Necrotizing soft tissue infection in two patients with multiple myeloma.

BACKGROUND: Necrotizing soft tissue infection (NSTI) remains associated with substantial morbidity and risk of death, especially in immunocompromised patients, such as those with multiple myeloma. Early diagnosis and treatment is crucial, yet particularly complicated in patients with atypical presentations and impaired host defenses. METHODS: A report of two cases of multiple myeloma and NSTI at a single institution. Review of pertinent international literature. RESULTS: Necrotizing soft tissue infections are rare in patients with multiple myeloma. However, when they occur, the presentation may be atypical, and morbidity is high. Anti-tumor chemotherapy must be suspended, worsening an already-guarded prognosis. CONCLUSIONS: A high index of suspicion for NSTI is necessary for immunocompromised patients, such as those with multiple myeloma, in view of the possibility of atypical presentation. Diagnosis may therefore be challenging, and a protracted course is possible because of host immunosuppression.

Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML.

We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m² for 7 days) and daunorubicin (60 mg/m² × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.