteremia (n=20); others (n=13)]. The median immune function (ng/mL ATP) of GvHD pts was significantly higher than that of clinically stable pts (342 +/−105 vs. 167 ng/mL +/−136 respectively), p<0.001. Pts with infections had a median 89 ng/mL ATP (+/−119), also statistically different (p=0.002) from stable pts. A pt with ATP value ≥ 300 ng/mL was more likely (RR=4) to develop GvHD than one with lower immune response. Similarly, there was a higher risk (RR=5) for infection in pts with an ATP ≤ 80 ng/mL. Relative risk curves for infection and GvHD intersected in the low immune response zone (140 ng/mL ATP). Following therapy for GvHD in 10 pts, ATP values rapidly decreased (193 ng/mL ATP +/−122) over 17 days (range 3–35) and were associated with improvement, while stable or increasing values (50 ng/mL ATP +/−99) were observed among 6 pts who failed to respond to GvHD therapy.
Conclusions: these data suggest that the FDA-approved ImmuKnow assay is an objective marker of risk for infection and GvHD, and of responsiveness to ISP therapy post-HSCT. Tailoring intensity and duration of ISP to risks of GvHD and infection in an individual pt may be possible and may improve outcomes. Validation of these preliminary data is ongoing.
Safety and Efficacy of Cytotoxic Chemotherapy after Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed Hematologic Malignancy.
Authors: Hardy Nancy M. , Odom Jeanne , Snow Kelly , Dean Robert , Pavletic Steven , Sportes Claude , Gress Ronald , Fowler Daniel H. , Bishop Michael R. 
Published: October 2019

Abstract
Relapse of hematologic malignancy is a major problem after allogeneic hematopoietic stem cell transplantation (alloHSCT), with limited treatment options of proven benefit other than donor lymphocyte infusions (DLI). Additionally, toxicity from treatment with cytotoxic chemotherapy after alloHSCT may differ from conventional treatments, and could include graft-versus-host disease, allograft failure, or increased risk of infection. We retrospectively reviewed treatment outcomes of 25 patients who received cytotoxic chemotherapy as treatment for relapsed hematologic malignancies after reduced-intensity, matched-sibling donor alloHSCT. Combination therapies included: EPOCH+/− rituximab (n=12 patients); “7&3” AML induction (ida/ara-c) (n=2); FLAG (n=2); asparaginase/6-MP/vincristine (n=1); R-ICE (n=1); MIME (n=1); BVP (n=1); and bortezomib/doxorubicin/dexamethasone (n=1). Single-agent therapies included: bortezomib (n=6); gemcitabine (n=4), vinorelbine (n=3); vincristine (n=1); methotrexate (n=1); and intrathecal methotrexate and/or cytarabine (n=5). A total of 133 cycles or doses were administered, of which 20 were supported with donor stem cell boosts, and another 9 were followed by nonmobilized DLI. There were 52 Grade 3 or higher toxicity episodes recorded, most commonly: neutropenia (10 episodes); infection with neutropenia (5 episodes); thrombocytopenia (6 episodes); and anemia (3 episodes). There were 12 episodes of CMV reactivation in 8 of 15 patients at risk, including 2 cases of pneumonitis and 1 case of colitis. GVHD flares were considered definitely chemotherapy-induced (2), possibly chemotherapy-induced (7), and unlikely chemotherapy-induced (2). Unusual events after treatment included culture-negative sepsis-like illness after bortezomib (n=2), secondary (11q23) AML of donor origin after one cycle of EPOCH (n=1) and diffuse alveolar hemorrhage after EPOCH (n=1). Seven patients achieved CR with therapy for post-transplant relapse, including three durable remissions. Four patients achieved PR and seven achieved disease stabilization. Median survival after starting cytotoxic therapy was 263 days. Timing of relapse appeared to be associated with survival, with median overall survival of 95 days for patients requiring therapy before Day 100 vs. 508 days for patients after Day 100 (p=0.0008). Treatment of relapse with cytotoxic chemotherapy after alloSCT is feasible and can result in durable remissions in a minority of patients. However, administration of cytotoxic therapy after alloHSCT requires monitoring and support for hematologic toxicities, GVHD and CMV reactivation; selected patients may benefit from prophylactic stem cell boosts or immune suppression.
Survival after Cytotoxic Therapy for Relapse after alloHSCT Survival after Cytotoxic Therapy for Relapse after alloHSCT