Core binding factor acute myeloid leukemia: the impact of age, leukocyte count, molecular findings, and minimal residual disease.

PURPOSE: Most patients with acute myeloid leukemia (AML) and genetic rearrangements involving the core binding factor (CBF) have favorable prognosis. In contrast, a minority of them still have a high risk of leukemia recurrence. This study investigated the adverse features of CBF AML that could justify investigational therapeutic approaches. PATIENTS AND METHODS: One hundred and fifty patients (median age 42 yr, range 16-69) with CBF AML (RUNX1-RUNX1T1 n = 74; CBFB-MYH11 n = 76) were prospectively enrolled into two consecutive CETLAM protocols at 19 Spanish institutions. Main clinic and biologic parameters were analyzed in the whole series. In non-selected cases with available DNA samples, the impact of molecular characterization and minimal residual disease (MRD) was also studied. RESULTS: Overall, complete remission (CR) rate was 89% (94% in ≤50 yr old and 72% in >50 yr, P = 0.002). At 5 yr, cumulative incidence of relapse (CIR) was 26 ± 1%, disease-free survival (DFS) 62 ± 6%, and overall survival (OS) 66 ± 4%. In multivariate analyses, leukocyte count above 20 × 10(9) /L, BAALC over-expression, and high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy (CT) led to increased relapse rate. Regarding OS, age >50 yr, leukocyte count above 20 × 10(9) /L, and increased MN1 expression were adverse features. CONCLUSION: Age, leukocyte counts, BAALC, and MN1 gene expressions as well as high copy numbers of RUNX1-RUNXT1 or CBFB-MYH11 after induction chemotherapy are useful tools to predict the outcome and should be considered for risk-adapted therapy.

Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab).

BACKGROUND: The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity of human immunodeficiency virus (HIV)-positive and HIV-negative patients with BL who were treated in an intensive immunochemotherapy-based and age-adapted trial. METHODS: A total of 118 adult patients (80 HIV-negative and 38 HIV-positive) aged 15 to 83 years were treated with 4 (nonbulky stages I-II) or 6 (stages II bulky, III-IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years. RESULTS: The clinical characteristics of HIV-positive patients were comparable with those who were HIV-negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow-up of 2.5 years, nonsignificant differences were observed in the 4-year disease-free survival and overall survival (OS) probabilities (77% and 63% for HIV-positive and 80% and 78% for HIV-negative patients, respectively). Young HIV-infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%. CONCLUSIONS: Age-adapted intensive immunochemotherapy is highly effective in both HIV-negative and HIV-positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival.

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases

Objetivo Investigar los factores de riesgo de mortalidad en pacientes con zigomicosis. Pacientes & Métodos Revisión retrospectiva de pacientes diagnosticados de zigomicosis documentada en 17 centros en España, comparando los datos demográficos y los factores de riesgo entre los pacientes que sobrevivieron y aquellos que fallecieron. Resultados Se identificaron 25 pacientes con zigomicosis probada. El lugar primario de la infección fue rino-órbito-cerebral (28%) e infecciones diseminadas o cutáneas / de tejidos blandos en el 20% de los pacientes cada una. Once pacientes (44%) recibieron tratamiento antifúngico anticipado o empírico; de estos pacientes, cuatro de ellos recibieron anfotericina B liposomal, un paciente recibió anfotericina B complejo lipídico y 6 pacientes recibieron otros antifúngicos. La tasa de mortalidad global fue del 72%. En el análisis univariado, los factores asociados a un mayor riesgo de muerte fueron la presencia de enfermedad hematológica maligna (p=0,03), neutropenia (p=0,03) y monocitopenia (p=0,008).Conclusión Los datos de nuestro estudio concuerdan con los de trabajos previos que habían documentado una elevada tasa de mortalidad en pacientes con zigomicosis invasiva, especialmente en aquellos con enfermedad hematológica maligna subyacente, y la necesidad de instaurar rápidamente un tratamiento antifúngico eficaz (AU)

Aim: To investigate mortality risk factors in patients with zygomycosis. Patients and Methods: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. Results: We identified twenty-five patients with proven zygomycosis. The primary site of infection wasrhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P = .03), neutropenia (P = .03) and monocytopenia (P = .008).Conclusion: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment (AU)

Mortality risk factors in patients with zygomycosis: a retrospective and multicentre study of 25 cases.

AIM: To investigate mortality risk factors in patients with zygomycosis. PATIENTS AND METHODS: Retrospective case history review of patients diagnosed with proven zygomicosis in 17 centres in Spain. We compared demographics and risk factors in patients who survived, and in those who died. RESULTS: We identified twenty-five patients with proven zygomycosis. The primary site of infection was rhino-orbito-cerebral (28%) and disseminated (20%) or cutaneous/soft infections (20%) of the patients. Eleven patients (44%) received preemptive or empirical antifungal treatment; of these patients, 4 received liposomal amphotericin B, 1 received amphotericin B lipid complex, and 6 received other antifungals. The overall mortality rate was 72%. In the univariate analysis factors associated with an increased risk of death were the presence of a haematological malignancy (P=.03), neutropenia (P=.03) and monocytopenia (P=.008). CONCLUSION: Our study supports previous research that has documented a high mortality rate among patients with invasive zygomycosis, especially among those with an underlying haematological malignancy, and the need for a rapid initiation of an effective antifungal treatment.

Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis of studies to evaluate the diagnostic accuracy of expression of CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection. METHODS: The analysis included studies of patients from all age groups that prospectively evaluated CD64 expression on PMNs for the diagnosis of bacterial infection. We evaluated the methodological quality of the studies according to the 25-item criteria developed by the Standards for Reporting of Diagnostic Accuracy (STARD) committee. We calculated a summary receiver operating characteristic (SROC) curve across studies included in the meta-analysis. RESULTS: The methodological quality score of the 13 included studies ranged from 9 to 16 points (maximum score was 25 points). The pooled sensitivity and specificity for CD64 expression on PMNs were 79% (95% CI: 70-86%) and 91% (95% CI: 85-95%), respectively. The area under curve (AUC) was 0.94. CONCLUSIONS: On the basis of this meta-analysis, CD64 expression on PMNs could be a useful diagnostic cell-based parameter of bacterial infections. However, published studies about this topic showed a low methodological quality.

Evaluation of low platelet counts by optical, impedance, and CD61-immunoplatelet methods: estimation of possible inappropriate platelet transfusion.

BACKGROUND: The Cell-Dyn Sapphire (Abbott Diagnostics) detects platelets (PLTs) with a CD61 monoclonal antibody directed against glycoprotein IIIa as well as impedance (IMP) and optical (OPT) technology. We decided to evaluate low PLT counts produced by IMP and OPT methods and to compare them with the CD61 method. We also examined the possibility of inappropriate PLT transfusion resulting from an inaccurate PLT count. STUDY DESIGN AND METHODS: We analyzed consecutive blood samples with OPT PLT counts of less than 50 x 10(9)/L. We performed the PLT count with the OPT, IMP, and CD61 methods and we compared the number of prophylactic PLT transfusion indications according to the PLT counts determined by the OPT and IMP methods with the number of prophylactic PLT transfusion indications according to our reference CD61 method. RESULTS: We collected 135 samples. In the bias analysis, the OPT method and the IMP method showed higher PLT counts when compared with the CD61 method (mean of difference 1.69 x 10(9) and 19.1 x 10(9)/L, respectively). We saw overtransfusion in 1.5% of cases and undertransfusion in 15.2% of cases (p = 0.01; McNemar's test) when we selected a threshold of 10 x 10(9)/L with the OPT method. We saw undertransfusion in 22.2% of cases (p = 0.03; McNemar's test) when we selected a threshold of 5 x 10(9)/L with the OPT method. CONCLUSIONS: Low PLT counts determined by the OPT and IMP methods showed some disagreement when compared with the CD61 method. This disagreement caused both PLT undertransfusion and overtransfusion.

Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia.

Current prognostic factors for acute myeloblastic leukemia (AML) are not sufficient to accurately predict the group of patients in the intermediate-risk category who will successfully respond to treatment. Distinct patterns of inherited functional genomic polymorphisms might explain part of these heterogeneous prognoses. We used the allelic discrimination method to identify polymorphisms in GSTT1, SULT1C2, CDA, SXR (drug metabolic pathways), XPD, XPA, XPG, ERCC1, TOP2A (DNA repair), VEGF (angiogenesis), and MDR1 (multidrug resistance) genes in 110 adult patients with intermediate-risk AML, enrolled in the CETLAM-99 prospective trial. A multivariate prognostic model adjusted for age, white blood cell (WBC) count, French-American-British group, cytogenetics, MLL rearrangement, internal tandem duplication of FLT3 (FLT3-ITD), induction courses to achieve complete remission, and germline polymorphisms, was used to detect independent risk factors associated with clinical outcome. This analysis showed an increased risk of refractoriness to chemotherapy in the group of patients with XPA variant alleles (RR = 14; P = .02). In the same model, increased relapse risk was associated with SULT1C2 heterozygosity (RR = 4.1; P = .004), FLT3-ITD (RR 3.3; P = .003), and MDR1 variant alleles (RR = 2.4; P = .02). Adverse prognostic variables for overall survival were XPA (RR = 3.4; P = .02) and MDR1 (RR = 2.1; P = .02) variant alleles, and WBC count (RR = 2.1; P = .02). These findings might be useful in selecting risk-adapted treatment strategies in intermediate-risk AML.