Time Elapsed from AML Diagnosis to Induction Chemotherapy Affects Overall Survival *

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 in Brazil. 41 AML (23 M, 18 F, 41 yrs, 18 84 yrs, from 2001 to 2004). There were 38 de novo AML and 3 secondary, median TDT was 6 days (range 1 82 d); the young ones were treated earlier than old ones (TDT 4 days vs 11, p = 0.07). 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). The OS was 15.1% in 2 yrs and 8.6% in 7 yrs. Our data suggest longer TDT, when analyzed continuously, predicted for lower CR rates and OS rates.


Introduction
Acute Myeloid Leukemia (AML) is a heterogeneous group of genetically diverse hematopoietic malignancies arising from blood cell progenitors.The management of AML represents a significant clinical challenge to haematologists and, although the incidence of the disease is relatively low, the clinical resources needed for its successful management are substantial (including, but not limited to early chemotherapy initiation, aggressive large broad antibiotic usage, early antifungal prescription, red blood cell and platelet transfusions) and consequently it is considered an oncologic emergency.The outcome for patients with AML depends greatly on the age of the patient and leukaemic cell karyotype and therefore different treatment strategies may be appropriate for different sub-groups of patients.To date, other key prognostic factors are FLT3-ITD status and response to induction chemotherapy [1][2][3].Usually, AML patients present at diagnosis with severe infections and other worsening medical conditions that demand prompt treatment [3].Due to AML nature and the need for immediate treatment induction chemotherapy is given simultaneously during medical treatment of other conditions or shortdelayed until life-threatening conditions are treated and medically managed and stabilized.
With regards to the time elapsed from AML diagnosis to the start of induction chemotherapy few new data were published specially in emergent countries in which the overall context is very unique due to limited resources and availability of specialized hematological care [4][5][6][7].In this paper we aimed to study retrospectively the effect of elapsed time from AML diagnosis to treatment (TDT) on overall survival OS in a group of patients from the public academic institution Hospital São Paulo, Brazil.

Material and Methods
Forty-one consecutively AML patients were consecutively studied (23 males and 18 females, median age: 41 yrs, range 18 -84 yrs) from Jan 1st, 2001 to Mar 31st, 2004.Last overall survival assessment was done 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 [1].Patients were treated with 3 + 7 daunorubicin (45mg/m 2 /d/3d), APL patients received ATRA-based regimen [8].The study was approved by the institution ethics committee.Kaplan-Meier and student t-test were used.

Results
Initially fifty-eight consecutive patients were studied.However seventeen patients unfit for intent to treatment chemotherapy due to poor medical conditions and were managed with supportive care onlu (e.g.blood and platelet transfusions, antibiotics, management of medical conditions, hydroxurea in patients with leukcocytosis).

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 [3,5,9,10].Despite chemotherapy regimen younger patients presented poorer OS compared to Northern Hemisphere patient series [3,10].Several reasons may account for such results: poorer performance status at diagnosis, delayed diagnosis (patients could be seen elsewhere or given blood/platelet transfusions in other clinics), and presenting bleeding and infectious complications at diagnosis, advanced disease (severe marrow failure, poor physical reserve).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 in the elderly group were: significant comorbidities, severe infectious complications, and delayed start chemotherapy due to logistics reasons (access to chemotherapy, 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 in this scenario.Thereupon measures to shorten the TDT should be taken: address a 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 that longer TDT, when analyzed continuously, predicted for lower CR rates and OS rates, hence we need to address identify factors and start therapeutic measures to aid decision making and improve OS in AML patients in our country.

Authors and Affiliations
Contribution: LAFP, wrote the paper, analysed data and followed up patients.MLC is in charge of the Leukemia Sector of Hematology Department and oriented treatment and follow up of patients as well as contributed to drawing the study and the paper.MY performed diagnosis, SSR analysed data.

Figure 1 .
Figure 1.Cumulative overall survival in AML patients.