Prognostic relevance of the FAB morphological criteria in chronic lymphocytic leukemia: correlations with IgVH gene mutational status and other prognostic markers.

Morphological examination is the routine first step in the diagnosis of hematological malignancies, including chronic lymphocytic leukemia (CLL). Atypical cell morphology according to the FAB criteria is known to herald disease progression. Several years ago, it was proposed that FAB morphology at diagnosis had a considerable prognostic impact. However, this proposal has not been widely adopted in practice. Thus we questioned the prognostic value of the morphological examination, which was performed retrospectively in 88 patients out of our 110 institutional registry patients (70 males and 40 females, median age 57 yrs) with CLL at diagnosis. We related the results to the more modern prognostic markers. Atypical FAB morphology was shown to correlate with IgVH gene mutation status, trisomy of chromosome 12 and deletion of 17p detected either by conventional G-banding or by fluorescence in situ hybridization (FISH) analysis. The correlation of FAB morphology with CD38 antigen expression or with the histopathological pattern of bone marrow infiltration was not significant. Overall survival (OS) data were available for 84 morphologically examined patients. The patients with atypical morphology (64 patients) had a significantly shorter OS (103 months) than the 20 patients presenting with typical CLL morphology (237 months; p=0.03). Only the mutation status of IgVH genes correlated more closely with OS (p=0.002). Of note, there was no leukemia-related death within "unmutated" cases who had typical FAB morphology (p=0.14), and vice versa, the mutation status had a significant prognostic impact within the morphologically atypical cases (p=0.01). Thus FAB morphology and the mutation status may yield complementary prognostic information. OS was affected both by the presence of cytogenetic aberrations (p=0.03) - most adversely by deletions of 17p and 11q, and by CD38 expression (p=0.003). We conclude that careful examination of peripheral blood smears according to FAB is a simple, cheap and valuable tool in the first-line assessment of prognosis of CLL patients and should not be overlooked even in 3rd millennium when more sophisticated prognostic markers are at hand. This ought to be confirmed in larger prospective studies with multivariate analysis of data.

[Use of photodynamic therapy for elimination of residual leukemic cells in autologous transplants of hematopoietic progenitor cells]. / Vyuzití fotodynamické terapie k odstranování reziduálních leukemických bunek z autologních transplantátu hematopoetických progenitorových bunek.

BACKGROUND: The increasing use of autologous hematopoietic cell support in various malignancies including leukemia and lymphoma currently bears the problem of tumor contamination of the graft with tumor cells which after re-infusion contribute to the disease relapses. It is therefore desirable to eradicate the cancer cell fraction of the graft without causing damage to the normal stem cell fraction. The purging processes based on photodynamic treatments appear to be perspective means for this purpose. METHODS AND RESULTS: We investigated the effects of 5-aminolevulinic acid (ALA)--based photodynamic treatment (ALA-PDT) on the proliferation of human leukemia cell lines HL60 (promyelocytic leukemia), ML2 (myelomonocytic leukemia) and HEL (erythroleukemia) by 3H-thymidine incorporation into the cell DNA, on the viability of cell lines HL60, HEL, DAUDI (B-cell leukemia) and JURKAT (T-cell lymphoma) as well as of blast cells of acute myeloid leukemia (AML) patients by flow cytometry-propidium iodide assay, and on the clonogenic activities of normal human bone marrow cells by in vitro cloning assays. Under the conditions used (treatment with 1 mM ALA for 4 h at 37 degrees C followed by exposure to blue light dose of 18 J/cm2) the number of proliferating HL60 cells was reduced by 2.4 logs, of ML2 cells by 3.2 logs and of HEL cells by 1 log. From the mononuclear cell preparations of AML patients the blast cells were substantially reduced in eight out of ten patients. The clonogenic activities of normal bone marrow progenitor cells were largely spared: 52.5 +/- 8.9% of colony-forming units--granulocytes macrophages (CFU-GM), and 48.6 +/- 9.7% burst forming units--erythrocytes (BFU-E). CONCLUSIONS: ALA-PDT appears to be usable principle for the depletion of residual leukemic cells from autologous transplants.