bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation in Renal Cell Carcinoma: The EIO Experience.
Authors: Pastano Rocco , Laszlo Daniele , Andreola Giovanna , Gigli Federica , Rabascio Cristina , Raia Valentina , Cazzanti Manuela , Peccatori Fedro , Martinelli Giovanni 
Published: April 2020

Abstract
Background. A less toxic approach than conventional allogeneic stem cell transplantation based on the use of a non-myeloablative and potent immunosuppressive regimen has been previously developed. Aim of such procedure is to establish a mixed chimerism engraftment and to get an immunologic effect against the tumor, eventually potentiated by donor lymphocyte infusion. Such effect is well known to occur in hematological malignancies and is under investigations in solid tumors, mainly renal cell carcinoma (RCC).
Patients and methods. From December 2003 to June 2004 we enrolled 8 pts, median age 57 (34–66), affected by metastatic RCC, in progressive disease (PD) after different lines of therapies. Conditioning regimen was the following: Fludarabine, 30 mg/m2, from day −4 to −2 followed by 2Gy TBI on day 0, when all pts received HLA matched related grafts. Prophylaxis of aGvHD was performed with administration of Cyclosporine (6.25mg/kg) p.o. bid from day −3 to +36 followed by a rapid tapering to +56 and mycophenolate mofetil (15mg/kg) p.o. bid, given from day 0 to +27.
Results. After transplantation five pts achieved a SD (62%), 2 experienced PD and response was not evaluable for one pt who died at +24. Three showed graft rejection at day +56, +90 and +120, respectively. After a median follow-up of 152 days (24–440), 3/8 (37%) patients are still alive: 2 in SD at +386 and +144, despite loss of graft in +90 and in +56, respectively and 1 in PD; 5 (62%) pts have died, 4 because of PD, 1 for aGvHD. Hematological toxicity was mild with no G4 neutropenia or thrombocytopenia; infections occurred in 2/8 (25%) pts, none was fatal. Incidence of aGvHD was 25%(2/8), one of which was G4 fatal aGVHD. No patient suffered from cGvHD.
Conclusions. Our results confirm this regimen is safe and feasible in patients affected by metastatic RCC, but further studies are necessary to clarify the high rate of graft rejections (3/8, 37%) and the low clinical activity of the regimen.
Low Progression-Free Survival for High-Risk Patients Treated with Reduced-Intensity Conditioning Regimen Allogeneic Stem Cell Transplantations with Volunteer Unrelated Donors.
Authors: Tabrizi Reza , Bijou Fontanet , Bouabdallah Krimo , Leguay Thibaut , Marit Gerald , Pigneux Arnaud , Gomez Aurelie , Belloc Francis , Lafarge Xavier , Boiron Jean-Michel 
Published: April 2020

Abstract
Reduced-intensity conditioning regimens (RICR) are increasingly used before allogeneic stem cell transplantation (SCT) for patients not eligible for myeloablative conditioning. The relapse and survival rates after RICR allogeneic SCT were studied in 19 high-risk patients treated between February 2002 and December 2004. Ten males and 9 females with a median age of 47 years (15–55) received PBSC transplantation from a 10/10 (n=15) or 9/10 HLA antigen-matched donor (n=4). Acute leukemia was the main diagnoses (n=12; 6 AML and 6 ALL), the other diagnoses were 3 multiple myeloma, 2 CML, 1 NHL, 1 CLL. All patients had high-risk disease: 12 had second or &gt; 2 complete remission, 5 second partial remission and 2 refractory disease. The preparative regimen consisted of cumulative dose of Busulfan 8mg/kg, Fludarabine 150 mg/m2 and ATG 7.5 mg/kg (Thymoglobulin, Genzyme, Lyon, France). Graft-versus-host disease (GVHD) prophylaxis regimen consisted of cyclosporine A and short-course methotrexate. Median follow-up was 14 months (5–39 months). Engraftment was complete in all but 2 patients with refractory disease and 14 patients achieved 100% donor CD3 (median 56 days, range 18–123). Grade 2 to 3 acute GVHD was seen in 3 (16%) patients, no grade 4 acute GVHD was observed. Grade 1 chronic GVHD was seen in 1 patient. Nine pts relapsed at a median time of 9.5 months, 3 pts had never reached a full CD3 donor chimerism. Twelve pts are alive, seven pts in complete remission, 2 pts with relapsed disease. Three pts relapsed and achieved a subsequent complete remission by chemotherapy, one of them received a second SCT, one a DLI and one other developed hepatic cGVHD and didn’t receive DLI. Five pts died from recurrent disease, One pt died from cerebral toxoplasmosis and one other from cerebral hemorrhage due to a secondary poor graft function. Survival rate was 73% (95% CI 0.52–0.93) at 6 months and 60% (95% CI 0.38–0.83) at 1 year. PFS rate was 73% (95% CI 0.52–0.93) at 6 months and 33% (95% CI 0.09–0.57) at 1 year. In conclusion, in this cohort of pts, the progression-free survival is unsatisfactory. This can be explained by the advanced stage diseases and the low incidence of cGVHD, probably due to high immunosuppressive treatment. A less intensive immunosuppressive protocol can be tested to improve the results in this particular group of patients.
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Clinical Effects of Unrelated-Donor or Related-Donor Hematopoietic Stem Cell Transplantation for Leukemia.
Authors: Liu Qifa , Sun Jing , Xu Dan , Wei Yongqiang , Zhang Yu , Ye Changxiong , Meng Fanyi 
Published: April 2020

Abstract
Patients and Methods: From February 2003 to May 2005, 118 patients with leukemia received URD-HSCT or RD-HSCT at our institution. 43 cases received URD-HSCT and 75 cases received RD-HSCT. The basic conditioning regimens were TBI (total-body irradiation) + CY (CTX) protocol or modified BuCY (hydroxyurea, busulfan, Ara-C and CTX) protocol. Fludarabine, cytosine arabinoside, etoposide and etc. were added to the basic conditioning regimens when treated patients with refractory leukemia or in NR. The 43 patients who were treated with URD-HSCT, included 43 patients matched at 6/6 HLA antigens based on conventional serologic typing methods, 11 at 5/6 HLA antigens, 1 at 4/6 HLA antigens and 1 at 3/6 HLA antigens. Among the 75 patients with RD-HSCT, 69 patients were matched at 6/6 HLA antigens serologically, 6 were matched at 5/6 HLA antigens. The basic protocol GVHD prophylaxis is CsA (cyclosporine) and methotrexate (MTX). Low-dose antithymocytes globulin (ATG) was added to the basic protocol when patients treated with URD-HSCT, and mycophenolate mofetil (MMF) and low-dose ATG added to the basic protocol were used in some patients with URD-HSCT.
Results and Conclusion: The patients treated with URD-HSCT or RD-HSCT have no significant differences in sex, age, disease type and pretransplantation condition. The overall survival was 57.5±0.83% and 58.7±10.5% in patients undergoing URD-HSCT and RD-HSCT, and the 3 year disease-free survival rate was 51.6±8.5% and 49.8±8.3%, respectively. The overall survival and 3 year disease-free survival differed little between unrelated and related transplantation(P&gt;0.05). The relapse rate of leukemia between URD-HSCT and RD-HSCT were 9.3% and 18.8%, respectively, and significant difference was noted (P&lt;0.05). II–IV° acute GVHD (aGVHD) occurred in 58.17% of the patients receiving URD- HSCT and in 33.00% of those with RD-HSCT, especially the incidence of III–IV° severe aGVHD in the two group was 16.0% and 9.0%, respectively, and there were significant differences, too. The mortality caused by GVHD in patients with URD-HSCT was 12.0% and that in RD-HSCT was 9.0%, and it differed little. The incidence of chronic GVHD (cGVHD) in patients who could be followed up after URD-HSCT was 51.15% and that in RD-HSCT was 53.85%, there was no significant difference. The mortality directly caused by infection in the two group was 7% and 4%, respectively, and there was no significant difference. Two patients with URD-HSCT died of venous occlusive disease (VOD), one hemorrhagic cystitis (HC) and one graft rejection, but there was no similar condition in RD-HSCT.
A Early Report of Bone Marrow Transplantation from HLA Mismatched Mother for β-Thalassemia Major.
Authors: Li Chunfu , He Yuelin , Zhang Yuming , Wu Xuedong , Ming Yang , Bai Jin 
Published: April 2020

Abstract
Objective: To study the possibility of Bone Marrow Transplantation for β-thalassemia major using an alternative donor from HLA mismatch mother.
Methods: Three patients withβ-thalassemia major were given a BMT from HLA one-antigen mismatched mothers. The patient-1 was 7 year old, patient-2 was 1.5 and patient-3 was 4, respectively. All of patients were boys The oldest was class III in the Pesano grouping and others were classI-II. Patient-1 and patient-3 were given the conditioning of TBI 300 rad, Bu 14mg/kg, Cy 160mg/kg and ATG-F (patient-1 was 90mg/kg, patient-3 was given 30mg/kg). Patient-2 was given Fudalabine 150mg/kg instead of TBI and ATG-F 30mg/kg. Infused nuclear cells were 5.3x10e8/kg for patient-1, 6x10e8/kg for patient-2 and 19.4x10e8/kg for patient-3, respectively. Donor of patient-3 received G-CSF from day −2 to day 0. The prophylaxis of GVHD included CsA+methylpregnisolone but patient-3 received additionally MMF and anti-CD25 monoclonal antibody (Daclizumab).
Results: Time of follow-up was 4 years for patient-1, 3.2 years for patient-2 and 10 months for patient-3. Patient-1 and patient-3 are EFS and with only mild acute GVHD. Patient-2 was no engraftment.
Conclusions: We conclude that BMT from HLA one-antigen mismatched mother may be used for patients withβ-thalassemia major in some developing countries, such as China, in where the convention treatment of thalassemia was not well performed, whereas there are only three cases in our experiment.
Results of High Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Chemo-Responsive Multiple Myeloma.
Authors: Ault Kenneth A. , Case Delvyn C. , Boyd Marjorie A. , Thomas Ervin J. , Aronson Frederick R. , Ebrahim Kurt S. , Hedlund Jaquelyn A. 
Published: April 2020

Abstract
29 patients with Stage III multiple myeloma have undergone transplantation at our institution over the past 10 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction &gt;40%, DLCO &gt; 50% of predicted and no other co-morbid conditions that would jeopardize sur-vival. In addition, there was demonstrated chemo-sensitivity of the disease with at least a 50% decrease in M-component and a decrease in marrow plasmacytosis to less than 10%. After treatment to maximal effect with VAD (3–6 cycles), peripheral blood stem cells were collected. The dose of CD34 positive cells ranged from 1.8 to 17.4 x106/kg. (median 11.4 x 106/kg). 8 patients treated prior to September 2000 received high dose therapy with Melphalan 140mg/m2 and fractionated TBI, 150cGy bid for 5 doses. Patients treated after September 2000 received Melphalan 200mg/m2 without radiation. The median age at transplantation was 52 years (range 29 to 71). There were no treatment related deaths. Days to achieve AGC&gt;500/ul ranged from 5 to 13 (average 6.8). The median length of follow up is 2.7 years. Currently 23 patients are alive, and 18 are free from progression. Overall survival at 5 years is 79%. Progression-free survival at 5 years is 43%.
Figure Figure
Our experience suggests that carefully selected patients with chemo-responsive multiple myeloma have relatively high rates of overall and progression free survival when compared to results reported for a broader population of patients.
Use of Low Dose Oral Vitamin K in the Treatment of Patients with INR Values of More Than 10.0.
Authors: Crowther Mark A. , Garcia David , Ageno Walter , Witt Daniel M. , Schulman Sam , Blostein Mark , Kovacs Michael J. , Kearon Clive , Anderson David , Wells Phil , Ginsberg Jeff S. , Selby Rita , Wang Luqi , Kahn Susan R. 
Published: April 2020

Abstract
The optimal therapy for patients who present with markedly prolonged INR values during warfarin therapy is undefined. Evidence suggests that the risk of bleeding increases directly with the degree of prolongation of the INR. Traditional therapy for patients with excessive warfarin associated anticoagulation has included warfarin withdrawal with or without vitamin K, transfusion therapy and admission to the hospital. As part of an ongoing international study, we prospectively enrolled 32 consecutive warfarin-treated patients presenting with an INR of more than 10.0. Eligible patients had no evidence of active bleeding or need for immediate correction of their INR. All patients received 2.5 mg of oral vitamin K, were not treated with coagulation factor replacement, and were followed over 90 days for clinical events and their INR response. Seventeen of the 32 patients were women, with an average age of 65.8 (range 31 to 89). Treatment of venous thrombosis and atrial fibrillation (12 patients each) were the most common indications for warfarin. Twenty-five patients had a target INR of 2.0 to 3.0; the remainder had a target of 2.5 to 3.5. The mean INR at presentation was 12.9 (range 10.0 to 21.2). Of the 25 patients with a recorded INR value on the day following vitamin K, 19 (76%) had an INR of 6.0 or less (range 1.6 to 17.5, mean 5.0, 2 less than 2.0). On day 7 after study drug, the mean INR was 3.5 (range 1.6 to 17.5). Six (19%) patients reported bleeding over the 90 days after study drug: 1 (3%) bleed was major (retroperitoneal hemorrhage diagnosed the day after study drug) and 3 patients reported epistaxis or bruising within three days of study drug. Two patients reported late bleeding; one had a fall on day 8 at which time the INR was 10.5, and the other had bleeding associated with a surgical procedure 25 days after study drug. No patients had suspected or confirmed thrombosis, and no patients died during follow-up. This the first prospective study of vitamin K monotherapy for patients with INR values above 10, and confirms prior retrospective analyses which suggest that low dose oral vitamin K effectively lowers the INR in such patients. Our preliminary results also suggest that coagulation factor replacement may be unneeded in such patients. The true risk of bleeding, and the impact of degree of prolongation of the INR on the vitamin K response, will require additional patient recruitment.
A Comparison of 3 Staging Systems for the Outcome Following Autologous Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma (MM).
Authors: Sohn Hee-Jung , Kim Kihyun , Lee Jae-Hoon , Bang Soo-Mee , Kim Dong Hwan , Lee Je-Jung , Suh Cheolwon 
Published: April 2020

Abstract
The Durie-Salmon (DS) stage has been the gold standard for stratification of MM patients. However, the system does not contain beta-2 microglobulin (B2M) widely recognized as the single most powerful prognostic parameter. Recently, The Southwest Oncology Group (SWOG) staging system (Jacobson JL, et al. Br J Haematol122:441–50, 2003) and the International Staging System (ISS) (Greipp PR, et al. J Clin Oncol23:3412–20, 2005) utilizing B2M have been proposed. We aimed to evaluate whether the stage assessed at the time of ASCT by DS, SWOG, or ISS predict outcome following ASCT in patients with MM. Between November 1996 and December 2004, a total of 141 patients with MM who were treated with ASCT at 5 institutions in Korea were available for this analysis. The distribution of patients’ stage at ASCT by 3 staging systems was as Table 1. With a median follow-up of 20 months from ASCT, the median event-free survival (EFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 11–21) and 56 months (95% CI, 38–74), respectively. The median survival of each stage group according to 3 staging systems at ASCT was as Table 2. Differences in EFS among the stage groups were not statistically significant. However, OS after ASCT was dependent on the SWOG stage at the time of ASCT and also significantly longer in patients with ISS stage I than others (NR vs. 39 months, P =.001). In this study, OS following ASCT was influenced by the stage according to SWOG or ISS, but not DS.
The distribution of patients by 3 staging systems Stage I II III IV DS 32 (23%) 23 (16%) 86 (61%) - SWOG 53 (38%) 66 (47%) 16 (11%) 6 (4%) ISS 85 (60%) 34 (24%) 22 (16%) - Median event-free survial and overall survival by 3 staging systems Stage I II III IV P EFS=evnet-free survival, OS=overall survival, NR=not reached, * in months EFS* DS 27 17 13 - .40 SWOG 22 15 24 4 .21 ISS 17 13 10 - .63 OS* DS NR 58 40 - .17 SWOG NR 41 32 17 .045 ISS NR 32 40 - .0042
Treosulfan-Based Tandem High-Dose Chemo-Immuno- Therapy with Autologous Stem Cell Transplantation for Relapsed and Refractory Aggressive B-Cell Lymphomas.
Authors: Reichle Albrecht , Holler Ernst , Berand Anna , Andreesen Reinhard 
Published: April 2020

Abstract
Feasibility and high efficacy of repetitive dose-intensive chemo-immuno-therapy in relapsed and refractory aggressive B-cell lymphoma (adjusted IPI at relapse 2 and 3) was proven by double-induction followed by tandem high-dose chemo-immuno-therapy with stem cell transplantation including a treosulfan-based conditioning regimen. For cytoreduction and stem cell mobilisation, 2 cycles of a cisplatin-based chemotherapy plus rituximab (R), R-VIPE or R-DHAP, were applied followed by two identical cycles of high-dose chemotherapy (HD-CT) consisting of treosulfan 14 g/m2 iv day −4 to day -2, carboplatin 300 mg/m2 iv day −4 to day −2 and etoposide 500 mg/m2 iv day −2 to day −4. Each HD-CT was combined with rituximab 375 mg/m2. Thirty patients (pts), mean age 53 years (range 35–68), stage III: n=9, stage IV: n=21, have been enrolled. 80% of the pts suffered from early relapse within 6 months (n=6) or refractory disease and no available matched related or unrelated donor (n=18), 6 pts had a late relapse (≥ 6 months). All patients received previously CHOP-based CTs. Histology revealed diffuse-large cell lymphoma (n=19), follicular lymphoma Grade 3 (n=6), immunoblastic lymphoma (n=3), and mantle cell lymphoma (n=2). In 7 pts both, low- and high-grade lymphomas were observed. Only one stem cell mobilization was necessary to collect sufficient CD34+ cells for two transplantations. Median hematologic recovery (&gt; 1.0 leukocytes/nl and platelets &gt;20/nl) after 1st and 2nd HD-CT was achieved by day 10 (8–11). No therapy-related death occurred. CTC °III and °IV non-hematologic toxicities were as follows: 11 of 29 pts after 1st HD-CT had °III toxicities (infection, vomiting, enteritis, stomatitis, diarrhea), after 2nd HD-CT 10 of 27 pts, respectively. Complete remission (CR 3 months post transplantation) was achieved in 22 of 30 pts (73%). CR was documented after double-induction (n=2), 1st HD-CT (n=9), and 2nd HD-CT (n=11), PR in 6 pts, and 2 pts had progressive disease during induction CT and HD-CT, respectively. At a median observation time of 19 months (range 3.6 to 4.6 months) 26 pts (87%) are alive. Sequential R-HD-CT results (in poor risk pts) in a median PFS of 14.0 months (CI 8.7 to 19.3 months), median overall survival (OS, intent-to-treat analysis) has not been reached (at 4 years 72%). In conclusion, treosulfan-based tandem R-HD-CT is feasible with a manageable toxicity profile. CR and continuous CR rates argue for a dose-response relationship even in high-risk patients with aggressive B-cell lymphomas. Some poor risk pts seem to be cured with the treosulfan-based HD-chemo-immuno-therapy. In cases of progression rescue therapies may be successfully administered as shown by the favorable OS rate. This study has now been extended as a multicenter trial.
Pathogenic Role of Surface Platelet Factor 4 Complexes in Heparin-Induced Thrombocytopenia: Diagnostic and Therapeutic Implications.
Authors: Rauova Lubica , Zhai Li , Kowalska M. Anna , Arepally Gowthami M. , Cines Douglas B. , Poncz Mortimer 
Published: April 2020

Abstract
Heparin-induced thrombocytopenia (HIT) is caused by antibodies that recognize complexes between high molecular weight heparin and Platelet Factor 4 (PF4). Current therapy with direct thrombin inhibitors is not effective in all cases, likely because it acts downstream of antibody-induced platelet activation. More directed therapies to the underlying pathology in HIT may be more effective. Heparin and PF4 only bind HIT antibodies over a narrow molar ratio of reactants at which ultralarge soluble complexes are formed. We asked whether similar complexes form between PF4 and endogenous platelet glycosaminoglycans (GAG) and their pathogenic role in experimental HIT. Platelet surface GAG:PF4 complexes are indeed antigenic over a narrow molar range of reactants. Heparin is not required for either HIT-IgG or a HIT-like monoclonal antibody KKO to bind to PF4 on human or mouse platelet surfaces in vitro, but enhances antigenicity when very high levels of surface PF4 are present. Antigenicity is maximal at a PF4 concentration of 50 μg/mL (well within the range that can be achieved within a thrombus) and ~25 μg/mL heparin (~0.5 U/mL, which is within the therapeutic range) optimally enhances antigenicity when surface PF4 levels were increased 4-fold. Using transgenic mice lines each with platelets expressing a different level of hPF4, ranging from 0.5 – 6 X’s human platelet levels and all expressing FcRγIIA, were given KKO. The different lines developed thrombocytopenia proportional in severity and duration to hPF4 expression. A standard subcutaneous (sq) heparininzing dose (20 U/kg, sq daily) prolonged the duration of severe thrombocytopenia in high hPF4 expressing mice. We reasoned that altering the ratio of PF4 to GAG in either direction would alter antigenicity and could block the development of thrombocytopenia. In accordance with this concept, both high concentrations of anionic heparin (100 U/kg, sq daily) and cationic protamine sulfate (2 mg/kg, sq daily) decreased KKO binding in vitro and prevented KKO-induced thrombocytopenia in vivo as a demonstration of successful therapeutic intervention. These studies affirm a central role of surface GAG:PF4 complexes in the development of HIT, suggest ways to identify patients at high risk to develop HIT even prior to heparin exposure, and offers a new and rationale therapeutic paradigm based on disrupting surface antigen formation.