Factors Affecting Long-Term Survival in Non-Transplanted Acute Myeloid Leukemia Patients.

Background: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of haemopoetic progenitor cells that can occur at any age but is most common in adults. Patients with AML are usually treated with combinations of chemotherapy and survial can be increased by allogenic hematopoietic stem cell transplantation (HSCT) in the intermediate and adverse cytogenetic risk groups. Few patients in these risk groups are long term survivors without HSCT. In order to study factors that are associated with long-term survival without HSCT, we performed a single center study on non-transplanted patients with disease-free survival more than two years.

Methods: Non-transplanted AML patients alive and in CR at least two years after diagnose (survival group (S)) were compared to non-transplanted patients that died within two years of the AML diagnose (non-survival group (non-S)). The data collected were age, gender, months with AML, hemoglobine, white blood cells, platelets, peripheral blast cells and percentage of blasts in the bone marrow at the time of diagnose, FAB classification, karyotype, mode of treatment, infectious complications such as Hepatosplenic candidiasis (HSC). All patients were diagnosed with AML at The Hematology Center, Karolinska University Hospital in Huddinge from 1997 to 2007.

Results: Of a total of 425 patients, only 18 patients were non-transplanted patients that could be assigned to the the S group.There were 94 persons in the control non-S group. There was a statistically significant difference in the gender distribution with more women in the S group than in the non-S group 89% versus 54% (p=0.02) and the average age was 61 years in the S group and 69 years in the non-S group (p=0.02). All the patients in the survival group had received intensive induction treatment compared to 59 (63%) patients in the non-S group. The patients not receiving intensive chemotherapy, received either substancially decreased doses of chemotherapy, including palliation, or decreased amount of days of chemotherapy. As expected, more patients in the S group had a favouble cytogenetic karyotype, 4 patients (22%) compared to 4 patients (4%) in the non-S group. Two patients in the S group had an adverse cytogenetic karyotype and these patients were 24 and 36 months from diagnose, repsectievely. Surprisingly, patients with HSC, considered to be a severe complication of AML and AML treatment, were significantly more frequent in the survival group 4 patients compared to 2 patients in the non-S group (p= <0.005). The diffrences in gender and HSC were still present when patients with favouble cytogenetic karyotype were excluded. Also when excluding patients who survived more then 60 days in the non-S group, and thus has the chance to develop HSC, the differences remained. Although, being a small study where the results need to be confirmed in a larger patient group, the results suggest that intensive chemotherapy is a prerequisite for long-term disease-free survival and that female gender is a good prognostic factor in these AML patients. Concerning the role of HSC for survival, more data is needed. from larger studies. However, our data supports the idea that the occurrence of HSC does not confer a worse prognosis in non-transplanted AML patients, and there may even be a association with improved survival. Possible reasons for this association may be immunologic activation by the fungal infection or interindividual differences in the pharmacokinetics of the chemotherapy agents, resulting in an association between higher drug concentrations, long neutropenia, fungal infections and improved antileukemic effect.