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Haemopoietic Stem Cell Transplantation for Rheumatoid Arthritis—World Experience and Future Trials
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
John A. Snowden, John J. Moore, Sarah J. Bingham, Steve Z. Pavletic, Richard K. Burt
In Leeds, seven patients with RA resistant to at least 4 DMARDs were mobilised with cyclophosphamide 2 g/m2 and G-CSF32. In six patients, the graft underwent CD34 selection and CD4 and CD8 negative purging in order to achieve at least a 5-log reduction in T-lymphocytes. In the seventh patient, insufficient cells were harvested to allow graft manipulation. All patients were conditioned with cyclophosphamide 200 mg/kg. Minimal transplant-related toxicity was observed. Patients have been followed-up for 36 months. All patients responded well initially with 4 of the 7 patients achieving at least a 50% reduction in ACR without disease modifying agents and this was maintained for up to 9 months (Fig. 2). All seven patients relapsed and were commenced on cyclosporin A. Three patients subsequently achieved ACR 70, one patient, ACR 50, one patient showed improvement but did not satisfy ACR 20 and two patients did not improve (Fig. 3). One patient continued to have minimal disease activity (but did not quite satisfy ACR remission criteria on account of a tender joint due to secondary osteoarthritis) at 36 months whilst only taking cyclosporin A 100 mg daily and prednisolone 5 mg daily. All patients had an improved quality of life and a reduction in disability score. Only one serious infective episode has occurred during follow-up: an infected toe wound at 18 months that required intravenous antibiotics. No other serious long-term complications have occurred.
Pleural disease induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Cyclophosphamide, an immunosuppressive alkylating agent, is used in the treatment of a variety of non-malignant and malignant diseases. Adverse effects include bone marrow suppression, haemorrhagic cystitis, bladder cancer and gastrointestinal intolerance. The first case of cyclophosphamide-induced lung injury was reported approximately 40 years ago. Since the initial report, approximately 20 additional cases of pulmonary toxicity have been reported.18
Overview of biological mechanisms of human carcinogens
Published in Journal of Toxicology and Environmental Health, Part B, 2019
Nicholas Birkett, Mustafa Al-Zoughool, Michael Bird, Robert A. Baan, Jan Zielinski, Daniel Krewski
Cyclophosphamide is an antineoplastic agent that is widely used in cancer treatment for its immunosuppressive properties. Metabolism of this drug has been extensively studied with respect to carcinogenicity. The parent compound is not carcinogenic by itself and requires hepatic metabolic activation. The two primary metabolites with carcinogenic potential are phosphoramide mustard and acrolein. Cyclophosphamide induces cancer of the bladder and acute myeloid leukemia.