Cyclophosphamide Treatment-Induced Leukopenia Rates In Anca-Associated Vasculitis are Influenced by Variant Cyp450 2C9 Genotypes

Schirmer, Jan Henrik; Bremer, Jan Phillip; Moosig, Frank; Holle, Julia; Lamprecht, Peter; Wieczorek, Stefan; Haenisch, Sierk; Cascorbi, Ingolf

doi:10.2217/pgs.15.176

Cited by 21 publications

(14 citation statements)

References 23 publications

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“…The main toxic effect of CPh is an acute inhibition of hematopoiesis, which manifests by the suppression of rapidly proliferating hematopoietic progenitor cells and results in the form of neutropenia. However, lymphopenia and erythropenia are also significant toxic side effects of CPh [ 2 , 3 ]. In clinical practice, cancer patients’ treatment with CPh and other cytotoxic agents is accompanied by marked thrombocytopenia, which was manifested by the inhibitory effect of CPh on later megakaryocyte progenitors [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice

et al. 2017

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Application of cytostatics in cancer patients’ chemotherapy results in a number of side effects, including the inhibition of various parts of hematopoiesis. Two sulfated polysaccharides, fucoidan from the seaweed Chordaria flagelliformis (PS-Fuc) and fucosylated chondroitin sulfate from the sea cucumber Massinium magnum (PS-FCS), were studied as stimulators of hematopoiesis after cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF) was applied as a reference. Both tested polysaccharides PS-Fuc and PS-FCS have a similar activity to r G-CSF, causing pronounced neutropoiesis stimulation in animals with myelosuppression induced by cyclophosphamide (CPh). Moreover, these compounds are also capable to enhance thrombopoiesis and erythropoiesis. It should be noted that PS-FCS demonstrated a greater activity than r G-CSF. The results indicate the perspective of further studies of PS-Fuc and PS-FCS, since these compounds can be considered as potentially promising stimulators of hematopoiesis. Such drugs are in demand for the accompanying treatment of cancer patients who suffer from hematological toxicity during chemo and/or radiation therapy.

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Section: Introductionmentioning

confidence: 99%

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice

et al. 2017

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“…Whilst not the focus of this review, it is important to note that the role of pharmacogenetics in the risk of excessive toxicity (due to high levels of bioactivation of this cytotoxic drug) have also been assessed. Associations between CYP2C19 and/or CYP2B6 , as well as other pharmacogenes such as ALDH , GSTP1 and CYP3A4 , and the severity of neutropenia or premature ovarian failure have been reported …”

Section: Therapeutic Outcomesmentioning

confidence: 99%

“…Associations between CYP2C19 and/or CYP2B6, as well as other pharmacogenes such as ALDH, GSTP1 and CYP3A4, and the severity of neutropenia or premature ovarian failure have been reported. 40,65,67,[70][71][72][73][74][75]…”

Section: Therapeutic Outcomesmentioning

confidence: 99%

The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes

Helsby

Yong

Kan

et al. 2019

Brit J Clinical Pharma

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Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for the role of germline pharmacogenetic variation in both plasma pharmacokinetics and clinical outcomes. There is a substantial indication from 13 pharmacokinetic and 17 therapeutic outcome studies, in contexts as diverse as haematological malignancy, breast cancer, systemic lupus erythematosus and myeloablation, that pharmacogenetic variation in both CYP2C19 and CYP2B6 influence the bioactivation of cyclophosphamide. An additional role for pharmacogenetic variation in ALDH1A1 has also been reported. Future studies should comprehensively assess these 3 pharmacogenes and undertake appropriate statistical analysis of gene–gene interactions to confirm these findings and may allow personalised treatment regimens.

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“…CYC is an inactive prodrug that is metabolized to an active metabolite, phosphoramide mustard, and the bladdertoxic metabolite acrolein, by cytochrome P450 enzymes. Functional variants in cytochrome P450 enzyme genes have been associated with increased leukopenia (but also increased efficacy) in AAV (20). CYC is associated with multiple serious adverse effects, many of which occur early (bone marrow suppression, infection, hemorrhagic cystitis, infertility), but others may occur more than 10 years after therapy has stopped (malignancy).…”

Section: Cyclophosphamidementioning

confidence: 99%

Complications of Immunosuppression in Glomerular Disease

Jefferson

2018

CJASN

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Most glomerular diseases are immunologically mediated disorders of the kidney and are common causes of ESKD. In addition to supportive therapy, a wide range of immunosuppressive agents are used in the management of patients with these conditions. Immunosuppression requires a careful balance of risk and benefits, and many of these agents have a narrow therapeutic window and require close monitoring. This review describes the side effects of immunosuppressive agents used in recent randomized, controlled trials of glomerular disease, and highlights some of the key adverse events that determine the choice and prescription of these medications.

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Cyclophosphamide Treatment-Induced Leukopenia Rates In Anca-Associated Vasculitis are Influenced by Variant Cyp450 2C9 Genotypes

Abstract: Patients with variant CYP2C9 are at increased risk for cyclophosphamide-induced leukopenia but may have a better chance to respond to treatment.

Cited by 21 publications

References 23 publications

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice

Fucoidan and Fucosylated Chondroitin Sulfate Stimulate Hematopoiesis in Cyclophosphamide-Induced Mice

The importance of both CYP2C19 and CYP2B6 germline variations in cyclophosphamide pharmacokinetics and clinical outcomes

Complications of Immunosuppression in Glomerular Disease

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