Recurrent Adult Acute Myeloid Leukemia
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
No standard regimen exists for the treatment of patients with relapsed acute myeloid leukemia (AML), particularly in patients with a first remission duration of less than 1 year.[1]
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A number of agents have activity in recurrent AML.[2,3] A combination of mitoxantrone and cytarabine was successful in 50% to 60% of patients who experienced relapse after initially obtaining a complete remission.[4] Other studies using idarubicin and cytarabine or high-dose etoposide and cyclophosphamide reported similar results.[3,5,6,7] Mitoxantrone, etoposide, and cytarabine (MEC) demonstrated a complete remission induction rate of 55% in a population including 30 patients with relapsed AML, 28 patients with primary refractory AML, and 16 patients with secondary AML.[8][Level of evidence: 3iiiDiv] However, in a phase III Eastern Cooperative Oncology Group (ECOG) (E-2995) trial of MEC with or without PSC388, a multidrug resistance modulator, complete response was only 17% to 25% in a population including relapse at less than 6 months after first complete remission, relapse after allogeneic or autologous bone marrow transplantation, second or greater relapse, primary induction failures, secondary AML, and high-risk myelodysplastic syndromes.[9][Level of evidence: 1iiDiv] Thus, treatments with new agents under clinical evaluation remain appropriate in eligible patients with recurrent AML.[10]
The immunotoxin gemtuzumab ozogamicin has been reported to have a 30% response rate in patients with relapsed AML expressing CD33. This included 16% of patients who achieved complete responses and 13% of patients who achieved a CRp, a new response criteria defined for this trial. CRp refers to clearance of leukemic blasts from the marrow, with adequate myeloid and erythroid recovery but with incomplete platelet recovery (though platelet transfusion independence for at least 1 week was required). Unclear is whether the inadequate platelet recovery is due to megakaryocyte toxic effects of gemtuzumab or to subclinical residual leukemia. The long-term outcomes of patients who achieve CRp following gemtuzumab are not yet known. Gemtuzumab induces profound bone marrow aplasia similar to leukemia induction chemotherapy and also has substantial hepatic toxic effects, including hepatic venoocclusive disease.[11,12] The farnesyltransferase inhibitor tipifarnib (R115777) demonstrated a 32% response rate in a phase I study in patients with relapsed and refractory acute leukemia (two complete responses and six partial responses in 24 patients treated) and has entered phase II trials.[13] Clofarabine, a novel purine nucleoside analogue, induced complete remissions in 8 out of 19 patients in first relapse as a single agent [14] and in 7 out of 29 patients when administered in combination with intermediate-dose cytarabine.[15][Level of evidence: 3iiiDiv]
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