For some regimens, it is rare. Cyclophosphamide-induced AML, when it happens, typically presents some years after treatment, with incidence peaking around 3—9 years. After nine years, the risk falls to background. When AML occurs, it is often preceded by a myelodysplastic syndrome phase, before developing into overt acute leukemia.
Cyclophosphamide-induced leukemia will often involve complex cytogenetics , which carries a worse prognosis than de novo AML. Most of the aldophosphamide is then oxidised by the enzyme aldehyde dehydrogenase ALDH to make carboxycyclophosphamide. Antimicrobial prophylaxis may be indicated in certain cases of neutropenia at the discretion of the managing physician. In case of neutropenic fever, antibiotic therapy is indicated.
Monitoring of complete blood counts is essential during cyclophosphamide treatment so that the dose can be adjusted, if needed. Cyclophosphamide treatment may not be indicated, or should be interrupted, or the dose reduced, in patients who have or who develop a serious infection. G-CSF may be administered to reduce the risks of neutropenia complications associated with cyclophosphamide use. Primary and secondary prophylaxis with G-CSF should be considered in all patients considered to be at increased risk for neutropenia complications.
The nadirs of the reduction in leukocyte count and thrombocyte count are usually reached in weeks 1 and 2 of treatment. Peripheral blood cell counts are expected to normalize after approximately 20 days.
Bone marrow failure has been reported. Urinary Tract and Renal Toxicity Hemorrhagic cystitis , pyelitis, ureteritis, and hematuria have been reported with cyclophosphamide. Discontinue cyclophosphamide therapy in case of severe hemorrhagic cystitis.
Urotoxicity bladder ulceration , necrosis , fibrosis, contracture and secondary cancer may require interruption of cyclophosphamide treatment or cystectomy. Urotoxicity can be fatal. Urotoxicity can occur with short-term or long-term use of cyclophosphamide.
Cyclophosphamide should be used with caution, if at all, in patients with active urinary tract infections. Aggressive hydration with forced diuresis and frequent bladder emptying can reduce the frequency and severity of bladder toxicity.
Mesna has been used to prevent severe bladder toxicity. Cardiotoxicity Myocarditis , myopericarditis, pericardial effusion including cardiac tamponade , and congestive heart failure , which may be fatal, have been reported with cyclophosphamide therapy Supraventricular arrhythmias including atrial fibrillation and flutter and ventricular arrhythmias including severe QT prolongation associated with ventricular tachyarrhythmia have been reported after treatment with regimens that included cyclophosphamide.
Particular caution is necessary in patients with risk factors for cardiotoxicity and in patients with preexisting cardiac disease. Monitor patients with risk factors for cardiotoxicity and with pre-existing cardiac disease.
Pulmonary Toxicity Pneumonitis, pulmonary fibrosis , pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis greater than 6 months after start of cyclophosphamide appears to be associated with increased mortality. Pneumonitis may develop years after treatment with cyclophosphamide. Monitor patients for signs and symptoms of pulmonary toxicity.
Secondary Malignancies Cyclophosphamide is genotoxic [see Nonclinical Toxicology]. This medication may rarely cause very serious effects on the heart, especially when used in high doses, or in combination with radiation treatment or certain other chemotherapy drugs e. Get medical help right away if you develop: This medication can lower the body's ability to fight an infection.
Notify your doctor promptly if you develop any signs of an infection such as fever, chills or persistent sore throat. Cyclophosphamide may lessen the chance of having children in both men and women. Sterility is usually temporary with this medication, but can be permanent in some cases. Consult your doctor for more details. Although cyclophosphamide is used to treat cancer, in some patients it may increase the risk of developing another form of cancer, sometimes months to years after treatment.
It is important to be closely monitored by your doctor during treatment. You should also see your doctor regularly after treatment is finished. Tell your doctor right away if you have any serious side effects, including: This medication may rarely cause very serious effects on the heart , especially when used in high doses, or in combination with radiation treatment or certain other chemotherapy drugs e. Get medical help right away if you develop: This medication can lower the body's ability to fight an infection.
Notify your doctor promptly if you develop any signs of an infection such as fever, chills or persistent sore throat. Cyclophosphamide may lessen the chance of having children in both men and women. Sterility is usually temporary with this medication, but can be permanent in some cases.
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