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Health Science Reports May 2022Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect... (Review)
Review
BACKGROUND
Bendamustine, a bifunctional mechlorethamine alkylating agent, is used in the treatment of patients with hematologic malignancies. Myelosuppression and cytotoxic effect arises quite often after bendamustine treatment. To date, there have been no recommendations for routine chemoprophylaxis for pneumonia (PCP) in patients under treatment with this agent. The present systematic review aimed to evaluate the existing data on bendamustine effects on pneumocystis pneumonia.
METHOD
English papers were systematically reviewed using Web of Science, Embase, Google Scholar, PubMed, and Cochrane library. There was no time constraint for the paper search. The used keywords included "Pneumonia, Pneumocystis"or "Pneumocystis Pneumonia"or "Pneumocystis jirovecii" and "Bendamustine hydrochloride or Bendamustine. "Through our search, 113 papers were found, 26 of which were chosen following a review of the titles and abstracts; ultimately, 10 were included in the research.
RESULT
A total of 10 studies (out of 113 studies) were retrieved. The papers were classified into seven case reports, two clinical trials, and one retrospective analysis study. The case reports included 14 patients diagnosed with PCP after bendamustine administration between 2003 and 2019. The patients' mean age was with a range of 66.8. Non-Hodgkin's lymphoma (including diffuse large B-cell lymphoma and mantle cell lymphoma) ( = 9, 60%), chronic lymphocytic leukemia ( = 4, 26.6%), and breast cancer ( = 2, 13.4%) were the most prevalent types of malignancy. Bendamustine, along with rituximab, were the most commonly prescribed chemotherapy regimens during the treatments. Finally, the mortality rate among the patients whose results were reported ( = 9) was 44.44% ( = 4).
CONCLUSION
The present review described PCP infection in patients with malignancies after the treatment with bendamustine, a chemotherapeutic agent associated with lymphopenia. Further research is required to determine the PCP risk in patients with bendamustine treatment and identify individuals who may benefit from prophylaxis.
PubMed: 35509412
DOI: 10.1002/hsr2.610 -
Cell Transplantation 2023High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma... (Meta-Analysis)
Meta-Analysis
BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus BEAM (Carmustine, Etoposide, Cytarabine, Melphalan) as Conditioning Regimen Before Autologous Haematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis.
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard of care for selected patients with refractory/relapsed Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NHL), and it is also used as first-line clinical consolidation option for some aggressive NHL subtypes. Conditioning regimen prior to ASCT is one of the essential factors related with clinical outcomes post transplant. The conditioning regimen of carmustine, etoposide, cytarabine, and melphalan (BEAM) traditionally is considered the standard of care for patients with lymphoma who are eligible for transplantation. Replacement of carmustine with bendamustine (BeEAM) was described as an alternative conditioning regimen in the autograft setting for patients with lymphoma. Several studies have reported inconsistent clinical outcomes comparing BeEAM and BEAM. Therefore, in the lack of well-designed prospective comparative studies, the comparison of BeEAM versus BEAM is based on retrospective trials. To compare the clinical outcomes between BeEAM and BEAM, we performed a meta-analysis of 10 studies which compared the outcomes between BeEAM and BEAM in patients autografted for lymphoma disease (HL or NHL). We searched article titles and compared transplantation with BeEAM versus BEAM in MEDLINE (PubMed), Cochrane library, and EMBASE database. Here, we report the results of nine main endpoints in our meta-analysis comparing BeEAM and BEAM, including neutrophil engraftment (NE), platelet engraftment (PE), overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse rate (RR), grade 3 mucositis, renal toxicity, and cardiotoxicity. We discovered that the BeEAM regimen was associated with a slightly better PFS [pooled odds ratio (OR) of 0.70, 95% confidence interval (CI), 0.52-0.94, = 0.02], lower RR (0.49, 95% CI, 0.31-0.76, = 0.002), higher mucositis (3.43, 95% CI, 2.29-5.16, = 0.001), renal toxicity (4.49, 95% CI, 2.68-7.51, = 0.001), and cardiotoxicity (1.88, 95% CI, 1.03-3.40, = 0.03). We also discovered that the two groups had equivalent NE (pooled WMD -0.64, 95% CI, -1.46 to 0.18, = 0.13), PE (pooled WMD -0.3, 95% CI, -1.68 to 2.28, = 0.77), OS (0.73, 95% CI, 0.52-1.01, = 0.07), and NRM (1.51, 95% CI, 0.76-2.98, = 0.24). The results of this meta-analysis show that the BeEAM regimen is a viable alternative to BEAM. More prospective comparisons between BeEAM and BEAM are required.
Topics: Humans; Carmustine; Transplantation, Autologous; Bendamustine Hydrochloride; Hematopoietic Stem Cell Transplantation; Cytarabine; Etoposide; Melphalan; Cardiotoxicity; Mucositis; Retrospective Studies; Neoplasm Recurrence, Local; Lymphoma, Non-Hodgkin
PubMed: 37350429
DOI: 10.1177/09636897231179364 -
The Cochrane Database of Systematic... Sep 2012Indolent B cell lymphoid malignancies include follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and marginal zone... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Indolent B cell lymphoid malignancies include follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and marginal zone lymphomas. Chronic lymphocytic leukaemia (CLL) is a lymphoid malignancy similar to small lymphocytic lymphoma (SLL) in its leukaemic phase.Indolent lymphoid malignancies including CLL are characterised by slow growth, a high initial response rate and a relapsing and progressive disease course. Advanced-stage indolent B cell lymphoid malignancies are often incurable. If symptoms or progressive disease occur, chemotherapy plus rituximab is indicated. No chemotherapy regimen has been shown to improve overall survival compared to a different regimen.Bendamustine is efficacious in the treatment of patients with indolent B cell lymphoid malignancies. A number of randomised controlled trials have examined the effect of bendamustine compared to other chemotherapy regimens in these patients. Improved disease control with no survival benefit is shown.
OBJECTIVES
To evaluate the efficacy of bendamustine therapy for patients with indolent B cell lymphoid malignancies including CLL.
SEARCH METHODS
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966 to May 2012), EMBASE (1974 to November 2011), LILACS (1982 to May 2012), databases of ongoing trials (accessed 30 April 2012) and relevant conference proceedings. We searched references of identified trials and contacted the first author of each included trial.
SELECTION CRITERIA
Randomised controlled trials that compared a bendamustine-containing regimen to other chemotherapy with or without immunotherapy.
DATA COLLECTION AND ANALYSIS
Two authors independently appraised the quality of each trial and extracted data from included trials. We estimated and pooled hazard ratios (HR) and risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
We included five trials randomising 1343 adult patients in the systematic review. Allocation and blinding were unclear in three trials and adequate in two. Incomplete outcome data and selective reporting were adequate in all trials. Trials varied in the type of lymphoid malignancy, bendamustine regimen and the comparator regimen. In the three trials that included patients with follicular lymphoma, mantle cell lymphoma and other indolent lymphomas the comparator treatment was cyclophosphamide, a combination of cyclophosphamide, vincristine, doxorubicin and prednisone, and fludarabine. Two trials included only patients with CLL and compared bendamustine to chlorambucil, and to fludarabine. We did not conduct a meta-analysis due to the clinical heterogeneity among trials. Bendamustine had no statistically significant effect on the overall survival of patients with indolent B cell lymphoid malignancies in any of the included trials (trials of moderate quality). Progression-free survival was statistically significantly improved with bendamustine treatment compared to other chemotherapy in three of the four trials that reported on it. One trial demonstrated a non statistically significant improvement of PFS. The risk of grade 3 or 4 adverse events was similar when bendamustine was compared to CHOP and fludarabine, and higher when compared to chlorambucil. Compared to chlorambucil quality of life was unaffected by bendamustine treatment (one trial, no meta-analysis).
AUTHORS' CONCLUSIONS
As none of the currently available chemotherapeutic protocols for induction therapy in indolent B cell lymphoid malignancies confer a survival benefit and due to the improved progression-free survival in each of the included trials, and a similar rate of grade 3 or 4 adverse events, bendamustine may be considered for the treatment of patients with indolent B cell lymphoid malignancies. However, the unclear effect on survival and the higher rate of adverse events compared to chlorambucil in patients with CLL/SLL does not support the use of bendamustine for these patients.The effect of bendamustine combined with rituximab should be evaluated in randomised clinical trials with more homogenous populations and outcomes for specific subgroups of patients by type of lymphoma should be reported. Any future trial should evaluate the effect of bendamustine on quality of life.
Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Cyclophosphamide; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Nitrogen Mustard Compounds; Prednisone; Recurrence; Vincristine; Waldenstrom Macroglobulinemia
PubMed: 22972131
DOI: 10.1002/14651858.CD009045.pub2 -
Bendamustine-induced immune hemolytic anemia: a case report and systematic review of the literature.Blood Advances Apr 2020Bendamustine can cause severe autoimmune hemolytic anemia (AIHA), which may require plasma exchange and aggressive immunosuppression. Bendamustine-induced AIHA can be...
Bendamustine can cause severe autoimmune hemolytic anemia (AIHA), which may require plasma exchange and aggressive immunosuppression. Bendamustine-induced AIHA can be delayed, and many, but not all, cases report prior exposure to fludarabine.
Topics: Anemia, Hemolytic; Bendamustine Hydrochloride; Humans
PubMed: 32343794
DOI: 10.1182/bloodadvances.2020001726 -
British Journal of Haematology Jul 2019The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of... (Comparative Study)
Comparative Study Meta-Analysis
The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of which has been shown to improve overall survival. The use of bendamustine is growing. A number of trials evaluated its efficacy for patients with indolent B-cell lymphoid neoplasms, including chronic lymphocytic leukaemia (CLL). To evaluate the efficacy of bendamustine in that population we performed a systematic review and meta-analysis of 9 randomised controlled trials (2726 patients). Bendamustine was compared to fludarabine-containing regimens, CVP (cyclophosphamide, vincristine, prednisolone), CHOP (CVP+ doxorubicin) and chlorambucil. Due to insufficient reported data, six of the nine trials were included in analysis of overall survival. Bendamustine was associated with a prolonged overall survival, (hazard ratio 0·79, 95% confidence interval 0·65-0·95). Data regarding quality of life was reported for two trials, therefore too scarce to pool. The risk of neutropenia was reduced with bendamustine treatment compared to other chemotherapy. Bendamustine induction is an efficacious option for patients with indolent lymphoma, and CLL. Maintenance therapy was not evaluated after bendamustine induction, and potentially there is an interaction between the two. Chemotherapy-free approach was shown to be efficacious for patients with CLL, while toxicity with that approach is not negligible.
Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Bendamustine Hydrochloride; Chlorambucil; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Maintenance Chemotherapy; Prednisone; Randomized Controlled Trials as Topic; Survival Rate; Vincristine
PubMed: 30980398
DOI: 10.1111/bjh.15901