A Comparative Study between Acute Myeloid Leukemia in Adolescent and Young Adults (AYA) Versus Non-AYA Patients: Single Center Experience

BackgroundAcute myeloid leukemia (AML) is considered disease of the elderly, with a median age at diagnosis of 68-70 years. Adolescent and Young Adult (AYA) patients (pts) are defined as patients between 15-39 years of age according to NCCN guidelines. AML represents 33% of hematologic malignancies or in adolescents and young adults (AYA). In our cancer center in Qatar, due to the unique structure of the population, we have a large number of AML cases diagnosed in AYA.

In this retrospective study we compare the clinical characteristics, cytogenetics, molecular prognostic markers, treatments given and outcomes of AML in AYA patients versus non-AYA

Methods We retrospectively analyzed data from the clinical database of our single tertiary hematology center, The National Center for Cancer Care and Research, Doha, Qatar. All patients diagnosed with AML during the period of January 2017 to December 2021 where included and divided into 2 groups, less than 40 years from (15-39) and second group above 40.

Results: The general demographic characteristics and other descriptive outcomes of the study populations (AYA; n =73; older pts , n = 78) are summarized in Table 1. The median age for AYA is 30 years while it was 53.9 years in the older group ( P<0.001). Males were predominant in both group, almost three times more than females (75 % and 78%). Asian are more in the AYA group with 63 % of the patients compared to 33% only in the older age group second to Arab population. At diagnosis, the Complete blood count in AYA versus non-AYA was as follows: a median hemoglobin of 8.5g/dl versus 8.75g/dl, white blood cells of 54 x10^3/uL, versus 36 x10^3/uL in the older group with considerably less platelets count in AYA (62 x10^3/uL) versus 96 x10^3/uL with statistically significant difference (p. 0.016). Non AYA group had lower percentage of blasts both in peripheral blood and bone marrow (BM), 40% and 60 % respectively compared to 60 % and 70% ( P= 0.02). BM was hypercellular in the majority of pts in both groups, while hypocellularity was seen only in 5 cases (8%) of AYA group compared to 10 pts (13%) in non-AYA (P=0.03). BM dysgranulopoiesis was equally reported in 29 patients (40 %) in both groups with no much difference in dyserythropoiesis and dysmegakaryopoiesis. Diploid karyotype was the mmost recurrent cytogenetic finding in both groups, however this was much less in AYA patients (32.8%) compared54 % in non-AYA. Core binding factor (CBF) rearrangements was much more detected in AYA pts, 22/73 pts (28%) compared to 9/78 pts (11%) in non-AYA group ,and the difference was statistically significant (P=0.03) . No difference in FLT 3-ITD positivity between both groups 13/73 pts (22%) in AYA, versus 15/79 (20%) in non-AYA. Similarly, NPM1 mutation was detected in 10/73 pts (17%) in AYA versus 11 pts (15%) in non-AYA. Fludarabine- based regimen (FLAG-Ida) was much more needed as salvage therapy in young group (34% of cases ) compared to only 15 % in the older group. Twenty-three pts of AYA (32%) underwent allogenic BM transplant while only 11/78 pts (15%)in non-AYA (P=0.01).

Within the older age group, the patients who received allogeneic BM transplant had clinically and statistically significant difference in the overall survival (OS) (24 month) compared to 11 months only in the patient with no transplant (p=0.04). Similarly, progression free survival (PFS) was 31 months compared to 13 months for those who didn't have SCT (P. 0.04). AYA group didn't show statistically significant difference between transplant and non- transplant patients in terms of OS (26 months vs 20 month) (p=0.7) or PFS (23 months VS 19 month, p=0.1). The median follow-up duration was 24 months for all groups, while its 11 months for those who were died. The median (OS) was comparable in both groups 23.14 months in AYA and 24.08 months in non AYA (p= 0.09).

Conclusion Large number of patients in our center diagnosed with AML in younger age compared to the international figures. There was no significant difference in most of the variables between the two groups, possible explanation, is that the non-AYA group themselves has median age of 53 years only. However, AYA group had significant higher percentage of CBF mutations, lower platelets count, higher blasts percentage and higher incidence of BM hypocellularity at presentation with statistically significant difference. Non-AYA group showed clear benefit in terms of OS and PFS for patient who received allogenic transplant.

No relevant conflicts of interest to declare.