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.

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.

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

Use of autologous bone marrow cells following high-dose chemotherapy (HDCT) for patients (pts) with recurrent lymphoma in whom stem cell harvesting from the peripheral blood was inadequate

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8124-8124
Author(s):  
G. Kumaran ◽  
J. Murray ◽  
D. Sweeney ◽  
E. Liakopoulou ◽  
J. A. Radford
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Bone Marrow Cells ◽  
Autologous Bone Marrow ◽  
High Dose Chemotherapy ◽  
Severe Neutropenia ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Non Hodgkin Lymphoma

8124 Background: HDCT with autologous stem cell rescue (ASCR) is an established treatment for recurrent Hodgkin and non- Hodgkin lymphoma (HL, NHL) but some of these pts fail to mobilise adequate numbers of CD34+ cells from the peripheral blood (PB). Harvest of bone marrow (BM) stem cells and use of these alone or in combination with PB derived cells is an option but there are concerns about feasibility and outcome. Methods: 29 pts who had HDCT after failed PB stem cell harvest between July 1999 and December 2005 were studied in terms of CD34+ cell yield (PB and BM), transfusion dependence, engraftment and survival. Results: There were 17 males and 12 females (median age 49yrs, range 19–66) with recurrent HL (n=16) or NHL (n=13). All had received at least 2 lines of chemotherapy (10 pts =3) and 7 had received radiotherapy (5 mediastinal, one neck and one abdominal field). Mobilisation of CD34+ cells from PB was attempted using chemotherapy followed by filgrastim. 22 pts proceeded to leukapheresis on the basis of predictive CD34+ counts (median collects 2; range 0–4) with a median total collect of 0.98×106 CD34+cells/kg (range 0.03–1.84). Subsequently, all pts had a BM harvest producing a median collect of 1.63x106 CD34+cells/kg (range 0.45–4.75). 29 pts then received BEAM/CBV followed by re-infusion of PB+BM cells except in 7 pts where only BM cells were available. In 26/29 pts surviving to day 100; total CD34+ cells infused, 2.37×106/kg (range 1.73- 5.0), time to neutrophils >0.5×109/L, 12 days (range 9–23), platelet units transfused, 6 (range 0–24), red cells units transfused 6 (range 0–18) (all medians). 2 pts continued to have red cell transfusions beyond day 100. 3/29 pts died due to severe neutropenia/septicaemia at days 23–25 (treatment related mortality 10.3%); the CD34+ dose received by these pts was 1.97×106/kg in 2 and 1.84×106/kg in 1. Beyond day 100, 9 pts have died from HL/NHL and 2 are lost to follow-up. Conclusions: In patients with HL/NHL who fail to mobilise adequate numbers of CD34+ cells from PB, a BM harvest can produce a combined BM/PB collect capable of producing haemopoeitic reconstitution following HDCT without excessive toxicity. No significant financial relationships to disclose.

Lymphopenia Prior High-Dose Chemotherapy Is a Major Prognostic Factor for Severe Infectious Complication after Autologous Blood Stem Cell Transplantation for Lymphoma’s Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2984-2984
Author(s):  
Hervé Ghesquières ◽  
Roch Houot ◽  
Céline Ferlay ◽  
Catherine Sebban ◽  
Thérèse Gargi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lymphocyte Count ◽  
Infectious Complication ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Risk Of Infection ◽  
Minor Response

Abstract Rationale: Host factors able to predict accurately the infectious risk after high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) would be very useful. We previously reported that lymphopenia immediately prior conventional chemotherapy (day 1) identifies a subgroup of patients at risk of early death (Ray-Coquard et al. Br J Cancer 2001). This model was then investigated for patients receiving HDCT and ASCT. Patients and Methods: Between 1993 and 2000, 146 patients with diffuse large cell lymphoma (69), burkitt lymphoma (2), T lymphoblastic lymphoma (5), mantle cell lymphoma (16), follicular lymphoma (27), MALT lymphoma (2), lymphocytic lymphoma and chronic lymphoid leukemia (7) and hodgkin lymphoma (18) received HDCT with (72) or without (74) Total Body Irradiation (TBI). Median age at time of HDCT was 50 years (range, 38–68). Patients were treated in first (35.6%), second (48.4%) and third or more (16%) line treatment. Complete and unconfirmed complete remission before HDCT was obtained in 45.2%, partial response in 47.9%, minor response in 2.1% and 4.8% of patients were treated in progressive disease. Median transplanted CD34+ cell number was 6.79 × 106/kg (range, 0.70–47.58). 25 patients received G-CSF injection after graft. The predictive value of pre HDCT (d1) lymphocyte count for the risk of infection during the first 100-days after ASCT was investigated on this series. Results: Median d1 lymphocyte count was 750/mm3 (range, 90–3900). Infectious events were 35 clinical severe infectious complications (20 pneumonia, 8 severe enterocolitis, 3 viral infectious, 2 invasive fungal infection, 1 soft tissue infection, 1 severe septicaemia), 8 (6%) intensive care unit transfert and 4 (3%) toxic deaths for infectious reason. Using logistic regression, patients with ≤ 1000 d1 lymphocyte count presented statistically more infectious events (39 vs. 8 p<0.01). 62 patients of this series (69%) had ≤ 1000 d1 lymphocyte count. Age at HDCT, disease type, tumour response before HDCT, used of TBI, performance status before HDCT, number of transplanted CD34+ cells were not predictive of risk of infection. During the hospitalization after graft, used of G-CSF, number of days of broad spectrum antibiotics and anti fungal treatment, documented bacterial infection, number of days of hospitalization, number of transfusion, duration of neutropenia under 500/μl and plaquets recovery were not statistically different between patients with ≤ or > 1000 d1 lymphocyte count. Conclusion: Pre HDCT (d1) lymphocyte count is a potent predictor of the risk of severe infectious complication. These data need to be confirmed in a validation series. As 69% of patients had ≤ 1000 d1 lymphocytes, we incline to analyse lymphocyte subset to provide more discriminative information about the risk of infectious complication after HDCT. This currently being investigated.

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

PROSPECTS FOR HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THE FIRST LINE OF THERAPY FOR AGGRESSIVE NON-HODGKIN’S LYMPHOMAS

2017 ◽  
Vol 63 (2) ◽  
pp. 326-328
Author(s):  
Larisa Filatova ◽  
Yevgeniya Kharchenko ◽  
Sergey Alekseev ◽  
Ilya Zyuzgin ◽  
Anna Artemeva ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
First Line ◽  
Hematopoietic Stem ◽  
Hodgkin's Lymphomas

Currently there is no single approach to treatment for aggressive diffuse large-cell B-cell lymphoma (Double-HIT and Triple-HIT). Accumulated world data remain controversial and, given the unfavorable prognosis in this subgroup, high-dose chemotherapy with autologous stem cell transplantation in the first line of treatment is a therapeutic option.

scholarly journals SS-4 High dose chemotherapy with autologous hematopoietic stem cell transplantation for CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii2-ii2
Author(s):  
Eisei Kondo
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Primary Cns Lymphoma ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Hematopoietic Stem

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is listed as a consolidation therapy option for primary central nervous system (CNS) lymphoma in the guidelines of western countries. The advantages of HDT-ASCT for primary CNS lymphoma as consolidation are believed to be high rates of long-term remission and lower neurotoxicity, even though its eligibility is limited to younger fit patients. In the Japanese guideline, HDT-ASCT for primary CNS lymphoma is however not recommended in daily practice, mainly because thiotepa was unavailable since 2011. The Japanese registry data for hematopoietic transplantation have shown that primary CNS lymphoma patients were treated with various HDT regimens and thiotepa-containing HDT was associated with better progression free survival (P=.019), lower relapse (P=.042) and a trend toward a survival benefit (Kondo E et al, Biol Blood Marrow Transplant 2019). A pharmacokinetic study of thiotepa(DSP-1958) in HDT-ASCT for lymphoma was conducted in 2017, and thiotepa was approved for HDT-ASCT in lymphoma this March, meaning that optimal HDT regimen for CNS lymphoma is now available in Japan. The treatment strategy of CNS lymphoma needs further development to improve survival and reduce toxicity.

scholarly journals Monotherapy with Intravenous Followed by Oral High-Dose Ciprofloxacin versus Combination Therapy with Ceftazidime plus Amikacin as Initial Empiric Therapy for Granulocytopenic Patients with Fever

2000 ◽  
Vol 44 (12) ◽  
pp. 3264-3271 ◽  
Author(s):  
Helen Giamarellou ◽  
Harry P. Bassaris ◽  
George Petrikkos ◽  
Wilhelm Busch ◽  
Michel Voulgarelis ◽  
...  
Keyword(s):  
Randomized Study ◽  
Empirical Therapy ◽  
Unknown Origin ◽  
Empiric Therapy ◽  
Oral Route ◽  
Severe Neutropenia ◽  
Combination Group ◽  
High Dose ◽  
Standard Regimen ◽  
Oral Ciprofloxacin

ABSTRACT The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm3) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; δ = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm3). However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

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