Waiting a short period of time for laboratory results to better characterize acute myeloid leukemia (AML) and design therapeutic approaches is a reasonable strategy, researchers in Toulouse, France, found after a retrospective review of 599 newly diagnosed AML patients treated by induction chemotherapy. The researchers studied the impact of time from diagnosis to treatment on overall survival, early death, and response rate and reported their results in the journal Blood. Other factors considered were pretreatment characteristics at diagnosis (such as age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, and secondary AML) and white blood cell (WBC) and platelet counts.
In multivariate analysis, time from diagnosis to treatment had no impact on overall survival (P = .4095) as compared to age older than 60, secondary AML, white blood cell count higher than 50 g/L, European LeukemiaNet risk groups, and ECOG performance status. Moreover, time from diagnosis to treatment was not associated with response rate or early death, the researchers reported.
The investigators noted that AML is very heterogeneous and while the morphologic diagnosis of AML can be done in a few hours, the results of cytogenetic tests can take a week or longer. “Thus, there is a dilemma between the potential benefit of genetically targeted therapy early at diagnosis and the risk of delaying the initiation of chemotherapy,” the authors stated. “This fear has been recently addressed by two North American centers in a retrospective study showing that the time from diagnosis to treatment independently predicted survival in younger but not older patients,” the researchers wrote. In that study by Sekeres et al (Blood 113:28-36, 2009), response rate and overall survival worsened after a treatment delay of 5 days. “On the basis of these results,” the current investigators noted, “it is commonly admitted that treatment of younger AML patients should be started with minimal delay.”
Acknowledging that their results differ, the French researchers noted that they found much less secondary AML (20% vs 45%) in both younger and older patients. “The other main difference resides in the chemotherapy regimen,” the investigators stated. “For induction therapy, we have invariably used daunorubicin (180 mg/m2) or idarubicin (40 mg/m2) in combination with standard-dose cytarabine. In contrast, induction chemotherapies were variable in the Sekeres study with several modalities of cytarabine administration, compounds other than anthracyclines (such as topotecan, cyclophosphamide, or clofarabine) used in combination with cytarabine, and no description of the dose of daunorubicin, which is crucial for complete response and overall survival. Lastly, we have no information on the modalities of consolidation therapies and the proportion of patients receiving allogeneic stem-cell transplantation,” the researchers added.
“It is unlikely that a randomized trial addressing the effect of [time from diagnosis to treatment] would be undertaken. Therefore, studies from other centers relating their own experience are needed,” the researchers concluded. “Since personalized therapies based on genetic features of AML are going to be developed, it is fundamental to have a clear vision of the impact of [time from diagnosis to treatment] on the outcome of AML patients. Although AML remains an oncologic emergency, our study suggests that, except for specific conditions, it does not seem unreasonable to wait for specialized laboratory tests in order to better characterize leukemias and design new therapeutic strategies.” ■
Bertoli S, et al: Blood, January 30, 2013 (early release online).