Time Elapsed From AML Diagnosis to Induction Chemotherapy Affects Overall Survival
Authors: Pelloso Luis Arthur F. , Rohr Sandra Serson , Yamamoto Mihoko , Chauffaille Maria de Lourdes L. F. 
Published: October 2019

Abstract
Abstract 4262
AML is a heterogeneous group of genetically diverse hematopoietic malignancies arising from blood cell progenitors and is considered an oncologic emergency. Patients present prognostic characteristics (specifically karyotype and age) that influence OS. Substantial progress achieved in AML therapy includes early chemotherapy initiation, aggressive large broad antibiotic usage, early antifungal prescription, RBC and platelet transfusions, HSCT, and development of new drugs. Most published AML data are from developed countries and only a few are from emergent ones in which the overall context is distinct. We aimed to study the effect of elapsed time from AML diagnosis to treatment (TDT) on OS in a group of patients from public Hospital Sao Paulo, Brazil. 41 consecutively AML patients were selected (23 males and 18 females, median age: 41 yrs, range 18 – 84 yrs) from Jan 1st, 2001 to Mar 31st, 2004 and last contact was on Jul 24th, 2011. AML diagnosis was set according to WHO classification and by G-banding karyotype (ISCN, 2009). Cytogenetic risk classification categories were adapted from MRC (Grimwade et al). Patients were treated with 3+7 daunorubicin (45mg/m2/d/3d), APL patients received ATRA-based regimen (Ruutu et al). Kaplan-Meier and student t-test were used.

Results:
38 were de novo AML and 3 secondary, median pretreatment WBC was 9.1/μ L (range 0.5–240/ μ L), median TDT was 6 days (range 1–82 d); 26 patients were young (<60yrs) and 15 old (>60 yrs). Cytogenetic risk distribution was: favorable 20.7%; intermediate 27.6%; unfavorable 27.6% and no metaphases 27.6%. 20 patients achieved CR (48.7%): 61.5% in the young group and 26.6% in the old. Median survival was 26.8 weeks (figure 1), 33 weeks for the young group and 10.7 weeks for the old (p =0.034). No statistical differences were found in Hb, WBC and platelet count among groups. Young patients tended to be treated earlier than old ones (TDT 4 days vs 11, p=0.07). An inverse correlation was seen in TDT with age, leukocyte, CR and OS. Longer TDT (> 10 d) was associated with worse CR rates (p=0.02) and OS (p=0.04). When patients were categorized into TDT from 1–4 d (I) vs > 5 (II), those from I presented better OS than II (p=0.004). When TDT was longer than 7 days OS decreased even more. Hb was higher in patients with TDT I vs II (8.3 vs 7.5 g/dL, p=0.03) but WBC (p=0.34) and platelet count (p=0.75) were not different. Patients with TDT of 10 d were younger than TDT >10 d (median age 41 vs 70 yrs, p=0.001). For the entire AML cohort OS was 15.1% in 2 yrs and 8.6% in 7 yrs.

Discussion:
The results showed that less than half of the patients reached CR. Younger patients presented better CR than elderly and this is similar to other series (Appelbaum et al; Juliusson et al). Despite chemotherapy regimen younger patients presented poorer OS compared to Northern Hemisphere series (Juliusson G et al). Several reasons account for such results: poorer PS, delayed diagnosis and bleeding and infectious complications. Elderly patients who were treated presented dismal OS and notably a median TDT almost three times longer than younger. Reasons for a longer TDT in AML were: significant comorbidities, severe infectious complications, and delay to start chemotherapy due to logistics reasons and the need to involve caregivers and family members to aid in decision making process. With more comorbidity in elderly population, reluctance toward intensive therapy is common and probable medical decision is critical with this.Therefore measures to shorten the TDT should be taken: address rapid AML diagnosis, evaluate and treat comorbidities, and develop a supportive and continuous system to promote early AML diagnosis and prompt treatment. Our data suggest longer TDT, when analyzed continuously, predicted for lower CR rates and OS rates therefore we need to address identify factors and start therapeutic measures to aid decision making and improve OS in AML patients in our country.

Disclosures:
No relevant conflicts of interest to declare.