bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keratinocyte-Growth-Factor-Prophylaxis: Positive Effect on Intestinal Mucositis Following Autologous and Allogeneic Peripheral Blood Stem Cell Transplantation in Haemtological Malignancies: A Sequential Cohort Study.
Authors: Grothe Wilfried , Bauer Martin , Rupprecht Andreas , Christopeit Maximillian , Muetherig Anke , Weber Thomas , Theurich Sebastian , Becker Mike , Behre Gerhard 
Published: October 2019

Abstract
Introduction: Keratinocyte Growth factor (KGF) prophylaxis reduces the extent and duration of mucosal barrier injury following intensive chemotherapy. Following this prophylaxis a marked reduction of infections and consecutively the need for antibiotic treatment can be observed. The extent of oral mucositis (OM) is easely to access. The extent of instestinal musocitis (IM) is more difficult to determine: The serum level of Citrulline, an intermediate product of the uric acid cycle mainly synthesized in the small intestine, serves as a marker of small intestine injury. Aim of the present study was to determine the extent of OM and IM before and after the introduction of KGF-prophylaxis in their treatment.
METHODS: In 09/2006 KGF (60μg/kg body weight per day, for 3 days before conditioning therapy respectively after HSCT) was introduced at our institution on a compassionate use basis. Five months before the introduction and thereafter the extent of OM and IM in autologous and allogeneic HSCT was evaluated prospectively. Beside routine clinical and laboratory values including the daily oral mucositis score (DMS) and daily gut score (DGS) the plasma citrulline level was determined in week 1 (W1), week 2 (W2) and week 3 (W3) following HSCT. Moreover the dosage of therapeutic intravenous (i.v.) antibiotic treatment with meropeneme, piperacilline/combactam and teicoplanin in addition to antibiotic prophylaxis was noted. Pt with oropharyngeal radiotherapy were excluded from analysis.
RESULTS: Until 04/2007 36 pt were evaluated. 27 pt underwent autologous and 9 allogeneic HSCT. 13 of the autologous and 6 of the allogeneic transplanted pt received KGF. In pt with KGF clinically significant OM and moderate to severe IM were seen less often (W1: 1/19 pt vs. 3/17 pt and W2: 1/19 pt vs. 2/17 pt without KGF). These differences were statistically non significant. Citrulline serum levels (in μmol/l) were significantly higher in pt receiving KGF (W2: average 16.8 vs. 15.9 in pt without KGF (p = 0.02)). The therapeutic use of i.v. antibiotics was lower for pt receiving KGF (average of 10.5 days vs. 26.8 days for pt without KGF (p = 0.0001)). Subgroup analysis confirmed the described tendencies in autologous HSCT.
SUMMARY: Even in this small number of pt a positive effect of KGF on oral and intestinal mucositis was detectable. The reduced need for therapeutic i.v. antibiotics seen as a tendency in this study should be re-evaluated in a prospective pharmacoeconomic study to prove cost effectiveness of KGF treatment.
Patient Safety in the Context of Disease Outcome and Effectiveness of Therapy.
Authors: Van Hoef Marlies E.H.M. 
Published: October 2019

Abstract
Safety is more than pharmacovigilance. Safety is also optimization of disease outcome with acceptable side effects. Safety is in this context related to effectiveness. Risk management in treatment is levering the risks an benefits. The process is characterized by five steps, risk definition, risk assessment, risk control, risk communication and risk review. In risk definition terms as safety, efficacy and effectiveness will be explained and related to the treatment. The risks of therapeutic measurements are characterized by the five classes of the common terminology criteria. The benefits of a treatment by among others efficacy, quality of life and effectiveness. In order to assess the risks literature review, analysis of scientific results, evaluation of risks related to prognostic factors for disease outcome are to be considered. In risk control, risk reduction or minimization and acceptance of certain risks will need to be considered. The role of therapeutic measurements as well as the disease stage and timing of therapy will be addressed in the context of in risk control. In risk communication explanation of this balance and the various forementioned parameters is important to offer most optimal prediction of beneficial disease outcome and effectiveness of a treatment. We will introduce the concepts described hereabove and address that limited side effects may actually be very unsafe in the context of effectiveness of therapy.
Empirical Antifungal Therapy for Patients with Neutropenia and Persitent Fever - Systematic Review and Meta-Analysis.
Authors: Goldberg Elad , Gafter-Gvili Anat , Paul Mical , Robenshtok Eyal , Vidal Liat , Leibovici Leonard , Shpilberg Ofer 
Published: October 2019

Abstract
Background: Opportunistic invasive fungal infections (IFIs) are a major concern in the management of immunocompromised patients with hematological malignancies. The practice of administering antifungal therapy to neutropenic patients with persistent fever has become a standard care. Conflicting data exists concerning the efficacy of empirical antifungal therapy.
Objectives: This study aims to evaluate if empirical antifungal therapy reduces mortality and prevents invasive fungal infections (IFI).
Methods: Systematic review and meta-analysis including randomized controlled trials (RCTs) comparing empirical antifungal treatment with placebo or no intervention (control), or another regimen, in neutropenic patients with persistent fever. The Cochrane Library, MEDLINE, conference proceedings and references were searched until 2007. Outcomes assessed were: All-cause mortality, documented IFI, and adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled.
Results: Our search yielded 26 trials, 6 of which compared polyenes or azoles to control, and 20 compared between different regimens of polyenes, azoles or glucan synthesis inhibitors. Compared to control, there was no difference in all-cause mortality (RR 0.98; 95% CI 0.58–1.66, 5 trials, Fig.1). The risk for developing documented IFI was lower (RR 0.23; 95% CI 0.08–0.65, 4 trials, 4 events in the treatment group versus 18 in the control). When azoles (fluconazole, ketoconazole, itraconazole, voriconazole) were compared to polyenes (amphotericin B in 8 trials, liposomal ampho B in 1 trial) there was a trend in favor of azoles for decreased all-cause mortality (RR 0.89; 95% CI 0.73–1.09, 9 trials) and for decreased documented IFI (RR 0.70; 95% CI 0.47–1.04, 8 trials). Adverse events of any kind were less frequent in the azole group (RR 0.40; 95% CI 0.34–0.66, 5 trials), as were those which required discontinuation (RR 0.48; 95% CI 0.38–0.62, 7 trials).
Conclusions: Our review demonstrates that empirical antifungal therapy does not reduce mortality. Although it reduces IFIs, data are based on a small number of trials and events. The use of amphotericin B as empirical antifungal therapy seems unwarranted since it appears to be less effective than azoles, with no mortality benefit and an increased rate of side effects. Future trials should pursue a pre-emptive approach using improved diagnostic tools (such as galactomannan testing, high resolution CT), to identify the patients for whom antifungal treatment is warranted.
Figure Figure
Immunoglobulin Prophylaxis in Patients Undergoing Hematopoietic Stem Cell Transplantation - Systematic Review and Meta-Analysis.
Authors: Raanani Pia , Gafter-Gvili Anat , Paul Mical , Ben-Bassat Isaac , Leibovici Leonard , Ofer Shpilberg 
Published: October 2019

Abstract
Background: Many studies have evaluated the role of polyvalent immunoglobulins (IVIG) and CMV-hyperimmune IVIG (CMV-IVIG) prophylaxis in patients undergoing hematopoietic stem cell transplantation (HSCT), with inconsistent results and implications for practice.
Objectives: To evaluate the role of IVIG and CMV- IVIG prophylaxis in HSCT.
Methods: Systematic review and meta-analysis of randomized controlled trials comparing IVIG or CMV- IVIG with placebo or no intervention (control) for prophylaxis in HSCT. The Cochrane Library, MEDLINE, conference proceedings and references were searched until 2007. Primary outcome: all-cause-mortality ; Secondary outcomes: CMV infections, acute graft versus host disease (GVHD), interstitial pneumonitis (IP), veno-occlusive disease (VOD) and adverse events. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled.
Results: Nineteen trials met inclusion criteria. IVIG was compared to control in 10 trials (7 IVIG in allogeneic HSCT, 2 allogeneic/autologous HSCT and 1 autologous HSCT). When IVIG was compared to control, there was no difference in all-cause mortality (RR 1.03; 95% CI 0.89–1.18, 6 trials, Fig.). There was a reduction in the number of CMV infections (RR 0.70; 95% CI 0.50–0.99, 4 trials) and in the number of episodes of IP (RR 0.61; 95% CI 0.43–0.87, 6 trials). There was no significant difference in the number of episodes of acute GVHD (RR 0.93; 95% CI 0.83–1.05, 6 trials). The risk for VOD was increased (RR 2.71; 95% CI 1.06–6.94, 3 trials) as were adverse events in the IVIG group (RR 8.12; 95% CI 3.15–20.9, 5 trials). CMV-IVIG was compared to control in 7 trials, all allogeneic HSCT. There was no difference in all-cause mortality (RR 0.86; 95% CI 0.63–1.16, 4 trials). In addition, there were no differences in the risk for developing CMV infections (RR 1.07; 95% CI 0.86–1.33, 7 trials), acute GVHD (RR 1.02; 95% CI 0.72–1.44, 5 trials) or IP (0.95; 95% CI 0.58–1.56, 5 trials).
Conclusions: Our review demonstrates that IVIG prophylaxis for HSCT reduces the risk for CMV infections and IP without a significant influence on mortality. The beneficial effects should be weighed against the higher incidence of adverse events, VOD, and cost associated with the use of prophylactic IVIG in HSCT patients. Conversely, the use of CMV-IVIG was not associated with a change in any of the parameters.
Outcomes Summary Outcome IVIG vs. control CMV-IVIG vs. control All Cause Mortality RR 1.03; 95% CI 0.89–1.18 RR 0.86; 95% CI 0.63–1.16 CMV infections RR 0.70; 95% CI 0.50–0.99 RR 1.07; 95% CI 0.86–1.33 acute GVHD RR 0.93; 95% CI 0.83–1.05 RR 1.02; 95% CI 0.72–1.44 IP RR 0.61; 95% CI 0.43–0.87 RR 0.95; 95% CI 0.58–1.56 VOD RR 2.71; 95% CI 1.06–6.94 No data Adverse events RR 8.12; 95% CI 3.15–20.9 RR 7.0; 95% CI 0.38–129.34 Figure Figure
GVHD Prophylaxis with Cyclosporine + Mycophenolate Mofetil Improves Outcome Compared to Cyclosporine Alone in Patients Receiving Reduced Intensity Conditioning Hematopoietic Stem-Cell Transplantation from Unrelated Donor for Hematological Diseases.
Authors: Brissot-Davaine Eolia , Moreau Philippe , Ayari Sameh , Delaunay Jacques , Guillaume Thierry , Pelletier Jean-Baptiste , Harousseau Jean-Luc , Chevallier Patrice 
Published: October 2019

Abstract
Introduction: As observed in myeloablative allograft, incidence of acute and chronic GVHD remains a major problem in patients receiving RIC HSCT in term of TRM and quality of life. So far, the best GVHD prophylaxis has not been yet established in this settings, as it could depend on the type of donor or of the RIC regimen. Thus, GVHD incidence is expected to be higher in patients receiving transplantation from unrelated donor compared to related donor. Here we have compared two GVHD prophylaxis regimen (Cyclosporine (CsA) alone vs CsA + Mycophenolate mofetil (MMF)) in patients receiving RIC allograft from unrelated donor in order to demonstrate the favourable impact of a stronger immmunosupressive treatment in term of overall survival (OS) due to less GVHD incidence.
Patients and Methods: We have studied retrospectively 40 successive patients from our institution who received RIC allogeneic HSCT from unrelated donor for haematological malignancies. Two GVHD prophylaxis regimen were administrated: CsA alone in Group 1 (n=19) from 2000 to 2005 and CsA +MMF in Group 2 (n=21) from 2005. Indeed, the observation of high incidence of acute GVHD in the former group conducted us to modify our strategy of GVHD prophylaxis. Almost all patients received a Slavin’s like RIC regimen associating Fludarabine, Busulfan and ATG. The graft consisted of peripheral blood stem cells for all patients except 4 patients in Group 1 who received bone marrow and 3 patients in Group 2 who received unrelated cord blood stem cells. The 2 groups were comparable in term of sex, status at transplant (CR1 vs others) and age at transplant (median age 49 years in Group 1 and 54 years in Group 2, p=0.05). Median follow-up for survival patients were 35 months and 12 months in Group 1 and 2 respectively. All patients have given informed consent.
Results: OS was significantly higher in Group 2: median 300 days (range: 36–2620 days) in group 1 versus median not reached (range: 181–812 days) in Group 2. OS was 40% at 1 year in group 1 compared to 92% in Group 2, p=0.0004. This discrepancy was due to the observation of a trend for higher acute GVHD grade III–IV occurrence in group 1 compared to Group 2 (75% vs 41%, p=0.21) and significant more deaths due to acute GVHD in Group 1 compared to Group 2 (4 patients vs 1, p<0.05). No difference was observed in term of relapse when comparing the 2 groups.
Conclusion: With restriction due to the short follow-up in Group 2, we demonstrated here the favourable impact of the combination of CsA + MMF as GVHD prophylaxis in patients receiving RIC transplant from unrelated donor as we demonstrate a significant benefit in term of overall survival due to less acute GVHD.
Post Transplant Lymphoproliferative Disorders (PTLD): Prevalence, Clinical Features and Outcome.
Authors: Colorio Cecilia , Puente Dolores , Rossi Andrea , Jaimovich Gregorio , Tabares Maria , Requejo Alejandro , Bonini Nicolas , Milovic Vera , Pombo Gonzalo , Feldman Leonardo 
Published: October 2019

Abstract
PTLD is a life threatening complication developing in 1–5% of transplant (Tx) recipients. Epstein Barr (EBV), Cytomegalovirus (CMV) and immunosuppression (IS) were identified as risk factors. Aggressive evolution and therapy related toxicity generate poor prognosis. We retrospectively analyzed data from 18 PTLD patients (pts) diagnosed at our hospital between March 1994- June 2007. All of them were at least one graft recipient and were under IS.
RESULTS: Out of 1206 adult Tx recipients, 18 (1,5%) developed PTLD. Ninety-four percent were men, mean age 42,9 years (range: 18–72). Our study comprises 10 heart, 2 kidney, 2 lung, 1 heart-lung, 1 liver and 2 non related allogeneic bone marrow (BM) recipients. IS protocols included Cyclosporin A (16 pts), Azathioprine (8), Mycophenolate mofetil (7), Tacrolimus (4) and antitymocyte globulin (2). Pretx recipients serology for EBV and CMV were positive in 87 and 94% respectively. Sixty-six percent (12/18) disclosed late onset PTLD (median 49 months), all of them were solid organ (SO) recipients. BM recipients developed the disease within the first 6 months after Tx. Fifty percent presented extranodal involvement, 3/18 with BM infiltration and 3/18 showed lymphoma in the graft. Histologycal findings: 15/18 B cell lymphoma (8/15 large cell lymphoma), 1 peripheral T cell lymphoma, 1 early lesion infectious mononucleosis-like PTLD, 1 polymorphic hyperplasia PTLD. Immunophenotype: 89% were CD20+. Fifty percent of the group achieved response, 7/9 with complete response(CR). Three/9 pts obtained CR with reduction of IS alone.Treatment included Rituximab (63% pts), CHOP (56%) and radiotherapy (25%). Eleven/18 pts died, 4 due to disease progression, 6 by sepsis and 1 because of underlying hematological disease relapse.
CONCLUSIONS: In our experience, PTLD was an uncommon complication. The late onset of the disease was the most frequent form of presentation among SO recipients. B cell lymphoma was the main diagnosis (83%). Fifty percent (9/18) achieved response and 78% of them showed CR. Disease progression and sepsis were the most important causes of death.
Bone Marrow Transplant (BMT) for Acute Myeloid Leukemia (AML) Patients with Translocation (6; 9).
Authors: Haddad Abdo S. , Smith April , Bolwell Brain , Kalaycio Matt 
Published: October 2019

Abstract
Response and long term outcome to chemotherapy treatment in patient with AML may differ significantly depending on many factors identified at the time of diagnosis. Age, cytogenetics, and history of myelodysplasia are predictors of survival in patients undergoing induction chemotherapy. AML characterized by t (6;9) (p23; q34) - DEK/CAN fusion occurs only in 1–5% of AML cases. This translocation involves recurrent breakpoints in the DEK gene on chromosome 6p23 andin the CAN gene on chromosome 9q34. It predicts a poor outcome with chemotherapy alone and BMT is usually recommended as a result. However, the curative potential of BMT for t(6; 9) AML patients is unknown. We reviewed our experience treating AML with BMT. Five patients with t (6; 9) AML and one with high-risk myelodysplastic syndrome (MDS) underwent BMT following induction chemotherapy. The prep regimen was Busulfan/Cyclophosphamide in all but one patients and standard GVHD prophylaxis was used. No patient received a T-Cell depleted graft. The median follow up of survivors was 24 months (9–38 months). Our small series provides intriguing data suggesting the potential for cure of patients with AML and t (6; 9). While our data requires confirmation in a larger series of patients, our results provide a rationale to recommend BMT to these high risk patient with AML.
Table 1: Characteristics Pt. # Dx Date Age BMT Remission tatus GVHD Relapse A/D Months (Pt. #) Patient number, (Dx) Diagnosis, (BMT) bone marrow transplant date, (GVHD) graft versus host disease, (A/D) Alive/Dead from initial diagnosis, (CR) Complete remission, Matched unrelated donor, and (MSD) Matched sibling donor 1 10/04 37 MSD 6/05 CR1 Yes No A +34 2 06/04 36 MUD 10/06 CR2 NO No A +38 3 03/06 50 MUD 7/06 CR1 NO Yes D +13 4 09/05 20 MUD 12/05 CR1 NO No A +24 5 11/06 39 MSD 2/07 CR1 Yes No A +9 6 10/06 41 MSD 2/07 Refractory No No A +10
Study on Effect Hemopoiesis Reconstituted of Auto-Mesenchymal Stromal Cells or Allo-Mesenchymal Stromal Cells Transplantion.
Authors: Wang Chun Yan , Tan Huo , Huang Zhen Qian , Li Hai Ming , Liu Dan , Zheng Run Hui 
Published: October 2019

Abstract
Objective: To study effect hemopoiesis reconstituted of auto-mesenchymal stromal cells (MSCs) or allo-mesenchymal stromal cells transplantion.
Methods: MSCs were obtained from transplantion patient or embryo by culturing in Zhongshan university stem cell center. 2 patient(SLE, lymphoma) were transplant auto-MSCs before transplantion auto- haemopoietic stem cell(HSC), MSCs were 2.43×107/kg,2.76×107/kg, CD34+ cells were 2.13×104/kg,2.54×104/kg. 2 patient(CML, lymphoma) were transplant allo-MSCs(from embryo) after transplantion (+60 and +180), patient with CML was allo-HSCT, patient with lymphoma was auto-HSCT. MSCs were 2.23×105/kg. Rasults: 2 patients with combination transplantation auto-MSCs and auto-HSC were not adverse effect, neutrophil≥0.5 ×109/ L were +1 day and +10 day, platelet ≥20 ×109/ L were +1day and +8 day, granulocyte deficiency time were 0day and 7days. Two patients were complete remission(273 day and 124 day). Another two patient hemopoiesis delay (after transplantation +60 and +180) were transplanted allo-MSCs(from embryo), one patient with CML rised blood cell after transplantion, but 10 days later the patient relapsed, bone marrow showed acute transformation of chronic myelocytic leukemia. The patient died due to giving up trentment. The patient with lymphoma were transplanted allo-MSCs (from embryo), blood cells transient rised, but blood cells decreased after one week. Now the patient were complete remission (+300 day), but blood cells were lower. The two MSCs (from embryo) transplantation were failure.
Conclusion: It is important that how to chose the MScs transplantation time. Combination transplantation auto-MSCs and auto-HSC can promote hemopoiesis re-establish, especially to fit old age patient. If patient with hemopoiesis delay after transplantation were trantplanted allo-MSCs maybe further research. [ key word] MSCs, transplantation, haemopoietic stem cell, hemopoiesis re-establish
High-Dose Therapy Followed by Autologous HSCT in Patients with Multiple Myeloma. Results of a Retrospective Multicenter Analysis Conducted by The Polish Myeloma Group.
Authors: Knopinska-Posluszny Wanda M. , Hellmann Andrzej , Taszner Michal , Dmoszynska Anna , Jedrzejczak Wiktor , Holowiecki Jerzy , Walewski Jan , Warzocha Krzysztof , Skotnicki Aleksander , Lange Andrzej , Kuliczkowski Kazimierz , Sulek Kazimierz , Komarnicki M. , Robak Tadeusz 
Published: October 2019

Abstract
In recent years high-dose therapy with autoHSCT has become the treatment of choice for eligible patients with multiple myeloma. This disease is now one of the most common indications for autotransplantation. The aim of this study was the clinical assessment of patients who underwent autotransplantation of progenitor cells and an analysis of the results of conducted treatment. The Polish Myeloma Group collected results of auto HSCT from 12 transplantology centres in Poland conducted between 1995 and 2006. We analyzed retrospectively the prognostic influence of pre-transplant characteristics on response and survival in 498 patients. Virtually all the patients received peripheral blood stem cell support after conditioning with melphalan (95%). We evaluated the influence of age, type of myeloma, Durie-Salmon stage, presence of renal impairment, plasma cell infiltration, albumin and b2 microglobulin level at diagnosis, status prior to and post HSCT, time from diagnosis to HSCT on overall survival (OS) and progression-free survival (PFS) to define patients with better prognosis. 232 females and 266 males underwent auto HSCT, and these included 297 (59,6%) with IgG, 97 (19,5%) with IgA, 31 (6%) with B-J, 22 (4,4%) with non-secretory myeloma. Bone structure changes were ascertained in 355 patients (71%). Bone marrow involvement higher than 20% was found in 282 patients (56,6%) at diagnosis. A decreased level of albumin (<35g/l) was determined in 168 patients (33,7%), and b2microglobuline level above 3,5 mg/l in 124 patients (24,9%). Transplantation of progenitor cells was conducted as consolidation of first line treatment following chemotherapy according to VAD in the majority of patients (74,7%). This number increased to 246 (49,4%) following transplantation. Double transplantation was conducted in 132 patients (26,5%). Median OS and PFS obtained were 3272 (1391–4232) and 1158 (102–3767) days respectively. CR achieved before transplantation, normal renal function, albumin level above 35g/l, b2 mikroglobulin below 3,5mg/l and DS stage I, were associated with a longer OS and PFS (p<0,05). This retrospective, multicenter study confirms the efficacy and safety of autoHSCT in multiple myeloma patients. Additional confirmation is given of the increased rate of CR, and the significantly prolonged survival observed in complete responders. Taking the above into account the employment of new drugs, such as thalidomide or bortezomib, which allow the achievement of a higher percentage of remissions should in the future bring about an improvement of the efficacy of transplantation in multiple myeloma.