cardiovascular-agents and Leukemia--Myeloid--Acute

Dexrazoxane (DEX) selectively blocks the development of irreversible diffuse myocardial toxicity induced by anthracyclines and related antitumor agents, such as mitoxantrone (MTX). Therefore, daunorubicin (DNR) should not be administered to patients with cumulative DNR doses higher than 550 to 700 mg/m2, which we used for remission induction and consolidation therapy in patients with acute myeloid leukemia (AML). To administer further doses of anthracyclines without risks in seven relapsed AML patients and in one patient with impaired heart functions receiving consolidation therapy, we used DEX as a cardioprotective agent. Patients received DEX 30 minutes before DNR 45 mg/m2 or MTX 10 mg/m2 in doses eight to 13 times higher (DNR) or 30 to 60 times higher (MTX) in the treatment cycle with 10 high doses (2,000 mg/m2/12 hr) of cytosine arabinoside plus two doses of DNR or MTX on the fourth and fifth day. When this cycle was used as reinduction therapy, complete remission was achieved in all five cases. A cycle of MTX and etoposide was given three times with DEX as consolidation. Myelotoxicity of the treatment cycles with DEX was similar to the cycles without it. Two patients received cumulative anthracyclines doses corresponding to more than 1,300 and 1,000 mg/m2 of DNR, respectively; the remaining five relapsed patients received 550 to 850 mg/m2 of DNR, all without signs of cardiac toxicity. Delayed administration of DEX after cumulative doses of DNR 500 mg/m2 in AML patients at relapse provides cardioprotection against DNR or MTX in combination with high doses of cytosine arabinoside. This type of chemotherapy seems to be effective for remission induction in relapsed, heavily pretreated AML patients or in patients with impaired heart functions.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Daunorubicin; Female; Heart Diseases; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Razoxane

The use of vascular endothelial growth factor inhibitors such as sorafenib is limited by a risk of severe cardiovascular toxicity. A 28-year-old man with acute myeloid leukemia treated with prednisone, tacrolimus, and sorafenib following stem cell transplantation presented with severe bilateral lower extremity claudication. The patient was discharged against medical advice prior to finalizing a cardiovascular evaluation, but returned 1 week later with signs suggestive of septic shock. Laboratory tests revealed troponin I of 12.63 ng/mL, BNP of 1690 pg/mL, and negative infectious workup. Electrocardiogram showed sinus tachycardia and new pathologic Q waves in the anterior leads. Coronary angiography revealed severe multivessel coronary artery disease. Peripheral angiography revealed severely diseased left anterior and posterior tibial arteries, tibioperoneal trunk, and peroneal artery, and subtotal occlusion of the right posterior tibial artery. Multiple coronary and peripheral drug-eluting stents were implanted. An intra-aortic balloon pump was placed. Cardiac magnetic resonance imaging revealed chronic left ventricular infarction with some viability, 17% ejection fraction, and left ventricular mural thrombi. The patient opted for medical management. Persistent symptoms 9 months later led to repeat angiography, showing total occlusion of the second obtuse marginal artery due to in-stent restenosis with proximal stent fracture, and chronic total occlusion of the right internal iliac artery extending to the pudendal branch. Cardiac positron emission tomography/computed tomography viability study demonstrated viable myocardium, deeming revascularization appropriate. Symptom resolution was obtained with no recurrences. Sorafenib-associated vasculopathy may follow a fulminant course. Multimodality cardiovascular imaging is essential for optimal management.

Topics: Adult; Antineoplastic Agents; Cardiotoxicity; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Defibrillators; Defibrillators, Implantable; Drug-Eluting Stents; Electric Countershock; Endovascular Procedures; Humans; Intra-Aortic Balloon Pumping; Leukemia, Myeloid, Acute; Male; Myocardial Infarction; Peripheral Arterial Disease; Protein Kinase Inhibitors; Sorafenib; Treatment Outcome

Cardiotoxicity is frequently present with anthracycline treatment. Most acute myeloid leukemia (AML) protocols use anthracyclines. Dexrazoxane has cardioprotective activity. The aim of this study was to evaluate cardioprotection of dexrazoxane in a prospective study. Fifty pediatric AML patients were treated with a Medical Research Council AML 10 modified protocol with dexrazoxane previous to any anthracycline dose. Cardiac function was evaluated at diagnosis, before every cycle, and every 6 months after the end of chemotherapy. Accumulative doses of anthracycline reached 424 mg/m (150 to 850 mg/m). Forty-eight patients (96%) received a dose higher than 300 mg/m. Twenty-eight percent had a grade of cardiotoxicity (24% grade 1 and 4% grade 2). Non 3 or 4 grade cardiotoxicity was seen. Cumulated anthracycline doses did not correlated with cardiotoxicity (P=0.815). The event-free survival was 53%, 15.7% died of disease, and 11.8% died free of leukemia. There is still not an agreement for the optimal method to reduce cardiotoxicity in children receiving anthracyclines. In our study, we could conclude that the use of dexrazoxane was effective cardioprotectant to allow a high-dose of anthracycline therapy. A randomized study is necessary to consolidate this asseveration.

Topics: Adolescent; Anthracyclines; Cardiovascular Agents; Child; Child, Preschool; Female; Follow-Up Studies; Heart Diseases; Humans; Infant; Leukemia, Myeloid, Acute; Male; Prospective Studies; Razoxane; Survival Rate; Treatment Outcome

Treatment of acute myelogenous leukemia is challenging in the setting of ischemic heart disease because anthracycline and anthracenedione drugs used in induction chemotherapy may potentiate myocardial dysfunction. We have managed two patients with coincident acute myelogenous leukemia and ischemic heart disease with the cardioprotectant drug dexrazoxane (ICRF-187), administered before each dose of mitoxantrone or idarubicin. Both patients tolerated their induction chemotherapy, developed marrow hypoplasia from chemotherapy, and achieved clinical remission. Dexrazoxane may have a role as a cardioprotectant in the treatment of select patients with acute myelogenous leukemia.

Topics: Adult; Aged; Cardiovascular Agents; Humans; Leukemia, Myeloid, Acute; Male; Myocardial Ischemia; Razoxane