Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk.

Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age ≥60 years compared to <60 years. One year survival was 100% among favorable NCCN risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p < 0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that associated with age ≥60 years (HR 2.2). We conclude that IAC is an effective AML induction regimen, NCCN leukemia risk predicts survival better than age in our population, and high intensity regimens can be justified in selected older patients.

Efficacy and Toxicity of Induction Therapy with Cladribine, Idarubicin, and Cytarabine (IAC) for Acute Myeloid Leukemia.

We report our single-center experience with cytarabine and idarubicin for induction therapy for acute myeloid leukemia (AML) with an additional 5 days of cladribine (IAC therapy). From July 2012 to September 2014, 38 patients completed a full course of IAC induction. Median patient age was 61 years, 61% of patients were ≥60 years old, and 71% were male. The complete remission (CR) rate was 63% following a single induction course, three patients (8%) required a second induction course to achieve CR, for an overall response rate of 71%. The median duration of severe neutropenia was 30.5 days. Thirty-two percent of patients developed mucositis, 76% experienced diarrhea, and 61% developed a rash. Incidence of CR following IAC induction therapy for AML was comparable to historical data, but with frequent diarrhea, rash, and fungal infections. This study found IAC efficacy and toxicity was similar irrespective of age.

Intra-CSF administration of chemotherapy medications.

Leptomeningeal carcinomatosis is a devastating complication of cancer and is likely increasing in incidence. The combination of widespread neuro-axial spread based on CSF flow and the blood-brain barrier (BBB) has favored immediate local delivery of antineoplastic agents. With the BBB, the leptomeninges can be a sanctuary site to systemic cancers and goal of therapy includes preventing involvement in this space. Current therapies with U.S. Food and Drug Administration (FDA) approval are limited to treat hematologic cancers. Although lacking FDA guidance, a wider array of therapies is available to treat solid tumors. We provide an updated examination on both well-established intra-CSF chemotherapies as well as agents having limited data, but reports of therapeutic benefit.