bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-Engraftment Serum C-Reactive Protein (CRP) Value as a Predictor of Acute Graft-Versus-Host Disease and Non-Relapse Mortality.
Authors: Fuji Shigeo , Kim Sung-Won , Fukuda Takahiro , Mori Shin-ichiro , Yamasaki Satoshi , Morita-Hoshi Yuriko , Ohara-Waki Fusako , Heike Yuji , Tobinai Kensei , Tanosaki Ryuji , Takaue Yoichi 
Published: April 2020

Abstract
Background: In a mouse model, it has been shown that inflammatory cytokines play a primary role in the development of acute graft-versus-host disease (GVHD). Here, we evaluated whether the pre-engraftment CRP value, which is used as a surrogate marker of inflammation, could predict post-transplant complications including GVHD.
Methods: The medical records of 224 adult patients (median age, 47 years; range, 18–68 y), who underwent conventional (CST, n=105) or reduced-intensity (RIST, n=119) allogeneic stem cell transplantation between January 2002 and July 2006 were reviewed retrospectively. Their diagnosis included AML (n=94), ALL (n=23), NHL (n=62), MDS (n=27) and others (n=18). Stem cell sources included bone marrow (n=108), peripheral blood stem cells (n=98) and cord blood cells (n=18). Patients were categorized according to the maximum CRP value during the pre-engraftment neutropenic period: the “low CRP” group (CRP &lt; 15 mg/dL) included 157 patients and the “high CRP” group (CRP≥15 mg/dL) included 67 patients. We assessed the occurrence of acute GVHD, non-relapse mortality (NRM) and overall survival.
Results: The incidence of documented infections during neutropenia was higher in the high CRP group (34% vs 17%, P=0.004). The CRP value was significantly lower after RIST than after CST (P=0.017) or after related than after unrelated transplantation (P&lt;0.001). A multiple logistic regression analysis showed that male sex, unrelated donor and HLA-mismatched donor were associated with high CRP values. The high CRP group developed significantly more grade II-IV acute GVHD, grade III-IV acute GVHD and NRM as shown in Figure 1 and 2. A multivariate analysis showed that a high CRP level was associated with an increased risk of grade II-IV acute GVHD, poor OS and high NRM.
Conclusion: The present findings suggest that the CRP value may reflect the net degree of tissue damage due to the conditioning regimen, inflammation, infection and allogeneic immune reactions, all of which lead to subsequent acute GVHD and NRM. Future clinical studies to evaluate the feasibility of earlier intervention and adjustment of GVHD prophylaxis based on monitoring of the early CRP value are warranted.
Fig 1 grade II-IV acute GVHD Fig 1. grade II-IV acute GVHD Fig 2 non-relapse mortality Fig 2. non-relapse mortality
Analysis of Predictive Power of Prednisone Dose at 3 Months of Treatment on CGVHD Prognosis.
Authors: Parker Pablo M. , Nakamura Ryotaro , Pullarket Vinod , Rosenthal Joseph , Smith Eileen P. , Snyder David S. , Zain Jasmine M. , Somlo George , Brown Annette , Kim Hanjoo , Palmer Joycelynne , Cai Ji-Lian , Delioukina Maria L. , Falk Peter M. , Karanes Chatchada , Kogut Neil M. , Krishnan Amrita , Nademanee Auayporn P. , O’Donnell Margaret R. , Popplewell Leslie , Sahebi Firoozeh , Spielberger Ricardo , Stein Anthony S. , Forman Stephen J. 
Published: April 2020

Abstract
Current CGVHD prognostic and staging systems are still undergoing development and have identified plt count; CGVHD types progressive(P), quiescent(Q), de novo(DN); KPS, and GI involvement as significant risk factors affecting outcome. A simple reproducible staging system such as used for AGVHD to apply in clinical trials is still lacking. We evaluated whether the PSE dose required to control CGVHD at 3 months from diagnosis would have a prognostic effect on survival and in and of itself serve as a criteria for secondary intervention or investigational therapy. We hypothesized that by 3 months from start of treatment patients would be on the lowest dose dictated by medical necessity rather than by physician driven dose preference. A retrospective analysis of charts from 109 patients diagnosed with CGVHD between 6/2000 and 6/2003 was done. Data collected included age, donor type(mud/sib), plt count, CGVHD type(P/Q/DN), KPS, GI involvement. Outcome analysis included survival and cause of death. PSE dose was calculated in mg/kg at 3 months from first diagnosis of CGVHD. With a median follow up of 47.2 months(range 6.6–67.2) relapse censored survival of patients on a 3 month PSE dose of more than .3 mg/kg was 53% compared to all lower doses 86%(P.03). In a univariate analysis only PSE dose (P .05) and KPS (P &lt;.01) were significant with plt count approaching significance (P .11). In a multivariate analysis again only PSE dose and KPS were significant (Table 1).
Table Univariate Multivariate Variable Value N # of deaths Hazard Rate Ratio (95% CI) p value Hazard Rate Ratio (95% CI) p value Prednisone at 3 month 0 20 1 Baseline 0.05 Baseline 0.1–0.14 18 2 3.0 (0.3–32.7) 3.7 (0.3–43.4) 0.33 0.15–0.29 22 3 2.9 (0.3–28.2) 3.4 (0.3–34.5) 0.32 0.3–0.59 16 7 9.8 (1.2–79.4) 9.3 (1.1–76.0) 0.04 0.6–0.99 0 0 n/a n/a n/a ≥1.0 0 0 n/a n/a n/a cGVHD class Denovo 29 5 Baseline 0.54 Progressive 23 7 1.9 (0.6–6.0) Quiescent 57 13 1.3 (0.5–3.8) Donor type Sibling 48 9 Baseline 0.40 Unrelated 61 16 1.4 (0.6–3.2) Platelet count at 3 month &lt;100 28 9 Baseline 0.11 Baseline ≥100 81 16 0.5 (0.2–1.1) 0.7 (0.2–2.3) 0.59 KPS at 3 month &lt;80 14 7 Baseline &lt;0.01 Baseline ≥80 95 18 0.2 (0.1–0.5) 0.3 (0.0–1.3) 0.03 Lower GI at 3 month No 98 22 Baseline 0.78 Yes 9 2 1.2 (0.3–5.2) Overall survival by Prednisone dose Overall survival by Prednisone dose
The analysis of this data to date suggests the PSE dose at 3 months may be an important independent clinical marker for subsequent CGVHD prognosis which could be used to decide which patients to include in 2nd line and experimental therapy trials.
Obesity Does Not Impact Outcome in Patients with AML/MDS Undergoing Allogeneic Transplantation.
Authors: De Padua Silva Leandro , Saliba Rima M. , de Lima Marcos , Okoroji Grace J. , Alousi Amin , Andersson Borje , Hosing Chitra , Sphall Elizabeth , Khouri Issa , Qazilbash Muzaffar , Anderlini Paolo , Kebriaei Partow , Champlin Richard E. , Jones Roy , Giralt Sergio , Popat Uday 
Published: April 2020

Abstract
Background: Impact of obesity on transplant outcome is unknown. We hypothesized that obesity increases allogeneic transplant related morbidity/mortality. We therefore performed a case control study of obese patients with AML and MDS undergoing allogeneic transplant (AlloSCT) at our institution.
Patients and Methods: Sixty one patients with AML or MDS and a Body Mass Index (BMI) greater than 35 were transplanted from 1987 and 2006. 61 control patients were identified with BMI less than 30. The patients had similar characteristics. Controls were matched for age (within 5 years), disease status (relapse or remission), donor type (sib or MUD) and conditioning regimen.
Results: The median weight of obese patients was 109.5 Kg (range 78–151.3 Kg). Obese and controls had similar distribution of age (median age 47 years and 46 years respectively). Likewise gender, disease status, and cytogenetic risk groups were similar in the two groups. The majority (62%) of patients in both groups had IV Busulfan based conditioning therapy, while 11% had a TBI based regimen and 26% in both groups had reduced intensity conditioning with Fludarabine and Melphalan. Donor was a matched sib in 65% of cases and 66% of controls. The median time between transplant day and discharge was 23 days (range 14–98days) in both groups. Only significant difference between the two groups was the presence of comorbidites in obese patients. 75% of cases had a comorbidty score of 3 or more compared to 38% of controls (p&lt;0.001) as defined by HCT index. Outcomes were similar in both groups. Two year non relapse mortality was 27% (95% CI: 18%-42%) in obese patients and 27% (95% CI: 17%- 41%) in control patients. Grade 3–4 toxicities occurred in 55% of cases compared to 42% of controls (p=0.2). Three-year disease free survival was 44% (95% CI: 31%- 57%) and 42% (95% CI: 29%- 55%) respectively in cases and controls. Median overall survival was 18 months for obese patients and 26 months for controls; 3-year overall survival was not significantly different in the two groups: 45% (95% CI: 31%- 58%) and 45% (95% CI: 31%- 58%) respectively for cases and controls.
Conclusion: Despite the higher prevalence of comorbidities in obese patients, obesity did not impair outcome in patients with AML/MDS undergoing AlloSCT. Hence, obesity should not be considered a contraindication to AlloSCT.
Evaluation of AMG 531 Efficacy in Splenectomized Patients with Chronic Immune Thrombocytopenic Purpura (ITP) in a Randomized Placebo-Controlled Phase 3 Study.
Authors: Gernsheimer Terry B. , Pullarkat Vinod , Senecal Francis M. , Aledort Louis M. , Kessler Craig M. , Sanz Miguel A. , Liebman Howard A. , Slovick Frank T. , Kelly Reggie , Guo Matthew , Nichol Janet 
Published: April 2020

Abstract
AMG 531 is a novel thrombopoiesis-stimulating peptibody that acts by stimulating the thrombopoietin (TPO) receptor. We report efficacy data in splenectomized patients from a randomized, double blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of AMG 531 in patients with chronic ITP. Sixty-three splenectomized patients were enrolled (placebo, 21; AMG 531, 42), with a median age of 52 years (range 26 to 88) and a mean baseline platelet count 14.7x109/L. Subcutaneous AMG 531 or placebo was administered weekly for 24 weeks at a starting dose of 1μg/kg, and adjusted to maintain a target platelet count of 50–200x109/L. The primary study endpoint was the incidence of a durable platelet response, defined as a platelet count ≥50x109/L for ≥6 weeks during the last 8 weeks of the 24 week treatment period in the absence of rescue medications. Sixteen of the 42 splenectomized patients (38.1%) receiving AMG 531 achieved a durable platelet response compared to 0/21 (0.0%) receiving placebo (p=0.0013). Overall response, defined as either durable or transient platelet response (≥4 weekly platelet responses), was observed in 33/42 (78.6%) patients receiving AMG 531, compared to 0/21 (0%) placebo patients. The mean number of weekly platelet responses (platelet count ≥50x109/L) was significantly greater in patients receiving AMG 531 (12.3/24 weeks, 51%) compared to placebo (0.2/24 weeks, 1%) (p&lt;0.0001). AMG 531 reduced the proportion of patients requiring ITP rescue medications, defined as either increase from baseline in dose of concurrent medication or use of new medication to increase platelet counts. Twelve of 21 (57.1%) placebo-treated patients received rescue medications compared to just 11/42 (26.2%) AMG 531-treated patients (p=0.0175). In addition, 12/12 (100.0%) AMG 531-treated patients compared to 1/6 (16.7%) placebo-treated patients either discontinued or reduced by &gt;25% their concurrent ITP medications. AMG 531 was well-tolerated. There were 2 treatment-related serious adverse events; 1 patient with elevated bone marrow reticulin that returned to baseline 3 months after withdrawal of AMG 531, and 1 patient experienced thrombosis that was successfully treated allowing study continuation. No patient developed neutralizing antibodies against either AMG 531 or endogenous TPO. In summary, AMG 531 was well-tolerated, and effectively increased and sustained platelet counts in splenectomized patients with ITP. AMG 531-treated patients required less frequent rescue medications in comparison to those receiving placebo, and were able to reduce their use of concurrent therapies.
Double Cord Blood Transplantation in Bone Marrow Failure Syndromes.
Authors: de Latour Regis Peffault , Rocha Vanderson , Robin Marie , Rodrigues Celso A. , Rea Delphine , Laghero Jerome , Traineau Richard , Ribaud Patricia , Ferry Christelle , Devergie Agnes , Gluckman Eliane , Socie Gerard 
Published: April 2020

Abstract
The outcome of severe aplastic anemia, refractory to immunosuppressive therapy or observed in case of Fanconi anemia (FA), is usually poor in the absence of Hematopoietic Stem Cell Transplantation (HSCT). Umbilical cord blood is an alternative stem cell source for patients without matched related or unrelated donors. However, single cord blood unit is associated with high transplant related mortality due to the low cell dose infused in previous highly transfused patients. We have driven the hypothesis that double cord blood transplantation (dCBT) could circumvent the cell dose problem. For the purpose of this study, we have studied 13 patients with bone marrow failure syndromes given 2 partially matched dCBT from 2004 to 2007. The diagnoses were FA (n=9), SAA (n=4) and PNH (n=1). Among those patients, 5 (39%) received a dCBT as a rescue of previous rejected transplants (2 SAA and 3 FA). All patients received a fludarabine-based regimen, with TBI (2 Gy) for 4 patients. Cord blood units were a 4/6 or 5/6 HLA A, B and DR match with the patient except one which was 3/6. Graft versus host disease (GVHD) prophylaxis consisted in CSA+MMF. Steroids were given from day 7 to day 14 and stopped in case of no GVHD. Five male (39%) and 8 female (61%) with a median age of 16 years (range 7–31) were treated. The cell doses infused were a median of 5.0 × 107 NC/Kg (4–9) and 5.3 × 105 CD34+ cells/Kg (2–8). Graft rejection was seen in 5 patients (2 previously allotransplanted). Among those patients, one displayed a temporary mixed chimerism before rejection and another presented an autologous reconstitution. Among the remaining 8 patients, the median time to an absolute neutrophils count &gt; 500 was 25 days (range 14–42) and the median time to a platelet count &gt; 20,000 was 39 days. In these last patients, we observed a complete donor chimerism with one cord blood unit during 100 days after dCBT. Acute GVHD grade II–III was scored in 9 patients (69%) (7 grade II, 2 grade III). No patients presented acute GVHD grade IV. Four patients out of 8 developed Chronic GVHD (3 limited and 1 extensive). Four patients died (1 GVHD, 2 fungal infection, 1 thrombotic microangiopathy). With a median follow-up of 13 months (range 1 to 19 months), the overall survival was 55% (±15%) for all patients. The median survival of patients who were transplanted twice was 50% (±25%). In conclusion, dCBT seems to be an option to treat patients with bone marrow failure syndromes and without a suitable compatible HLA donor. Those results need to be established on a large number of patients to warrant the inclusion of dCBT in the treatment strategy of diseases with high risk of rejection.
Unrelated Cord Blood Cell Transplantation for Acquired Severe Aplastic Anemia: The Report from the Japan Cord Blood Bank Network.
Authors: Kojima Seiji , Yoshimi Ayami , Taniguchi Shuichi , Hara Junichi , Matsui Toshimitsu , Kato6 Shunichi 
Published: April 2020

Abstract
Treatment approaches for patients with severe aplastic anemia (SAA), who failed immunosuppressive therapy and lack a bone marrow donor remains a great challenge. Unrelated cord blood transplantation (UCBT) has not been recommended for SAA because of historical poor outcome with high rate of engraftment failure. To evaluate the current feasibility of UCBT in SAA, we retrospectively analyzed the outcomes of 31 patients (median age 28 years old; ranged 0.9–72.3 years old) with SAA, who received UCBT as the first graft between 1998 and 2006 in Japan. Median disease duration before UCBT was 337 day (31–5063 days). By serology, HLA loci were matched in 4 recipient-donor pairs and mismatched (1–2 loci) in 27 patients. A minimum cell count of 2 × 107 nucleated cells/kg body weight was infused in all patients. Engraftment was observed in 17 of 24 evaluable patients. The median times to achieve a neutrophil count ≥ 0.5 × 109/l and a platelet count ≥ 50 × 109/l were 19 days (range 12–35 days) and 59 days (range 39–145 days), respectively. The results of chimerism analysis were available in 9 of them and all of them showed complete donor chimerism (&gt;99%) except one with autologous recovery. Late rejection was seen in one patient. Acute GVHD (≥ grade II) was observed in 5 of 18 evaluable patients (grade II; n=4, grade III; n=1) (cumulative incidence =17.1%) and chronic GVHD was observed in 4 of 14 evaluable patients (extensive: n=1, limited: n=3) (cumulative incidence =19.7%). Currently, 13 patients are alive, having survived for median 22.5 months (ranged 3 to 77 months) after UCBT (overall survival at 2 years=40%). Causes of death of 18 patients were following: graft failure (n=7), bacterial/fungal infections (n=3), hepatic veno-occlusive disease (n=3), and others (n=5). The conditioning regimen appeared to be the most important factor for the outcome and low dose total body irradiation (2–4 Gy) + fludarabine (90–250/ mg/m2) and cyclophosphamide (50–100 mg/kg or 2250/mg/m2) (n=5) gave the best outcome with 80% of survival. The GVHD prophylaxis with single agent (cyclosporine or tacrolimus) related with a better engraftment rate than 2 or more agents (84.4% vs 47.3%, p=0.02). These results suggest that UCBT can be a salvage treatment for patients without a bone marrow donor and warrant further evaluation in prospective studies. Optimization of conditioning regimen will improve the engraftment and outcome of UCBT.
Unrelated Cord Blood Transplanation for Malignant Lymphoma: A Retrospective Study from the Japan Cord Blood Bank Network (JCBNW).
Authors: Takita Morihito , Yuji Koichiro , Yamaguchi Takuhiro , Matsumura Tomoko , Kami Masahiro , Sakamaki Hisashi , Kouzai Yasushi , Okada Masaya , Osugi Yuko , Kobayashi Ryuji , Inoue Masami , Takahashi Satoshi , Murata Makoto , Kai Shunro , Kato Koji , Nagamura Tokiko , Taniguchi Shuichi , Kato Shunichi 
Published: April 2020

Abstract
Unrelated cord blood transplantation (u-CBT) may provide a treatment option for patients with malignant lymphoma (ML) who have failed other conventional therapies and do not have a compatible donor available. Japan Cord Blood Bank Network (JCBNW) has established a registry for u-CBT as a quality management and promotion of CBT. We have analysed 271 patients with ML (aggressive lymphoma=189, indolent lymphoma=52) transplanted from 1999–2006 and reported to JCBNW. The median follow-up was 19 months (1–85) and the median age was 47 years (1–75). At transplant, 83% of the patients are non-CR and 23% had received previous autologous transplants. The conditioning regimen varied according diasease and centers: reduced intensity conditioning regimens (RIC) were used in 49% and ATG/ALG was added in 5% of the cases. GVHD prophylaxis consisted of CsA alone (23%), CsA/sMTX (28%), TAC alone (18%), TAC/sMTX (11%) and others (20%). The median nucleated cell dose infused was 2.6 × 10^7/kg and the graft was HLA identical (6/6) (HLA A and B low resolution and DRB1 allelic typing) in 37 cases, 5/6 in 110, and 4/6 in 122. Median time to neutrophil recovery (&gt;500/mm3) was 22 days (0–61) and 39 days for platelets recovery (&gt;20.000/mm3). The probability of neutrophil recovery was 80%. Grades II–IV aGVHD was observed in 50%. Treatment-related mortality (TRM) was observed in 107 patients (39%), and 61% of them were related to infection. The overall survival (OS), disease-free survival (DFS), and cumulative incidences of disease progression at 2 years after u-CBT were 28%, 21%, and 11%, respectively. In a multivariate analysis, chemoresistance, bacterial infection, and cGVHD were identified as adverse prognostic factors for overall survival. The development of grades II–IV aGVHD was associated with higher rate of DFS, which suggested the existence of a graft versus lymphoma effect. Althouth u-CBT can be an effective therapeutic option for patients with refractory ML, more work is still needed to decrease TRM.
Immunological Responses in CLL Patients Vaccinated with Autologous Dendritic Cells Loaded with Apoptotic Bodies (Apo-DC).
Authors: Choudhury Aniruddha , Palma Marzia , Hansson Lotta , Widen Karin , Eriksson Ingrid , Nasman-Glaser Barbro , Adamson Lars , Osterborg Anders , Mellstedt Håkan 
Published: April 2020

Abstract
We have previously established the suitability of dendritic cells that have endocytosed apoptotic B-CLL cells (Apo-DC) as an antigen presentation platform to stimulate autologous antileukemic immune responses. The safety as well as immunological and clinical efficacy of Apo-DC vaccination was tested in a phase I/II clinical trial. CLL patients (Rai stage 0–2) who did not require concurrent therapy were leukapheresed and CD14+ monocytes as well as CD19+ B-CLL cells were purified immunomagnetically. Dendritic cells were generated ex vivo with GM-CSF and IL-4. Apoptotic bodies were obtained by irradiating B-CLL cells and overnight culture. DC were allowed to endocytose the apoptotic bodies and further matured with TNFα. The first cohort of 5 patients received 4 doses of the vaccine 2 weeks apart and a 5th dose at week 14. Each vaccine dose comprised of 107 autologous Apo-DC. The second cohort of 5 patients received the vaccine in a similar schedule with the addition of 75 μg of GM-CSF (Leukine™, Berlex Laboratories, Richmond VA) with every vaccine administration. Patients are scheduled to be monitored for a minimum of 52 weeks which has been completed for all of the patients in cohort 1 and is ongoing for cohort 2 The vaccine was well tolerated and occasional, low-grade toxicity was associated with the administration of GM-CSF. 4/5 patients in cohort 1 and 3/5 patients in cohort 2 responded immunologically in terms of increase in T cell proliferation or γ-IFN ELISPOT against autologous leukemic targets compared to prevaccination levels. Analysis of T cell responses at week 8 and week 16 following vaccination did not demonstrate an obvious augmentation of immunity by GM-CSF. One patient in cohort 1 demonstrated a transient decrease in WBC counts but no significant clinical responses have been noted thus far. Our results demonstrate that it is feasible to enrich monocyte precursors and generate Apo-DC for vaccinating patients with high count B-CLL. No significant toxicity was associated with this approach to vaccination therapy. The clinical efficacy of Apo-DC vaccination in CLL remains to be determined at the termination of the clinical trial.