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Antineoplastic Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
An oral bifunctional alkylating agent, chlorambucil (Leukeran), is a nitrogen mustard-type agent used to treat chronic leukemia and lymphomas. Chlorambucil has been used to treat breast, trophoblastic, and ovarian carcinomas. Two case reports of this agent used in pregnancy reported unilateral (left) renal and ureter agenesis in the infants whose mothers used the drug during pregnancy (Shotton and Monie, 1963; Steege and Caldwell, 1980). However, causal inferences cannot be made based on case reports.
Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
In animal studies, there has been some suggestion that there may be inheritable chromosomal aberrations caused by exposure of germ cells to chlorambucil and melphalan (50). In humans, cardiac and renal defects, including renal agenesis, have been reported with fetal exposure to chlorambucil in the first trimester (51,52). Still, others have described the use of chlorambucil throughout pregnancy with delivery of normal infants (51).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Chlorambucil is mainly used either alone or in combination therapy for the treatment of some lymphomas and chronic leukemias (e.g., chronic lymphocytic leukemia, CLL), and is well tolerated by most patients. However, in younger patients with CLL, fludarabine is now more frequently used as first-line therapy. Chlorambucil is also used for treating Hodgkin’s disease, indolent non-Hodgkin’s lymphoma, Waldenström macroglobulinemia, polycythemia vera, trophoblastic neoplasms, and ovarian carcinoma. In addition, it has been used as an immunosuppressive drug for treating various autoimmune and inflammatory conditions, such as nephrotic syndrome.
Systemic Immunosuppression in Cornea and Ocular Surface Disorders: A Ready Reckoner for Ophthalmologists
Published in Seminars in Ophthalmology, 2022
Chlorambucil is also an alkylating agent, which inhibits cell proliferation by DNA cross linking.47 This drug is similar to cyclophosphamide in terms of its utility in severe inflammation as well as its side effect profile.48–51 Adverse effects of this drug include bone marrow suppression, alopecia, teratogenicity, sterility, and increased risk of malignancies.41,52 Bladder toxicity, however, is not associated with chlorambucil use.11 Chlorambucil can be administered either as short-term high-dose or a long-term low-dose therapy. In the former approach, the initial dose is 2 mg daily for 1 week which is then increased by 2 mg/ day weekly.4 The dose is increased until suppression of inflammation is achieved. A CBC is recommended weekly initially, and then monthly after a stable dose is reached.4 If bone marrow suppression is detected, as manifested by white blood cell count below 2400 cells/µl or platelet count less than 100000/µl, chlorambucil is discontinued. The total duration of chlorambucil therapy should not exceed 6 months53,54 The more conventional low dose approach consists of a daily dose of 0.1 to 0.2 mg/kg, which is continued for one year after remission has been attained.53,54
Can early intervention with pharmacotherapy reduce the morbidity and mortality of chronic lymphocytic leukemia?
Published in Expert Opinion on Pharmacotherapy, 2018
Shuo Ma, Leonidas C. Platanias
Chlorambucil has been a commonly used cytotoxic agent for CLL treatment for several decades. The French Cooperative Group on CLL reported in 1998 the results of two sequential large randomized clinical trials to determine whether chlorambucil treatment benefits patients with indolent CLL. The studies included a total of 1535 patients with previously untreated stage A CLL [6]. In the first trial, 609 patients were randomly assigned to receive either daily chlorambucil (0.1 mg per kilogram of body weight per day) or no treatment; in the second trial, 926 patients were randomly assigned to receive either intermittent chlorambucil plus prednisone (0.3 mg of chlorambucil per kilogram per day for 5 days every month and 40 mg of prednisone per square meter of body-surface area per day for 5 days every month) or no treatment. There was no age limit on this study. Median follow-up for the first and second trials exceeded 11 and 6 years, respectively. Although chlorambucil-based treatment slowed disease progression, there was no effect on overall survival. Compared to the untreated group, the relative risk of death in the treated group was 1.14 (95% confidence interval, 0.92–1.41; P = 0.23) in the first trial and 0.96 (95% confidence interval, 0.75–1.23; P = 0.74) in the second trial, with 76% and 69% of patients, respectively, having a response to therapy. The authors concluded that chlorambucil does not prolong survival in patients with stage A CLL and that treatment of indolent CLL is unnecessary [6].
Minimal residual disease in chronic lymphocytic leukemia: A consensus paper that presents the clinical impact of the presently available laboratory approaches
Published in Critical Reviews in Clinical Laboratory Sciences, 2018
Ciprian Tomuleasa, Cristina Selicean, Sonia Cismas, Anca Jurj, Mirela Marian, Delia Dima, Sergiu Pasca, Bobe Petrushev, Vlad Moisoiu, Wilhelm-Thomas Micu, Anna Vischer, Kanza Arifeen, Sonia Selicean, Mihnea Zdrenghea, Horia Bumbea, Alina Tanase, Ravnit Grewal, Laura Pop, Carmen Aanei, Ioana Berindan-Neagoe
MRD outcome for different therapies based on rigorously selected patient groups according to age, prognostic factors, and comorbidities is important for appropriate decision making. There are many closed or ongoing studies regarding MRD outcome for different therapeutic regimens including fludarabine/cyclophosphamide/rituximab (FCR), bendamustine and rituximab (BR), as well as novel anti-CD20 agents. Chlorambucil is a prominent oral alkylating agent and has been used to treat CLL for the past 60 years. In recent years, it has become less popular due to availability of better and safer alternatives for fit patients, but it is still largely used in treating elder, frail patients [72–74]. Cyclophosphamide and low-dose etoposide can also be used as single agent therapies. Bendamustine was approved for CLL treatment after it has been proven to have better tolerability than fludarabine, especially in renal impaired patients [75,76].