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.

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia.

The interaction of acute myeloid leukemia (AML) blasts with the leukemic microenvironment is postulated to be an important mediator of resistance to chemotherapy and disease relapse. We hypothesized that inhibition of the CXCR4/CXCL12 axis by the small molecule inhibitor, plerixafor, would disrupt the interaction of leukemic blasts with the environment and increase the sensitivity of AML blasts to chemotherapy. In this phase 1/2 study, 52 patients with relapsed or refractory AML were treated with plerixafor in combination with mitoxantrone, etoposide, and cytarabine. In phase 1, plerixafor was escalated to a maximum of 0.24 mg/kg/d without any dose-limiting toxicities. In phase 2, 46 patients were treated with plerixafor 0.24 mg/kg/d in combination with chemotherapy with an overall complete remission and complete remission with incomplete blood count recovery rate (CR + CRi) of 46%. Correlative studies demonstrated a 2-fold mobilization in leukemic blasts into the peripheral circulation. No evidence of symptomatic hyperleukocytosis or delayed count recovery was observed with the addition of plerixafor. We conclude that the addition of plerixafor to cytotoxic chemotherapy is feasible in AML, and results in encouraging rates of remission with correlative studies demonstrating in vivo evidence of disruption of the CXCR4/CXCL12 axis.

Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients.

STUDY OBJECTIVE: To describe the characteristics and clinical outcomes of hematopoietic stem cell transplant (HSCT) recipients who received adjunctive cytomegalovirus intravenous immune globulin (CMV-IVIG) for probable or proven CMV disease. DESIGN: Retrospective cohort study. SETTING: Large, university-affiliated, tertiary-care medical center. PATIENTS: Thirty-five adult HSCT recipients who received at least one dose of CMV-IVIG for adjunctive treatment of probable or proven CMV disease between January 1, 1999, and December 31, 2007. MEASUREMENTS AND MAIN RESULTS: All-cause mortality at hospital discharge was the primary outcome. All patients received an allogeneic HSCT. Twenty-six patients (74%) had pneumonitis, nine (26%) had enteritis, and 29 (83%) had CMV viremia. All patients received concomitant antiviral therapy; 31 (89%) received ganciclovir, and 14 (40%) received foscarnet. All-cause mortality at hospital discharge was 49% (17 patients). Patient characteristics associated with mortality included requiring intubation for CMV pneumonia (11 [79%] of 14 nonsurvivors vs 3 (25%) of 12 survivors, p=0.016) and earlier disease onset after HSCT (median 48 days for nonsurvivors vs 106 days for survivors, p<0.001). In the multivariate analysis, only requiring intubation for CMV pneumonia remained a significant risk factor for increased mortality. A low rate of adverse events was attributed to CMV-IVIG, with mild hypertension (two patients [6%]) and erythema and chills (one patient [3%]) being the most common. CONCLUSION: The mortality rate in our study population was similar to previous reports in the literature and may be somewhat lower than rates reported with antiviral monotherapy. Our analysis suggests that factors associated with mortality include the need for intubation and, possibly, earlier onset of CMV disease after HSCT. Treatment with CMV-IVIG appears to be well tolerated in HSCT recipients. These findings support further trials of CMV-IVIG efficacy in this setting.

Assessment of an alternative meropenem dosing strategy compared with imipenem-cilastatin or traditional meropenem dosing after cefepime failure or intolerance in adults with neutropenic fever.

STUDY OBJECTIVE: To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia. DESIGN: Retrospective, single-center cohort study. SETTING: 1250-bed urban academic medical center. PATIENTS: One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively. CONCLUSION: The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.