bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence of Two Distinct Histological Subtypes of Follicular Lymphoma and Burkitt’s-Like Lymphoma in the Single Lymph Node: A Case Report and Literature Review.
Authors: Nagoshi Haruhisa , Miyamoto Kou , Sano Fumiaki , Kyou Aki , Nishio Yuji , Miura Ikuo , Koike Junki 
Published: October 2019

Abstract
Transformation to a high-grade lymphoma occurs in approximately 20% to 30% of cases of follicular lymphoma, usually to diffuse large B-cell lymphoma and small cases to Burkitt’s or Burkitt-like lymphoma, are reported. This transformation from follicular lymphoma to Burkitt’s lymphoma, namely the mechanism of the acquisition of c-MYC gene to tumor cells already immortalized by BCL2, are not completely understood. Case: A 49-year-old man visited our hospital because of high fever and generalized lymph node swelling for several weeks. The WBC count was 20x109/l including 60% of Burkitt-like blasts. Immunophenotype was positive for CD10, CD19 and CD20. FISH analysis with IGH/BCL2 probe set and sprit signal of 5′c-MYC /3′c-MYC showed positive for 79.3% and 3.9%, respectively. Needle biopsy of the bone marrow (BM) consisted of cells large non-cleaved lymphocytes arranged diffusely. Immunophenotype was positive for CD10, CD20, CD45LCA, CD79a, and strongly positive for MIB-1 by immunohistochemistry. FISH analysis of BM cells was performed as same way of peripheral blood (PB), and the result showed similar findings with peripheral blast cells. Excision biopsy of the neck lymph node showed effacement of architecture with the presence of 2 distinctive components in absolutory separated with each other. The first component consisted of follicles, some showing predominance of small-to medium-sized cells, termed centrocyte. The second consisted of large non-cleaved cells, known as centroblasts. The follicular lesion was positive for CD10, CD20, CD79a and BCL2 by immunohistochemistry. On the other hand, the diffuse component, the Burkitt-like lesion, was positive for CD10, p53 and strongly positive for MIB-1, but negative for CD20, CD79a and BCL2. The diagnosis was interpreted as a follicular lymphoma, grade 2, composite a Burkitt-like lymphoma in a diffuse pattern in the single lymph node. After he underwent 2 courses of chemotherapy, he relapsed in the cerebrospinal fluid. Inverted cells showed positive for CD10, CD19 but negative for CD20 and CD79a. FISH analysis of inverted cell was strongly positive for IGH/BCL2 and sprit signal of c-MYC, 98.8% and 98.5% respectively. Mukhopadhyay et al. reported the first case of the transformation of follicular lymphoma to Burkitt-like lymphoma within a single lymph node (Human Pathol. 2005, 36, 571). One study of transformed follicular lymphoma, 8% harbored c-MYC translocations (Blood 1992, 80, 756). We estimated that major gene expression was IGH/BCL2 with harbored c-MYC translocations in lymphoma cells and in a subset of follicular lymphoma, the gain of a c-MYC translocation confers an additive oncogenic stimulus and gain the inhibition of apoptosis by BCL2 combined with the cell growth activity by c-MYC.
High-Dose Dexamethasone Reduces Bortezomib-Induced Thrombocytopenia.
Authors: Quach Hang , Prince Miles H. , Honemann Dirk , Westerman David , Milner Alvin D. , Barron Austin , Harrison Simon 
Published: October 2019

Abstract
Introduction: Bortezomib (B)-induced thrombocytopenia is a well documented adverse event; platelet nadir occur typically around day 10–12 of B therapy. The exact mechanism remains unknown but is not associated with reduced/abnormal marrow megakaryocytes. We postulated that corticosteroids could modulate the impact of B on the platelet budding, release or survival.
Method: A retrospective analysis was performed on patients with relapsed or refractory multiple myeloma, treated with B (1.3mg/m2 IV bi-weekly q3 weeks) ± Dex (20mg/d on day of, and day after, bortezomib) at our Institute between February 2005 to February 2007. Data was abstracted regarding patients’ baseline characteristics, platelet count at the beginning, at nadir, and the percentage of platelet reduction as well as the number of platelet transfusions with each treatment cycle. Comparisons of these parameters between the two groups were performed using the two-sample t-test.
Results: Forty one patients received a median of 4 cycles (range 1–10) of B ± D. Seven patients had dex only episodically with different cycles of B, and were excluded from analysis. Of the remaining 34 patients, 16 pts had a total of 75 cycles with dex, and 18 pts had a total of 65 cycles without dex. Baseline characteristics were similar in both groups including age, stage of disease, percentage of bone marrow plasma cell infiltration and mean platelet count prior to cycle 1 (196 × 109/l in the B+Dex group vs.160 × 109/l in the B without Dex group; p=0.27). Patients who received dexamethasone had a higher mean platelet count at the start of each new cycle (217 × 109/l vs. 171 × 109/l; p=0.002), a higher nadir platelet count (149 × 109/l vs. 88 × 109/l; p<0.001) and a lower mean platelet reduction (33% vs. 51%; p<0.001) per treatment cycle. Patients who did not receive dex required more platelet transfusions (p=0.004); on average 1 adult pool platelet per treatment cycle. Those who required transfusions had lower baseline platelets at the beginning of cycle 1.
Conclusion: Bortezomib induces a reduction of platelets by approximately 50% and concurrent Dex administration reduces both the incidence and depth of bortezomib-associated thrombocytopenia, resulting in a subsequent reduction in platelet transfusion requirements. We believe that dexamethasone is likely having an effect on either platelet release or survival through anti-apoptotic mechanisms at the megakaryocyte or platelet level, or by enhancing platelet survival. Clearly further studies are required to investigate the underlying mechanisms. We recommend the concurrent use of dexamethasone for patients with low baseline platelets being treated with bortezomib.
Neuropathy in Multiple Myeloma Patients Treated with Bortezomib: A Multicenter Experience.
Authors: Caravita Tommaso , Petrucci Maria Teresa , Spagnoli Alessandra , Siniscalchi Agostina , Offidani Massimo , Federico Vincenzo , Falco Patrizia , Rizzo Manuela , Palumbo Antonio , de Fabritiis Paolo 
Published: October 2019

Abstract
INTRODUCTION: Bortezomib (B) is the first proteasome inhibitor to be used in clinical practice and has been recently approved for second line treatment of multiple myeloma (MM) patients(pts). Several trials demonstrated that Bortezomib is relatively well tolerated; however, manageable non-hematologic and hematologic toxicity has been reported. The dose limiting toxicity is peripheral neuropathy (PN), reported up to 35% of the patient population.
AIM: We evaluated the incidence and severity of PN in 179 MM patients that received B as single agent or in combination.
MATERIAL AND METHODS: Patients characteristics were as follows: median age was 66.7 years (range: 32–82) with 52% male; 55 patients were at the onset of the disease, 124 were pre-treated. Median time from diagnosis to treatment with B was 25.4 months (range 0–111), median value of β2-microglobulin was 3.02 (0.2–20). Risk factors for PN included prior use of thalidomide in 68 patients (38%), vincristine in 75 patients (41.8%) and 15 patients (8.8%) had diabetes mellitus.
RESULTS: Patients received bortezomib alone (?) or in combination with either dexamethasone (n=52), or chemotherapy (n=114) or thalidomide (n=38). Overall, the response rate (≥PR) was 86%. PN of grade ≥2 was observed in 73 pts (41%); grade 3–4 occurred in 32 (18%). Median time to the onset of bortezomib-related PN was 84 days (range, 10–449) after bortezomib initiation. In most cases (93%), patients had sensory symptoms, while 5 patients (7%) experienced both sensory and motor symptoms. Bortezomib-related PN led to therapy discontinuation in 31 pts (17%). For PN treatment, pts received mostly supportive therapy (analgesics, gabapentin, pregabalin, amitriptyline and vitamin supplements). Of the 31 patients with bortezomib-related PN that required discontinuation, resolution or improvement occurred in 16 (51.6%), at a median time of 140 days (range, 27–346) from B discontinuation. Data analysis of the PN risk factors (age, diabetes, sex, β2M, neurotoxic pre-treatment) showed a significant association with age >75 years (p<0.013) and a trend with thalidomde pre-treatment (p=0.07); noteworthy, PN risk was not increased in pts treated with bortezomib and thalidomide in combination. Furthermore, responses were independent to PN.
CONCLUSIONS: In our experience, PN is a relatively frequent side effect of bortezomib treatment, generally manegeable by dose reduction or discontinuation and reversible in the majority of pts. Patients with advanced age can be considered at higher risk, while the combination of thalidomide and bortezomib did not increase the risk of PN. Further studies are needed to better define the PN pathogenesis and develop optimal strategies to improve the B related PN management.
Non-Myeloablative Allogeneic Stem Cell Transplantation (NMT) Overcomes the Adverse Effects of Treatment Resistance and High Beta-2-Microglobulin in Patients with Mantle Cell Lymphoma (MCL): An Analysis of 123 Transplantations at the MD Anderson Cancer Center.
Authors: Tam Constantine S. , Ledesma Celina , Korbling Martin , Fayad Luis E. , Wang Michael , Alousi Amin , Hosing Chitra , Kebriaei Partow , Rondon Gabriela , Giralt Sergio A. , Anderlini Paolo , Popat Uday , Couriel Daniel , Pro Barbara , Samuels Barry , Hagemeister Frederick , Champlin Richard E. , Khouri Issa F. 
Published: October 2019

Abstract
BACKGROUND: MCL remains incurable with cytotoxic therapy, but may be susceptible to immune-based modalities. Since the availability of NMT(1997) and rituximab(1999), we have employed the following risk-adapted strategy: patients (pts) in first remission after one chemotherapy (REM1) were offered autologous SCT (ASCT) with high-dose rituximab (R), and pts beyond REM1 were offered NMT if a donor was available, and ASCT+R if not. In order to assess the success of this strategy, we analyzed the results of 17 years of MCL transplantation at our center, including ASCT pts transplanted without R as historical controls.
METHODS: 52 pts in REM1 (ASCT1) and 36 pts beyond REM1 (ASCT2) received ASCT with (43%) or without (57%) R, and 35 pts beyond REM1 received NMT with fludarabine, cyclophosphamide & R. ASCT1, ASCT2 and NMT pts were balanced for age, Ann-Arbor stage, B-symptoms, LDH and B2m, but NMT pts were more heavily pretreated (p=0.01) and were further from initial diagnosis (p=0.02) than ASCT2 pts.
RESULTS {ASCT}: 96% & 91% of ASCT1 & ASCT2 pts were in CR following transplantation. Chemoresistance was an important determinant of ASCT outcome, with ASCT1 pts experiencing superior median PFS (42 v 27 months, p=0.009) and OS (94 v 52 months p=0.01) than ASCT2. B-symptoms and B2m≥3.0mg/L adversely affected OS in both ASCT groups. There was a trend to improved PFS for the 20 ASCT1 pts who received R, with no events in 10 pts followed between 24 to 94 months, compared with a continuous pattern of progression in non-R pts (p=0.06). {NMT}: 94% of pts were in CR after transplantation, and the 42 month current-PFS was 57%. In contrast to the ASCT pts, OS following NMT was not affected by high B2m, although B-symptoms remained significant (p=0.03). Despite all pts being transplanted beyond REM1, a plateau in survival was evident with no deaths occurring among 11 pts followed between 46 to 98 months (figure). Actuarial non-relapse mortality (NRM) at 90 days, 12 months and 2 years were 0%, 13% and 20% respectively. Neither the stem cell source (related 69% v unrelated 31%) nor a history of previous autologous transplantation (n=6) had a significant impact on NMT outcome (p>0.30 for PFS, OS and NRM).
CONCLUSIONS: These results suggest that ASCT is most effective in pts transplanted in REM1, in whom the addition of R may have improved PFS. NMT is effective in overcoming the adverse impact of prior chemotherapy and high B2m, and remains the modality of choice for pts beyond first remission.
Figure Figure
Organ-Specific T Cell Receptor Repertoire in Target Organs of Murine Graft-Versus-Host after Haploidentical Bone Marrow Transplantation.
Authors: Fu Yue Wen , Wu De Pei , Chen Feng , Feng Yu Feng , Chong Wei Rong , Zhu Zi Ling , Zhu Ping 
Published: October 2019

Abstract
Objective Haploidentical bone marrow transplantation (Haploidentical-BMT) usually has high morbidity and mortality associated with the early complication of SCT and severe GVHD. GVHD-associated T-cell clones can be identified in GVHD-affected tissues. In our study, Murine CB6F1(H-2b/d, [male]) and C57BL/6(H-2b, [female]) haploidentical-BMT GVHD model was established and proved a novel method to study the characteristics of T cell receptor repertoire in target organs of murine GVHD and research the molecular characteristics of T cell receptor BV complementarity determining region3 (TCRBV CDR3) repertoires of these monoclonal T cells in liver, skin and ileum.
Methods Murine haploidentical BMT model was established, RT-PCR was used to amplify 24 subfamily genes of TCRBV from liver, skin, ileum, spleen and kidney, PCR products were further analyzed by genescan to evaluate the clonality of BV subfamily and characteristics of CDR3, monoclonal bands were obtained thorough denaturation polyacrylamide gel electrophoresis and sequenced. A group of CDR3 molecules were obtained from GVHD-target tissues.
Results GVHD occurred as early as days 14 and was proven by histology in liver, skin and ileum. After BMT, it emerged a number of new monoclonal and oligoclonal T cells in GVHD-target tissues, while kidney was not affected by GVHD and infiltrated by polycolnal T cell. 48 TCRBV CDR3 molecules of monoclonal T cells which obtained from liver, skin, ileum in different times after BMT have six C’-terminal motifs(TEVFF, DTQYF, YEQYF, A EQ (Y F/FF), QNTLY F, AE T L Y F)and use restricted JB genes(JB1.1, JB2.5, JB2.7, JB2.1, JB2.4, JB2.3).
Conclusion Through murine haploidentical BMT GVHD model, TCRBV CDR3 was detected in GVHD-target tissues (liver, skin, ileum) and found that it emerged a number of monoclonal or oligoclonal T cells which associated with the development of GVHD and existed conserved CDR3 motifs.
Reduced Intensity Allogeneic Transplantation Provides High Disease-Free and Overall Survival in Patients (Pts) with Advanced Indolent NHL and CLL: CALGB 109901.
Authors: Shea Thomas C. , Johnston Jeffrey , Walsh William , Farag Sherif , McCarty John , Bashey Asad , Isola Luis , Stewart Marc , Kelly Michael , Owzar Kouros , Linker Charles 
Published: October 2019

Abstract
Reduced intensity allogeneic stem cell transplantation has been used increasingly to treat patients with both aggressive and indolent diseases such as low grade NHL and CLL. Most reports have consisted of single institution or registry data. We report here a prospective Cooperative Group study by CALGB in which 45 patients were treated at 11 CALGB institutions.
Methods: Patients < 70 years of age with a matched sibling donor and recurrent or refractory low grade NHL or CLL, high-risk CLL in first remission, mantle cell lymphoma or prolymphocytic leukemia were eligible. Patients were required to have CrCl > 40, DLCO > 40%, RNEF > 30% and LFTs < 3 × ULN. Disease must have been stable or responsive to the most recent previous therapy. The preparative regimen included 30 mg/m2 fludarabine × 5, and 1 gm/m2 cyclophosphamide × 3. The graft was G-CSF mobilized PBSC, and tacrolimus and low-dose MTX (5 mg/m2) on days 1,3,and 6 was used for GVHD prevention. Tacrolimus was tapered from day +90 to +150 in the absence of GVHD. Standard infectious disease prophylaxis, supportive care, and G-CSF from day +5 to engraftment were employed. DLI was given for stable or progressive disease, not loss of chimerism alone.
Results: 47 pts were enrolled with 44 eligible and evaluable; median age 53; 23 NHL, 14 CLL, 2 PLL, 4 mantle cell and one unknown. 27% developed ≥ grade 2 acute GVHD and 47% (18% extensive) chronic GVHD. TRM at 6 months was 2% and was 7% overall. Mortality at 2.6 year f/u is 25% due to GVH, sepsis, or 2nd malignancy (9%) and progressive disease (7 pts,16%). Estimated 2 yr DFS is 71% (CI 54–82) and OS is 76% (CI 60–87). Grade 4 AEs included 4 pneumonia/ pneumonitis, 1 PE, 1 VOD and 1 second malignancy (pancreatic CA). Documented infectious events included 32% viral, 41% bacterial, and 20% fugal. For T cell (CD3), the median chimerism at day 180 was 98% and 99% in peripheral blood and bone marrow; > 90% chimerism was present in 64% and 66% respectively. For unfractionated, the median chimerism at day 180 was 99% and 98% in peripheral blood and bone marrow; > 90% chimerism was present in 65% and 70% respectively.
Conclusion: These encouraging results indicate that a high CR and DFS rate can be obtained with low TRM without use of anti-CD20 therapy in a Cooperative Group trial of matched related allogeneic transplant in patients with low grade NHL or CLL. Appropriate patients should be considered for such therapy when standard treatments are no longer capable of achieving prolonged remissions.
Overall and Disease-Free Survival Overall and Disease-Free Survival
Marked Improvement of Skin Involvement in Severe Progressive Systemic Sclerosis after Transplantation of Mesenchymal Stem Cells from an Allogeneic Haploidentical Related Donor.
Authors: Christopeit Maximilian , Schendel Marit , Mueller Lutz Peter , Keyszer Gernot , Behre Gerhard 
Published: October 2019

Abstract
Introduction. Mesenchymal stem cells (MSC) show immunosuppressive capacity in an allogeneic host. Severe progressive systemic sclerosis (SSc) is an autoimmune disease in which prognosis is worsened in individuals presenting with diffuse cutaneous, lung and renal involvement. Immunosuppression can improve the course of the disease.
Methods. We transplanted a 41 year old female patient suffering from diffuse cutaneous systemic sclerosis with MSC from her father after in vitro expansion of the MSC.
Results. The patient presented with a remarkable clinical response. Her ulcer surface decreased, the 17 Site Modified Rodnan Skin Score, vascular ultrasound, mouth aperture, the Visual Analogue Scale for pain (VAS), the Valentini Activity Score and the Hannover Functional Questionnaire showed encouraging improvements. The patient did not experience any adverse events during the first 300 days after transplantation.
Conclusions. The transplantation of MSC from a haploidentical donor into a patient with systemic sclerosis is feasible, safe and effective. Furthermore is the transplantation of MSC from a haploidentical donor into an adult without severe pharmacological immunosuppression at the time of transplantation feasible and safe.
Bone Marrow Sinusoidal Endothelium Undergoes DNA Damage and Repair Following Lethal Irradiation.
Authors: Li Xiao-Miao , Hu Zhongbo , Jorgenson Marda L. , Wingard John R. , Slayton William B. 
Published: October 2019

Abstract
In the light of the possibility that adult bone marrow cells possess hemangioblast ability, work from our laboratory demonstrates that the bone marrow sinusoids remain predominantly host-derived following bone marrow transplant when ionizing irradiation is used as the conditioning regimen. To determine the effect of lethal irradiation to the host sinusoidal endothelial cells, we performed four apoptosis related assays and two cell proliferation assays on bone marrow sections at various time points during the first two weeks post-irradiation. We found:
Phosphorylated H2AX was present in both hematopoietic and sinusoidal endothelial cells. However, only hematopoietic cells showed caspase-3 dependent apoptosis. Three days after radiation, some sinusoidal endothelial cells became TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay) positive, but were activated caspase-3 and ISOL (in situ oligo ligation assay) negative, suggesting non-apoptotic DNA fragmentation. TUNEL positive endothelial cells were present in non-transplanted irradiated bone marrow 7–13 days post-irradiation while after 7 days, there were almost no TUNEL positive endothelial cells in transplanted animal, demonstrating that donor cells support sinusoidal endothelial survival. In some endothelial cells, TUNEL signal was concentrated in discrete areas of the nucleus, suggesting a repair process that involves the localization and removal of damaged DNA fragments. Very few sinusoidal endothelial cells were Ki67 positive and even fewer were BrdU positive, demonstrating that endothelial cell division is not a major mechanism for the survival of bone marrow sinusoidal system after irradiation on the short term.
These results demonstrate that sinusoidal endothelial cells undergo DNA damage and repair after lethal irradiation for bone marrow transplant. These results may explain, in part, why patients with impaired DNA damage/repair mechanisms have engraftment defects.
Development of a Cell Based Vaccine for the Immunotherapy of Acute and Chronic Leukemia by the Use of Autologous Dendritic Cells Loaded with Monoclonal Antibody Treated or Irradiated Leukemia Cells.
Authors: Duncan Caroline J. , Johnson Peter R.E. , Roddie Patrick H. 
Published: October 2019

Abstract
Dendritic cell (DC) vaccines in leukemia show promise as a novel treatment modality however to date clinical evidence of efficacy has been limited. This is likely to be as a consequence of a combination of factors, which include insufficient immunogenicity of the DC vaccine and vaccination taking place in an environment adverse for generation of effective immune responses i.e. in patients with active disease. Our study aims to generate more efficient cytotoxic T cell (CTL) responses by improving DC uptake and presentation of leukemia cells in the remission state and will be applicable to both acute and chronic leukemias. Monoclonal antibodies (MoAbs) have been used to treat malignant cells prior to co-culture with DCs to enhance cross-presentation and generation of specific CTLs. We investigated whether this approach could improve DC induction of CTL responses in comparison to DCs loaded with UVB irradiated apoptotic leukemia cells. In this in vitro study we generated dendritic cells from adherent mononuclear cells (differentiation with GM-CSF and IL-4) of patients in remission following chemotherapy for acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). The immature DCs were loaded with autologous leukemia cells from the patients’ presentation samples. The presentation leukemia cells were treated with either UVB irradiation or appropriate monoclonal antibodies (the anti-CD33 MoAb Mylotarg in AML and CML; the anti CD20 MoAb Rituximab or the anti-CD 52 MoAb Alemtuzumab in CLL). Apoptosis was assessed by Annexin/Propidium iodide labelling. Treatment of the leukemia cells by different MoAbs induced varying degrees of apoptosis. DC uptake of antibody treated or apoptotic leukemia cells was assessed by dual colour staining. Leukemia cells were stained with PKH and DCs labelled with FITC-CD80 or CD86. DC uptake was more efficient with MoAb treated cells irrespective of the degree of apoptosis induced by the MoAb. DCs were matured with TNFa for two days then co-cultured with autologous T cells for one week. T cell subsets and Regulatory T cells were assessed on the presentation and remission samples.The T cells were harvested and their cytoxicity assessed in an Interferon Gamma (IFNg) ELISPOT assay where the unmodified blasts were used as stimulators. Initial results show enhanced anti-leukemia activity in the MoAb treated group as compared to the irradiated group. A similar set up using allogeneic DCs and T cells confirmed the augmentation of CTL responses with MoAb treatment of leukemia cells.The use of MoAb in this setting shows promise for improvement in the success and applicability of DC vaccine strategies in leukemia.