Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: Analysis of persistent and new‐onset cytopenia

Gozzetti, Alessandro; Defina, Marzia; Fabbri, Alberto

doi:10.1002/cncr.28443

Cited by 9 publications

(4 citation statements)

References 8 publications

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“…Cyclophosphamide (Cy) is one of the most widely used alkylating agent and a major constituent of combined chemotherapy regimens [1]. Cy has a high cytotoxicity on tumor cells and therefore it is used in the treatment of acute and chronic leukemias [2,3], multiple myeloma [4], lymphoma [5,6], autoimmune diseases [7] and patient preparation for bone marrow transplant [1,8]. However, Cy has low specificity and it has a broad spectrum of cytotoxic effects on normal cells [9].…”

Section: Introductionmentioning

confidence: 99%

Probiotic Lactobacillus strains protect against myelosuppression and immunosuppression in cyclophosphamide-treated mice

Salva

Marranzino

Villena

et al. 2014

International Immunopharmacology

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Section: Introductionmentioning

confidence: 99%

Probiotic Lactobacillus strains protect against myelosuppression and immunosuppression in cyclophosphamide-treated mice

Salva

Marranzino

Villena

et al. 2014

International Immunopharmacology

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“…However, the age and comorbidities of the individuals being treated often limit the applicability of these standard treatments. [ 1 , 2 , 5 – 7 , 11 ]. Ibrutinib is a new drug for the treatment of patients with chronic lymphocytic leukemia.…”

Section: Discussionmentioning

confidence: 99%

Ibrutinib-Associated Nail Plate Abnormalities: Case Reports and Review

Manica

Cohen

2017

Drug Saf - Case Rep

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Chronic lymphocytic leukemia is a lymphoproliferative disorder characterized by a gradual accumulation of neoplastic B-lymphocytes. Ibrutinib is a novel therapy for chronic lymphocytic leukemia. Ibrutinib therapy has been associated with nail plate abnormalities. Other common cutaneous adverse events caused by ibrutinib appear to be bruising, hair changes, pruritus, and rashes. We describe the clinical features of two patients with chronic lymphocytic leukemia: a 79-year-old woman and a 53-year-old man who developed nail plate abnormalities approximately 6 and 4 months, respectively, after beginning ibrutinib therapy. We also review the characteristics of other patients with chronic lymphocytic leukemia with ibrutinib-associated nail plate abnormalities. The PubMed database was used to search the following terms: abnormal, abnormalities, adverse, brittle, chronic, cutaneous, dystrophy, events, effects, ibrutinib, lymphocytic, leukemia, nail, plate, and side. The relevant referenced papers generated by the search were reviewed. In conclusion, ibrutinib is used to treat chronic lymphocytic leukemia. It is usually well-tolerated. Many patients receiving ibrutinib will develop nail plate abnormalities. This adverse event is not a drug-limiting toxicity.

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“…Inhibition of CHK1 in various cancer types harboring p53 mutation including breast cancer, multiple myeloma, colon carcinoma, pancreatic cancer, and brain glioblastoma resulted in cell death mainly via mitotic catastrophe when simultaneously exposed to DNA damage. Currently, several CHK1 inhibitors (e.g., Sch 900776, GDC0425, GDC0575) are evaluated in clinical trials, highlighting the therapeutic advantage and benefits of a checkpoint abrogation approach in anticancer treatment (48)(49)(50).…”

Section: Discussionmentioning

confidence: 99%

Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition–Associated Checkpoint Abrogation

Mikami

Medová

Nisa

et al. 2015

Molecular Cancer Research

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Signaling via the MET receptor tyrosine kinase has been implicated in crosstalk with cellular responses to DNA damage. Our group previously demonstrated that MET inhibition in tumor cells with deregulated MET activity results in radiosensitization via downregulation of the ATR-CHK1-CDC25 pathway, a major signaling cascade responsible for intra-S and G 2 -M cell-cycle arrest following DNA damage. Here we aimed at studying the potential therapeutic application of ionizing radiation in combination with a MET inhibitor, EMD-1214063, in p53-deficient cancer cells that harbor impaired G 1 -S checkpoint regulation upon DNA damage. We hypothesized that upon MET inhibition, p53-deficient cells would bypass both G 1 -S and G 2 -M checkpoints, promoting premature mitotic entry with substantial DNA lesions and cell death in a greater extent than p53-proficient cells. Our data suggest that p53-deficient cells are more susceptible to EMD-1214063 and combined treatment with irradiation than wild-type p53 lines as inferred from elevated gH2AX expression and increased cytotoxicity. Furthermore, cell-cycle distribution profiling indicates constantly lower G 1 and higher G 2 -M population as well as higher expression of a mitotic marker p-histone H3 following the dual treatment in p53 knockdown isogenic variant, compared with the parental counterpart.Implications: The concept of MET inhibition-mediated radiosensitization enhanced by p53 deficiency is of high clinical relevance, as p53 is frequently mutated in numerous types of human cancer. The current data point for a therapeutic advantage for an approach combining MET targeting along with DNA-damaging agents for MET-positive/p53-negative tumors.

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Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: Analysis of persistent and new‐onset cytopenia

Cited by 9 publications

References 8 publications

Probiotic Lactobacillus strains protect against myelosuppression and immunosuppression in cyclophosphamide-treated mice

Probiotic Lactobacillus strains protect against myelosuppression and immunosuppression in cyclophosphamide-treated mice

Ibrutinib-Associated Nail Plate Abnormalities: Case Reports and Review

Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition–Associated Checkpoint Abrogation

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