Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians.

BACKGROUND: The aim of this study was to evaluate changes in quality of life scores and their association with therapy and survival in unselected elderly patients with acute myeloid leukemia. DESIGN AND METHODS: From February 2003 to February 2007, 113 patients aged more than 60 years with de novo acute myeloid leukemia were enrolled in a prospective observational study. Two different quality of life instruments were employed: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) and a health-related quality of life questionnaire for patients with hematologic diseases (QOL-E). RESULTS: Forty-eight patients (42.4%) received intensive chemotherapy and 65 (57.6%) were given palliative treatments. Age greater than 70 years (P=0.007) and concomitant diseases (P=0.019) had a significant impact on treatment allocation. At diagnosis, general quality of life was affected [median QOL-E standardized score 54, interquartile range 46-70; median EORTC global score 50, interquartile range 41-66]. Most patients were given a good ECOG Performance Status (< 2), which did not correlate with the patients' perception of quality of life. At multivariate analysis, palliative approaches (P=0.016), age more than 70 years (P=0.013) and concomitant diseases (P=0.035) each had an independent negative impact on survival. In a multivariate model corrected for age, concomitant diseases and treatment option, survival was independently predicted by QOL-E functional (P=0.002) and EORTC QLQ-C30 physical function (P=0.030) scores. CONCLUSIONS: Quality of life could have an important role in elderly acute myeloid leukemia patients at diagnosis as a prognostic factor for survival and a potential factor for treatment decisions.

Survivin expression in chronic myeloid leukemia.

In this study, we investigated the expression of survivin (SVV) in 44 patients with typical Ph-positive chronic myeloid leukemia (CML) in different phases of the disease as well as in 20 matched healthy donors. We found a very high SVV expression in a predominant percentage of CML patients. We also observed a significantly increased SVV expression in patients in accelerated/blastic phase of the disease compared to patients in chronic phase. Moreover, SVV expression levels correlated in all CML patients with % of Ph-chromosome positive cells, with Bcr-Abl expression levels and with WBC-count. Based on this finding we suggest that SVV detection and monitoring in CML could represent both a useful biomarker and attractive candidate for devising new targeted and combined therapies in CML.

Flow cytometric detection of aneuploid CD38(++) plasmacells and CD19(+) B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients.

DNA aneuploidy has been used as a genetic marker of malignancy in multiple myeloma (MM). CD38 and CD138 expression and absence of CD22 and CD19 may define plasmacells (PC). Several authors support evidences of circulating plasmacells, and their role in relapse after autologous stem cell transplantation has been hypothesised. The existence of B-lymphocytes belonging to the myeloma clone is still controversial. If CD19 or CD22 positive B-lymphocytes are part of the myeloma clone, there should be evidence of myeloma-specific genetic markers in this population. Using DNA content measurement in combination with CD19 or CD38 detection in a multiparametric flow cytometry analysis, we studied bone marrow and peripheral blood of 10 aneuploid MM patients. In the bone marrows of all these 10 aneuploid patients (100%), we detected CD38(++) aneuploid plasmacells ( 27 +/- 17%, mean +/- S.D.) and a small number of CD19(+) aneuploid lymphocytes ( 0.11 +/- 0.074%). In 100% of these patients, we also detected CD38(++) aneuploid circulating plasmacells ( 0.6 +/- 0.9 %) and a small number of CD19(+) aneuploid lymphocytes (0.03 +/- 0.04%). In this study, we detected aneuploid CD19(+) lymphocytes and CD38(++) plasmacells in bone marrow and peripheral blood of all MM patients. A crucial role for the detection of aneuploid CD19(+) cells was played by the acquisition of a sufficient number of CD19(+) lymphocytes by using a "live gate" acquisition and "continuous gating" analysis. With the techniques used in this study, it was possible to detect aneuploid B lymphoid cells among normal diploid B cells. The significance of this finding is controversial and opened to different interpretations.

Familial B-cell chronic lymphocytic leukemia in a population of patients from Southern Italy.

We investigated the prevalence of chronic lymphocytic leukemia (CLL) in 9650 relatives of 510 CLL patients from 5 different regions (Apulia, Basilicata, Campania, Calabria, and Sicily) of Southern Italy. Data collection included a family history questionnaire. In our series of 510 CLL patients, 53 families with 2 or more individuals who had chronic lymphoproliferative disease (CLD) or other hematological malignancies were identified. In these families, 27 cases of CLL, 10 of indolent non-Hodgkin's lymphoma, and 7 of multiple myeloma were identified in relatives of CLL probands. Twenty-two relatives developed hematological malignancies other than CLD (19, acute leukemia; 3, chronic myeloid leukemia). In this study the prevalence of CLD in relatives of 510 CLL patients was 8.6% (44/510), and the prevalence of CLL in the same series was 5.2% (27/ 510). Considering the presence of clusters of individuals with hematological malignancies, overall our series contained 4 families showing a cluster with more than 2 cases. The most frequent pattern of affected family members was represented by 39 families (39/53 [73%]) with affected siblings or cousins only. Twenty siblings had CLL. The other families showed a multigenerational pattern with an affected parent-offspring relationship in only 11 (21%) of the cases and with a combination of the first 2 categories in 3 (6%) of the families. In 8 families belonging to both the last 2 mentioned groups, the affected offspring had an earlier disease onset than their parents, suggesting anticipation. We estimated the size and examined the pattern of familial aggregation of hematological malignancies, in particular CLL/CLD, in a specific geographical area. CLL was the most frequent disease in relatives, mainly siblings, of our CLL patients. Our results may be a contribution to the characterization of the epidemiological distribution pattern of CLL.

BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B.

The BCR-ABL oncoprotein of chronic myelogenous leukemia (CML) localizes to the cell cytoplasm, where it activates proliferative and antiapoptotic signaling pathways. We previously reported that the combination of the ABL kinase inhibitor imatinib mesylate (IM) and the nuclear export inhibitor leptomycin B (LMB) traps BCR-ABL inside the nucleus, triggering the death of the leukemic cells. To evaluate the efficacy of the combination of IM and LMB on human cells we collected CD34-positive cells from 6 healthy donors and myeloid progenitors from 35 patients with CML. The sequential addition of IM and LMB generated the strongest reduction in the proliferative potential of the leukemic cells, with limited toxicity to normal myeloid precursors. Furthermore, nested reverse transcriptase-polymerase chain reaction (RT-PCR) analysis on colonies representative of each experimental condition demonstrated that the combination of IM and LMB was the most effective regimen in reducing the number of BCR-ABL-positive colonies. The efficacy of the 2-drug association was independent of the clinical characteristics of the patients. Our results indicate that strategies aimed at the nuclear entrapment of BCR-ABL efficiently kill human leukemic cells, suggesting that the clinical development of this approach could be of significant therapeutic value for newly diagnosed and IM-resistant CML patients.

T cell receptor delta-chain gene rearrangement in a novel case of adult NK cell leukemia.

Malignancies arising from natural killer (NK) cells are being increasingly recognized as distinct clinicopathological entities. We here report the characteristics of a peculiar case of NK-cell acute leukemia with unusual agranular morphology and rearrangement of the T-cell receptor (TCR) delta-chain gene.

Multidrug resistance mechanisms in chronic lymphocytic leukaemia.

We evaluated the presence of P-glycoprotein (P-gp)-170, multidrug resistance protein (MRP), lung resistance protein (LRP)-56 and Bcl-2 in CD19-positive cells from 100 cases of chronic lymphocytic leukaemia (CLL). P-gp-170 was found in 73% of the CLL cases with no significant difference regarding stage or previous treatment. LRP-56 protein was homogeneously distributed with no differences for stage or treatment. MRP protein was detected at a low level of expression in 49.4% of CLL patients with no differences for stage or treatment. Bcl-2 protein was expressed at a high level in all CLL patients and higher levels were found in the advanced stage. This leads us to conclude that P-gp, MRP, LRP-56 and Bcl-2 are frequently expressed in CLL. P-gp, MRP and LRP are not correlated to stage or previous treatment. Bcl-2 is higher in advanced-stage patients. The clinical and biological significance of these zMDR mechanisms in CLL remains to be fully explained.