Incidence and characteristics of lymphoid malignancies in untreated myelodysplastic syndromes.

We have analyzed 1,198 patients with untreated myelodysplastic syndromes (MDS) with two main objectives: (1) to determine the prevalence of lymphoid malignancies (LM) in MDS patients; and (2) to ascertain whether there is some relationship between the MDS subtype and the LM type. In fourteen of 1,198 primary MDS patients (1%) (4 with refractory anemia, 3 with refractory anemia with ring sideroblasts, 2 with refractory anemia with excess of blasts and 5 with chronic myelomonocytic leukemia) a LM was detected. In all cases, the LM was of the B-cell type: 6 cases of chronic lymphocytic leukemia, 5 cases of lymphoplasmacytoid lymphoma, and 3 cases of multiple myeloma. B-cell malignancy did not prevail in any MDS subtype and no correlation was observed between the different varieties of both diseases. In conclusion, in this large series, 1% of the untreated patients with MDS had B-cell malignancy, an association that in most cases is likely to be merely coincidental.

[Cytogenetic abnormalities in seven patients with the Sezary syndrome]. / Alteraciones citogenéticas en siete pacientes con síndrome de Sézary.

The cytogenetic studies performed on 7 patients diagnosed of Sezary's syndrome are reported. The chromosomal study was made after 72 hours of culture of phytohaemagglutinin-stimulated peripheral blood. The 7 patients had abnormal karyotypes, the numeral alterations involving chromosomes 10 and 13, whereas the structural abnormalities affected chromosomes 1, 2, 4, 6 and 14. The large-cell variant has been associated with tetraploidy and the small-cell variant with diploidy, but this fact was not confirmed in the present series.

Cytogenetic studies in five patients with Sézary syndrome.

A cytogenetic study was performed in five patients with Sézary syndrome. Metaphases were obtained from a phytohemagglutinin-stimulated lymphocyte culture. The five patients showed abnormal karyotypes. The chromosomes preferentially involved in numerical aberrations were chromosomes 10 (monosomy) and 13 (monosomy); involved in structural changes were chromosomes 1, 2, 4, 6, and 14. In our series, all patients showed progression of the disease.

Isochromosome 17q as a sole anomaly: a distinct myelodysplastic syndrome entity?

We report four patients with myelodysplastic syndrome (MDS) with isochromosome i(17q) as the sole chromosomal anomaly. One patient was classified as refractory anemia (RA) and three as refractory anemia with excess of blasts (RAEB). All four patients shared several features such as male sex, advanced age, severe anemia, as well as a bone marrow with myeloproliferative characteristics: hypercellularity, prominent baso- and eosinophilia, and marked increase of micromegakaryocytes. We suggest that patients with i(17q) as the sole chromosomal anomaly may identify a distinct MDS with characteristics between MDS and chronic myeloproliferative disorders (CMPD).

Abnormal chromatin clumping in leucocytes: a clue to a new subtype of myelodysplastic syndrome.

We report 6 patients with myelodysplastic syndrome, all of whom showed a bizarre nuclear anomaly within the neutrophils that was characterized by extensive clumping of chromatin into large blocks separated by clear zones, generally associated with a lack of segmentation. Anaemia, thrombocytopenia, variable leucocyte counts with leucoerythroblastic picture, marrow hypercellularity with granulocytic hyperplasia and moderate dysplastic changes in erythroblastic and megakaryocytic lines were present at diagnosis. 2 patients had normal karyotypes and a 3 showed a deletion of chromosome 14. 5 out of 6 patients had pneumonia at diagnosis. The median survival was short (5 months) and haemorrhagic complications were the cause of death in 4 patients. The clinical features and the evolution of these and other reported cases suggest that the presence of abnormal chromatin clumping in leucocytes might be a clue to a new subtype of myelodysplastic syndrome.

Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients.

Therapy planning in patients with myelodysplastic syndromes (MDSs) is complicated by its high prognostic heterogeneity. Forty-one patient and disease characteristics at onset of 370 patients with MDS were analyzed to identify significant prognostic factors for survival and transformation to acute myeloblastic leukemia (AML), and to develop and validate a regression model for predicting survival. Multivariate regression analysis showed that the total bone marrow percentage of blast cells, age, platelet count, WBC count, and hemoglobin level were the characteristics more significantly associated with survival in the overall series. The bone marrow percentage of type I blast cells was the most important factor predicting transformation into AML. Proportional hazards regression analysis in a randomly selected training sample of 240 patients demonstrated that the combination of total bone marrow percentage of blast cells, platelet count, and age had the strongest predictive relation to survival length. The resulting regression models, continuous and categorized, were validated in the remaining test sample of 130 patients by demonstrating its capability of segregating patients into low-, intermediate-, and high-risk groups, with distinctively different survival curves (P less than .0001). A scoring system derived from the categorized model also had a great prognostic value (P less than .0001). These regression models and the simpler scoring system may be accurately used for decision-making regarding therapy in MDS patients.

Chronic myelomonocytic leukemia--clinicobiological characteristics: a multivariate analysis in a series of 70 cases.

In a series of 70 patients diagnosed according to the FAB criteria, 42 clinical and biological disease characteristics were analyzed in order to identify significant prognostic factors by means of univariate and multivariate analysis. The univariate analysis identified ten parameters associated with poor prognosis: Symptoms of anemia, WBC over 10 x 10(9)/l, presence of blast cells, myeloid precursors or erythroblasts in peripheral blood (PB), high bone marrow (BM) cellularity, severe dysthrombopoiesis, percent of blast cells in BM and high serum levels of bilirubin and LDH. The Cox proportional hazards regression method revealed that the combination of high leukocyte counts and BM percentage of blast cells had the strongest predictive relation to survival length (p = 0.002 and p = 0.060 respectively). A new multivariate analysis treating the presence of myeloid and erythroid precursors in PB as a single variable selected only this as the most significant prognostic factor (p = 0.001). Both regression models allowed us to discriminate two significantly different risk groups of patients.

[Prediction of survival in myelodysplastic syndrome. Analysis of 2 scoring systems with prognostic value]. / Predicción de la supervivencia en los síndromes mielodisplásicos. Análisis de dos sistemas de puntuación con valor pronóstico.

The wide prognostic variability of myelodysplastic syndromes (MDS) complicates decision-making regarding the choice and evaluation of alternative treatments to transfusional and antiinfectious supportive measures. Due to its simplicity the Bournemouth scoring system seems to have achieved wide acceptance for establishing the prognosis in MDS patients. The aims of this study were to examine the Bournemouth system in a series of 370 patients with MDS and to evaluate the capability of the prognostic index recently proposed by our group to better define the outcome predicted by the former. The Bournemouth scoring system identified 3 risk groups, A (0-1 points), B (2-3 points) and C (4 points), in the whole series (p less than 0.0001) and it allowed us to stratify refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t) patients into two distinct prognostic groups (p = 0.03 and p = 0.01, respectively). This scoring system did not show a significant value in RA with ringed sideroblasts (RARS) and chronic myelomonocytic leukemia (CMML) patients (p greater than 0.05). Our prognostic index clearly segregated patients in the whole series into low- (0-1 points), intermediate- (2-3 points) and high-risk (4-5 points) groups (p less than 0.00001) as well as stratifying ARSA (p = 0.0005), CMML (p less than 0.0001) and RAEB and RAEB-t patients (p less than 0.00001) into different prognostic subset, although it failed to demonstrate a significant predictive value in RA patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Myelodysplastic syndromes: a study of 101 cases according to the FAB classification.

The myelodysplastic syndromes (MDS) are a group of closely related disorders characterized by chronic cytopenias with cellular marrow, poor prognosis and refractoriness to treatment. We studied 101 consecutive cases of MDS diagnosed over a 7-year period. Peripheral blood (PB) and bone marrow (BM) samples were reviewed and classified according to the proposals of the French-American-British (FAB) cooperative group for MDS. The combined analysis of the initial laboratory features and qualitative haematological abnormalities readily allowed the distinction between the different subgroups. Thirty-two of 79 cases (40.5%) evolved towards other diseases, frequently acute leukaemia (24/79, 30%), or transformed into other MDS (7/79, 9%). In five cases, initially classified as refractory anaemia (RA) or refractory anaemia with ring sideroblasts (RAS), a transitory change to another type of MDS--two chronic myelomonocytic leukaemias (CMML), two refractory anaemias with excess of blasts (RAEB) and one refractory anaemia with excess of blasts 'in transformation' (RAEB-t)--was observed before the evolution towards acute leukaemia. This provides a new link between all these syndromes and increases the number of transitions to other MDS. Overall prognosis was very poor, with differences between subgroups. RA had the best prognosis whereas RAEB-t had the worst one. This study shows that the FAB classification is readily usable and defines well-characterized subgroups of MDS, although there are frequent transitional forms, and as the natural history of the MDS unfolds they may convert into another. The actual poor prognosis and the frequent evolution towards acute leukaemia makes necessary to investigate new methods of treatment for these disorders.