bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors Associated with VOD with RIC and MAC Hematopoietic Stem Cell Transplant and the Early Estimation of VOD
Authors: Nagakura Shoichi , Kiyokawa Tetsuyuki , Hidaka Michihiro , Yano Takahiro , Sunami Kazutaka , Okamura Seiichi , Uike Naokuni , Hamaguchi Motohiro , Matsui Takahiro , Horibe Keizo , Sato Kensaku , Kawakita Toshiro , Kawano Fumio 
Published: April 2020

Abstract
BACKGROUND: Despite recent increase of reduced intensity conditioning (RIC) transplantation, mortality rates after RIC and myeloabrative conditioning (MAC) HSCT remain high and hepatic veno-occlusive disease (VOD) cannot accurately predicted.
OBJECTIVE: To determine the value of risk factors associated with the development of VOD after allergenic HSCT with RIC and MAC. Estimating VOD based on clinical factors may further improve results of allogenic HSCT.
PATIENTS AND METHODS: A retrospective review of 415 consecutive allogenic HSCT was performed with attention to VOD, pre-transplant factors and laboratory data in five hematopoietic cell transplantation centers between 2000 and 2005. Patients underwent transplantation with MAC (n=247) or RIC (n=168). Main outcomes and risk factors were analyzed in multivariable analyses (a logistic regression model) with RIC and MAC. Three kind of laboratory data set, pre-transplant (day −10), post-transplant (day 20) and differences from pre-transplant to post-transplantation were analyzed.
RESULTS: VOD occurred in 65 of 415(15.7%) transplant recipients; 40 of 247(16.1%) with MAC and 25 of 168(14.9%) with RIC. Multivariate analyses identified risk factors with the development of VOD with MAC (albumin level, creatinine level) and with RIC (HCT-CI, number of prior chemotherapy regimen, ALT) in pre-transplant laboratory data set. The risk factors of VOD were identified in post-transplant and differences (Table). The Akaike’s information criterion (AIC) of risk factors with differences was better than with the post-transplant.
CONCLUSION: Our results provided risk factors of VOD with MAC and RIC. The estimation of VOD before transplantation may be useful for the selection of conditioning regimens. Differences of laboratory data with the time course of transplant may be useful for the early diagnosis of VOD.
MAC Pre-transpant data Post-transplant data Differences data OR P-Value OR P-Value OR P-Value Age - - 0.945 0.0090 - - Alb 0.290 0.0125 - - - - Cr 10.204 0.0307 1.786 0.0039 1.984 0.0139 TPro - - 0 358 0.0019 - - TBi I - - 1.385 0.0027 1.314 0.0037 Ara-C - - 5.000 0.0139 goodness of fit AIC 106.727 126.499 86.931 RIC Pre-transpant data Post-transplant data Differences data OR P-Value OR P-Value OR P-Value Sex - - 3.401 0.0446 - - HCTCI 3.922 0.0050 2.000 0.0123 - - ImpScore 2.000 0.0314 - - - - TPro - - 0.366 0.0091 - - TBi I - - 1.675 0.0042 2.273 0.0004 ALT 0.969 0.0432 - - - - CY - - - - 5.682 0.0447 goodness of fit AIC 61.552 91.09 52.808
EPOCH-F: A Novel Salvage Regimen for Multiple Myeloma Prior to Reduced-Intensity Allogeneic Stem Cell Transplantation
Authors: Jamshed Saad , Fowler Daniel , Neelapu Sattva , Dean Robert M. , Steinberg Seth M , Odom Jeanne , Snow Kelly , Gress Ronald E , Bishop Michael R 
Published: April 2020

Abstract
Variation in baseline host immune status contributes to inconsistent donor engraftment and may impede maximal graft-versus-myeloma effects after reduced-intensity allogeneic stem cell transplantation (RI-alloSCT) for advanced multiple myeloma. We performed a phase II study to determine the efficacy of a novel salvage regimen, EPOCH-F, which was designed to provide immune depletion and disease control prior to RI-alloSCT, in 22 patients with advanced multiple myeloma. EPOCH is an infusional chemotherapeutic regimen consisting of etoposide, vincristine and adriamycin, with prednisone, cyclophosphamide and fludarabine and given in 21 day cycles prior to RI-alloSCT. Patients received at least 1 and no more than 5 cycles of EPOCH-F gudied by peripheral blood CD4+ T cell count. Pts achieving adequate lymphodepletion proceeded to RI-alloSCT; otherwise patients proceeded to RI-alloSCT after 5 cycles or if there was disease progression during EPOCH-F, regardless of CD4 count. Median age was 53 years (range, 36–65); median time from initial therapy to transplant was 12 months (range, 2–168). Median number of prior therapies was 2 (range, 1–8), while 63% had chemotherapy sensitive disease. 68% of patients had received a novel agent. Patients received a median of 3 cycles (range, 1–5) of EPOCH-F. Therapy was well tolerated with manageable toxicities, mostly hematologic. Neutropenia (grade IV) was the most common toxicity seen in 77% of the administered cycles with only 6 episodes of neutropenic fever. Median lymphocyte count decreased from 1423/μL (range, 335–2788) to 519/μL (range, 102–1420); CD4 count decreased from 320/μL (range, 130–1366) to 115/μL (range, 30–309). In 21 evaluable patients, the overall response rate to EPOCH-F was 22% and 68% had stable disease. 13% of patients achieved CR/nCR. Only 1 patient progressed while on therapy. 20 patients received allograft from HLA matched sibling donors and were evaluable for engraftment. Median Day 100 chimerism was 100% (range 60–100, mean 95). 70% of patients achieved ≥VGPR including CR/nCR, while CR/nCR was seen in 40% of the patients. Median overall survival was 46.1 months. 10 (50%) patients are currently alive. Acute GVHD (grade II–IV) was seen in 47% and chronic GVHD (grade III–IV) was seen in 52% of patients. Treatment-related mortality at 100 days was 5% and 30% at 60 months. EPOCH-F is an active regimen which facilitates consistent and rapid full donor engraftment following RI-alloHSCT from related donors in patients with advanced multiple myeloma.
EBV Associated-Pneumonia in Patients with Post-Transplant Lymphoproliferative Disease after Hematopoietic Stem Cell Transplantation
Authors: Liu Qifa 
Published: April 2020

Abstract
Background. Traditionally, reactivation or infection of Epstein-Barr virus (EBV) after hematopoietic stem cell transplantation (HSCT) most often induces post-transplant lymphoproliferative disease (PTLD). In recent years, it is reported that it may manifest in patterns other than PTLD.
Methods. To investigate PTLD and PTLD accompanied by EBV associated- pneumonia among 323 patients after HSCT and discribe the clinical manifestation of PTLD accompanied by EBV associated-pneumonia.
Results. Seven cases of PTLD with primary presentation as extravisceral lymphoid tissue were identified. Five cases were diagnosed of CD20+ diffuse large B-cell lymphoma, 1 cases CD20+ polymorphic B-cell hyperplasia and 1 case CD3+CD45RO+ peripherial T-cell lymphoma-unspecified. Six patients were associated with EBV and 1 case was not in 7 cases of PTLD. Three patients were diagnosed of EBV associated-pneumonia and chest computed tomography revealed multifocal patchy and diffuse ground-glass attenuation in both lungs. EBV-DNA was positive in bronchoalveolar lavage fluid. There were mainly CD3+ T cells with the absence of CD19+ and CD20+ B cells in cytology analysis of BAL fluid. Lung biopsy showed that patients had interstitial and intra-alveolus infiltrates of main CD3+ T cells and part of CD68+ macrophages without CD19+ and CD20+ B cells. The patients with PTLD accompanied by EBV associated-pneumonia had hyperpyrexia and dyspnea. The diseases aggravated rapidly and eventually all died within two weeks since the onset of PTLD.
Conclusion. It is not rare for EBV associated-PTLD accompanied by EBV associated- pneumonia after HSCT. Cytology of BAL fluid and lung biopsy may help to the diagnosis.
QuantiFERON®-CMV for Immune-Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Morello Enrico , Pagani Elisabetta , Monsurrò Vladia , Cavattoni Irene , Coin Silvia , Larcher Clara , Tridente Giuseppe , Cortelazzo Sergio 
Published: April 2020

Abstract
Background: CMV infection represents a major complication of allo-SCT affecting transplant related mortality and morbidity. Anti-viral therapy is toxic and prolonged treatment could affect graft function. Monitoring specific immune response against CMV could optimize the timing for anti-viral therapy administration in order to avoid related toxicity and to reduce CMV related mortality and morbidity. A recent ELISA based test (QuantiFERON®-CMV) could measure specific (anti-HCMV) and aspecific production of IFN-γ in whole blood.
Aims: to test the reliability of QuantiFERON®-CMV in a cross sectional study in order to identify patients at risk of CMV disease after alloHSCT.
Methods: QuantiFERON®-CMV is an in vitro diagnostic test using a peptide cocktail simulating human cytomegalovirus proteins (CMV) to stimulate cells in heparinised whole blood. Detection of interferon-γ (IFN-γ) by ELISA is used to identify in vitro responses to these peptide antigens that are associated with CMV infection. The IFN-γ response in the CMV Ag tube is considered positive if &gt; 0.2 UI/mL as defined by the manufacturer. The mitogen-stimulated plasma sample was used as an IFN-γ positive control (PC) for each specimen tested. CMV reactivation and disease were defined according EBMT recommendations.
Results: Among 92 tests no correlation between pp65 antigenemia and IFN-γ production was proved (p=0,346). However, among the 41 tests showing lower levels of anti-HCMV IFN-γ production (&lt;0.2 IU/mL) 8 tests belonging 4 patients were associated with CMV disease, whereas among the 51 tests showing higher levels of anti-HCMV IFN-γ production (&gt;=0.2 IU/mL) none were associated with CMV disease (p=0.001), RR 2.5 (CI95% 1.951–3.321).
Conclusions: QuantiFERON®-CMV doesn’t seem to represent a significant reliable test for risk of viremia after alloHSCT, but patients with prolonged lower levels of anti-HCMV IFN-γ production (&lt;0.2 IU/mL) are at risk of CMV disease. Prospective studies are required in order to identify the correlation between viremia and the need for treatment.
Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) in Patients with Multiple Myeloma (MM): Long Term Follow-up in a Single Centre Series
Authors: Benakli Malek , Ahmednacer Redhouane , Talbi Amina , Mehdid Farih , Belhadj Rachida , Rahmoune Nadia , Harieche Farida , Zerhouni Fatiha , Hamladji Rose-Marie 
Published: April 2020

Abstract
Background: RIC allo-SCT has been proposed as a strategy for retaining the graft versus myeloma effect of allo-SCT while decreasing transplant related mortality (TRM). Here, we retrospectively studied a series of 15 patients (pts) with MM treated by RIC allo-SCT.
Patients and methods: Between April 2001 and December 2007, 15 pts with MM underwent RIC allo-SCT with an HLA-identical sibling donor. Initially, 8 pts had MM with Ig G, one IgA, 2 light chains, 3 non-secretory and one undetermined. Three pts were stage II and 12 stages III. At time of allo-SCT, 6 pts were in complete remission and 9 in refractory/progressive disease (2 received prior autologous transplants). Median age was 48 years (range, 38–60) and the sex-ratio (M/F) 1,5. Median time from diagnosis to RIC allo-SCT was 18 (range, 6–76) months. The conditioning regimen included Fludarabine 150mg/m2 and Melphalan 140mg/m2. GVHD prophylaxis consisted of association cyclosporine (cSA) and mycophenolate (MMF). All pts received G-CSF mobilised peripheral blood stem cells, with a median CD34+ cell count: 4,5.106/kg (range, 1.92–13).
Results: Neutropenia occurred in all pts and the median duration of aplasia was 8 (range, 5–14) days. Only 3 pts (20 %) required red blood cells transfusions and 12 pts (80 %) needed platelets transfusions. Acute GVHD was observed in 6 cases (40 %) including 4 cases of grade II–IV. Eight pts (72 %) had chronic GVHD, of whom 5 with an extensive form. Three pts (20 %) had CMV reactivation at a median time 91 (range, 53–158) days after transplantation. Four pts (26 %) had late onset relapse at a median time of 826 (range, 248–1370) days. TRM was 33 % at one year after RIC allo-SCT. With a median follow-up of 50 (range 14–86) months, 5 pts (33 %) are still alive in complete remission with full donor chimerism. Ten pts (66 %) died (2 early severe infections, 3 acute GVHD, 3 after relapse, one myocardial infarction, and one public highway accident). Overall and progression-free survivals at 7 years are 37,5 % and 31,2 % respectively.
Conclusion: This study suggests that RIC allo-SCT is a potential therapy for relapsed MM. However, TRM and relapse remain a matter of concern, likely due to the inclusion of refractory and heavily pretreated pts with many comorbid conditions. Future protocols, should aim for better patient selection, focussing on those pts in first chemosensitive relapse.
Hematopoietic Stem Cell Defects in Novel Fanconi Anemia Mouse Models
Authors: Parmar Kalindi , Kim Jung Min , Shimamura Akiko , Stuckert Anna , DeLoach Mary K , Zhu Kaya , Mauch Peter M. , Kutok Jeffery , Aster Jon , Akashi Koichi , Gilliland D. Gary , D’Andrea Alan D. 
Published: April 2020

Abstract
Fanconi Anemia (FA) is an autosomal recessive disease characterized by congenital defects, crosslinker hypersensitivity, progressive bone marrow failure, and a defect in hematopoietic stem cell (HSC) function. There are thirteen known Fanconi Anemia genes (A, B, C, D1, D2, E, F, G, I, J, L, M, N) and disruption of these genes appears to account for a variable degree of HSC dysfunction. Another gene (Usp1), encoding a deubiquitinating enzyme which is not a FA gene per se, is a critical regulator of the FA pathway. Understanding the mechanism of action of the FA proteins may allow better diagnosis and treatment for Fanconi Anemia and other aplastic anemia patients. Here, we have characterized mouse models for FA, including Fancd2−/− and Usp1 −/− mice. Similar to a previously reported Fancd2 mouse model (Houghtaling S et al, Genes & Development, 17:2021–2035, 2003), the Fancd2−/− mice developed in our laboratory displayed FA phenotypes including cellular hypersensitivity to mitomycin C (MMC), hypogonadism and reduced fertility. Interestingly, Usp1−/− mice developed for the first time in our laboratory exhibited severe FA phenotypes, with increased cellular hypersensitivity to MMC, 80% perinatal lethality, testicular atrophy, and depletion of germ cells. Quantitative assessment of the Fancd2 protein expression in the bone marrow using the AQUA imaging system demonstrated low levels of Fancd2 staining in the Lin+ cells compared to the Lin− cells in wild-type (WT) mice, with an absence of Fancd2 expression in the Fancd2 −/− mice. Analysis of hematopoietic parameters in both the Fancd2 and Usp1 mouse models showed normal white blood cell counts and normal hemoglobin levels in the peripheral blood. However, bone marrow from Fancd2−/− mice as well as Usp1−/− mice exhibited phenotypic and functional differences compared to the bone marrow from WT mice. Multiparameter flow cytometric analysis of bone marrow revealed increased frequencies of MEPs (megakaryocyte-erythroid progenitors) in Usp1−/− mice and decreased frequencies of LSK (Lin-Sca-1+Kit+) population in Fancd2−/− mice in comparison to WT controls. In addition, bone marrow from both Fancd2−/− mice and Usp1−/− mice contained significantly reduced frequencies of late-developing day 28 CAFCs (cobblestone area-forming cells) compared to the bone marrow from WT mice. Furthermore, lethally irradiated recipients transplanted with bone marrow from Fancd2−/− or Usp1−/− mice showed reduced donor-type blood cell chimerism at 16 weeks post-transplant, compared to the recipients transplanted with WT bone marrow. Collectively, our data indicate that mice deficient in Fancd2 or Usp1 have hematopoietic stem cell defects and that these mouse models can be useful for development of therapeutics for FA.
Unrelated Donor Hematopoietic Stem Cell Transplantation for Treatment of High-Risk Leukemia
Authors: Depei Wu , Tang Xiao wen , Sun Ai ning , Fu Zheng -zheng , Miao Miao , Jin zheng Ming , Qiu Hui ying , Chang Wei rong , Zhu Xia ming 
Published: April 2020

Abstract
objective: To investigate the efficacy of unrelated donor hematopoietic stem cell transplantation(URD-HSCT) for high-risk leukemia.
Methods: From June 2001 to July 2008, 62 patients of high-risk leukemia underwent HSCT with unrelated donor. The median age was 24(6~49)years. There were 21 unrelated donor’s grafts came from Buddhist Tzu Chi Stem Cells center in Taiwan, and 41 unrelated grafts came from Red Cross Society of China Hematopoietic Stem Cell Marrow Donor Program Administration Center. Seventeen patients received bone marrow transplantation and another 45 patients received peripheral blood stem cell transplantation. Fifty patients were fully matched with their donors for HLA loci A and B as well as for HLA-DRB1. Eight of 62 patients had 1 molecular loci mismatch and 4 of 62 patients had 2 molecular locus mismatch. The conditioning regimen consisted of modified BU/CY or modified total body irradiation(TBI) plus CY. Eleven patients received cyclosporine (CSA), short-term methotrexate (MTX) and mycophenolate mofetil (MMF) as the regimen of prophylaxis of GVHD. Forty |four patients received CSA, MTX and MMF plus ATG/ALG for GVHD prophylaxis. The combination of CSA, MTX, MMF,ATG/ALG and CD25 monoclonal antibody for preventing GVHD in 4 patients. Other two patients received Tacrolimus, short-term MTX and ATG to prevent GVHD.
Results: The incidence and severity of regimen-related toxicity were mild. The median number of MNC and CD34 positive cell was 4.48×108/kg and 4.06×106/kg respectively. The median time of the engraftment of neutrophil and platelet was 13 days and 16 days posttransplant respectively. The incidence of infection posttransplant was 48%. The complicated pneumonitis occurred frequently (67%), The incidence of grade I–II and grade III–IV acute GVHD was 17% and 23% respectively. Limited chronic GVHD occurred in 17% patients and extensive cGVHD presented in 14% patients. Median follow up was 6 (range 1 `85) months after transplantation. 83% patients achieved full donor chimerism(FDC) detected by STR-PCR and FISH. While 17% patients presented mixed chimerism (MC) and 10 of them converted to unstable MC. Among them 4 patients presented graft rejection and 6 patients suffered from relapse. Decreasing values of donor chimerism were detected prior to the relapse of disease. Furthermore the treatment related mortality (TRM) was 16%(10/62), The incidence of relapse was 10%. Until now 37 patients are still alive. The 5-years expected survival was 52.2%.
Conclusion: URD-HSCT can be an effective and curable approach for high risk leukemia with higher incidence of GVHD and infection. The treatment for the severe and deadly GVHD and pulmonary infection are still major problems need to be resolved in the future.
Unrelated Cord Blood Transplants in Children with Acute Leukemia: Experience of a Single Center
Authors: Ferreira Rosa Branca , Vaz Carlos Pinho , Barbosa Isabel , Roncon Susana , Campilho Fernando , Carvalhais Alzira , Martinho A. , Campos Antonio 
Published: April 2020

Abstract
Allogeneic stem cell transplantation is an accepted treatment modality for selected malignant diseases. However, the ability to identify suitable related or unrelated donors can be difficult in some patients (pts). Alternative sources of stem cells such as cord blood (UCB) provide a readily available graft mainly for pediatric patients. Between October 1996 and May 2008, 23 consecutive patients (pts), with a median age of 6 years old (range:1 – 11), 13 male and 10 female, underwent UCB transplant for the treatment of acute lymphoblastic leukemia (n= 15), acute myeloid leukemia (n=7) and acute byphenotypic leukemia (n= 1). Conditioning regimen consisted of intravenous busulfan (3.2 mg/kg/day x 4 days), cyclophosphamide (120 mg/Kg) and rabbit antithymocyte globuline (15 mg/Kg) ±melphalan (140 mg/m2) and GVHD prophylaxis consisted of a calcineurin inhibitor and MMF or MTX. All grafts were HLA mismatched. The median infused cell doses were, respectively 3.2× 107/kg (range: 1.2–21) and 1.27×105/kg (range:0.2–4.3) for nucleated cells (NC) and CD34 + cells. Engraftment occurred in 18 pts (75%). Five pts failed engraftment, of wich 4 underwent a second transplant (3 autologous and 1 haploidentical) and 1 died of infection at day +59. Grade II–IV acute GVHD occurred in 12 pt and chronic GVHD in 2 of 14 pt at risk. With a median follow up of 1,5 years (range: 3 months-9.5 years), overall survival (OS) at 3 years is 40% (± 13%) and event free survival (EFS) at 3 years is 32% (± 11%). Non relapse mortality (NRM) was 13.6 % (± 7.3%). UCB transplants represents a valuable alternative to bone marrow or peripheral blood especially for pts requiring urgent transplant or lacking an HLA matched unrelated donor and having the potential advantage of an immune tolerance allowing successful transplantation despite HLA disparity
Allogeneic Stem Cell Transplantation Following Reduced Intensity Conditioning Regimen for Treatment of Refractory Leukemia
Authors: Jiang Jieling , Wang Chun , Yan Shike 
Published: April 2020

Abstract
Objective To evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) following reduced intensity conditioning (RIC) regimen in the treatment of relapsed and refractory leukemia.
Methods Fourteen patients with acute myeloid leukemia, eleven patients with acute lymphocyte leukemia and two patients with chronic myeloid leukemia blast phase received allo-HSCT following RIC regimen consisting of fludarabine and small or moderate dose total body irradiation (TBI). Patients received mobilized peripheral stem cell from HLA matched siblings (n=11), at least 5/6 matched unrelated donor (n=10) or haploidentical related donor (n=6). All patients were in advanced disease before transplantation. Graft versus host disease (GVHD) prophylaxis program consist of cyclosporin A plus mycophenolate mofetil or short-term methotrexate, or these three drugs combination; CD25 monoclone antibody and ATG were also used in patients with unrelated or haploidentical donors.
Results Sustained engraftment was attained in 22 patients, the median time to ANC &gt;0.5×109/L was 13 days (range: 11~17days), and the median time to BPC &gt; 50×109/L was 19 days (range: 12~42days). Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in 20 patients with a median of 14days (range: 7~70 days). With a median follow-up of 9 months (range, 1~44months), the incidences of acute GVHD and chronic GVHD were 50% (11/22) and 41.2% (8/17) respectively. The transplant related mortality was 25.9% (7/27), mainly from graft failure (n=4), intracranial hemorrhage (n=1), acute GVHD (n=1), and severe infection(n=1). At the time of last follow up, ten patients relapsed, eleven patients were alive and leukemia free. Probabilities of overall survival for AML and ALL patients were (51.9±13.4)% and (32.7±15.0)% at 2 years, respectively. It seems that AML patients had a better outcome than ALL patients, but there was no significant difference (289).
Conclusion Allogeneic stem cell transplantation following fludarabine and TBI based RIC regimen could be used in the treatment of relapsed and refractory leukemia with well tolerance and low transplant related mortality from which patients may be benefit.