bluuebunny/crossref_metadata_2025_split huggingface dataset:
GM-CSF in Stem Cell Transplant (SCT) Recipients: Impact of Graft-Versus Host Disease on Invasive Fungal Infections (IFIs)
Authors: Safdar Amar , Rodriguez Gilhen , Georgescu Georgina , Champlin Richard 
Published: April 2020

Abstract
Background: GM-CSF is thought to be beneficial in SCT patients with IFI. The impact of GM-CSF in SCT recipients with GVHD and IFI was evaluated
Methods: A retrospective case-matched (GM-CSF [n = 12] vs. no GM-CSF [n = 27]) study was undertaken to compare outcomes if IFIs diagnosed &gt;100 days following transplantation during 2000–2006. A response was defined as complete or partial response (CR/PR) and considered 3 months after IFI diagnosis or earlier in patients with earlier response. All value are given as median ± s.d. The systemic antifungal therapy in &gt; 60% of patients included echinocandin and anti-mold triazole, or polyene agent.
Results: Please refer to the table below. Patients who received GM-CSF were younger (age 36 ± 17 vs. 51 ± 13 years); neutropenic (&lt;500 cells/uL) at onset of infection (50% vs. 11%; P = 0.014); had lower monocyte counts (10 ± 236 vs. 220 ± 575 cells/uL; P = 0.021) and frequently required intensive care unit stay (50% vs 15%; P = 0.043). A 50% response was observed in the GM-CSF treated SCT recipients with GVHD and IFIs, whereas, 41% response occurred in the group who received no concurrent Gm-CSF (P = 0.6). Similarly, IFI-associated deaths were less frequently observed in GM-CSF treated patients (41%) compared with 55% seen in patients who had not received GM-CSF (P = 0.7). There was a slight increase in survival among SCT recipients treated with GM-CSF (48 ± 21 days vs. 34 ± 19 days in no GM-CSF group P = 0.05)
Conclusions: Late fungal infections in SCT recipients with GVHD, when treated with GM-CSF-based therapy had comparable outcomes despite having significantly more neutropenia, severe monocytopenia and ICU stay.
Characteristics GM-CSF N = 12 (5% No GM-CSF N = 27 (%) p-value Underlying Disease-Leukemia Relapsed/refractory Cancer 10 (83) 5 (42) 18 (67) 6 (22) 0.12 0.26 Proven and probable IFI 9 (75) 21 (78) 1 GVHD (extensive) 5 (42) 14 (52) 0.57 High Dose Steroids 7 (58) 18 (67) 0.72 Disseminated IFI 3 (25) 4 (15) 0.65 Breakthrough IFI 10 (83) 25 (93) 0.57 APACHI II Score at time of IFI diagnosis 11+/−4 (range 5–18) 12+/−3 (range 5–19) 0.47
CD3−cd(16+56)+ Cell Dose Is An Important Factor Determining Clinical Outcomes in Patients Undergoing Unmanipulated HLA-Identical Sibling Hematopoietic Stem Cell Transplantation
Authors: Tang Xiaowen , Peng Biyun , Zhu Mingqing , Depei Wu , Sun Aining , Ruan Changgeng 
Published: April 2020

Abstract
Background: It has been suggested that the dose of the cellular components in the graft may influence the outcome of transplantation, especially CD3 |CD(16+56)+ cell(NK cell) is believed to play an important role in improving the transplant outcome in terms of preventing graft-versus-host disease(GVHD) and graft rejection, and as a mediator of the graft-versus-leukemia(GVL) effect. The current study attempted to evaluate the role of CD3−CD(16+56)+ cell dose on the outcome of HLA-identical sibling hematopoietic stem cell transplantation.
Methods: We retrospective analyzed the outcomes of 72 patients receiving HLA-identical sibling hematopoietic stem cell transplantation between July 2005 and May 2008 in the first Affiliated Hospital of Soochow University. Diagnoses of these patients included acute leukemia(AL)(n=34), chronic myeloid leukemia(CML) (n=29), aplastic anemia(AA) (n=4), malignant lymphoma (n=3) and multiple myeloma (n=2). The median follow-up time is 19 months (range 0.5–36 months) after transplantation. Transplanted doses of CD3 |CD(16+56)+ cell were analyze in relation to engraftment, GVHD, infectious events, relapse and survival.
Result: The median dose of NK cell in bone marrow grafts from patients receiving G-CSF-mobilized was 0.91× 107/Kg. Therefore the group received a dose of CD3 |CD(16+56)+ cell above 0.91×107/Kg wass a higher group. There were no significant difference between two groups for neutrophil and platelet recovery. The incidence of II°-‡W°aGVHD in low group was much more than that of high group(41%VS 18.2%, P&lt;0.05). and there was a significantly higher incidence of infection in patients receiving a lower dose of CD3 |CD(16+56)+ cell (46.1%VS 21.2%, P&lt;0.05). However there was no significant association between CD3-CD(16+56)+ cell and either cGVHD or relapse.
Conclusions: High dose of CD3−CD(16+56)+ cell may play an important role in improving the outcome of transplantation in terms of reducing aGVHD and infection.
Allogeneic Stem Cell Transplantation for Core Binding Factor Alpha-Positive Adult Acute Myelogenous Leukemia with a Reduced Intensity Conditioning Regimen Consisting of Intravenous Busulfan, Fludarabine, and 400 cGy Total Body Irradiation
Authors: Kim Heeje , Min Woo-Sung , Cho Byung-Sik , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Lee Jong-Wook , Kim Chun-Choo 
Published: April 2020

Abstract
Translocation (8;21) in core binding factor alpha acute myelogenous leukemia (CBFA-AML) leads to the generation of the AML1-ETO fusion gene, which is generally associated with a favorable prognosis. Nevertheless, in line with recent reports based on mutation studies of the c-kit, FLT3, and Ras genes, we have also experienced poor clinical outcomes in some patients with CBFA-AML, with rapid relapse of patients within a few months of conventional intensive chemotherapy with cytosine arabinoside or even autologous stem cell transplantation (SCT) for patients in complete remission (CR). A few studies have used SCT as part of the therapeutic approach for CBFA-AML. To study the role of SCT, in light of the advances of transplant techniques, we performed a prospective study combining SCT with a novel reduced intensity conditioning (RIC) regimen. There were 10 men and 3 women with a median age of 42 years (range 17–50). Seven patients were categorized as CBFA-AML with additional cytogenetic abnormalities. Two patients had either FLT3-ITD or c-kit mutations. All CBFA-AML patients in CR received one cycle of consolidation chemotherapy before undergoing allogeneic SCT. Four patients had HLA-matched unrelated donors and the other donors were HLA-matched siblings. The preparative regimen comprised fludarabine 30 mg/m2 on days–6 to –2, intravenous busulfan (Busulfex, Kirin-Brewery, Japan) 3.2 mg/kg/d on days–5 to –4, and fractionated total body irradiation (TBI) 200 cGy × 2 on day–1. Cyclosporine A (CsA) and a short course of standard dose methotrexate were used to prevent graft-versus-host disease (GvHD). If no acute GvHD occurred, the CsA was tapered over 4~8 weeks with the intent to discontinue by 3 to 5 months. All patients were engrafted successfully. Eleven patients are alive at a median follow-up of 12 months (range 3–18). Four (31%) out of 13 patients developed acute GvHD, and none were grade &gt;II. Six patients (46%) developed chronic GvHD and three of them were extensive type. Of the three patients who died, two received SCT from HLA-matched sibling donors and died due to relapse at 8 and 10 months post-transplant, respectively; the other, who had received SCT from an HLA-matched unrelated donor, died at 7 months due to sepsis combined with extensive chronic GvHD in CR. The estimated 2-year overall survival and event-free survival rates were both 77%. We suggest that allogeneic SCT with this novel RIC for heterogeneous CBFA-AML patients is a feasible option with no detrimental post-transplant complications and less frequent relapse. Further, well-designed studies with more patients, comparing our regime to conventional high-dose chemotherapy, are needed to confirm these findings.
T-Cell Depleted Unrelated Donor Stem Cell Transplants Appear to Be of Value for Adult Philadelphia Chromosome Negative ALL Patients and Should Be Evaluated Prospectively in New Large Group Studies
Authors: Patel B. R , Kirkland Keiren , Pearce R. , Clark Richard E , Craddock Charles F. , Liakopolou Effie , Fielding Adele K , Mackinnon Stephen , Olavarria Eduardo , Potter Michael N , Russell Nigel H. , Shaw Bronwen E. , Goldstone Anthony H. , Marks David I 
Published: April 2020

Abstract
Matched sibling allogeneic haematopoietic stem cell transplantations (HSCT) in first complete remission (CR1) result in superior survival compared to standard chemotherapy in adult patients with acute lymphoblastic leukaemia (ALL). However, application is limited by donor availability. The role of unrelated donor (URD) transplantation in ALL in CR1 is not clearly delineated. We report a retrospective series of URD transplants in 55 adults with Philadelphia chromosome (Ph) negative acute lymphoblastic leukaemia (ALL) in CR1 reported to the British Society of Blood and Marrow Transplantation registry from 1993 to 2005. Median follow-up of survivors was 55.2 months (range 17–160). Median age was 25.5 years (range 15.7–50). Eighty nine percent of patients had at least one adverse prognostic feature. Sixty six percent of transplants were matched at 10 of 10 loci and 34% were mis-matched. T cell depletion (TCD) was carried out by in-vivo Campath administration in 96% of recipients with additional ex-vivo TCD in 21% of these patients. The estimated actuarial Overall survival (OS), Disease free survival (DFS) and non relapse mortality (NRM) were 59%, 57% and 19% at 5 years respectively. The overall incidence of Grade II–IV and III–IV GVHD was 25% and 7% respectively. The actuarial estimate of extensive chronic GVHD was 22 % at 5 years. HLA mismatching at 2 alleles or antigens was associated with poorer survival (RR=3.22, (1.08–9.64). T depleted URD HSCT can result in good OS and low TRM for adults with high risk ALL in CR1 and merits prospective comparison with other methods of GVHD prophylaxis.
Busulfan and Cyclophosphamide for Hemopoietic Stem Cell Transplantation from Related and Unrelated Donors in Patients with Myelodysplastic Syndrome
Authors: Shi Jimin , Huang He , Cai Zhen , Luo Yi , Zheng Weiyan , He Jingsong , Xie Wanzhuo , Li Li , Ye Xiujin , Zhang Jie , Lin Maofang 
Published: April 2020

Abstract
The myelodysplastic syndromes (MDS) are clonal hemopoietic disorders, characterized by ineffective hemopoiesis resulting in single or multilineage peripheral blood cytopenias, dysplastic morphology in single or multiple lineages, and, in many patients, clonal cytogenetic abnormalities. Hematopoietic stem cell transplantation is currently the only therapeutic modality that is potentially curative. A total of 17 patients (aged 16–40 years; median, 26 years) with MDS were treated with busulfan (BU 3.2 mg/kg/d, −7 d `−4 d,) plus cyclophosphamide (CY, 60 mg/kg, −3 d `−2 d)and hemopoietic stem cell (HSC) transplantation from related (n =5) or unrelated donors (n =12). At the time of transplantation, 13 patients had less than 5% myeloblasts in the marrow, and 4 patients had more advanced disease. Mycophenolate mofetil combined with cyclosporin A and methotrexate was used for prevention of acute graft-versus-host disease after transplantation. Lipo prostaglandin E1 was used in prophylactic regimen for hepatic venoocclusive disease. All but 2 evaluable patients had engraftment. Neutrophil count began to be higher than 0.5×109/L on 15 days after BMT. Platelet count began to be higher than 20×109/L on 18 days after BMT. The Kaplan-Meier estimates of 3-year relapse-free survival (RFS) were 57%, and only one patient relapsed after six months of transplantation. Non relapse mortality (NRM) at 100 days was 12%. Thus, a targeted BUCY regimen provided effective transplant conditioning for patients with MDS receiving transplants from HLA identical siblings or alternative donors.
Timing of G-CSF Injection for Effective Autologous Stem Cell Collection
Authors: Kim Jeong-Eun , Suh Cheolwon , Choi Yunsuk , Kim Eun Kyoung , Sohn Byeong Seok , Park Inkeun , Yoon Dok Hyun , Yoo Changhoon , Jang Geundoo , Kim Shin , Lee Dae Ho , Kim Sang -We , Lee Jung Shin 
Published: April 2020

Abstract
Granulocyte colony-stimulating factor (G-CSF) has been given approximately 12 hours before leukapheresis in the patients who are planned to do autologous stem cell collection. The objective of this study was to identify better timing of G-CSF administration which improves the efficacy of autologous stem cell collection. A total of 262 patients (157 male and 105 female patients, ages from 15 to 66 years with median of 49 years) who underwent autologous stem cell collection from January 2000 to March 2008 were included. The patients were diagnosed with Hodgkin’s lymphoma (N=19), non-Hodgkin’s lymphoma (N=131) and multiple myeloma (N=112). Peripheral blood stem cells were mobilized with lenograstim (Choongwae Pharma Corp., Seoul, Korea) following chemotherapy, such as cyclophosphamide (N=141), ESHAP (Etoposide, methylprednisolone, Ara-C and cisplatin, N=73) with (N=14) or without rituximab (N=59) and other chemotherapy regimens (N=48). Before November 2004, patients received lenograstim injection at a dose of 10 μg/kg subcutaneously at 8:00 PM and underwent peripheral stem cell collection on next day (N=129). After then patients received lenograstim injection at 6:00 AM and underwent peripheral stem cell collection at the same day (N=133). Injection of lenograstim at 6 AM was superior to injection of lenograstim at 8 PM with greater numbers of total collected CD34+ cells/kg in shorter duration of leukapheresis procedures (13.29 × 106 versus 8.51 × 106 CD34+ cells/kg; p=0.001, 2 versus 3 leukapheresis procedures; p=0.035). The median number of CD34+ cells/kg collected at first leukapheresis was also greater in 6 AM group (3.94 × 106 versus 2.47 × 106 CD34+ cells/kg; p=0.001). Stem cell collection efficacy defined as ratio of total collected CD34+ cells per days of leukpaheresis were 5.34 and 2.96, respectively. It was significantly better in the group of patients received lenograstim injection at 6 AM (p=0.001). The median number of patients who achieved a total collected CD34+ cells &gt; 5 × 106/kg was also greater in 6 AM group (113 versus 96; p=0.002). The present study shows that injection of lenograstim at 6 AM improves the efficacy of stem cell collection with greater number of collected CD34+ cells/kg in shorter duration of leukapheresis procedures compared to that of 8 PM group.
Immunologic Recovery after Autologous Transplant in Multiple Myeloma and Progression Free Survival
Authors: Trigo-Miranda Fernanda Maria Rodrigues , Bergantim Rui Cordeiro , Pinto Ricardo Moreira , Guimarães Patricia , Guimaraes Jose E. 
Published: April 2020

Abstract
Several factors influencing disease progression and survival have been identified in multiple myeloma (MM). We analysed a series of 49 consecutive patients with MM that underwent autologous haematopoietic progenitor cell transplant (HPCT) in one center regarding the following variables: use of G-CSF for haematopoietic recovery post-transplant; recovery of normal IgM levels at day +100 post-transplant; levels of lymphocytes namely of the CD4+ and CD8+ subsets also at day +100. Before 2006, all patients had G-CSF starting 24 hours after the cell infusion until neutrophil &gt; 500×10^9/L in two consecutive days; in the years 2006–2008, no G-CSF was given to transplanted patients. A historical comparison was done and at the time of this study no significant difference in progression free survival (Kaplan-Meyer analysis), was detected between the two groups, possibly due to the shorter follow-up of the “no G-CSF” (n=19) group; nevertheless median progression free survival (PFS) in the “G-CSF” group was 12 months while median PFS was not attained in the “no G-CSF” group (median follow-up = 7 months). Post transplant IgM levels were also determined in 39 patients. Eighteen patients recovered normal IgM levels at day +100 (46.8 %) and 21 (53.8 %) did not. Comparison of Kaplan-Meyer curves for the two groups did not show any statistically significant difference but there is a sharp difference between median PFS of the “low IgM” (10 months) and the “normal IgM” (27 months) groups. CD4/CD8 ratio was determined in 18 patients at day +100. The ratio varied between 0 and 0.63 (median – 0.305). No correlation was found between post-transplant IgM recovery and CD4/CD8 ratio. In conclusion, in our series of MM patients treated with autologous HPCT we could not find a definite relationship between immunologic recovery and response to treatment although there is a trend to a better outlook of the patients which recover normal IgM levels. It is also uncertain whether use of G-CSF in the post-transplant period would have any effect on disease behaviour.
Significance of Rising Levels of Minimal Residual Disease in Patients with Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia (Ph+ CML) in Complete Cytogenetic Response (CGCR)
Authors: Kantarjian Hagop M , Shan Jianqin , Jones Dan , O’Brien Susan , Rios Mary Beth , Jabbour Elias , Cortes Jorge 
Published: April 2020

Abstract
Background . Patients with Ph+ CML receiving tyrosine kinase inhibitors (TKIs) are frequently monitored for response by quantitative polymerase chain reaction (QPCR) studies for minimal molecular disease. The clinical significance of rising levels of QPCR in CGCR is uncertain.
Study Aims . To evaluate the relevance of increases of QPCR levels in patients with CML in CGCR on therapy.
Study Group and Methods . Of 258 patients on imatinib therapy for newly diagnosed CML, 116 patients in durable CGCR on imatinib therapy for at least 18 months had significant QPCR increases (documented at least twice) as defined by literature reports. These were analyzed by the achievement of major molecular response (MMR; QPCR &lt; 0.05%), and by the degree of QPCR increase.
Results. The outcome of patients by disease status (still in MMR vs. loss of MMR vs. never in MMR) and by the QPCR level increase are shown in the Table. Only 13 of 116 patients (11%) with significant QPCR increases had CML progression; 11 of them were among 44 patients (25%) who either lost a MMR or never had a MMR, and had &gt; 1 log increase of QPCR. The 5-year survival of all 116 patients was 92%, suggesting the minimal relevance of QPCR increases in patients in CGCR.
Conclusion . Most patients with significant QPCR increases remain in CGCR. Patients who lose a MMR or never achieve a MMR, and have &gt; 1 log increase of QPCR, should be monitored more closely, and may be evaluated for mutations of BCR-ABL kinase domain and considered for investigational therapeutic interventions. Allogeneic stem cell transplant should not be considered in view of the excellent survival.
Outcome of Patients in CGCR by QPCR Increases
Disease Status QPCR Log increase No. Patients CML Progression Median follow-up from QPCR increase in months (range) Persistent MMR Any 28 0 36 (3–62) Loss of MMR &gt;0.5–1 12 0 34 (14–59) &gt;1–2 25 3 31 (6–52) &gt;2 11 4 45 (20–57) Not in MMR &lt;1 32 2 35 (10–70) &gt;1 8 4 25 (12–56)
The Alternative Breakpoint Region (ABR) of BCL6 Is An Active Transcribed Region in Germinal Center B Cells and May Serve as An Enhancer
Authors: Shen Yulei , Ramachandrareddy Himabindu , Chan Wing C. , McKeithan Timothy 
Published: April 2020

Abstract
Chromosomal translocations at 3q27 involving BCL6 occur in two different regions. Rearrangements with breaks within the major breakpoint region (MBR), comprising the first exon and part of the first intron of BCL6, are among the most common genetic abnormalities in of B-cell non-Hodgkin lymphoma, whereas breaks within an alternative breakpoint region (ABR), located between 245 and 285 kb 5′ to BCL6, have also been reported in follicular lymphoma grade and a small group (6.4%) of diffuse large B-cell lymphomas (DLBCLs). As a result of the MBR translocation, BCL6 expression is deregulated by promoter substitution with either immunoglobulin (Ig) genes or non-Ig genes as partners. A role for deregulated BCL6 expression in the pathogenesis of DLBCL has previously been confirmed in a mouse model. However, the biological role of the more distant ABR region is still not known. Using real-time PCR, we identified in the ABR region an evolutionarily conserved DNase I hypersensitive site (named Far5) which contains a conserved composite binding site for transcription factors PU.1 and IRF4, both of which play important roles in B-cell differentation. Further studies demonstrated that chromatin in the Far5 region, 190kb upstream of BCL6 promoter, has an open configuration in DHL6, Granta 519 and U266 cell lines. Far5 DNA showed enhancer activity by a luciferase reporter assay. PU.1 binds to Far5 in vivo (DHL16 cell line) by a chromatin immunoprecipitation (ChIP) assay, and PU.1 binds in vitro to the conserved PU.1/IRF composite site in Far5 synergistically with either IRF4 or IRF8. ChIP-on-chip assays showed Far5 histone H3K4 monomethylation, a chromatin modification associated with gene enhancers and other regulatory elements. In addition, we identified a transcript upstream of the Far5 region that is specifically expressed in germinal center (GC) B cells, but not at other stages of B-cell differentation. These results indicated that Far5 may play a role in selective expression of intergenic transcripts in GC B-cells. In other genes, intergenic transcription plays a role in looping between distal regulatory regions and the promoter. Our data showed that ABR region is constitutively active in GC B-cells and may play an important role in increasing BCL6 transcription when naïve B cells differentiate into GC B-cells. Further investigation of interactions between the ABR and the BCL6 promoter will uncover the regulatory function of the BCL6 ABR in B-cell differentiation and B-cell lymphomas.