End points to establish the efficacy of new agents in the treatment of acute leukemia

Abstract

IntroductionDuring 2006, nearly 16 000 people will be diagnosed with acute leukemia in the United States and despite many important advances in diagnosis and therapy, the majority will die of their disease. 1 Acute myeloid leukemia (AML), which accounts for 75% of acute leukemias, is a disease predominantly of adults with a median age at diagnosis of 68 years and a 75% overall mortality. 2 The mortality rate of AML is highly age related with 5-year survival of approximately 50% in children, approximately 30% in adults younger than age 60, and less than 5% in those over age 60 years. 3-5 Acute lymphocytic leukemia (ALL) comprises approximately 25% of acute leukemia cases. Two thirds of ALL cases occur in children who have, on average, cure rates approaching 85% with contemporary therapy. 6 The prognosis is poorer for adults, with a cure rate of approximately 35% in those aged 20 to 60 years, but only 5% in those older than 60 years. 7 Thus, acute leukemia in adults and children represents a spectrum of diseases ranging from those with a very poor prognosis, such as AML in older patients, to diseases such as childhood ALL where cure rates are high. However, even for those subtypes with high cure rates, the "cost" of cure may be substantial with short-and long-term side effects. Therefore, new agents are needed to extend survival, improve cure rates, and avoid undesired treatment-related toxicities.

Prognostic Factors in Elderly Patients with AML and the Implications for Treatment

“…59 Phase 2 data support the use of allogeneic HSCT with a nonmyeloablative, reduced-intensity conditioning regimen for elderly patients with AML in first CR. 60 However, the applicability of this postremission therapy to older patients remains to be seen.…”

Non-intensive treatment with low-dose 5-aza-2′-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients

“…As the older patients often have no sibling donor, bridging time to donor identification is very important. 2 With non-intensive therapy, patients may receive outpatient management and thus need not lose their fitness during this period.…”

“…Thus, innovative approaches are urgently needed to bridge time to transplantation. 2 Recently, non-intensive treatment with low-dose azanucleosides has been developed for older patients with higher-risk MDS. 3,4 Low-dose azanucleosides show a particularly interesting activity in inducing cytogenetic remissions in MDS patients with chromosome 7 abnormalities and other poor-risk cytogenetics.…”

Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation

“…1 In 20% to 30% of the AML patients, mutations in the Flt3-receptor tyrosine kinase (Flt3-RTK) occur, leading to internal tandem duplications in the juxtamembrane domain of the receptor (FLT3-ITD). 2,3 FLT3-ITD dictates a particularly poor clinical outcome.…”