Acute Myeloid Leukemia (AML). Diagnosis, Therapy and Outcome Results from Tawam Hospital. a Retrospective Review

Introduction

Acute Myeloid leukemia (AML) is a heterogeneous group of malignant disorders of myeloid hematopoetic cells. These cells have a maturation arrest in different stages of development leading to accumulation of immature cells. This gives rise to the different symptoms and signs of disease secondary to anemia, thrombocytopenia and neutropenia.

The current WHO classification broadly divides AML into 4 main groups based on morphology, immunophenotyping, genetics and clinical features. These include AML with recurrent genetic abnormalities, AML with myelodysplasia related changes; therapy related AML and AML not otherwise specified (NOS).

Therapeutically AML can be divided into 2 main groups; Acute promyelocytic leukemia (APML) and non APML.

Methods

Tawam Tumor registry was searched for patients with diagnosis of AML from January 2010 till December 2012. Patient records were then reviewed and data was collected.

Results

We identified 49 patients with pathologically confirmed diagnosis of AML. 19/49 patients were diagnosed with AML with recurrent cytogenetic, 5/49 with MDS related or therapy related and 25 with AML NOS

Cytogenetic Analysis of this cohort of 49 patients with AML showed that 15 patients (30%) had APML with 15;17 translocation, 4 patients had 8;21 translocation, 5 had complex or poor risk cytogenetic while 13 had normal karyotype. In 12/49 patients Karyotyping failed due to growth failure. Status of FLT3 and NPM1 are not known for the entire cohort.

Demographics

The median age of the cohort was 38 years (range 20 to 84 years). Older adults (age 65 years or more) make a minority of this cohort (8%). Male to female ration was 3.5:1.

Treatment

In patients with Non APML Induction therapy was a combination of Cytarabine and Idarubicin for adults < 65 years of age and with good performance status. Older adults or adults with poor performance status or co-morbidities were either given hypomehtylating agents, Clofarabine or supportive care. Patients achieving complete remission (CR) were given consolidation with High Dose Cytarabine (HIDAC) as per CALGB protocol. Only a minority of patients were able to go for allogeneic stem cell transplantation in CR1

Patients with APML were treated with ATRA, Idarubicin/Mitoxantrone and Cytarabine as per PETHEMA protocol on a risk adjusted plan. This was followed by 2 year maintenance with ATRA, 6 MP and Methotrexate.

Outcome of Treatment

In non APML patients 62 % (17) achieved CR with induction therapy. Induction therapy failure was observed in 18 % (5) while there were 5 early deaths observed (during aplasia). 7 patients were treated with hypomethylating agents or best supportive care. Only 1patient was able to achieve CR (after cycle 4 of 5-azacitidine). Consolidation therapy was given to 17 patients achieving CR. With a median follow up of 15 months (range 9-24 months) 9 patients are alive and disease free while 17 patients have been lost to follow up. 8 out of these 17 patients were in remission at their last follow up.

In APML patients the CR rate was 93%. There were no cases of induction failure and only 1 case of early death (7%) due to hemorrhage. With a median follow up of 17 months (range 11-41 months) 11 patients are in molecular CR while 3 have been lost to follow up.

Conclusion

This is the first analysis of patients who were diagnosed with AML in a tertiary care center in UAE. The results show that the median age of patients our cohort is low as compared to international reports (approximately 38 vs. 65 years). Older adults (> 65 years of age) make only a minority of the AML cohort in Tawam Hospital. Response to induction therapy is comparable to international standards (60-80%) for AML and > 90% for APML.

We also report a twofold higher incidence of APML as compared to internationally reported data (30% vs.12%). This has a very significant diagnostic and therapeutic impact on the management of AML patients at our institute leading to increase vigilance and institution of ATRA at the earliest clinical suspicion of APML.