Myelodysplastic features and myeloperoxidase (MPO) deficiency have been investigated in a series of 336 cases of de novo acute myeloid leukemia (AML) to clarify their impact on the outcome of such patients and to compare with the previous results from the literature. Dysplastic features were defined according to the FAB criteria. Trilineage disease (TLD) was observed in 11.6% of patients (39 cases), and the complete remission rate (CR) was 56.4% for TLD patients compared to 74.4% for patients without any dysplastic features (p = 0.03). The effects of dysgranulopoiesis (DysM) alone or in combination were assessed using a logistic regression analysis. This analysis revealed that only DysG had any effect on CR rate (p = 0.013). The CR rate for patients with DysG was 56.6% and 71.5% for patients without DysG. We were unable to find any correlation between MPO deficiency, dysplastic features and CR rate. Cytogenetic analysis could be assessed for 119 patients. For patients with DysG, 10 karyotypes were normal and 20 were abnormal compared to 48 normal and 41 abnormal for patients without DysG (p = 0.05). We conclude that the presence of DysG in de novo AML exerts a negative effect on the ability to achieve a CR and is related to a higher frequency of cytogenetic abnormalities.
"In this case the second leukaemia has no clonal relation to the first leukaemia. However, at the initial diagnosis of APL (the first leukaemia ) our case showed myelodysplastic changes in the background myelopoiesis which are seldom seen in APL (Brito-Babapulle et a1, 1987; Goasguen et al, 1992). This fact supports another hypothesis that the MDS clone coexisted with APL, and chemotherapy was effective in ablating the APL clone, but clonal haemopoiesis of MDS remained and then took advantage over the APL clone and eventually transformed to AML as M1. "
"Although AML/TLD is thought to be de novo AML and different from the leukaemias that evolve from myelodysplastic syndromes (MDS) or secondary leukaemia in which morphological dysplasia is often seen, little is known about the biological significance of the trilineage dysplasia (TLD) of mature haematopoietic cells in de novo AML. Several groups have reported on the clinical features of AML/TLD, but cytogenetic findings of AML/TLD have not been fully investigated yet and would provide further important biological information (Brito-Babapulle et al, 1987; Estienne et al, 1990; Goasguen et al, 1992; Kuriyama et al, 1994). In this study, we analysed the karyotypes of de novo AML registered on the Japan Adult Leukaemia Study Group (JALSG)-AML92 trial (Miyawaki et al, 1999) and compared the data between AML/TLD and non-TLD. "
[Show abstract][Hide abstract] ABSTRACT: Acute myeloid leukaemia (AML) with trilineage dysplasia (AML/TLD) is de novo AML recognized by the morphological dysplasia of three mature cell lines in the presence of leukaemic blasts. We studied the karyotypes of AML/TLD of patients with de novo AML, except for those with the French-American-British classification M3, who were enrolled onto the Japan Adult Leukaemia Study Group (JALSG)-AML 92 trial. Morphological and cytogenetic analyses were performed in 559 patients and TLD phenotype was found in 155 patients (27.7%). The 511 patients with informative morphological and cytogenetic data were classified into three groups according to karyotype: favourable, intermediate and adverse risk groups (92, 375 and 44 patients respectively). Normal karyotype was the most frequent as a total, and among both the non-TLD and TLD patients (164 patients 45.3% and 78 patients 52.7% respectively). All but one patient with AML/TLD was classified into the intermediate or adverse cytogenetic risk group. TLD phenotype was associated with lower remission rate and shorter overall survival but it did not influence disease-free survival. Although we did not find any specific cytogenetic abnormalities for AML/TLD, the rarity of favourable karyotypes among TLD patients indicates the biological difference between AML/TLD and AML/non-TLD.
British Journal of Haematology 02/2003; 120(1):56-62. DOI:10.1046/j.1365-2141.2003.03981.x · 4.71 Impact Factor
"Re-establishing an MGUS phase after AT does not have the same poor outcome as entering a myelodysplastic phase after treatment for acute leukaemia, in which rapid progression to a second overt leukaemia phase is the rule (Goasguen et al, 1992). With regard to re-establishing an MGUS phase post transplantation, a recent report showed that in 3/8 MM patients a low but detectable intraclonal diversity in the complementarity determining regions existed (Taylor et al, 2000), suggesting the presence of both a minor MGUS clone, which can still undergo further somatic mutations (Sahota et al, 1996), and a major MM clone, which shows no further intraclonal variability (Bakkus et al, 1992). "
[Show abstract][Hide abstract] ABSTRACT: Although outcome in multiple myeloma (MM) patients has improved significantly with the introduction of autotransplants (AT), the curability of this approach remained to be demonstrated. Therefore, we analysed outcome and prognostic factors using a logistic regression model in 515 consecutive newly diagnosed and previously treated patients intended to receive melphalan-based tandem transplants with follow up of > or = 5 years. One quarter of patients had event-free survivals (EFS) > or = 5 years with no further relapses seen after 7 years (46 patients on plateau). On multivariate analysis, factors associated with EFS > or = 5 years were absence of chromosome 11 and 13 abnormalities (odds ratio: 6.1), < or = 12 months of preceding standard-dose therapy (SDT) (OR: 2.6) and beta-2 microglobulin (B2M) level < or = 2.5 mg/l at time of first AT (OR: 1.7). Patients with only favourable variables (25%) had a 7-year EFS in excess of 35%, compared with 15% and 10%, respectively, with one (43%) or two unfavourable variables (27%), and 0% for 5% of patients with three unfavourable variables (P < 0.0001). Using a 1-year landmark analysis to allow for guaranteed time and thereby excluding early treatment failures, attaining a complete remission (CR) had no significant effect on long-term survival. Our data are consistent with cure in MM patients with a CR duration . or = 7 years and re-establishment of a monoclonal gammopathy of undetermined significance (MGUS) phase in those with persistent evidence of disease post transplantation, but without disease progression > or = 7 years.
British Journal of Haematology 02/2002; 116(1):211-7. DOI:10.1046/j.1365-2141.2002.03231.x · 4.71 Impact Factor
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