Impact of Dose-Adjusted Melphalan in Obese Patients Undergoing Autologous Stem Cell Transplantation.

Limited guidance exists for dosing melphalan for autologous stem cell transplantation (ASCT) in the obese patient population, because the current literature reports conflicting clinical outcomes between obese and nonobese patients. In 2014, the American Society for Blood and Marrow Transplantation published conditioning chemotherapy dosing guidelines for obese patients and recommended dosing of melphalan using actual body weight (ABW) in the body surface area calculation. The practice at Barnes-Jewish Hospital has consistently been to dose melphalan using adjusted body weight (AdBW), with a 20% correction when a patient weighs ≥120% of his or her ideal body weight (IBW). The purpose of this study was to compare outcomes of melphalan ASCT in patients with multiple myeloma between obese (≥120% IBW) and nonobese (<120% IBW) populations. This retrospective, single-center study included adult patients with multiple myeloma undergoing first ASCT with melphalan conditioning between January 2009 and December 2012. Patient demographic data, transplantation characteristics, and clinical outcomes were collected. The primary outcome was 3-year event-free survival (EFS). Secondary outcomes included response at 100 days post-transplantation, 3-year overall survival, treatment-related mortality (TRM), time to neutrophil engraftment, and hospital length of stay (LOS). To ensure that melphalan dosage adjustment in the obese population did not impact efficacy, the primary outcome was assessed using a noninferiority design, with a predetermined noninferiority margin of 7%. Assuming a 70% 3-year EFS in the nonobese population, a noninferiority margin of 7%, a power of 80%, and an α value of .05, an analysis of 280 patients was required. A total of 270 patients, including 171 (63%) obese patients and 99 (37%) nonobese patients, met our inclusion criteria. Baseline characteristics were well matched between the 2 cohorts, including high-risk cytogenetics, disease severity at diagnosis, and use of maintenance therapy, with the only detectable differences related to weight itself. The 3-year EFS was 41% for the total cohort, with fewer events occurring in the obese cohort compared with the nonobese cohort (51% versus 40%; P = .0025). The 95% lower confidence limit established noninferiority. High-risk cytogenetics, disease severity at diagnosis, and therapy response pre- and post-ASCT were all associated with significantly shorter EFS. No between-group differences in TRM, time to engraftment, or hospital LOS were noted. This retrospective, single-center study found that using AdBW to dose melphalan in obese patients was not inferior to the nonobese population in terms of 3-year EFS. This study adds to the limited evidence on melphalan dosing and suggests that transplantation efficacy is not affected by AdBW dosing in obese patients. Further studies are needed to provide additional insight into the pharmacokinetic differences and best dosing practices for obese patients.

Olanzapine Reduces Chemotherapy-induced Nausea and Vomiting Compared With Aprepitant in Myeloma Patients Receiving High-dose Melphalan Before Stem Cell Transplantation: A Retrospective Study.

INTRODUCTION: Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan. PATIENTS AND METHODS: We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint. RESULTS: The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant. CONCLUSION: Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.

Effect of Linezolid on Hematologic Recovery in Newly Diagnosed Acute Myeloid Leukemia Patients Following Induction Chemotherapy.

OBJECTIVE: Assess the effects of linezolid on hematologic outcomes in newly diagnosed patients with acute myeloid leukemia (AML) following induction chemotherapy. DESIGN: Single-center, retrospective, observational, cohort study. SETTING: Large, tertiary care academic medical center. PATIENTS: A total of 225 patients ≥ 18 years admitted between December 2010 and 2013 with newly diagnosed AML were assessed for inclusion. Patients were identified through the use of ICD-9 codes and chemotherapy ordered via the computerized physician order entry system. Sixty-eight patients met inclusion criteria and were grouped into two arms based on antimicrobial treatment: LZD group (linezolid plus gram-negative antimicrobial, n=21) or control group (vancomycin or daptomycin plus gram-negative antimicrobial, n=47). INTERVENTIONS: The LZD group received linezolid ≥ 72 hours. The control group received vancomycin or daptomycin ≥ 72 hours. If patients switched extended gram-positive therapy, they were included in the LZD group as long as they had received ≥ 72 hours of linezolid. MEASUREMENTS/RESULTS: The primary end point of time to neutrophil recovery was not statistically different (28 days for LZD group vs 26 days for control group; p=0.675). The preplanned subgroup analysis of patients who received ≥ 14 days of linezolid demonstrated statistically similar median times to neutrophil recovery (29 days for LZD group vs 26 days for control group; p=0.487). Total duration of extended gram-positive antimicrobial therapy was significantly longer in the LZD group (27 days vs 16 days; p<0.001). Secondary end points not found to be statistically significant included platelet count at time of neutrophil recovery, duration of neutropenia, and length of hospital stay. CONCLUSIONS: There were no significant differences in hematologic outcomes in newly diagnosed AML patients who received linezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia.

Long-term treatment with temozolomide in malignant glioma.

Six months of maintenance temozolomide (TMZ) following concurrent TMZ chemotherapy and radiation therapy has become the standard of care in the treatment of glioblastoma. In addition, TMZ has also been used to treat other forms of glioma although less evidence of efficacy exists. TMZ administration longer than 6months is common in clinical practice, but it is unusual for the drug to be administered longer than 1 to 2years. We report five patients who received long-term treatment with TMZ chemotherapy at normal dosing levels. One of these patients was diagnosed with glioblastoma, two with anaplastic astrocytoma, one with gliosarcoma, and one with oligo-astrocytoma. The length of treatment in our group of patients ranged from 45 to 85 cycles of TMZ. Common Terminology Criteria for Adverse Events (CTCAE) developed by The National Cancer Institute was used to classify toxicity. Two patients experienced no toxicity per CTCAE guidelines. One patient experienced grade I thrombocytopenia, one developed grade I leukopenia, and one experienced both grade I thrombocytopenia and grade I nausea, all which resolved with either withholding TMZ for 1month or supportive treatment. Our report provides evidence that long-term TMZ chemotherapy is a therapeutic option when appropriately monitored.

The reversal of inhibitors in congenital hemophilia.

Hemophilias A and B are heritable bleeding disorders characterized by deficient baseline levels of factor VIII (fVIII) and factor IX (fIX), respectively. Standard treatment for acute bleeding events and for prophylaxis in patients with severe disease consists of recombinant fVIII and fIX infusions. The development of alloantibodies, or inhibitors, is a serious complication of congenital hemophilia that may impair the effectiveness of fVIII and fIX, leading to increased morbidity and cost of therapy. When inhibitors are present, bypassing agents such as recombinant activated factor VII and factor eight inhibitor bypass agent are available for treatment of bleeding events. Although usually effective, they are costly treatments. Immune-modulatory therapy may reverse inhibitors, allowing fVIII and fIX to be used again. Immune tolerance induction is the chief treatment option to decrease inhibitor levels, but about 20-30% of patients fail this treatment. Alternatively, multiple immune-modulating agents have been tried with limited success. Rituximab, an anti-CD20 monoclonal antibody, is one therapy that has been successful in reducing inhibitor titers in multiple case reports. Although current evidence is limited and questions regarding its use and place in therapy still exist, this agent shows promise for the future.

Emergency pharmacist impact on health care-associated pneumonia empiric therapy.

PURPOSE: Health care-associated pneumonia (HCAP) is a serious infection dependent on proper treatment that often presents in the emergency department (ED) and deviation from treatment guidelines appears to be high. This study was conducted to evaluate the impact of emergency medicine pharmacists (EPhs) on adherence of empiric antibiotic therapy to guideline recommendations. METHODS: A retrospective chart review of adult patients with HCAP who presented to an academic medical center ED from September 1, 2008 to June 30, 2010 was conducted. The control group included those patients with HCAP who presented to the ED outside of the EPhs' hours (23:00-13:00), and the treatment group consisted of those patients who presented during the EPhs' hours (13:00-23:00). RESULTS: The 81 patients presenting inside the EPhs' hours were significantly more likely to receive guideline adherent empiric antibiotics than the 70 patients presenting outside the EPhs' hours (49.38% vs 25.7%, P = .005). Also, patients in the treatment group received antibiotics in a shorter amount of time (11.37 vs 15.56 hours, P = .272) and at more appropriate doses (85.2% vs 77.1%, P = .29) although these outcomes were not statistically significant. CONCLUSION: The presence of the EPh significantly increased the likelihood of at-risk patients receiving empiric antimicrobial therapy consistent with guideline recommendations.