Manual differential cell counts help predict bacterial infection. A multivariate analysis.

We developed logistic regression models that combine information from the automated CBC and manual 100-cell differential counts to predict bacterial infection. The logistic models were fitted from a case group of 116 patients with proven bacterial infection and a control group of 930 presumably uninfected outpatients. A 4-variable, 15-parameter model, which includes automated absolute neutrophil, manual band, and manual immature granulocyte counts, performed best with a receiver operating characteristic (ROC) curve area of 89%. A more practical 2-variable model including automated absolute neutrophil and manual band counts performed almost as well with an ROC curve area of 86%. The automated neutrophil count-only model is less informative with an ROC curve area of 78%. The combined information from automated and manual differential cell counts more accurately predicts bacterial infection than automated counting alone. Despite these modest improvements, the high cost of manual differential cell counts dictates careful patient selection. The supplemental information gained from manual differential counts is most useful for patients with low to normal neutrophil counts (8,000/microL [8.0 x 10(9)/L] or less). Further studies are indicated to determine the characteristic patient populations deriving maximal benefit from this information.

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.