AML in Israel: Younger Age at Diagnosis Does Not Improve Prognosis.

AML is generally considered a disease of the elderly, with a mean age of diagnosis in the Western world is approximately 60 years of age or older. Important prognostic parameters include: age, karyotype and new molecular markers (NPM1 and FLT3). Treatment in a tertiary care facility also may improve survival. We elected to examine these parameters and the long term outcome of AML patients (pts) treated in our institution which is an academic tertiary care center, among the largest in Israel.

We reviewed clinical data on pts with AML (de novo and secondary) treated at Hadassah in the years 1992-2009. Karyotype was determined by conventional cytogenetics and FISH analysis or molecular analysis when appropriate. Good prognosis karyotype was considered to include t(8;21), t(15;17) and inv16. FLT3 ITD (internal tandem duplications) and NPM1 analysis was determined on all pts for whom DNA was available, using PCR and either acrylamide gel electrophoresis (FLT3) or melting point analysis (NPM1). Kaplan Meier analysis determined duration of survival. Statistical significance was determined using Log rank and Chi square test, with significance set at a level of p<0.01.

293 patients were included, of which 236 (80%) had de novo AML and 57 (19.5%) had secondary AML, either following an antecedent hematological disease (AHD) such as MDS (n= 32, 11%) or therapy related AML (t-AML) (n=25, 8.5%). Our standard protocol for AML includes 7+3 induction and high dose Ara-C consolidations. Bone marrow transplantation (BMT), either allogeneic or autologous, is performed in high risk cases depending on donor availability. The mean age at diagnosis of the 293 pts was relatively young (all pts= 47.7±18.3 yrs; de novo AML= 45.6±17.6 yrs; secondary AML= 56.2±18.6 yrs; t-AML= 48.6±16.6 yrs). Mean age at diagnosis for Arab pts was 44.2±16.7, as compared to Jewish pts (49.4±18.6). For de novo AML Arab pts, mean age at diagnosis was 43.3±16.4 as compared to de novo Jewish pts (46.9±18). The male to female ratio was 60/29 (2.06) for Arab pts and 99/102 (0.97) for Jewish pts, 53/25 (2.12) and 80/78 (1.02) for de novo Arab and Jewish pts respectively. In the de-novo AML group, 58 (24%) had a good prognosis karyotype. In the entire group of pts, 108 (37%) had normal karyotype and 62 (21%) had FLT3 ITD. Of the 108 normal karyotype pts, 34 (31%) were found to have FLT3 ITD, and 17 (16%) were found to harbor NPM1 mutations; of the NPM1 positive patients, 12 (70%) were FLT3 ITD negative. Treatment with intention to cure was administered to 218 (92%) of the de novo AML and 36 (63%) of the secondary AML pts. Other pts received best supportive care. Eighty six (29%) pts underwent allogeneic BMT and 12 (4%) underwent autologous BMT. The 5 year survival was 35% and the 10 year survival was 17% with no difference between Arabs and Jews. Good prognosis karyotype significantly improved survival as did younger age, and absence of FLT3 ITD.

We conclude that in our institution, the median age of diagnosis of AML is more than two decades younger than that reported in literature. The reason for this may be demographic or related to environmental exposures such as smoking. The preponderance of male Arab pts is most likely due referral bias. The young age of the Arab male pts may be due to occupational or environmental exposures, such as smoking. Our treatment protocols and supportive care are similar to those used in Western countries. Despite these factors, survival was not as good as might be expected according to age, karyotype and FLT3 ITD status. Further studies are needed to elucidate the etiology of these findings.

No relevant conflicts of interest to declare.