Remission Induction with Cladribine, Cytarabine and Idarubicin (CAI) in Elderly Patients with Relapsed AML - A Pilot Study.

Elderly (>55 years) patients with relapsed acute myeloid leukemia (AML) generally have a poor prognosis mainly due to a low rate of 2^nd complete remission (CR). Commonly, salvage therapy consists of regimens including fludarabine. However, results have been disappointing and the efficacy of fludarabine in AML is questionable. In contrast, there is evidence that 2CdA, another purine analogue, has single drug activity in AML as well as enhancing the effect of other cytostatic drugs such as ARA-C. Here we present data from a pilot study evaluating CAI: Cladribine (2CdA) in addition to cytarabine (ARA-C) with idarubicin (Ida) as a salvage therapy in relapsed AML.

Patients and Methods: Two treatment protocols were tested from May 2005 to May 2006 at our institution:

• 2CdA 5 mg/m²/12 h, d 1–5, ARA-C 1000 mg/m²/12 h, d1-5 and Ida 12 mg/m²/d, d1-3

• 2CdA 5 mg/m²/12 h, d 1–3, ARA-C 1000 mg/m²/12 h, d1–3 and Ida 8 mg/m²/d, d1–3.

Results: Nine patients were included in the study after written informed consent. Eight of them are evaluable to date. Three patients received protocol A (median age 57 years), whereas 5 received protocol B (median age 65 years). Although one patient died during neutropenia and one patient had refractory disease, response after one cycle of CAI was favourable in 6 patients: 4 achieved CR and 2 CR with incomplete regeneration (response rate 75%). Of those, 3 patients went on to receive further consolidation therapy with a second cycle of CAI, one with ARA-C/Ida and one with 2CdA/ARA-C. Toxicity was predominantly neutropenia with subsequent infectious complications: median duration of neutropenia was 28 days (IQR 22–34) with all patients experiencing febrile neutropenia (median duration 8 days IQR 3–9) and 4 episodes of septicemia. The second course of CAI resulted in an even longer duration of neutropenia: 37 days (IQR 16–50) with all patients having septicaemia. Of the 6 responding patients 2 died subsequently, one of a second relapse and the other of neutropenic sepsis after the 2^nd course of CAI. The other 4 patients are still alive (follow-up 4 months to 1 year).

Next steps: Because of these promising results we decided to pursue the study but change the protocol as follows:

1. Patients will only be treated according to protocol B,

2. application of growth factors from day 15 onwards will be mandatory,

3. antibiotic prophylaxis with a chinolone and twice weekly Cotrimoxazole will be mandatory and

4. a second cycle will omit idarubicin.

Conclusion: Combination therapy with cladribine, cytarabine and idarubicin appears to be feasible and successful in elderly patients with relapsed AML. However, infections are a serious complication warranting intensive supportive care.