Abstract
Introduction: Interim disease evaluation and its timing during induction chemotherapy (day 14 or day 21) for patients with acute myeloid leukemia (AML) remains controversial. It has been suggested that failure to achieve complete remission (CR) at day 21 is associated with a poor prognosis. Nonetheless, the significance of persistent disease and the need for an early double induction is questionable.
Methods: We performed a retrospective single center study at the American University of Beirut Medical Center, Lebanon, approved by the institutional review board, to evaluate the early response to induction chemotherapy in patients with AML, assessing the significance of residual disease at day 21 and its impact on progression free and overall survival (PFS and OS respectively). Consecutive patients with newly diagnosed (N=48) or recurrent AML (N=4), excluding acute promyelocytic leukemia, treated over an 8 year period (2008-2016), with available post induction bone marrow evaluation at day 21 were included (Table 1). Medical records for enrolled patients were reviewed to identify the morphological/molecular assessment of the bone marrow at presentation and then at day 21 post induction, in addition to significant outcomes including mortality and risk of relapse.
RESULTS: We identified a total of 52 patients over the specified period. The median age at diagnosis was 49.5 (range 18-74). 26 patients (50%) had an abnormal karyotype, out of which 6 patients had a complex karyotype. 34 patients (65 %) achieved morphological remission at day 21 with <5% blasts on bone marrow evaluation, while 18 patients had residual/progressive disease. All patients did not receive re-induction chemotherapy before day 28. 7 patients or around 39% of those with early residual disease later achieved complete remission by day 28. There was a mild increase in the risk of relapse/progression in those with early residual disease (HR 1.2, p-value<0.05), but no statistically significant increase in terms of in-hospital mortality, taking into account that only 2 patients died during hospitalization for induction therapy, both of whom had residual disease at day 21. Risk of death at last follow up was slightly higher among those with residual disease at day 21 (HR 1.3, p-value <0.05). However, a statistically insignificant improvement in PFS/OS was noted in those achieving early remission.
CONCLUSION: Early residual disease post induction chemotherapy for AML does not appear to be a significant prognostic indicator. Disease evaluation should thus be individualized, since many patients with residual blasts ultimately achieve CR by day 28 without the need for re-induction therapy. Larger prospective studies are needed to confirm the need and significance of day 21 marrow evaluation, and those who would benefit from it for prognostic and therapeutic indications.
No relevant conflicts of interest to declare.
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