Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience.

The Swedish population-based acute myeloid leukemia registry contains data from 3251 patients (excluding acute promyelocytic leukemia) diagnosed between 1997 and 2006. Informative cytogenetic data from 1893 patients were retrospectively added, including 1054 patients aged between 60 and 79 years. Clonal abnormalities were found in 57% of the informative karyotypes. Karyotypic patterns differed by age: t(8;21), inv(16) and t(11q23) were more common in younger patients, whereas loss of 5q, 7q and 17p, monosomal karyotype (MK) and complex karyotypes were more common in older patients. Loss of 5q, 7q and 17p often occurred together within MK. Patients with 5 chromosome abnormalities had worse overall survival than those with fewer abnormalities or normal karyotype in all age groups. Loss of 5q, 7q and/or 17p had, in contrast to MK, a further negative impact on survival. Multivariable Cox regression analyses on risk factors in patients <80 years with cytogenetic abnormalities and intensive treatment revealed that age and performance status had the most significant impact on survival (both P<0.001), followed by sex (P=0.0135) and a karyotype including -7/del(7q) (P=0.048).

Activation of granulocytes in patients treated with chemotherapy.

It is well known that patients with granulocytopenia due to chemotherapy are susceptible to life-threatening infections. To determine whether or not granulocyte function is also impaired by chemotherapy, respiratory burst, CD11b and CD18 expression were analysed by flow cytometry in granulocytes from 10 patients with haematological malignancies: before and after the commencement of high-dose chemotherapy and in the recovery phase. As a comparison, the same granulocytic functions were analysed in patients treated with low-dose hydroxyurea and in healthy volunteers. The granulocytes were activated by Staphylococcus aureus and Staphylococcus epidermidis. A decreased ability to mobilize CD18 in the recovery phase was seen, but the significance of this finding must be evaluated carefully owing to the small patient number.

Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells.

Topoisomerase IIalpha (topo IIalpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.