Prognostic Impact of Time from Diagnosis to Initial Chemotherapy for Acute Myeloid Leukemia
Authors: Kamoda Yoshimasa , Hangaishi Akira , Hayashida Hiroki , Uchibori Yusuke , Iizuka Hiromitsu , Kida Michiko , Usuki Kensuke 
Published: October 2019

Abstract
Background: Acute myeloid leukemia (AML) has been considered as oncologic emergency and therefore, immediate initiation of chemotherapy is common in clinical practice. On the other hand, waiting until cytogenetic and molecular results return could offer individualized therapies according to the risk stratifications of AML based on cytogenetic or molecular abnormalities. There are few data on the impact of delaying induction chemotherapy on the prognosis of AML. According to one study, time from diagnosis to initial treatment (TDT) of more than 5 days had adverse impact on younger AML patients, but not older patients (Sekeres et al. Blood 2009). Another study showed TDT had no impact on overall survival (OS) at all age (Bertoli et al. Blood 2013). We retrospectively analyzed the impact of TDT on outcome of newly diagnosed AML patients in our institution.
Methods: This study included 145 newly diagnosed non-M3 AML patients who were treated with induction chemotherapy in our institution between 2008 and 2017. Patients received various kinds of induction therapy including anthracycline, cytarabine, azacitidine and investigational drugs as initial therapy. Associations of TDT with patient characteristics available at diagnosis and complete remission (CR) rate and OS were examined.
Results: The median age was 66 years (range, 18-88) and the median TDT was 1 day (range, 0-91). Cytogenetic risk group was favorable in 13 (9%), intermediate in 93 (64%) and adverse in 39 (27%) according to Medical Research Council cytogenetic classification. NPM1 mutation was detected in 11 of 38 (29%) evaluable patients and FLT3-ITD was in 8 of 45 (18%). Shorter TDT was significantly associated with progressive disease including younger age, poor performance status, de novo AML, elevated white blood cell (WBC) count, elevated percentage of bone marrow blasts, elevated lactate dehydrogenase levels (all P < 0.05). CR rate was 52% and median OS was 431 days. TDT had significant impact on CR rate (P = 0.004) but not OS (P = 0.978). However, after adjustment for age, cytogenetic risk groups and WBC count, the association with both CR rate and OS was not significant (P = 0.581 and P = 0593, respectively). Furthermore, TDT was not associated with early death in univariate analysis (p = 0.186).
Conclusion: TDT is significantly associated with progressive disease, but not with outcome in newly diagnosed AML. These results suggest that, except for special situations, delaying initial treatment by a short period of time to wait for the results of laboratory tests may be acceptable, allowing for individual therapies. To verify the prognostic effect of TDT, further investigation in a larger cohort is required.
Disclosures: No relevant conflicts of interest to declare.

Disclosures
Usuki: Ono Pharmaceutical: Speakers Bureau; Novartis: Speakers Bureau; SymBio Pharmaceuticals Limited.: Research Funding; Pfizer Japan: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding; Boehringer-Ingelheim Japan: Research Funding; Sumitomo Dainippon Pharma: Research Funding, Speakers Bureau; GlaxoSmithKline K.K.: Research Funding; Janssen Pharmaceutical K.K: Research Funding; Celgene Corporation: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding; Shire Japan: Research Funding; Takeda Pharmaceutical: Speakers Bureau; Chugai Pharmaceutical: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Nippon Shinyaku: Speakers Bureau; Mochida Pharmaceutical: Speakers Bureau; MSD K.K.: Speakers Bureau.