bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation Represents a Feasible and Effective Treatment Strategy for Advanced Mycosis Fungoides and Sezary Syndrome.
Authors: Soligo Davide , Onida Francesco , Saporiti Giorgia , Volpe Aldo Della , Marino Cristian , Annaloro Claudio , Rambaldi Alessandro , Bruno Benedetto , Berti Emilio , Deliliers Giorgio Lambertenghi 
Published: October 2019

Abstract
Sezary syndrome (SS) and advanced tumor-stage mycosis fungoides (MF) have an aggressive clinical course, ultimately leading to a very short survival. Because patients are often elderly and show poor clinical conditions, conventional allogeneic hematopoietic stem cell transplantation is associated with a undesirable high TRM; therefore, allogeneic reduced-intensity conditioning (RIC) HSCT represent an attractive and worth-investigating strategy of cure in this disease setting. In our Institutions, from September 2000 to May 2006, fifteen patients with advanced mycosis fungoides or Sezary Sindrome underwent RIC allogeneic hematopoietic stem cell transplantation either from HLA-identical sibling, or from HLA-matched unrelated donor, or from unrelated cord blood. Conditioning regimens for patients with HLA-identical sibling included fludarabine/cyclophosphamide/TBI200 up to 2001, then pentostatin/TBI200. Patients who underwent unrelated transplants were treated with melphalan/CP1H/Fludarabine/TBI200 combination. All patients (10 males and 5 females) had a clinical diagnosis of MF (10 pts) or SS (5 pts) confirmed by histopathology, immunohistochemistry and molecular biology. Median age was 48 years (range 38–65). Median time from diagnosis to transplant was 48 months (range 13 to 252). Disease stage for all patients was from IIIB to IVB. GVHD prophylaxis included oral Cy-A from day 0 to day +100 and oral MMF from day 0 to day +27, then tapered within 2 weeks. The source of donor stem cells was peripheral blood and bone marrow for siblings and MUD, respectively. A complete clinical remission was achieved in 10 patients, whereas 2 patients obtained a VGPR. Five patients died from various complications (3 with progressive disease, 1 in CR e 1 in PR) within a period ranging from 33 days to 8 months after transplant. A full donor chimerism was achieved within 6 months in 8 out of 10 evaluable patients, whereas no engraftemnt was observed in 2 patients (1 MUD and 1 UCB). 5 patients experienced acute GVHD of grade I–II, while limited chronic GVHD occurred in 7 patients. With a median follow-up of 38 months (range 2–70), ten patients were alive with an estimated overall survival greater than 60% at five years (Figure 1), whereas 7 patients were alive and disease-free at the last follow-up. Based on these highly encouraging results, we conclude that RIC allogeneic HSCT represents a feasible and effective treatment for advanced mycosis fungoides and Sezary Syndrome. Further studies in larger patient populations are warranted to confirm the curative potential of this strategy.
Overall Survival in MF/SS following RIC allo-HSCT Overall Survival in MF/SS following RIC allo-HSCT
Tissue Plasminogen Activator (t-PA) and Plasminogen Activator Inhibitor-1 (PAI-1) in Essential Thrombocythemia and Polycythemia Vera and Thrombotic Complications.
Authors: Cacciola Rossella R. , Di Francesco Ernesto , Giustolisi Rosario , Cacciola Emma 
Published: October 2019

Abstract
Thrombotic complications are frequent in patients with essential thrombocythemia (ET) and polycythemia vera (PV). While a thrombin- and tissue plasminogen activator (t-PA)-regulated release of t-PA and plasminogen activator inhibitor-1 (PAI-1), respectively, has been shown and an association between elevated t-PA and PAI-1 and thrombogenesis has been studied for several vascular diseases, few studies have concentrated on the correlation between t-PA and PAI-1 levels and thrombogenesis in these myeloproliferative disorders. Therefore, we investigated prothrombin fragment 1+2 (F1+2), as marker of thrombin generation, and t-PA and PAI-1 in patients with ET and PV and thrombosis. We included 44 patients, 22 ET (5 men and 17 women, mean age 55 years) and 22 PV (17 men and 5 women, mean age 60 years) who fulfilled PVSG. The mean duration of disease was 4.5 years. Most received cytoreduction, such as hydroxyurea (13 ET and 14 PV), interferon-alpha (2 ET), anagrelide hydrochloride (5 ET) or phlebotomy (8 PV). None of studied patients had thrombotic risk factors. Of 44 patients, 25 (12 ET and 13 PV) developed thrombosis, whereas 19 (10 ET and 9 PV) did not. Measurements were assayed by ELISA. All patients had increased F1+2 (2.8±2.8 nmol/L vs 0.7±0.2 nmol/L) (p=0.001). t-PA and PAI-1 were higher in those patients with previous thrombosis than in asymptomatic patients (130±62 ng/ml vs 89±69 ng/ml and 45±20 ng/ml vs 57±27 ng/ml, respectively) (p=0.043 and p=0.085, respectively). A positive correlation there was between F1+2 and t-PA and t-PA and PAI-1 (p<0.0001 and p<0.0001, respectively). These findings suggest that a disfibrinolysis may be in ET and PV and that t-PA and PAI-1 may be predictive additional factors of the thrombotic tendency of these patients.
Experimental Study on Prevention of GVHD by Selective Elimination of Alloreactive Donor Lymphocytes Prior to Stem Cell Transplantation.
Authors: Chen Bao-An , Dong Wei-Min , Ding Jia-Hua , Deng Xiao-Jing , Zhao Gang , Gao Chong , Sun Yun-Yu , Wang Jun , Cheng Jian , Chen Ning-Na , Fei Fei 
Published: October 2019

Abstract
Objective: To investigate a new concept aiming for induction of graft-vs-leukemia (GVL) effect prior to stem cell transplantation (SCT). Mismatched lymphocytes given pre-SCT will be followed by selective elimination of alloreactive donor lymphocytes, thus avoiding lethal graft-vs-host disease (GVHD).
Methods: Female (BALB/c×C57BL/6)F1 mice (H-2d/b) as recipients received sublethal total body irradiation (TBI) of 4 Gy (60Coγ-ray) on day 0 followed by being inoculated with 0.5×107 P388D1 leukemia cell line on day 1, injection of 1.5×107 allogeneic splenocytes supplied by C57BL/6 male mice(H-2b)for induction of GVHD, intraperitoneally injection of cyclophosphamide (Cy) (200 mg/kg) or TBI (9 Gy) were given on day 7, one day later, treated mice were rescued with 3×107 syngeneic bone marrow cells supplied by (BALB/c×C57BL/6)F1 male mice(H-2d/b). Recipients were observed clinical manifestation, phenotype, re-establishment of haematogenesis, histopathologic changes of internal organs suffered from GVHD and investigated donor chimerism by the semi-quantitate analyses of polymerase chain reaction (PCR). Data was analyzed by SPSS 10.0 software and expressed as mean ± SD.
Results: Recipients had no occurrence of leukemia and GVHD by selective elimination of alloreactive donor lymphocytes by Cy and TBI, survived more than 210 days, to become complete-donor chimerism on day +21. The ratio of chimerism descended subsequently, but still displayed mixed-chimerism on day +90. Control mice died of evident GVHD, leukemia or other death-related-transplantation within 20 to 36 days(p<0.01). Attempting to induce GVL effects by mismatched lymphocytes given before stem cell transplantation followed by selective elimination of alloreactive donor lymphocytes, thus avoiding graft-vs-host disease (GVHD) was feasible.
The Role of Selective Depletion of Alloreactive Donor T Cells in Graft-Versus-Host Disease after Allogeneic Bone Marrow Transplantation.
Authors: Chai Yihuan , Qiu Huiying , Lv Hui 
Published: October 2019

Abstract
One of the main goals in allogeneic bone marrow(BM) transplantation is the abrogation of graft-versus-host disease (GVHD) with the preservation of antileukemia and antiviral activity. The Study present a selective T cell depletion strategy based on the physical separation of the alloreactive T cells, which were identified by expression of two activation-induced antigens (CD25 and CD69). T cells from C57BL/6(H-2b) mice were first activated with BALB/c (H-2d) recipient spleen cells in a 2-day mixed-lymphocyte-culture (MLC). Following this activation, this compound is selectively depleted based on expression of two activation-induced antigens CD25 and CD69 using magnetic cell sorting. The depleted cells or the untreated cells were then rechallenged respectively in a secondary MLC, with the same stimulator cells or a third-party (DBAH-2k) or tumor- specific (SP2/0, BALB/c-origin myeloma) cells. Cells proliferation were assayed at the indicated time points(1, 2, 3, 4, 5 days). These treated cells or control-cultured cells (2.0×106) mixed with 5.0×106 BM cells from C57BL/6 were transfused respectively by the trail vain into the lethally irradiated BALB/c to observe the survival time, GVHD incidence and pathological analysis. MLC assays demonstrated that this technique led to a significant decrease in alloreactivity of donor cells(29.02~64.17%), which at the same time preserved reactivity against third party cells(49.61~75.69%)and anti-tumor cells(61.14~68.62%). The mice in the group of control-coclutured were died of acute GVHD within 24days. The 7 recipient mice in the treated group were free of acute GVHD, and 3 mice were died of acute GVHD (aGVHD) within 23 days. MACS-based ex-vivo depletion of alloreactive donor T cells based on expression of two activation-induced antigens (CD25 and CD69) could inhibit anti-host responses, by contrast, anti-SP2/O and anti-third-party responses were preserved. Cotransplantation of these selected depleted cells and BM cells could reduce aGVHD.
Double-Stranded RNA Acts as a Strong Danger Signal in Human Myeloid Leukemia Cells Leading to Increased Immunogenicity.
Authors: Berneman Zwi N. , Smits Evelien L.J.M. , Ponsaerts Peter , Cools Nathalie , Van de Velde Ann L.R. , Gadisseur Alain P. , Schroyens Wilfried A. , Van Tendeloo Viggo F.I. 
Published: October 2019

Abstract
Leukemic cells exert immunosuppressive effects that interfere with dendritic cell function and hamper effective anti-leukemic immune responses. Recently, Toll-like receptor 3 (TLR3) was characterized in dendritic cells as an intracellular double-stranded (ds)RNA receptor which is triggered by viral infection or incubation with the synthetic dsRNA analogue polyriboinosinic polyribocytidylic acid [poly(I:C)], leading to maturation and activation of dendritic cells. Until now, little was known on the expression of TLR3 in leukemic cells and their responsiveness to dsRNA treatment. We assessed TLR3 expression in primary and transformed acute myeloid leukemia (AML) cells and hypothesized that the immunogenicity of AML cells could be improved by treatment with the synthetic TLR3 agonist poly(I:C), thereby mimicking viral infection of these leukemic cells. In view of this hypothesis, we electroporated or pulsed transformed and primary AML cells with poly(I:C) and analyzed the effect of poly(I:C) loading on TLR3 expression, costimulatory molecules, cytokine production and allogeneic T cell response. We also assessed the uptake of poly(I:C)-loaded leukemic cells by immature dendritic cells and the subsequent effect on dendritic cell activation and maturation status. We observed that primary and transformed AML cells respond to poly(I:C) electroporation by upregulation of TLR3 expression, apoptosis, elevated levels of costimulatory molecules CD80 and CD86 and by production of type I interferons (IFN). Furthermore, poly(I:C)-electroporated AML cells induced interferon-gamma production by allogeneic T cells. Upon phagocytosis of poly(I:C)-electroporated AML cells, dendritic cells showed an increased expression of maturation markers and marked production of proinflammatory cytokines. In contrast, this set of immune effects was absent or suboptimal when AML cells were passively pulsed with poly(I:C), indicating the superiority of transfection over pulsing with poly(I:C). These results demonstrate that poly(I:C) electroporation is a promising novel strategy to increase the immunogenicity of AML cells.
Partly MHC Matched Allogeneic Tumor Specific T Cells Mediate Tumor Regression without Inducing GVHD in Immunosuppressed Host.
Authors: Boni Andrea , Muranski Pawel , Wrzesinski Claudia , Kaiser Andrew , Paulos Chrystal , Palmer Douglas , Gattinoni Luca , Restifo Nicholas P. 
Published: October 2019

Abstract
Adoptive cell transfer (ACT) immunotherapy following lymphodepleting conditioning is a promising strategy for the treatment of metastatic solid tumors, however the difficulties in generating autologous tumor specific lymphocytes for every patient has significantly limited its applications. Allogeneic partly matched tumor specific T cells could be used for patients in whom autologous cells are not available, however their rapid rejection by the host restricts this approach. When CD8+ pmel-1 T cells from B6-BALB-C F1 (b/d) were transferred into B16 tumor-bearing B6 mice (b/b) or into a different F1 (b/k), these tumor-specific T cells were rapidly rejected, and had no impact on the tumor regression. Here we show that following myeloablative conditioning, the adoptive transfer of allogeneic, major histocompatibility mismatched tumor-specific T lymphocytes resulted in the regression of large vascularized tumors. The ability of adoptively transferred allogeneic T cells to mediate tumor regression was directly proportional to the dose of irradiation given prior T cell transfer which also correlated with the in vivo survival of the transferred cells. At the highest irradiation dose used (i.e. 11 Gy) allogeneic T cells could survive for as long as 4 weeks and their efficacy was comparable to syngeneic tumor-reactive T cells. In addition we found that the risk of inducing a graft versus host (GVH) reaction was minor when the specificity of transferred TCR is confined. In fact co-transfer of transgenic cells and small amounts of open repertoire T cells (2*10e4) able to react with the host did not result in any measurable toxicity whereas co transfer of greater quantities (2*10e5 or more) could cause fatal GVHD effect. Interestingly GVH reaction was associated with an improved tumor treatment, though this effect was transient as most of the animals succumbed to GVHD. Here we demonstrate that allogeneic T cells might represent an important tool in cancer immunotherapy allowing treatment of patients for whom it is not possible to obtain autologous cells. Furthermore the possible synergy between tumor specific allogeneic T cells and GVH effect could be exploited in bone marrow transplant protocols.
AMD3100 Plus G-CSF Mobilizes the Majority of Non-Hodgkin’s Lymphoma (NHL), Multiple Myeloma (MM), and Hodgkin’s Disease (HD) Patients Who Failed Prior Mobilization with Other Regimens.
Authors: Calandra Gary , McCarty John , McGuirk Joseph , Barlogie Bart , Crocker Sue-Anne , Badel Karin 
Published: October 2019

Abstract
Background: AMD3100, an inhibitor of SDF1 binding to CXCR4, synergizes with G-CSF to allow mobilization of sufficient CD34+ cells/kg for autologous transplantation in pts unable to collect adequate CD34+ cells with G-CSF alone. Therefore, a single patient use (SPU) protocol for AMD3100 was adopted for more than one patient entry per site and termed Compassionate Use Protocol (CUP). The only difference of standard of care was the addition of AMD3100 to a G-CSF mobilization on the evening prior to each day of apheresis. Pts who could not proceed to apheresis due to low peripheral blood counts or pts who did not collect a minimum of 2 × 10^6 CD34+ cell/kg were eligible.
Methods: Overall, more than 280 patients with proven poor mobilization including 137 NHL, 73 MM, and 31 HD have been included in CUP. A data audit was performed to validate data from pts with either non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), or Hodgkin’s Disease (HD). Sites were selected based on most patients entered, >3 of all diseases entered at a site, and sites conducting an AMD3100 trial. Audit included all pts, regardless of success or failure of the outcome; all information was collected on CRFs. Success of outcome was collection of ≥ 2×10^6 CD34+ cells/kg during the CUP procedure. CUP apheresis was done on day 5 after G-CSF (10mg/kg SC QD) and AMD3100 (240mg/kg SC Q10 PM) starting day 4.
Results: Charts and CRFs were available for review for 115 pts; 63 (55%) were NHL patients from 29 sites, 35 (30%) were MM from 23 sites and 17 (15%) were HD from 13 sites. Of these pts, 58% were male, the median age was 59 years (range 21–77), 88% were Caucasian, and patient weight ranged from 43–128 kg. Prior treatments included a median of two regimens of chemotherapy in each of the three groups. Safety was generally favorable with no drug-related SAE’s and with an AE profile similar to that seen in research trials. The rates of successful collection of ≥ 2×10^6 CD34+ cells/kg per disease state as well as prior mobilization regimen are summarized in table 1. The median number of mobilizations for the successful patients was 3 days for NHL and HD and 4 for MM. Eighty-eight of the patients underwent transplantation with any cells. For example, of the 47 NHL patients transplanted, 24 had CUP only cells and 23 had mixed cells. The median number of days to engraftment was 11 for PMN and 18 for platelets. Long term follow up is limited, but there do not appear to be graft failures. At least 12 of the pts have died.
Conclusions: AMD3100 in a poor mobilizer population is generally safe and well tolerated and is very effective in mobilizing > 2×10^6 CD34+ cells/kg.
Mobilization success rate by disease state: overall and prior mobilization regimen Overall Prior Cytokine Prior Chemotherapy NHL 60% 53% 68% HD 76% 78% 75% MM 71% 73% 71%
Donor T-Cell Chimerism Does Not Predict Relapse and Response to Donor Lymphocyte Infusion for a Patient of Secondary Acute Myeloid Leukemia after Reduced-Intensity Allogeneic Hematopoitic Stem Cell Transplantation.
Authors: Tang Xiaowen , Zhang Qiurong , Wu De Pei , Feng Yufeng , Sun Aining 
Published: October 2019

Abstract
We analyzed donor chimerism(DC) in unfractionated(UF) and CD3+ cells from a secondary acute myeloid leukemia patient who relapsed after reduced-intensity allogeneic hematopoitic stem cell transplantation(RIST) and had undergone donor lymphocyte infusion(DLI). Sequential and quantitative chimerism was performed by multiplex PCR amplification of STR markers (STR-PCR). The peripheral blood(PB) every 3 days and bone marrow every week were collected for chimerism analysis. The patient presented hematological relapse 26 months after the first RIST. There were 31.5% blast cell in the bone marrow smear and presented additional abnormal chromosome [44,XY,-7,dic(16,17)]. While UF donor chimerism from PB and CD3+ fraction donor chimerism from PB and BM were always full donor chimerism (range, 96.4%~98.1%). However UF chimerism from BM was 64.9% at the same time point. Afterwards the patient received 4 times of dose-escalated donor lymphocytes infusion (DLI) with CD3+ cell from 1*107/kg to 1.0*108/kg. Unfortunately the patient hasn’t response to this therapy. The blast cell in BM smear augment from 31.5% to 51.5%. UF chimerism from BM ranged from 55.2 to 46.5%. But UF DC from PB and CD3+ fraction DC from PB and BM ranged from 95.5% to 98%. In conclusion, Our result suggest that in this AML patient the donor T-cell chimerism and unfractionated chimerism in PB can not predict relapse and response to donor lymphocyte infusion. and the reason is not clear.
Transient Mixed Chimerism after Stem Cell Transplantation Can Induce Durable Molecular Complete Remissions in Chronic Myelogenous Leukemia.
Authors: Ruiz-Arguelles Guillermo J. , Gomez-Almaguer David , Ruiz-Delgado Guillermo J. , del Carmen Tarin-Arzaga Luz 
Published: October 2019

Abstract
Three patients with Ph1 (+), BCR/ABL+ chronic myelogenous leukemia were allografted, two with unrelated compatible placental blood cells and one from an HLA compatible sibling. The three patients engrafted successfully, achieved mixed chimerism and all cleared the BCR/ABL fusion transcript. Despíte the fact that the three patients lost the partial chimerism, they have remained in complete molecular remissions 7 months, fourteen months and five years after the allografts. It is possible that the iatrogenic induction of a transient chimerism and in turn of a transient graft versus leukemia effect, might have a role in the induction of the sustained molecular remission of these three individuals with CML despite the fact that the three patients lost the graft; however other possible explanations can be offered. A longer follow up of the patients is mandatory to further clarify these observations.
Disappointing Outcomes of Peripheral T Cell Lymphoma after Autologous Stem Cell Transplantation.
Authors: Smith Stephen D. , Sweetenham John William , Rybicki Lisa , Brown Stacey , Dean Robert M. , Kalaycio Matt , Sobecks Ronald , Andresen Steve , His Eric , Pohlman Brad , Bolwell Brian J. 
Published: October 2019

Abstract
The role of high dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell NHL following HDT have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Older retrospective studies found comparable survival rates after ASCT for pts with T-cell and B-cell NHL.1,2 In this study, we report our single center experience over one decade using a uniform high-dose regimen for patients with PTCL.
Patients and Methods
The transplant database of the BMT program at Cleveland Clinic was reviewed, and 32 patients undergoing ASCT for PTCL between 1996 and 2005 were identified. Twenty-one patients (66%) had anaplastic large cell lymphoma (ALCL), and 11 (34%) had peripheral T cell, not otherwise specified (PTCL-NOS). Patient characteristics are summarized in table 1.
Stem cell mobilization with VP16 and GCSF priming provided a median CD34 cell dose of 5.01× 106/kg (range 2.05–29.69). Patients received a preparative regimen consisting of busulfan (either 1 mg/kg orally or 0.8mg/kg IV for 14 doses), followed by VP16 60 mg/kg IV continuous infusion, then cyclophosphamide 60mg/m2 IV daily for two days. Standard supportive care measures were employed.
Results
Recovery to 500 neutrophils/uL occurred at a median of 10 days post transplant (range 9–12 days) and platelet recovery to 20 000 at a median of 14 (range 7–60) days.
Kaplan-Meier 5 year overall survival and relapse-free survival for all patients is 34% and 18%, respectively; median survival for all patients is 36 months (see figure 1). Median follow-up of 10 survivors is 25 months. No obvious plateau was observed on the overall or relapse fee survival curves. No significant difference in outcomes based on subgroup (ALCL versus PTCL-NOS) was observed. Staining for anaplastic lymphoma kinase (ALK) was available for 11 (of 21 total) anaplastic T cell lymphoma patients: 4/5 ALK-positive patients are alive compared to 2/6 ALK-negative patients at last follow-up. Four of five patients undergoing ASCT as consolidation following initial therapy are alive at a median 25 months.
Based on this small patient population, and in contrast to some recent studies, our results suggest a poor outcome for patients with PTCL after ASCT. The outcome for pts undergoing ASCT in first remission, and for ALK-positive (versus ALK-negative) ALCL, requires prospective investigation.
Table 1: Patient Characteristics Characteristic N (%) ALCL 21 (66) PTCL NOS 11 (34) Male 21 (66) Age: median(range) 44 (16-69) 2 prior chemo regimens 22 (69) 3 or more prior chemo regimens 7 (22) Transplant in first remission 5 (16) Relapsed/Refractory 25 (78)
Figure Figure