Survival Outcomes in Patients with Intermediate Risk Acute Myeloid Leukemia: A Single-Center Retrospective Review

Objectives

Acute Myeloid leukemia (AML) is a heterogeneous disease with high morbidity and mortality. These patients can be stratified into favorable, intermediate and adverse-risk groups based on their cytogenetic and molecular profile.

We analyzed the outcomes of the intermediate risk patients in our center to evaluate the results and to report the differences between the intensity of the treatments, chemotherapy alone versus allogeneic stem cell transplantation (SCT).

Methods

A total of 53 patients diagnosed in Hospital Universitari Son Espases between 2012 and 2019 with AML, classified as intermediate risk disease (based on ELN 2017 criteria), and candidates to intensive treatment were analyzed.

Results

The median age at diagnosis was 61 years (range 17-74), 28 males and 25 females. Regarding the diagnosis, almost 50% were AML with mutated NPM1, AML with myelodysplasia-related changes and AML therapy-related.

Thirty percent of the patients had FLT3-ITD mutation (78.6% of them with high ratio). Twenty eight percent had NPM1 mutation. The 75.5% received cytarabine and anthracycline induction chemotherapy and the remaining 24.5% received a combination of cytarabine, anthracycline plus etoposide. Twenty percent of the patients (11) died during the induction therapy, the main of them due to infections. Of the 42 patients alive, 36 (85.7%) achieved a complete remission, 4 a partial response (9.5 %) and 2 patients (4.8%) were refractory. All of the patients went under consolidation: 39 (73.5%) with chemotherapy alone and 14 (33 %) with SCT (4 of them immediately after salvage therapy without hematopoietic recovery). Three patients received a HLA identical sibling SCT (21.4%), 3 a matched unrelated donor (21.4%), 5 (35.7%) an haploidentical SCT, 1 patient (7.1%) a cord blood stem cell transplantation and 2 patients an autologous SCT (14.3%).

The median follow-up of the whole group of patients was 22 months (2.6-86). The median overall survival (OS) was 18 months (CI 95%: 10-25) and the median progression free survival (PFS) was 9 months (CI 95%: 4- 14).

Patients who went under transplantation achieved a PFS of 18.5 months compared with 7.8 months in no transplantation patients (p=0.159).

Patients with non-mutated FLT3-ITD have a median PFS of 14 months compared with 7 months in patients with mutated FLT3-ITD (p=0.333).

Excluding the patients who died during induction therapy, 11 patients with mutated FLT3-ITD went into consolidation therapy. Three received SCT and 8 chemotherapy alone. The median OS of the SCT group was 18.5 versus 13.6 months in the chemotherapy group (CI 95% 4.3-22.9; p=0.4). The median PFS of the SCT group was 6.17 months (CI 95% 2.06-10.3), similar to the chemotherapy group where was 7.6 months (CI 95% 5.03-10.66; p=0.7).

Twenty-eight patients with non-mutated FLT3-ITD received consolidation therapy, 6 of them went into SCT. OS in the transplant group was 46.4 months (CI 95%: 44.6-48.2; p= 0.4) compared with 35.3 months (CI 95%: 11.7- 58.3; p=0.4) in the non-transplantation group. PFS of transplant group was 18.1 month (CI 95%: 9.5-26.22) superior to PFS in chemotherapy group that was 9.4 months (CI 4.65-14; p=0.7).

Patients with mutated FLT3-ITD who did not received an FLT3 tyrosine kinase inhibitor (TKI) had a PFS of 6 months (0-13.8) compared with those that received an FLT3 TKI who did not reach the median survival rate.

Conclusions

Our outcomes are similar to the ones described in the literature. We confirm that patients with intermediate risk who underwent transplantation have better outcomes that the ones treated with chemotherapy alone.

Moreover, we confirm that the prognosis is better in patients with non-mutated FLT3-ITD. SCT increase the OS in FLT 3-ITD mutated patients, although the PFS is similar in both groups (SCT vs chemotherapy), taking into account the small size of our sample and the short follow up period in many patients.

The better outcome observed in FLT3 tyrosine kinase inhibitor treated patients indicates that this can be a promising therapy in AML patients.