Conditioning without Antibiotic Prophylaxis May Not Increase Infection Related Mortality in Allogeneic Hematopoeitic Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4374-4374
Author(s):  
Aj ay Sharma ◽  
Velu Nair ◽  
Satyaranjan Das ◽  
Deepak Kumar Mishra ◽  
Jyoti Kotwal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Bacterial Infections ◽  
Antifungal Agents ◽  
Fungal Infections ◽  
Primary Prophylaxis ◽  
Infection Prophylaxis ◽  
Gram Positive ◽  
Related Mortality

Abstract Background: Hematopoeitic stem cell transplantation (HSCT) is the standard of care in a large number of disorders for over three decades all over the world. Despite significant improvements in conditioning protocols, the mortality still remains significantly high and peri-transplant infections continue to be a big challenge. A number of regimens for primary prophylaxis against various infections are being used during conditioning with varying success in reducing the incidence of infections. But it might result in increasing incidence of resistant infections besides increasing the transplant cost. Objectives: To evaluate the impact of infection prophylaxis upon infection related mortality in allo-HSCT. Materials and Methods: We analyzed the data of 96 consecutive stem cell transplants performed in our centre between 1998 and 2006. We did not use any prophylaxis for bacterial or fungal infections in these cases. A total of 86 patients underwent HSCT for various indications at our 3 bedded bone marrow transplantation unit (BMTU). The mean age was 24 years (range: 2–45). The indications for allogeneic transplants were CML: 28, AML: 8, ALL: 5, CLL: 1, MDS: 1, Thalassemia major: 12, PRCA: 1 and Aplastic/Fanconi’s anemia: 4. The indications for autologous transplants included multiple myeloma (15), NHL (8), AML(7) and solid tumors (5) Allogeneic transplants were performed with full HLA matched siblings. The conditioning was done with standard Busulfan-Cyclophosphamide (Bu-Cy) based protocols for leukemia; Fludarabine, Cyclophosphamide & ATG for PRCA and aplastic anemia and Bu-Cy-ATG for thalassemia. The median cell dose was 6.8 × 108 (range: 2.7–11.7) MNC/Kg. The median day of engraftment (ANC > 500/mm3) was day 10 (range 7–20). None of the patients received primary prophylaxis with any antibiotics or antifungal agents during conditioning. Patients who developed neutropenic fever or the evidence of bacterial or fungal infections were treated with empirical therapy based on our hospital infection policy based antimicrobial protocols. Results: A total of 64 patients developed documented infections. Amongst these the positive bacteriological cultures were obtained from blood (64%) followed by urine (12%), sputum (8%) and catheter related infections (5%) The antibiotics were changed if specific organism could be identified. Antifungal agents were started empirically if fever continued 48 hours after initiation of initial antibiotics even if no causative agent was identified. 78 (92 %) patients required antibiotics. Total 38 patients had documented bacterial infections. The majority of bacterial infections (56%) occurred in the first 30 days following SCT. The organisms identified were mainly Gram negative bacteria (77% e.g, E Coli-68%, Pseudomonas aeroginosa-13%, Enterobacter-2%, Klebsiella pneumoniae-2%) with a few gram positive organisms (23%). The gram positive organisms were Staphylococcus aureus (13%) and Coagulase negative staphylococcus (8%). 05 patients developed septicemia with fatal multi-organ failure. The 100 day mortality due to infections has been 9 (9.2 %) and one year infection related mortality was 13%. This rate of infections was not significantly higher as compared to he rates when antibiotics & antifungals were used as prophylaxis Fungal infections were documented in 19 patients(Candida: 57%, Aspergillus: 33% and Zygomycetes: 10%) Conclusion: The study demonstrates that adherence to a well planned infection control strategy for transplant units and strict preventive measures can ensure a low incidence of infections with success rates comparable to any developed country. Although the number is small to make any definite conclusion, there is a feasibility of avoiding prophylactic use of antibiotics in conditioning regimens, thereby, decreasing the risk of resistant infections besides bringing down the cost of transplant procedure which has a great bearing on the availability of transplant to all eligible patients in a country like India where affordability is restricted greatly by cost factors.

R-DHAP Immunochemotherapy Is An Effective Remission-Induction Treatment For CLL Patients With Fludarabine Refractory Disease With Or Without Deletion 17p, Enabling The Majority To Proceed To Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2883-2883
Author(s):  
Michel Van Gelder ◽  
Wendim Ghidey ◽  
Martine ED Chamuleau ◽  
Jan Cornelissen ◽  
Eefke J Petersen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Fungal Infections ◽  
Remission Induction ◽  
Induction Treatment ◽  
Infection Prophylaxis ◽  
Refractory Disease ◽  
Bulky Disease

Abstract Introduction Allogeneic stem cell transplantation (alloSCT) is the only potentially curative treatment for relapsed CLL patients with fludarabine refractory disease and/or a deletion 17p del(17p). Retrospective analyses identified bulky disease and lack of response to last treatment as predictors for poor survival. There is an unmet need for active salvage regimens for these high-risk patients, but so far prospective data on salvage regimens prior to alloSCT are lacking. Here we report our results with R-DHAP remission-induction studied in a prospective international multicenter phase 2 study. The rationale for R-DHAP is formed by in vitro studies showing that platinum induces p53 independent cell death. Patients up to the age of 70 years with fludarabine refractory CLL (defined, according to the EBMT consensus, as relapse within 1 year after fludarabine monotherapy or within 2 years after fludarabine plus a monoclonal antibody) and/or with relapsed CLL with a del(17p) , and with an indication for treatment were eligible for inclusion. Patients received at least 3 cycles of R-DHAP salvage therapy (rituximab on day 1 (375mg/m2 1st cycle, 500 mg/m2 later cycles), cisplatinum 100mg/m2 (day 1), cytarabine 2x2000mg/m2 (day 2) and dexamethasone 40mg days 1-4) every 4 weeks. Response to R-DHAP was determined according to 2008 IWCLL guidelines. Results Forty patients have been included from February 2009 till April 2012. One patient was ineligible because of Richter’s syndrome at the time of inclusion. The median age was 59 years (range 43-69) and the median number of prior therapies was 2 (range 1-5). Twenty-four patients completed at least 3 cycles of R-DHAP. Due to long donor search. two of these received 4 cycles, two 5 and 1 six cycles. Nine patients received only one or two cycles of R-DHAP because of toxicity, and two patients never received R-DHAP due to poor performance. Overall response rate (ORR) for all 39 eligible patients was 56%: 6 CR (15%), 16 PR (41%). Five patients had SD (13%) and 2 PD (5%). ORR rates in patients with bulky lymphadenopathy (>5 cm, n=18) and in those having del(17p) (n=17) was 67% and 53% respectively. In the first 16 patients four infection related deaths occurred (3 septic shock and 1 encephalitis). After an amendment optimizing infection prophylaxis, no additional severe bacterial or fungal infections or infection related deaths were observed. Twenty-six patients proceeded to alloSCT (67%). With a median follow-up of 16 months (range 6-42 months) 2-years progression-free survival (PFS) and overall survival (OS) after transplantation is 63% and 72% respectively. Sixteen are free from progression and 3 progressed but are still alive. Seven patients died (3 from acute GVHD, 2 due to encephalopathy, 2 other reasons). Conclusion R-DHAP is an effective remission-induction regimen for fludarabine-refractory CLL patients even in those having bulky lymphadenopathy and/or del(17p), enabling a high percentage of patients to proceed to alloSCT resulting in a high PFS and OS at 2 years. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Evaluation of the Bacterial Etiologies of Infections in Patients Undergoing Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5850-5850
Author(s):  
Lokman Hizmali ◽  
Umit Tapan ◽  
Haluk Eraksoy
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Bacterial Infection ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Bacterial Infections ◽  
Bacterial Isolates ◽  
Gram Positive ◽  
Hematopoietic Stem

Abstract Objectives: Bacterial infections increase morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). The characteristics of the bacteria causing infections in these patients undergo dynamic changes both globally and locally during the transplantation process. The etiology of bacterial isolates and analysis of changes in the antibiotic sensitivities are crucial for the selection of appropriate prophylactic and empiric therapies. In this study we aimed to evaluate the first episode of bacterial infection in patients undergoing allogeneic or autologous hematopoietic stem cell transplantation and to identify bacterial isolates and the resistance profile of causative bacteria. Materials and Methods: In this retrospective study, the charts of 195 patients who underwent allogeneic or autologous hematopoietic stem cell transplantation between January 2010 and December 2013 were reviewed. Ninety-six patients who had microbiologic evidence of bacterial infection were included in the study. The culture results from the first infectious episode during the transplantation process were evaluated. Patients were grouped according to the type of transplantation, and categorized according to the transplantation process, presence of neutropenia and infection status. Microbiological examination of samples obtained for culture and sensitivity analysis were performed according to standards of the National Committee for Clinical Laboratory Standards Institute (CLSI). Results: Gram-negative and Gram-positive bacteria were identified in 54.2% and 44.8% of the infectious episodes, respectively. Poly-microbial etiology was identified in only 1.0% of these episodes. E. coli and coagulase-negative staphylococci (CoNS) were the most frequently isolated pathogens. In the early stage infections, Gram-positive organisms were more frequently isolated (72.1%) (p=0.042) and a significantly larger number of patients had undergone autologous stem cell transplantation (p<0.001). This situation was explained by the absence of antimicrobial prophylaxis in the autologous group, intensive induction chemotherapy, presence of catheter and mucosal damage. The frequency of extended-spectrum β-lactamase (ESBL) was found to be very high in the allogeneic group compared to the autologous group (36.4% vs. 13.3%). All of the staphylococcal isolates in the allogeneic group were noted to be methicillin resistant. Conclusions: Treatment and prophylaxis have become increasingly more challenging with the infections caused by resistant pathogens. It is imperative to carefully monitor causative agents of bacterial infections and to plan prophylactic and empiric treatments according to characteristics of the individual patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Incidence of infections during the application of high-dose chemotherapy with autologous stem cell transplantation

2021 ◽  
Vol 2 (4) ◽  
pp. 352-361
Author(s):  
Milica Milošević ◽  
Jelena Bila ◽  
Dejana Stanisavljević ◽  
Milena Todorović-Balint
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Fungal Infections ◽  
High Dose ◽  
Gram Positive ◽  
Gram Negative ◽  
Documented Infection

Introduction: Autologous stem cell transplantation (AHSCT) is a well-established therapy for hematologic malignancies. Changes in transplantation strategies and improvement in supportive care have significantly altered the incidence and pattern of infections in these patients. Aim: Evaluating the frequency of infections in the first 30 days after AHSCT, as well as the possible influence of the number of CD34 + stem cells in the graft and of the engraftment parameters: ALC500_20 (absolute lymphocyte count 0.5x109 / L per day + 20), ANC500_11 (absolute neutrophil count 0.5x109 / L per day + 11), and PLT20_13 (platelets 20x109 / L per day + 13), on the occurrence of infections. Materials and methods: The retrospective cohort study examined 80 patients above the age of 20 years, diagnosed with multiple myeloma (MM), non-Hodgkin's (NHL) or Hodgkin's lymphoma (HL), treated at the Clinic for Hematology of the Clinical Center of Serbia, in the period between July 2006 and December 2017. All episodes of fever and/or documented infection during neutropenia have been reported. Results: The average survival after AHSCT was 34.5 months. A total of 54 patients (67.5%) had a documented infection. Gram-positive infections were five times more common than gram-negative. In gram-positive isolates, coagulase-negative staphylococcus - CoNS was the most common (37.0%) pathogen, followed by Streptococcus a haemolyticus (12.4%). Among gram-negative isolates, Escherichia coli was present in 62.5% of the cases, while Klebsiellaspp. and Ralstonia pickettii were represented with an equal frequency of 12.5%. Fungal infections were rare (Candida spp., 10.0%). Viral infections were verified in 5 (6.3%) patients (Herpes zoster virus 3.8% and H1N1 2.5%). Conclusion: The number of CD34+ stem cells in the graft, as well as the rate of hematopoietic reconstitution, i.e., the achievement of ALC500_20, ANC500_11, and PLT20_13, were not statistically significant for the development of infections in the early phase after AHSCT.

scholarly journals Day100 Score predicts moderate-severe cGVHD, transplant mortality, and survival after hematopoietic cell transplantation

2021 ◽  
Author(s):  
Elisabetta Metafuni ◽  
Irene Maria Cavattoni ◽  
Teresa Lamparelli ◽  
Anna Maria Raiola ◽  
Anna Ghiso ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Validation Cohort ◽  
Predictive Score ◽  
Training Cohort ◽  
Graft Versus Host ◽  
Related Mortality

The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGvHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified four independent predictors of moderate-severe cGvHD: gammaglutamyltransferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0-1), intermediate (2-3) and high (4) score. The cumulative incidence (CI) of moderate-severe cGvHD was 12%, 20% and 52% (p&lt;0.0001) in the training cohort, and 13%, 24% and 33% (p=0.002) in the validation cohort. The 5 year CI of transplant related mortality (TRM) was 5%, 14%, 27%(p&lt;0.0001) and 5%, 16%, 31%(p&lt;0.0001), respectively. The 5 year survival was 64%, 57%, 54%(p=0.009) and 70%, 59%, 42%(p=0.0008) in the two cohorts respectively . In conclusion, Day100 score predicts cGvHD, TRM and survival, and, if validated in a separate group of patients, could be considered for trials of pre-emptive therapy.

scholarly journals NRF2 -617 C/A Polymorphism Impacts Proinflammatory Cytokine Levels, Survival, and Transplant-Related Mortality After Hematopoietic Stem Cell Transplantation in Adult Patients Receiving Busulfan-Based Conditioning Regimens

2020 ◽  
Vol 11 ◽  
Author(s):  
Jingjing Huang ◽  
Chenxia Hao ◽  
Ziwei Li ◽  
Ling Wang ◽  
Jieling Jiang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Clinical Outcomes ◽  
Cell Transplantation ◽  
Proinflammatory Cytokine ◽  
Hematopoietic Stem ◽  
Cytokine Levels ◽  
Conditioning Regimens ◽  
Related Mortality

Busulfan (BU) is widely used in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). The exposure-escalated BU directed by therapeutic drug monitoring (TDM) is extremely necessary for the patients with high-risk hematologic malignancies in order to diminish relapse, but it increases the risk of drug-induced toxicity. BU exposure, involved in the glutathione- (GSH-) glutathione S-transferases (GSTs) pathway and proinflammatory response, is associated with clinical outcomes after HSCT. However, the expression of genes in the GSH-GSTs pathway is regulated by NF-E2-related factor 2 (Nrf2) that can also alleviate inflammation. In this study, we evaluated the influence of NRF2 polymorphisms on BU exposure, proinflammatory cytokine levels, and clinical outcomes in HSCT patients. A total of 87 Chinese adult patients receiving twice-daily intravenous BU were enrolled. Compared with the patients carrying wild genotypes, those with NRF2 -617 CA/AA genotypes showed higher plasma interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α levels, poorer overall survival (OS; RR = 3.91), and increased transplant-related mortality (TRM; HR = 4.17). High BU exposure [area under the concentration-time curve (AUC) &gt; 9.27 mg/L × h)] was related to BU toxicities. Furthermore, NRF2 -617 CA/AA genotypes could significantly impact TRM (HR = 4.04; p = 0.0142) and OS (HR = 3.69; p = 0.0272) in the patients with high BU AUC. In vitro, we found that high exposure of endothelial cell (EC) to BU, in the absence of Nrf2, elicited the hyperstimulation of NF-κB-p65, accompanied with the elevated secretion of proinflammatory cytokines, and led to EC death. These results showed that NRF2 -617 CA/AA genotypes, correlated with high proinflammatory cytokine levels, could predict inferior outcomes in HSCT patients with high BU AUC. Thus, NRF2 -617 CA/AA genotyping combined with TDM would further optimize personalized BU dosing for sufficient efficacy and safety endpoint.

scholarly journals Strategies to upgrade safety for at-home autologous stem cell transplantation in multiple myeloma patients.

2020 ◽  
Author(s):  
Luis Gerardo Rodríguez-Lobato ◽  
Alexandra Martínez-Roca ◽  
Sandra Castaño-Díez ◽  
Alicia Palomino-Mosquera ◽  
Gonzalo Gutiérrez-García ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Hospital Readmissions ◽  
Primary Prophylaxis ◽  
Outpatient Setting ◽  
The Impact ◽  
At Home

Abstract Background. Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT.Methods. Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning + 1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT.Results. The incidence of NF among the groups was reduced (64%, 44%, and 24%; P < 0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI > 2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P < 0.001); and for hospital readmission: age ≥ 60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05).Conclusions. G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT.

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