Influence of obesity on efficacy and toxicity of induction chemotherapy in patients with newly diagnosed acute myeloid leukemia.

Increased body mass index (BMI) is associated with increased risk of treatment-related complications and inferior overall survival in patients with acute myeloid leukemia (AML). We retrospectively evaluated the association between percentage of ideal body weight (IBW) and complete remission (CR) among 63 newly diagnosed, previously untreated patients with AML. The median percentage of ideal body weight was 121% (range 86-246%). Thirty-three percent of patients were obese (≥ 130% IBW). In multivariate analysis, obesity was not associated with CR (odds ratio [OR] = 0.97, p = 0.88), overall survival (hazard ratio = 0.48, p = 0.52), platelet recovery by 30 days (OR = 1.14, p = 0.52) or neutrophil recovery by 30 days (OR = 1.12, p = 0.60). Obesity was also not associated with any differences in non-hematologic toxicity. CR rates were not significantly different comparing patients not dose-adjusted to patients with obesity-related adjustments (CR = 86% vs. 67%, p = 0.55). Empiric dose reductions based on obesity did not result in significantly different CR rates.

Evaluation of methylene blue, thiamine, and/or albumin in the prevention of ifosfamide-related neurotoxicity.

SUMMARY: A serious adverse effect that can limit the utility of ifosfamide is neurotoxicity, known as ifosfamide-induced encephalopathy (IIE). Information regarding the usefulness of prophylactic administration of methylene blue, thiamine, and albumin to reduce the incidence of IIE is scarce. We present the results of a retrospective chart review evaluating the incidence of IIE in adult patients who received ifosfamide to treat sarcoma at the University of Washington within a 2-year period. Patients who received methylene blue, thiamine, and/or albumin were compared to patients who did not receive these prophylactic agents concurrently with ifosfamide. The primary objective was to evaluate if prophylaxis is associated with a reduced incidence of IIE. Identifying risk factors associated with IIE was a secondary objective. The cost of using prophylaxis with ifosfamide administration was reviewed. RESULTS: A total of 166 cycles were included. For the primary endpoint, more cycles in the prophylaxis group had patients with symptoms of IIE (21.1% in the prophylaxis group vs. 8.4% in the nonprophylaxis group); p =0.026. The average number of risk factors per cycle was the same in each group; however, the type of risk factors differed. CONCLUSIONS: Prophylaxis was not associated with a reduced incidence of IIE, and it does not appear to delay time to onset of symptoms at our institution. RESULT: of this study provide no support for using methylene blue, thiamine, and/or albumin as routine prophylaxis when administering ifosfamide to adults with sarcoma.

Chronic lymphocytic leukemia: putting new treatment options into perspective.

Chronic lymphocytic leukemia (CLL) is a monoclonal B-cell malignancy that afflicts mainly older individuals. Since many patients are diagnosed in the earliest stages, the course of the disease may be indolent and asymptomatic, requiring no therapy. For those who are diagnosed in advanced stages or whose disease becomes symptomatic, treatment is indicated. Advances in identifying prognostic factors, such as cytogenetics, IgHV mutational status, CD38, TP53, and ZAP-70, are helping physicians better predict who is more likely to have progressive disease and thus needs more frequent monitoring. Some of these prognostic factors are also helping to guide therapy choices as they can predict response to treatment and/or duration of response. Recent advances in treatment options have moved beyond traditional management with alkylating agents and purine analogs into regimens combining these two chemotherapy classes with monoclonal antibodies targeting CD20. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) has become the most effective therapy option to date for CLL. Compared with fludarabine and cyclophosphamide, FCR has shown higher complete response rates and longer progression-free survival. Bendamustine, a unique alkylating agent with purine analog properties, has recently been approved by the FDA for treatment of CLL and provides a new alternative to existing therapies. Initial trials combining bendamustine with rituximab are showing promise for both untreated and relapsed/refractory disease. Other agents recently approved and/or being tested, such as ofatumumab, flavopiridol, and lenalidomide, are demonstrating activity in the relapsed setting.

Identification of genes with abnormal expression changes in acute myeloid leukemia.

Acute myeloid leukemia (AML) is one of the most common and deadly forms of hematopoietic malignancies. We hypothesized that microarray studies could identify previously unrecognized expression changes that occur only in AML blasts. We were particularly interested in those genes with increased expression in AML, believing that these genes may be potential therapeutic targets. To test this hypothesis, we compared gene expression profiles between normal hematopoietic cells from 38 healthy donors and leukemic blasts from 26 AML patients. Normal hematopoietic samples included CD34+ selected cells (N = 18), unselected bone marrows (N = 10), and unselected peripheral bloods (N = 10). Twenty genes displayed AML-specific expression changes that were not found in the normal hematopoietic cells. Subsequent analyses using microarray data from 285 additional AML patients confirmed expression changes for 13 of the 20 genes. Seven genes (BIK, CCNA1, FUT4, IL3RA, HOMER3, JAG1, WT1) displayed increased expression in AML, while 6 genes (ALDHA1A, PELO, PLXNC1, PRUNE, SERPINB9, TRIB2) displayed decreased expression. Quantitative RT/PCR studies for the 7 over-expressed genes were performed in an independent set of 9 normal and 21 pediatric AML samples. All 7 over-expressed genes displayed an increased expression in the AML samples compared to normals. Three of the 7 over-expressed genes (WT1, CCNA1, and IL3RA) have already been linked to leukemogenesis and/or AML prognosis, while little is known about the role of the other 4 over-expressed genes in AML. Future studies will determine their potential role in leukemogenesis and their clinical significance.