A novel effective and safe consolidation for patients over 60 years with acute myeloid leukemia: intermediate dose cytarabine (2 x 1 g/m2 on days 1, 3, and 5).

PURPOSE: High-dose intermittent cytarabine is an effective postremission treatment for patients with acute myeloid leukemia (AML). This regimen is a safe approach in patients < 60 years but produced severe neurotoxicity in the elderly. EXPERIMENTAL DESIGN: We have established a dose-reduced age-adapted consolidation using intermediate dose (IDAC; 2 x 1 g/m(2) i.v., days 1, 3, and 5) for AML patients >/= 60 years. Forty-seven de novo AML patients in complete remission (CR; median age, 70 years) were scheduled to receive four consolidation cycles of IDAC. RESULTS: In 25 of 47 patients (53%), all four cycles were administered: 9 (19%) received three cycles; 7 (15%) received two cycles; and 6 patients (12%) one cycle. Treatment was well tolerated without neurotoxicity. The median number of days with severe neutropenia (absolute neutrophil count < 500/microl) was 9. Neutropenic fever occurred in 22 of 47 patients (49%) during the first cycle, in 24 of 41 (60%) during the second, in 15 of 34 (44%) during the third, and in 18 of 25 (72%) during the fourth cycle. Only 1 patient died during consolidation (cardiac failure). The median overall survival, disease-free survival, and continuous CR were 10.6, 15.5, and 15.9 months, respectively. The probability of overall survival, disease-free survival, and continuous CR at 5 years were 18, 22, and 30%, respectively. CONCLUSIONS: IDAC is a safe and effective postremission therapy for elderly patients with AML.

The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination.

Bone marrow cells of 325 adults with acute leukemia were immunophenotyped using a panel of monoclonal antibodies proposed by the European Group for the Immunological Characterization of Leukemias (EGIL). Of these, 97.2% could be assigned clearly to myeloid or lymphoid lineage (254 acute myeloid leukemias [AMLs], 48 B-cell lineage acute lymphoblastic leukemias [ALLs], 14 T-cell lineage ALLs), 1.8% as biphenotypic, and less than 1% as undifferentiated. Immunologic subtyping of ALLs revealed an association between early precursor phenotypes and coexpression of myeloid antigens, particularly CD15/CD65s coexpression and pre-pre-B cell-specific phenotypes and genotypes. The common ALL phenotype was associated with BCR-ABL translocation. Among AMLs, CD2 coexpression was almost exclusively restricted to French-American-British subtypes M3 variant and M4Eo and related molecular aberrations. The most valuable markers to differentiate between myeloperoxidase-negative AML subtypes M0 and ALLs were CD13, CD33, and CD117, typical of M0, and intracytoplasmic CD79a, intracytoplasmic CD3, CD10, and CD2, typical of B cell- or T cell-lineage ALL. Our results confirm excellent practicability of the EGIL proposalfor immunologic classification of acute leukemias. For myeloperoxidase-negative AMLs, we suggest a scoring system based on markers most valuable to distinguish between AML-M0 and ALLs.

Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients.

Published recommendations for the optimal dosing regimen of ceftazidime in critically ill patients with continuous venovenous haemofiltration (CVVH) differ. The aim of this prospective study was to analyse the pharmacokinetic and pharmacodynamic parameters of ceftazidime during CVVH with a high-flux polysulphone membrane, and derive a dosage recommendation. Twelve critically ill patients (five female, seven male) with acute renal failure undergoing CVVH using a 0.7 m(2) polysulphone high-flux membrane were investigated. All patients received ceftazidime 2 g i.v. q8h. Peak ceftazidime concentrations were 58.2 +/- 11.6 mg/L, with trough concentrations 14.0 +/- 3.2 mg/L at the arterial port. The elimination half-life, haemofiltration clearance, volume of distribution and total removal were 4.3 +/- 0.6 h, 32.1 +/- 7.9 mL/min, 36.4 +/- 6.4 L and 74.5 +/- 6.5%, respectively. Based on these pharmacokinetic parameters and that maximal killing is at 4 x MIC we recommend at least ceftazidime 2 g i.v. q8h.