tretinoin and Ventricular-Dysfunction--Left

To evaluate a regimen including high-dose mitoxantrone in previously untreated adults with AML, 45 patients aged 21-59 (median 41) were given cytarabine, 3 g/m2 days 1-5, mitoxantrone, 80 mg/m2 day 2 and etoposide, 150 mg/m2 days 1,3,5. Post-remission therapy consisted of 5 cycles combining the same agents at reduced doses. Complete remission was seen in 36 patients. The observed 3-year survival is 28%. Cytogenetic pattern and CD34 expression correlated with response and survival. Significant toxicity included myelosuppression, mucositis, diarrhea and hyperbilirubinemia. Ventricular ejection fraction was generally reduced, with clinical cardiac dysfunction in only 2 patients. This high-dose mitoxantrone combination can be administered to young adults with AML with tolerable toxicity and results comparable to those of other dose-intensive regimens.

Topics: Actuarial Analysis; Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Conjunctivitis; Cytarabine; Disease-Free Survival; Etoposide; Female; Gastrointestinal Diseases; Humans; Hyperbilirubinemia; Leukemia, Myeloid; Male; Methylprednisolone; Middle Aged; Mitoxantrone; Remission Induction; Risk; Stomatitis; Stroke Volume; Survival Analysis; Survival Rate; Treatment Outcome; Tretinoin; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Humans; Leukemia, Promyelocytic, Acute; Male; Myocardium; Neoadjuvant Therapy; Tretinoin; Ventricular Dysfunction, Left; Young Adult

The objective of this study was to evaluate the role of retinoic acid in experimental postinfarction myocardial remodeling. Wistar rats were subjected to myocardial infarction (MI) and treated with retinoic acid (RA), 0.3 mg/(kg x d) (MI-RA, n = 29), or fed a control diet (MI, n = 34). After 6 mo, the surviving rats (MI-RA = 18 and MI = 22) underwent echocardiograms, and isolated hearts were tested for function in vitro. The cross-sectional area of the myocyte (CSA) and interstitial collagen fraction (IC) were measured in a cross section of the heart stained by hematoxylin-eosin and picrosirius red, respectively. The CSA was smaller in the MI-RA group [229 (220,234) microm2] [medians (lower quartile, upper quartile)] than in the MI group [238 (232,241) microm2] (P = 0.01) and IC was smaller in the MI-RA group [2.4 (1.7, 3.1)%] than in the MI group [3.5 (2.6, 3.9)%] (P = 0.05). The infarct size did not differ between the groups [MI = 44.6 (40.8, 48.4)%, MI-RA = 45 (38.6, 47.2)%]. Maximum rate of rise of left ventricular pressure (+dp/dt) was greater in the MI-RA group (2645 +/- 886 mm Hg/s) than in the MI group (2081 +/- 617 mm Hg/s) (P = 0.05). The other variables tested did not differ between groups. Retinoic acid supplementation of rats for 6 mo attenuates the ventricular remodeling process after MI.

Topics: Animals; Antineoplastic Agents; Male; Myocardial Infarction; Rats; Rats, Wistar; Tretinoin; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling