Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia

Abstract

Summary:Stem cell transplantation (SCT) may be the only curative option for patients with relapsed or refractory leukaemia, that is, high-risk (HR) leukaemia. Several salvage regimens have been used to cytoreduce disease before SCT, but disease progression or treatment toxicity limits numbers of patients receiving SCT. Here, we report our experience with high-dose cytarabine and amsacrine (Araamsa) to salvage patients with HR-leukaemia in the context of SCT. A total of 34 patients with HR-leukaemia (20 AML, 12 ALL, two advanced CML) received 3 g/m 2 / day cytarabine for 5 days and amsacrine 200 mg/m 2 /day for 3 days. Disease response was observed in 62% of patients. Toxicity was limited to neutropenic fever, one patient developed cerebellar toxicity and there was one treatment-related death. A total of 17 patients proceeded to SCT (12 allografts and five autografts). Median survival (OS) of all patients was 10.8 months (95% CI 7.8-21). Patients who were consolidated with SCT after salvage therapy had a superior median OS of 29.4 months (95% CI 12.5-upper limit not reached, n ¼ 17) than those who did not receive SCT (6.7 months, CI 1.5-8.6, Po0.0001). Median disease-free survival with SCT (23 months) was higher than after treatment with salvage chemotherapy alone (6.7 months, P ¼ 0.0002). Thus Araamsa can be used effectively to salvage HR-leukaemia, enabling further consolidation with SCT.

Biology and management of relapsed acute myeloid leukaemia

“…Nor is there evidence that altering the schedule of re‐induction therapy (timed‐sequential therapy) is of value (Yin et al , 2001). A number of small studies have shown encouraging results with combinations of high‐dose Ara‐C and amsacrine (Jehn & Heinemann, 1990; MacCallum et al , 1993; Tauro et al , 2003) and this regimen requires further validation in phase 3 studies. The benefit of P‐gp inhibition in patients with relapsed AML remains controversial.…”

Amsacrine combined with etoposide and methylprednisolone is a feasible and safe component in first‐line intensified treatment of pediatric patients with high‐risk acute lymphoblastic leukemia in CoALL08‐09 trial

“…In addition, amsacrine in combination with etoposide and high-dose methylprednisolone was used as salvage therapy for relapsed and refractory ALL with moderate treatment-related morbidities. [8][9][10][11][12][13] Based on these results, we introduced amsacrine, etoposide, and high-dose methylprednisolone as a new add-on treatment element for primary high-risk ALL.…”

“…Amsacrine demonstrated promising efficacy in mostly adult patients with refractory acute myeloid leukemia (AML) when combined with etoposide or cytarabine. In addition, amsacrine in combination with etoposide and high‐dose methylprednisolone was used as salvage therapy for relapsed and refractory ALL with moderate treatment‐related morbidities 8–13 . Based on these results, we introduced amsacrine, etoposide, and high‐dose methylprednisolone as a new add‐on treatment element for primary high‐risk ALL.…”