Reduced Rate of Infectious Complications Following Bloodless Autologous Peripheral Blood Stem Cell Transplants (APBSCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5453-5453 ◽  
Author(s):  
Patricia A. Ford ◽  
Barbara A. Matthews ◽  
Nicole M. Brown
Keyword(s):  
Breast Cancer ◽  
High Dose Chemotherapy ◽  
Infectious Complications ◽  
High Dose ◽  
Blood Transfusions ◽  
Risk Of Infection ◽  
Infection Rates ◽  
Autologous Transplants ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract While blood transfusions can be life saving, the associated risk of transfusing allogeneic blood is significant. The most common patient fears are transfusion-transmitted diseases such as HIV, Hepatitis B and C and West Nile Virus; however, the known risk of transmitting these diseases is quite small. More common complications are due to immunosuppression which can cause an increased risk of cancer recurrence in the oncologic patient and a significantly increased risk of infection. In trauma patients, it has been shown that the risk of infection increases with each additional unit of blood transfused. Currently, about 2.2 units of platelets and 3.3 units of red blood cells are administered following high-dose chemotherapy and an APBSCT. At the Center for Bloodless Medicine and Surgery at Pennsylvania Hospital, many procedures are now being completed without the use of blood products. We have previously reported the ability to perform bloodless APBSCT (Ballen, et al. J Clin Oncol2004;22:4087-4094). Knowing that blood transfusions can increase the risk of infection, we wanted to evaluate this transfusion-free population to determine if there was a correlation between infection rates and blood transfusions in the high risk transplant population. We performed a retrospective chart review of 46 patients with multiple myeloma (22), lymphoma (22) and breast cancer (2) who underwent a bloodless APBSCT in our center. Prior to transplantation, all patients recieved standard transplant doses of cyclophosphamide, carmustine and etoposide (BCV) or Melphalan. A PubMed search was performed and the closest data set in terms of patient demographics was a study by Pereira, et al. who report the rate of infectious complications in 75 patients with myeloma (30), lymphoma (30) and breast cancer (15) who were transfused liberally following high-dose chemotherapy and APBSCT (Pereira, et al. Eur J Haematol2006;76:102-108). In our bloodless patients, 37% of the patients had at least one infection, compared to Pereira and colleagues’ rate of 68% (see table). Our results are also reported in the average number of infections per patient. This comparison demonstrates a substantial reduction in the rate of infection in the bloodless population. While immunosuppression and the resulting increased infection rates have been correlated to blood transfusions in other patients populations, to the best of our knowledge this is the first report that suggests decreased infection rates in transfusion-free transplant patients. This data provides further evidence to support the practice of blood management strategies in order to reduce or eliminate blood transfusions. Patients with at least one infection All infections per person Bacterial per person Viral per person Fungal per person Unknown per person Autologous Transplants (Pereira, et al.) 68% .64 .53 .01 .07 .03 Bloodless Autologous Transplants 37% .41 .39 0 0 .02

Since blood transfusion is linked to the magnitude of the surgical procedure, comparing transfused patients to untransfused patients will always be confounded by infection risks due to factors related to the procedure. To control for these factors one must compare patients transfused with red cells from different sources or prepared in a manner which minimize infection risk. Patients transfused with homologous blood have infection rates several fold higher than recipients of equal values of autologous blood undergoing the same operative procedure (20-23). Homologous blood recipients have significantly longer hospital stays attributed to treating infections. The cost of a blood transfusion exceeds the cost of collection, storage and administration because of transfusion's association with length of stay. In this era of cost-containment the association with prolonged stay may ultimately curtail the use of blood. Homologous blood can be filtered to remove donor leukocytes which may be contributing to immune suppression and infection risk. A prospective randomized trial comparing the infection rates among colorectal cancer patients receiving filtered and unfiltered blood has been conducted (9). There were 17 infectious complications among the 56 recipients of whole blood and one infectious complication among the 48 recipients of filtered blood. Infections were prevented by the seemingly simplistic addition of a $25/filter to every bag of blood transfused. These clinical studies are very convincing: homologous blood transfusion is associated with increased risk of infection in every clinical situation examined. In multivariate analyses transfusion was a significant predictor of infection after consideration of other variables measured and in the majority of those studies transfusion was the single most significant factor. Patients receiving homologous blood exhibited an incidence of infectious complications that was approximately four times higher than patients receiving autologous blood. The association of transfusion with infection is found among patients undergoing surgery for cardiac, orthopedic and gastrointestinal disorders and for trauma as well as among unoperated patients transfused for bums and gastrointestinal bleeding. The observation that nosocomial infections are increased in these studies argues strongly that the association of transfusion with infection is not simply a reflection of transfusion as a marker of tissue destruction and contamination. Infections that develop in transfused patients away from the site of trauma or in the absence of trauma, cannot be attributed to the quantity of tissue destroyed or to the degree of bacterial contamination. Filtered blood can remove leukocytes and prevent postoperative infections. Since filtering blood can significantly reduce the incidence of infection among transfused patients, all transfused blood will be passing through filters in the very near future. EXPERIMENTAL STUDIES RELATING BLOOD TRANSFUSION TO INCREASED RISK OF INFECTION Patients are extremely heterogeneous and even in prospective randomized trials, factors which influence patients' participation affect the outcome despite double-blinding and randomization. In animal studies using syngeneic strains with identical housing, lighting, access to food and water, control over the extent of injury, use of antibiotics and exposure to other variables the influence of a single variable such as blood transfusion can be measured. Dr. Waymack's laboratory has intensively studied parameters which interact with transfusion in

1995 ◽  
pp. 296-296
Keyword(s):  
Blood Transfusion ◽  
Autologous Blood ◽  
Experimental Studies ◽  
Infection Risk ◽  
Infectious Complications ◽  
Risk Of Infection ◽  
Infection Rates ◽  
Homologous Blood ◽  
Increased Risk ◽  
The Cost

scholarly journals Antibody Dependent Enhancement of Infections after High Dose Chemotherapy

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1047-1047 ◽  
Author(s):  
Jens Magnus Bernth-Jensen ◽  
Bjarne Kuno Møller ◽  
Steffen Thiel ◽  
Anette Tarp Hansen
Keyword(s):  
Stem Cell ◽  
Serum Sample ◽  
Unknown Origin ◽  
High Dose Chemotherapy ◽  
Severe Neutropenia ◽  
High Dose ◽  
Serum Concentrations ◽  
Risk Of Infection ◽  
Increased Risk ◽  
Pathogen Survival

Background: High dose chemotherapy (HDT) burdens patients with a high risk of serious infections while neutropenic. The role of host antibodies as risk factors for infections is unclear. Our aim was to investigate if pre-HDT levels of IgG antibodies against terminal Galα3Gal (anti-αGal) predict infections. Anti-αGal is reported to be the most abundant antibody in human plasma and is able to recognize most sepsis-causing Gram-negative bacteria. The antibody exerts poor complement activation, which promotes pathogen survival by blocking access of more effective complement activators. This may be particularly problematic in neutropenic patients. Thus, we hypothesized that patients with high anti-αGal serum concentrations are particularly prone to suffer infections following HDT. Methods: We conducted a clinical cohort study on patients ≥16 years receiving HDT with autologous stem cell transplantation for myelomatosis (MM) or non-Hodgkin lymphoma (NHL) at Department of Hematology, Aarhus University Hospital, Denmark from 25 November 2009 through 26 June 2015. Of eligible patients (N=308), we excluded previous transplanted (N=14), those without a pre-HDT serum sample available for anti-αGal quantification (N=115), and recipients of plasma transfusion/IgG substitutions within 90 days before the pre-HDT serum sample and until end of follow-up (N=9). All included received prophylactic antimicrobial therapy (levofloxacin and fluconazol) and filgrastim. Serum anti-αGal was quantified using an in-house Time-resolved Immuno-Fluoremetric Assay. We ascertained infectious episodes within 30 days following the date of autologous stem cell re-infusion through review of all medical charts and data retrieval from the laboratory information systems, blinded for anti-αGal concentrations. Infectious episodes were defined as fever (≥38.5°C) or hypothermia (<36°C) prompting antibiotic treatment and CRP > 21 mg/L preceded by at least 24 hours without any of these. We used a Cox proportional hazards model to investigate the association between anti-αGal concentrations and risk of infection, with adjustment for total plasma IgG concentrations, ABO blood group, comorbidity, and underlying disease (MM or NHL) in the adjusted hazard ratios (HR). Optimum cutoff for dichotomizing was determined from ROC analysis applying Youden´s J statistic and groups were compared by Kaplan-Meier method. Results: We included 170 patients (MM, 55%; males, 58%; median age 62 years). Severe neutropenia was transient in all, with blood neutrophils increasing to above 500/µL on median day 11 (range 8-18). We identified one infectious episode in 103 patients (61%) and two episodes in six (3.5%) patients. The infectious episodes began during severe neutropenia in 92% of the patients. The infection types were fever of unknown origin (FUO) (72%), pneumonia (19%), catheter related (4.3%), typhlitis (1.7%), C. difficile colitis (1.7%), and hypothermia of unknown origin (0.87%). None died from infections. Pre-HDT serum was collected on median day -31 (range -142- -16). Anti-αGal was detectable in all but one sample, averaging 0.51 mg/dL (range: 0.016-12). Overall, anti-αGal concentrations predicted infectious episodes (all types), crude HR 1.2 (95% confidence interval (CI) 1.1-1.4), adjusted HR 1.1 (95% CI: 1.0-1.3). Using anti-αGal at 1.3 mg/dL as cut-off, we identified that patients with higher concentrations (N=41) experienced considerably increased risk of infectious episodes (crude estimates): all types, HR 1.7 (95% CI: 1.3-3.2); FUO, HR 2.0 (95%CI: 1.5-4.5); and pneumonia HR 2.1 (95%CI: 0.83-8.7). Discussion: We found that high anti-αGal serum concentrations predict an increased risk of infection after HDT. These findings support that anti-αGal may critically enhance pathogen-survival in the neutropenic host. Studies of other cohorts and mechanistic studies are required. Our findings may pave the way for future optimized risk stratification and therapeutic measures. Disclosures No relevant conflicts of interest to declare.

High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: Past or future?

2001 ◽  
Vol 28 (4) ◽  
pp. 377-388 ◽  
Author(s):  
Roy D. Baynes ◽  
Roger D. Dansey ◽  
Jared L. Klein ◽  
Caroline Hamm ◽  
Mark Campbell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem

Gamma knife radiosurgery in patients with advanced breast cancer undergoing bone marrow transplant

2002 ◽  
Vol 97 ◽  
pp. 663-665 ◽  
Author(s):  
Kenneth J. Levin ◽  
Emad F. Youssef ◽  
Andrew E. Sloan ◽  
Rajiv Patel ◽  
Rana K. Zabad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
High Dose Chemotherapy ◽  
Advanced Breast ◽  
High Dose ◽  
Initial Management ◽  
Content Type ◽  
Fine Print

Object. Recent studies have suggested a high incidence of cognitive deficits in patients undergoing high-dose chemotherapy, which appears to be dose related. Whole-brain radiotherapy (WBRT) has previously been associated with cognitive impairment. The authors attempted to use gamma knife radiosurgery (GKS) to delay or avoid WBRT in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow transplantation (HDC/ABMT) in whom brain metastases were diagnosed. Methods. A retrospective review of our experience from 1996 to 2001 was performed to identify patients who underwent HDC/ABMT for advanced breast cancer and brain metastasis. They were able to conduct GKS as initial management to avoid or delay WBRT in 12 patients following HDC/ABMT. All patients were women. The median age was 48 years (range 30–58 years). The Karnofsky Performance Scale score was 70 (range 60–90). All lesions were treated with a median prescription dose of 17 Gy (range 15–18 Gy) prescribed to the 50% isodose. Median survival was 11.5 months. Five patients (42%) had no evidence of central nervous system disease progression and no further treatment was given. Four patients were retreated with GKS and three of them eventually received WBRT as well. Two patients were treated with WBRT as the primary salvage therapy. The median time to retreatment with WBRT was 8 months after the initial GKS. Conclusions. Gamma knife radiosurgery can be effectively used for the initial management of brain metastases to avoid or delay WBRT in patients treated previously with HDC, with acceptable survival and preserved cognitive function.

scholarly journals ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue

1999 ◽  
Vol 10 (8) ◽  
pp. 903-905 ◽  
Author(s):  
J. Crown ◽  
B. Coiffier ◽  
H. Cortés-Funes ◽  
Th. Guillaume ◽  
L. Kanz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Dose Chemotherapy ◽  
Position Paper ◽  
High Dose

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

scholarly journals The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Weiqing Liu ◽  
Shumin Ma ◽  
Lei Liang ◽  
Zhiyong Kou ◽  
Hongbin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Large Scale ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cancer Type ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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