Reducing mortality associated with immediate treatment complications of adult leukemias.

Analysis of data from 806 patients with newly diagnosed adult acute myelocytic leukemia (AML) (not including acute promyelocytic leukemia [APL] patients) treated at M.D. Anderson Cancer Center from 1995 through 1999 indicated that among patients entering a particular week of induction therapy, mortality rates were 6%, 8%, 6%, 9%, and 6% during weeks 1 to 2, 3 to 4, 5 to 6, 7 to 8, and 9 to 10, respectively. Because the mortality rate was not higher in the period immediately after treatment began, a definition of the period covered by the term "immediate" is somewhat arbitrary rather than "biologic," as might be the case if the early weeks were distinguished by a particularly high mortality rate. M.D. Anderson researchers have focused on the treatment complications and deaths occurring in the first 4 weeks after the beginning of induction therapy. In the first week, infection contributed to 71% of the deaths and pulmonary hemorrhage associated with diffuse alveolar damage contributed to 44%; the incidence of infection rose while the incidence of hemorrhage decreased during weeks 2 to 4. The associations between 4-week mortality rates with age, performance status, and white blood cell (WBC) count are well known. Study data suggest that elevated pretreatment levels of uric acid and tumor necrosis factor-alpha (TNF-alpha) levels are similarly associated with 4-week mortality. The prognostic significance of hyperuricemia appears independent of WBC, creatinine, and TNF-alpha. M.D. Anderson investigators have studied the roles of pheresis, TNF-alpha receptor-blocking agents, continuous venovenous dialysis, and newer antifungal agents in reducing early mortality. In particular, data from a retrospective M.D. Anderson analysis of pheresis (146 patients with WBC > 50,000 +/- microL) suggest that the value of this procedure is questionable. Preliminary data also point to the potential value of the TNF-alpha alpha receptor blocker etanercept (Enbrel, Immunex Corp, Seattle, WA) in patients at high risk of early death. Data from a randomized M.D. Anderson trial suggest that oral fluconazole plus itraconazole capsules are equivalent to liposomal amphotericin in antifungal prophylaxis. Because neither alternative appears satisfactory, researchers at M.D. Anderson are examining the role of intravenous itraconazole, which produces higher concentrations than itraconazole capsules in prophylaxis, and the role of FK 463 in treatment of fungal infections. Copyright 2001 by W.B. Saunders Company.