Epidemiological studies in de novo and secondary acute leukemia

Abstract Background Acute leukemia (AL) is a rare blood cancer with poor prognosis in adult patients. Socioeconomic factors are known to impact cancer outcomes, but have not been adequately examined among adult AL patients. Acute myeloid leukemia (AML) secondary to another myeloid malignancy, irradiation or chemotherapy (s-AML), constitutes a quarter of AML patients and is considered to confer a poor prognosis. Still, population based characterization of s-AML is scarce, and the role of allogeneic hematopoietic cell transplantation (a-HSCT) in s-AML is poorly studied. The main aims of this thesis were: i) Investigate the incidence and survival of adult AL in regions with major socioeconomic differences (Estonia and Western Sweden) during a quarter of a century.ii) To in depth explore s-AML regarding incidence and prognostic factors. iii) Elucidate role for stem cell transplantation in s-AML in a large population-based setting. Method We have analysed all adult patients in the Swedish Acute Leukemia Registry, and comparable Estonian data. Results and conclusion The conclusion is that during 1982-2006, relative survival for Estonian elderly AL patients has gradually improved and almost equals Western Sweden. However, few patients live after five years. For AL patients under 65, relative five-year survival has increased from almost zero to approximately 20% for Estonian, and from 20 to 55% for Swedish patients during our 25-years study. We conclude that socioeconomic differences have a major impact on survival for AL, especially in younger patients. S-AML constitutes approximately 25% in a large population-based setting, and has a striking impact on survival in younger AML patients (<65 years), whereas less prognostic value among the elderly.In a nationwide population-based Swedish setting, there is virtually no long-term survival in patients with s-AML without hematopoietic transplantation. A-HSCT was superior to conventional chemotherapy in secondary AML patients, and should be considered for all eligible patients at diagnosis

Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML

Age but not Philadelphia positivity impairs outcome in older/elderly patients with acute lymphoblastic leukemia in Sweden

ObjectivesOlder/elderly patients with acute lymphoblastic leukemia (ALL) are poorly represented in clinical trials. MethodsUsing Swedish national leukemia registries, we investigated disease/patient characteristics, treatment choices, outcome, and the impact of an age-adapted protocol (introduced in 2009) in this population-based study of patients aged 55-85years, diagnosed with ALL 2005-2012. ResultsOf 174 patients, 82% had B-phenotype, 11% Burkitt leukemia (excluded), and 7% T-phenotype. Philadelphia chromosome positivity (Ph+) occurred in 35%. Of the 155 B- and T-ALL patients, 80% were treated with intensive protocols, and 20% with a palliative approach. Higher age and WHO performance status 2 influenced the choice of palliation. Intensive, palliative, and both approaches resulted in complete remission rate 83/16/70% and 3-year overall survival (OS) 32/3/26%. The age-adapted protocol did not improve outcome. With intensive treatment, platelet count 35x10(9)/L and age 75years were adverse prognostic factors for OS, Ph+ was not. Male sex was an adverse prognostic factor in the 55-64 year age-group. ConclusionsWe report a high frequency of Ph+ in older/elderly patients, with no evidence of poorer outcome compared to Ph-negative disease. Overall prognosis for elderly patients with ALL remains dismal, despite the use of age-adapted treatment