Feasibility of Outpatient Consolidation Chemotherapy and Toxicity in Elderly Patients with AML.

Consolidation chemotherapy is frequently administered on an outpatient basis in younger AML patients. However, the safety of this maneuver in older patients is unclear owing to increased co-morbidities and declines in performance status (PS) in these patients.

215 newly diagnosed AML patients aged >60 years were referred to Princess Margaret Hospital between 2002 and 2005. Of these, 108 received non-protocol treatments (32 non-intensive experimental therapy, 12 intensive chemotherapy on a study protocol, and 64 palliative therapy). The remaining 107 (50%) received standard induction chemotherapy with curative intent, consisting of cytarabine 100 mg/m²/day CIVI x 7 days and dauorubicin 60 mg/m² IV daily x 3 (3+7). Patients achieving CR were eligible to receive two consolidations, with 3+7 (C#1) followed by mitoxantrone 10 mg/m² daily x 5 plus etoposide 100 mg/m² IV daily x 5 (C#2). All patients underwent cardiac assessment prior to each cycle with MUGA scan. If the ejection fraction (EF) dropped to < 50% or had fallen by >10%, amsacrine (100 mg/m² IV daily x 5) was substituted for the anthracycline. Consolidation was administered on an inpatient or outpatient basis according to physician discretion. Inpatient consolidations were administered to patients judged to have significant co-morbidities and poor PS post-induction, while the remaining patients were given consolidation on an outpatient basis, with twice weekly monitoring until hematologic recovery. Oral antibiotic and antifungal prophylaxis was used. Febrile neutropenia (FN) was treated with inpatient IV broad-spectrum antibiotics.

The median age of patients was 68 years (range, 60-84). 59 of 107 pts (55%) achieved a CR and a further 5 patients a leukemia free state with induction chemotherapy. 55 patients achieving CR proceeded to consolidation therapy on protocol. 38/55 pts. (69%) received C#1 as outpatient; the rate of admission for FN in these patients was 45%. 39/55 pts (71%) went on to receive a second consolidation cycle. Reasons for attrition post-C#1 included medically unfit (6 pts), persistent aplasia (3) and relapse (4). 32/39 (82%) pts received C#2 as outpatient; the rate of admission for FN was 59%. There were no treatment related deaths during consolidation therapy. Among patients proceeding to consolidation, 35/55 (63%) had a significant decline in LVEF during, or at completion of, treatment: >10% drop in LVEF in 31 pts. and LVEF <50% in 17 pts (7 of these to <40%); 24/35 pts received a change in consolidation chemotherapy as a result. At a median follow-up of 11.0 months, 80/107 (75%) have died; the median overall survival (OS) was 11.4 months, 3 year OS for all patients was 20%. For those patients obtaining CR, the median relapse-free survival (RFS) was 8.4 months. There was no significant difference in RFS and OS between patients switched to amsacrine versus those receiving standard protocol (p=0.15 and 0.31 respectively).

We have demonstrated that post-remission consolidation chemotherapy can be safely administered on an outpatient basis in the majority of otherwise medically fit elderly AML patients in CR-1 using this regimen. Approximately one half will require admission for febrile neutropenia, but treatment related mortality is low. Cardiac toxicity with this anthracycline-intensive regimen is significant, and close monitoring of LV function is required. Switching anthracycline drug to amsacrine during post-remission therapy does not appear to adversely affect outcome.

No relevant conflicts of interest to declare.