bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gelatin-Coated Insert-Well Culture Markedly Improved In Vitro Culture of Primary Myeloma Cells.
Authors: Abroun Saeid , Otsuyama Ken-Ichiro , Shamsasenjan Karim , Islam Khademul , Amin Jaki , Asaoku Hideki , Kawano Michio M. 
Published: October 2019

Abstract
In order to clarify the pathogenesis of multiple myeloma (MM) and identify the molecular target for MM treatment, it is important to understand the biology and molecular mechanism of survival and proliferation of myeloma cells in vitro and in vivo. Still, it is hard to keep primary myeloma cells viable at least for 2 weeks in vitro, and these cells rapidly enter apoptosis even in the presence of IL-6. Co-culture with BM stromal cells is considered to be one of the most important factors as well as addition of cytokines for improvement of in vitro culture of primary myeloma cells. Based on our previous data, we devised a new method where bone marrow mononuclear cells (BMMNC) from BM aspirates were put inside insert-wells (8.0 um pore size, #3182, BD) coated with gelatin in the presence of the mixture of cytokines (galectin-1, SDF-1, IL-6 and IGF-1) in the serum-free synthetic medium; addition of galectin-1 and SDF-1 was essential especially at the beginning of this culture. By this method, we observed that BM stromal cells attached to gelatin and survived well with rather low proliferation; myeloma cells interacted well with these stromal cells. Thus, we could maintain viability of primary myeloma cells at least for 4 weeks and the recovery of viable myeloma cells (CD38++ cell) appeared to be about 80% in 30 cases of MM we examined. Phenotypic data also showed that ratio of immature (MPC-1−) and mature (MPC-1+) myeloma cells in the BMMNC before culture was approximately maintained after 2 or 4 weeks in this method. Therefore, these results suggest that gelatin-coated insert-well culture can control the viability of stromal cells and thus maintain the culture of primary myeloma cells in vitro. This new method would contribute to the further understanding of biology and drug sensitivity of primary myeloma cells.
Hepcidin Overproduction Mediates the Anemia of Multiple Myeloma.
Authors: Sharma Sanjai , Nemeth Elizabeta , Chen Yi-Hsiang , Huston Alissa , Roodman G.D. , Goodnough Julia , Ganz Tomas , Lichtenstein Alan 
Published: October 2019

Abstract
Hepcidin is a liver-produced protein that has been implicated in the anemia of chronic inflammatory/infectious disease. Hepcidin expression is stimulated during infection/inflammation and, by downregulating the iron exporter ferroportin, hepcidin prevents release of iron from macrophages and enterocytes. This results in a decrease in delivery of iron to maturing erythrocytes and significant anemia. Since IL-6 is the major cytokine upregulating hepcidin expression during inflammation/infection and, since high levels of IL-6 are often present in multiple myeloma (MM), we initiated the current study examining a role of hepcidin in the anemia of MM. Pretreatment urinary hepcidin levels were determined in 44 patients with stage III MM. The mean level of hepcidin (191ng/mg of creatinine) was significantly higher than normal controls (64.5ng/mg of creatinine). In contrast, patients with MGUS did not demonstrate elevated hepcidin levels. In the subset of MM patients without renal insufficiency (n=27) a marked inverse correlation was seen between hemoglobin level at diagnosis and hepcidin level (r= −0.46, p=0.014). This correlation is even more impressive because anemia in general (when not due to hepcidin overexpression) results in a decrease in hepcidin levels. These data strongly supported hepcidin upregulation as a major cause of anemia of MM. The hepcidin level also correlated with serum ferritin levels (n=28, r=0.37, p=0.048). A role for IL-6 in hepcidin upregulation was suggested by a significant correlation between hepcidin levels and C-reactive protein, an IL-6 targeted gene (n=28, r= 0.57, p=0.0012). However a correlation between hepcidin and serum IL-6 levels just missed significance (n=27, r= 0.36, p= 0.0599). Furthermore, real time PCR in vitro studies also suggested that IL-6 played a role but could not completely account for all cases of hepcidin upregulation. As compared to normal serum, sera from six MM patients (with known elevated hepcidin levels) significantly induced hepcidin RNA in a liver cell line, Hep3B. In the patients with co-existing high IL-6 levels, the serum-induced hepcidin RNA was prevented by anti-IL-6 and anti-IL6 receptor antibodies. However, in the patients with lower IL-6 levels, these blocking antibodies were unable to prevent sera-induced hepcidin RNA. Additional studies on myeloma cells isolated from marrow of a patient with high hepcidin level demonstrated an absence of hepcidin RNA in the resting or IL-6 stimulated state, indicating that the MM cells themselves do not participate in the increased production of hepcidin. These data strongly support the notion that enhanced expression of hepcidin is an important cause of the anemia of MM and suggest a role of IL-6 and other, yet to be identified, serum factors in the hepcidin upregulation.
Cyclosporine-Induced Nephrotoxicity and Dose Adjustments in Bone Marrow Transplantation.
Authors: Piran Sanaz , Piran Siavash , Stanley Fiona , Walker Irwin 
Published: October 2019

Abstract
Background and hypothesis: Cyclosporine is administered to all patients undergoing allogeneic bone marrow transplantation in Hamilton. It is given intravenously at first then orally after engraftment. The manufacturer’s recommendation is to use a dose ratio of 1:3, IV to oral; the Hamilton unit uses a ratio of 1:2, yet has observed frequent rises of cyclosporine to toxic levels. We wished to confirm that the dose conversion ratio of 1:2 is associated with significantly high cyclosporine levels and nephrotoxicity.
Methods and Results: Thirty-five consecutive patients undergoing allogeneic bone marrow transplantation at McMaster University Medical Centre were studied. We included patients who were diagnosed with a hematological cancer i.e. leukemia (76%), lymphoma (18%), or myelodysplastic syndrome (6%), and who underwent chemotherapy. The patients’ plasma cyclosporine levels were measured 4–5 days after its initiation and with every dose adjustment, and serum creatinine levels were measured daily. Forty four percent of the patients were males. In 53% of the patients 1:2 IV to oral conversion ratio caused elevation of plasma cyclosporine levels to the toxic range (p<0.001). The toxic cyclosporine levels were seen 5+/−2 days post IV to oral dose adjustment. Furthermore, 43% of these patients developed acute renal failure and significant elevation of their serum creatinine levels (p<0.001).
Conclusion: The traditional conversion rate of 1:2–3 for intravenous to oral cyclosporine is associated with rises in plasma cyclosporine to toxic levels and significant rises in serum creatinine level. We recommend that this conversion rate be lowered to 1:4/3 and further studied.
Severity, Frequency, and Risk Factors for Oral Mucositis after BEAM High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation and Preliminary Results with Palifermin Versus Best Supportive Care.
Authors: Strobel Eva-Susanne , Bauchmüller Kris , Ihorst Gabriele , Engelhardt Monika 
Published: October 2019

Abstract
Mucositis being an adverse effect of high-dose chemotherapy (hd CTx) may compromise results of peripheral blood stem cell transplantation (PBSCT). Keratinocyte growth factor can effectively decrease its severity and frequency. Here, the mucositis rate after BEAM hd CTx followed by auto-PBSCT was analyzed. A total of 50 patients (median age: 55 years, range; 19–70) with high-risk, refractory or relapsed lymphoma were included in a prospective analysis at our center, and mucositis was graded according to WHO. After BEAM-hd CTx, WHO grade 2 mucositis developed in 30%, grade 3 in 10% and grade 4 in 4%. Odds ratios (OR) for mucositis grade 2 or higher were increased to 2.1 (95% CI 0.6–6.7) for female sex, to 1.9 (CI 0.5–6.7) for higher pretreatment (>8 CTx-cycles), and 3.1 (CI 0.9–10.5) with previous mucositis. We found no association for older age, lymphoma type (indolent vs. high-grade NHL/Hodgkin’s disease), previous radiotherapy, Karnofsky index, oral hygiene or leukopenia prior to auto-PBSCT. The OR for mucositis with parental nutrition was estimated with 2.2 (CI 0.6–7.7) and for opioid use with 8.7 (CI 2.2–33.7) (p=0.0025), both being directly influenced by the extend and severity of oral mucositis. As expected, myelosuppression was the main toxicity of hd-BEAM: WBC >1.000/ml were reached after a median of 10 days (range 7–15), platelets >20.000/ml after 11 days (range 7–45). The median numbers of red blood cell and platelet units transfused were 5 (range 1–21) and 4 (range 1–35), respectively. The event free survival at 6, 12 and 24 months was 81.9% (CI 71.2–92.6%), 70.5% (CI 57.3–83.6%), and 66% (CI 51.2–80.9%), and the overall survival 83.9% (CI 73.7–94.1%), 79.2% (CI 67.7–90.8%) and 79.2% (CI 67.7–90.8%), respectively. Subsequently, 10 lymphoma patients have been accrued in the follow-up study comparing palifermin to best supportive care (BSC) after hd-BEAM conditioning. All 5 patients receiving palifermin showed only WHO grad 1 mucositis, whereas in the control group one patient each had grade 1, 2 and 3 mucositis and 2 patients are still being treated. In conclusion, we found females, extensive pretreatment and previous mucositis as potential risk factors for the development of mucositis, the latter greatly influencing parental nutrition and opioid use. Although the incidence of grade 2–4 mucositis varies with different CTx-schedules and -intensity, it severely affects supportive measures. Decrease in its severity and duration will substantially reduce side-effects of PBSCT further.
Adding Palifermin in Allogeneic and Autologous Stem Cell Transplantation Resulted in Reduced Oral Mucositis and Enhanced Intestinal Mucosal Recovery Measured by Citrulline Serum Levels.
Authors: Langner Stefan , Staber Philipp B. , Zebisch Armin , Zinke-Cerwenka Wilma , Sill Heinz , Linkesch Werner , Greinix Hildegard , Kalhs Peter , Rabitsch Werner , Neumeister Peter 
Published: October 2019

Abstract
Background: In this ongoing prospective open label study we evaluate the effect of Palifermin on the development of oral and intestinal mucositis in 25 patients undergoing allogeneic or autologous hematopoietic stem cell transplantation (allo/auto-HSCT).
Methods: Twenty-five patients, transplanted for acute or chronic leukemia (n=20) and non-Hodgkin’s lymphoma (NHL, n=5) received 60 μg Palifermin per kilogram of body weight per day for three consecutive days before the initiation of conditioning therapy and immediately after HSCT. The control group comprised 9 patients diagnosed with acute leukaemia (n=6) and NHL (n=3). In the Palifermin group the distribution between allo- and auto-HSCT was 16 and 9 compared to 5 and 4 in the control group. Conditioning therapy consisted of fractionated total-body irradiation/Cyclophosphamide in case of leukemia and chemotherapy only based regimens in NHL patients. Oral mucositis was graded daily according to World Health Organisation (WHO) criteria. The intestinal mucosal barrier damage was assessed by analyzing Citrulline serum levels on HSCT days -12, -6, 0, +7, +14 and +21.
Results: No severe side effects were observed in our patient cohort. Our preliminary analysis demonstrates a significant decrease in the incidence of oral mucositis WHO grade 3 or 4 with 24 percent in the Palifermin group as opposed to 78 percent in the control group (p=0,013). The median duration of mucositis was 4,7 days (range 0–19) in the Palifermin group compared to 9,3 days (range 0–19) in controls (p=0,037). Whereas 17 evaluable patients in both groups showed a similar decline in Citrulline serum concentrations until day +7 - reflecting a maximal intestinal mucosal barrier injury at this timepoint - a significantly faster recovery of Citrulline levels (18,5 vs 13,8 μM, p=0,04) in Palifermin recipients at day +21 could be found. The use of opioid analgesics as determined by morphine equivalents (median 105mg vs 112mg) was almost equal. However, there was a trend in the duration of total parenteral nutrition (14 vs 18 days, p=ns) in favor of the Palifermin group. Acute graft versus host disease grade I-IV was observed in 29%, grade III-IV in 21% of Palifermin treated patients after an allo-HSCT.
Conclusions: Palifermin was generally well tolerated and reduces the incidence and duration of WHO grade 3 and 4 oral mucositis. Further, it promotes a faster recovery of intestinal mucosal damage in allogeneic and autologous HSCT recipients.
Chronic Graft-Versus-Host Disease-Related Membranous Nephropathy: Report of 3 Cases.
Authors: Zhu Kanger , Zhu Wei-jian , Zhang Tao 
Published: October 2019

Abstract
Objective: To investigate the clinical manifestation, pathological features, management and prognosis of chronic graft-versus-host disease (cGVHD)-related membranous nephropathy following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: Clinical and pathological data from 3 patients with nephrotic syndrome following allo-HSCT were retrospectively analyzed.
Results: cGVHD-related membranous nephropathy occurred in 3 out of 150 patients (2%) undergoing allo-HSCT in our BMT unit. 3 patients, with two male and one female, median age of 15 years, and median interval of 11 months between diagnosis and post-transplantation, typically presented with full nephrotic syndrome, including heavy proteinuria (median 8.1 g/24h), edema, hypoalbuminemia (median 29.6 g/L), and hypercholesterolemia (median 11.7 mmolL). A major finding of renal biopsy that was consistent with membranous nephropathy in early stage was diffusely thickened glomerular basement membranes (GBMs) with deposits of IgG along it. All patients showed evidence of cGVHD. Two patients responded well to steroid, with gradual improvement of clinical symptoms and disappearance of proteinuria, and are still alive without evidence of relapse. But the other one died of disseminated hemorrhagic varicella one month following immunosuppressive therapy.
Conclusion: These findings suggest that the kidney may be the target organ of alloimmunity, and membranous nephropathy may be one of clinical manifestations of cGVHD, which is response to steroid, resulting in disappearance of proteinuria. It is necessary for transplant physicians to keep in mind the possibility of cGVHD-related membranous nephropathy when a case of nephritic syndrome is encountered.
Isolated Oral Lichen Planus as Manifestation of Chronic GvHD Predicts Improved Survival after Reduced Intensity Allogeneic Stem Cell Transplantation.
Authors: Visser Otto J. , Kara Sema , Leidekker Maaike , Janssen Jeroen J.W.M. , van der Waal Isaac 
Published: October 2019

Abstract
In reduced intensity allogeneic stem cell transplantation an increasing incidence of a lichen planus-like disorder of the oral cavity as manifestation of chronic graft versus host disease (cGvHD) has been reported, sometimes combined with a similar condition in the genital area. Oral lichen planus GVHD (OLP-GvHD) can occur as a single manifestation of cGvHD, without other organs affected. It resembles classic oral lichen planus both clinically and histologically. Clinical symptoms are a painful, burning sensation, diminished taste, loss of appetite and hyposalivation, sometimes resulting in problems with medication intake. Clinical examination is the main key in the diagnosis of OLP-GvHD. In some cases (modest) alterations of liver function can be detected as well. Apparently, no GvHD of the skin or digestive tract is present.
From January 2004 to March 2006, we performed a total of 96 RIST transplantations. All patients systematically underwent pretransplantation examination, including high quality photographs of the oral mucosa, by an oral medicine specialist. During follow up, 24 patients (25%) were diagnosed with OLP-GvHD without concomitant cGvHD of other organs. The diagnosis was based on clinical features, histopathology and by exclusion of any other causes (e.g. viral or yeast infections). Digital photographs of the oral lesions were compared with routinely taken pretransplantation photographs. Isolated OLP-GvHD (+/− modest liver function tests), was treated with topical dexamethasone elixer (0.11 mg/ml), if not successful (7/25 patients) also with tacrolimus ointment (0.1% + hypromellose 4000 mpa). After a median follow up of 12 months, a significant improvement of overall survival was seen in patients diagnosed with OLP-GvHD as compared with those with more extensive cGvHD or no cGvHD. The mean duration of local therapy of the oral cavity was 135 days and nearly all symptoms disappeared.
We conclude that after reduced intensity allogeneic stem cell transplantation the occurrence of OLP-GvHD predicts superior survival rates. Local treatment is sufficiently effective.
Figure Figure
Rapid Immune Reconstitution after a Reduced-Intensity Conditioning Regimen and a CD3-Depleted Haploidentical Stem Cell Graft for Pediatric Refractory Hematologic Malignancies.
Authors: Chen Xiaohua , Hale Gregory A. , Barfield Raymond C. , Benaim Ely , Leung Wing H. , Knowles James , Horwitz Edwin M. , Woodard Paul , Kasow Kimberly A. , Yusuf Usman , Behm Fred G. , Hayden Randall T. , Shurtleff Sheila A. , Turner Victoria , Srivastava Deo Kumar , Handgretinger Rupert 
Published: October 2019

Abstract
Haploidentical hematopoietic stem cell transplantation (HaploHSCT) from a mismatched family member (MMFM) donor offers an alternative option for patients who lack an HLA-matched donor. The main obstacles to successful haploidentical hematopoietic stem cell transplantation from a mismatched family member donor are delayed immune reconstitution, vulnerability to infections, and severe graft-versus-host disease (GvHD).
Method: We designed a reduced-intensity conditioning regimen that excluded total body irradiation and anti-thymocyte globulin. The graft was immunomagnetically depleted of CD3+ T-cells (CD3 negative selection) and contained a large number of both CD34+ and CD34− stem cells and most other immune cells especailly NK cells. This protocol was used to treat 22 pediatric patients with refractory hematologic malignancies.
Results and Discussion: After transplantation, 91% of the patients achieved full donor chimerism. They also showed rapid recovery of CD3+ T-cells, T-cell receptor excision circle counts, TCRβ repertoire diversity and NK-cells during first four months post-transplantation. The incidence and extent of viremia were limited and no lethal infection was seen. Only 9% of patients had grade 3 acute GvHD, while 27% patients had grade 1 and another 27% had grade 2 acute GvHD. This well-tolerated regimen appears to accelerate immune recovery and shorten the duration of early post-transplant immunodeficiency, thereby reducing susceptibility to viral infections. Rapid T-cell reconstitution, retention of NK-cells in the graft, and induction of low grade GvHD may also enhance the potential anti-cancer immune effect.
Lymphoma and Peripheral Neuropathy: Sudden Weakness in a Patient with T-Cell Lymphoma.
Authors: Muslimani Alaa , Daw Hamed 
Published: October 2019

Abstract
Introduction: Lymphomas (both Hodgkin’s and Non-Hodgkin’s [NHL]) can affect the peripheral nervous system and cause peripheral neuropathies in 5–8 % of patients. The mechanisms by which this can occur include directly infiltrating nerves, paraneoplastic mechanism, metabolic and infectious processes, and side effects of treatment. Most neurological complications occur in NHL, the majority being B-cell NHL. Only few cases have been reported T-cell NHL and acute inflammatory demyelinating polyradiculopathy. We report once such case.
Case: A 70-year-old female initially presented with left nostril lockage and maxillary sinus pressure. Examination revealed a black mass in the left nostril and swelling of the nose, including left nasal-lacrimal area. The rest of the physical exam was unremarkable. Biopsy revealed natural killer/T-cell (NK/T-cell) lymphoma nasal type, an aggressive but uncommon lymphoma in the United States. She underwent CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. Positron emission tomography (PET) scan was negative for lesions in chest, abdomen and pelvis. Three weeks after completing chemotherapy, she presented with acute lower extremity paraparesis. On examination, she had absent lower extremity reflexes. A computed tomography scan of the brain revealed a tumor infiltrating the left orbit. After undergoing numerous investigations including, lumbar puncture and magnetic resonance imaging (MRI) cervical and thoracic spine, electromyography and nerve conduction studies revealed abnormal findings suggestive of inflammatory demyelinating polyradiculopathy.
She was treated with intravenous immunoglobulin without significant improvement. Soon after, she had facial nerve involvement that was confirmed on an MRI of the brain. Six months after the initial diagnosis of nasal NK/T-cell lymphoma, the patient’s symptoms worsened and she was referred to hospice and expired.
Conclusion: Nasal NK/T-cell lymphoma often follows an aggressive course. The majority of peripheral neuropathy cases in NHL are chemotherapy related. Although most cases of peripheral neuropathy occur in B-cell NHL, this is a case of T-cell NHL associated with acute inflammatory demyelinating polyradiculopathy.
Pre-Transplant Smoking and Transplant-Related Mortality from Pulmonary Causes in Recipients of Allogeneic Stem Cell Transplants.
Authors: Magalhaes-Silverma Margarida , Leopold Christina , Cater Thomas , Hohl Raymond , Gingrich Roger 
Published: October 2019

Abstract
BACKGROUND: The success of allogeneic stem cell transplantation (SCT) is limited by transplant-related mortality (TRM). Death from pulmonary causes is a major contributor to TRM. Several factors influence TRM from pulmonary causes. We have analyzed the effect of cigarette smoking on pulmonary related TRM.
METHODS: From January 2000 through April 2006 240 patients (pts) underwent allogeneic related or unrelated SCT. Diagnosis included ALL in 22 pts, AML in 90 pts, CLL in 11 pts, CML in 11 pts, Lymphoma in 49 pts, MDS in 29 pts, MM in 9 pts, SSA in 4 pts, solid tumors in 5 pts, other in 4 pts; median age of the pts was 50 years (range 18–70); 148 were males and 92 females; 48 pts received a reduced intensity regimen and 192 an ablative regimen; 117 pts received TBI; 123 pts were non-smokers (Group I) and 117 pts smokers. Amongst the smokers 86 pts provided pack/year information. In this group 46 pts (Group II) had a pack/year history < 30 and 40 pts (Group III) of ≥ 30.
RESULTS: 70/123 pts in Group I are deceased with 44% surviving. In this group causes of death included disease progression/relapse in 17 pts, infection in 17 pts, organ failure in 13 pts, GVHD in 11 pts, other in 3 pts and pulmonary related TRM in 8 pts (6.5 ± 4%). 29/46 pts in Group II are deceased with 36% surviving. In this group causes of death included diseaseprogression/relapse in 10 pts, infection in 8 pts, organ failure in 1pt, GVHD in 3 pts, other in 2 pts and pulmonary related TRM in 5 pts (10.9 ± 9%). 31/40 pts in Group III are deceased with 22% surviving. In this group causes of death included disease progression/relapse in 11 pts, infection in 6 pts, organ failure in 5 pts, GVHD in 2 pts, other in 2 pts and pulmonary related TRM in 5 pts (12.5 ± 10 %).
CONCLUSION: Smoking contributes to transplant-related mortality from pulmonary causes after allogeneic stem cell transplantation in a dose-related manner. In future analysis the interaction between smoking and other variables will be explored.
Smoking and Outcomes Pt Group Surviving Pts (%) Deceased Pts (%) Pulmonary TRM Group I ( n=123) 44% 56% 6.5% Group Ii (n=46) 36% 64% 10.9% Group III ( n=40) 22% 78% 12.5%