Joan-Lluis Vives-Corrons

Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance

The actuarial probability of malignant transformation and the impact on expected survival were analysed in a series of 128 persons diagnosed with monoclonal gammopathy of undetermined significance (MGUS) over a 20‐year period. At a median follow‐up of 56 months the M‐component remains stable in 101 patients (78·9%), 14 patients (10·9%) have died from non‐related disorders and 13 (10·2%) have developed malignant transformation of MGUS (multiple myeloma, 10; primary amyloidosis, two; Waldenströms macroglobulinaemia, one). The actuarial probability of malignant transformation at 5 and 10 years was 8·5% and 19·2%, respectively. When different presenting features were analysed for predictive value of the malignant transformation, the IgA type of MGUS was the only variable associated with a higher probability of such an event (P<0·025). Although no significant difference was observed between the survival probability of persons with MGUS and that of the control population, the development of malignant transformation was associated with a shorter survival (P<0·001).

Clinical significance of the presence of myeloid associated antigens in acute lymphoblastic leukaemia

We have analysed the immunological characteristics of blasts from 89 acute lymphoblastic leukaemia (ALL) cases (62 adults and 27 children), by using a panel of antilymphoid and myeloid associated monoclonal antibodies (McAb) and the APAAP method, which detects membrane and cytoplasmic expression of antigens.

ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes

Schistocytes are fragments of red blood cells (RBCs) produced by extrinsic mechanical damage within the circulation. The detection of schistocytes is an important morphological clue to the diagnosis of thrombotic microangiopathic anemia (TMA). Reporting criteria between different laboratories, however, are not uniform, owing to variability of shape and nature of fragments, as well as subjectivity and heterogeneity in their morphological assessment. Lack of standardization may lead to inconsistency or misdiagnosis, thereby affecting treatment and clinical outcome. The Schistocyte Working Group of the International Council for Standardization in Haematology (ICSH) has prepared specific recommendations to standardize schistocyte identification, enumeration, and reporting. They deal with the type of smear, method of counting, morphological description based on positive criteria (helmet cells, small, irregular triangular, or crescent‐shaped cells, pointed projections, and lack of central pallor). A schistocyte count has a definite clinical value for the diagnosis of TMA in the absence of additional severe red cell shape abnormalities, with a confident threshold value of 1%. Automated counting of RBC fragments is also recommended by the ICSH Working Group as a useful complement to the microscope, according to the high predictive value of negative results, but worthy of further research and with limits in quantitation.

Bone marrow assessment in B‐cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients

To evaluate the relative merits and prognostic value of bone marrow aspirate and bone marrow biopsy in the assessment of bone marrow infiltration in B‐cell chronic lymphocytic leukaemia (CLL), two observers independently reviewed the percentage of lymphocytes in bone marrow aspirate (lymphocytic infiltration, LI) and the bone marrow histological pattern (BMP) in 258 patients. The inter‐observer reproducibility and agreement was higher for BMP than for LI. BMP was an independent prognostic factor for survival in the whole series, whereas LI only had independent predictive value in stage A patients. In the entire series, disease progression was predicted by either BMP and LI, whereas in stage A patients only by BMP. Regarding low‐risk CLL (smouldering CLL or A′′1 substage), BMP led to a more reproducible identification of these clinical forms than LI. In conclusion, although both BMP and LI are of value to estimate bone marrow infiltration in CLL and to predict the outcome of the disease, BMP is more reliable and reproducible than LI.

The value of detecting surface and cytoplasmic antigens in acute myeloid leukaemia

The immunophenotype of leukaemia cells from 60 patients with acute myeloid leukaemia (AML) was analysed with the APAAP technique using a panel of anti‐myeloid and lymphoid associated monoclonal antibodies (McAb). Cells from all cases, including three with negative cytochemical features, were labelled by at least one of the anti‐myeloid McAb CD13, anti‐myeloperoxidase (anti‐Mpo), and/or CD14. The most sensitive marker was GD13, since it was positive in 90% of cases. In two out of three AML cases defined as MO‐AML, CD13 was expressed in the cytoplasm but not on the membrane; in these three cases peroxidase (Mpo) was not detected by conventional cytochemistry, but could be demonstrated in all of them using the McAb anti‐Mpo. The simultaneous expression of GD14 and CD68 McAb was often confined to the M4 and MS FAB AML subtypes (92% cases) as compared to the others: Ml, M2, M3 (18% cases). Lymphoid antigens were rarely positive (TdT +: 13%, CD7 +: 15%, CD19 +: 5%) and none of the AML cases were CD3+ or CD10 +. By contrast, CD4 was expressed in blasts from 44% of cases and this was not restricted to AML with a monocytic component (M4, M5) but also found in other subtypes. There were no significant differences in the clinical or prognostic features according to the positivity or negativity with TdT and CD4. By contrast, expression of CD7 was associated with refractoriness to the treatment or short complete remission duration, although the number of patients is too small to draw firm conclusions. Our findings support the clinical and diagnostic relevance of immunophenotypic studies in AML.

Triosephosphate isomerase deficiency with hemolytic anemia and severe neuromuscular disease. Familial and biochemical studies of a case found in Spain

SummaryA 16-month-old girl of Spanish origin with chronic hemolytic anemia and severe neuromuscular disease was found to have markedly reduced triosephosphate isomerase (TPI) activity in her erythrocytes, leukocytes, and platelets. Both parents and some other family members had moderately reduced erythrocyte TPI activity in accordance with the autosomal recessive mode of inheritance in this enzymopathy. Latex ingestion and latex-stimulated histochemical NBT reduction by the patients granulocytes were normal.Zymosan-stimulated superoxide radical (

Hereditary hemolytic anemia with erythrocyte pyrimidine 5′-nucleotidase deficiency in Spain

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Chronic neutrophilic leukemia with marked myelodysplasia terminating in blast crisis

) formation, not previously studied in TPI-deficient granulocytes, was also within normal limits. Starchgel electrophoresis of TPI in both erythrocytes and leukocytes of the proposita and her parents was normal. Molecular studies of deficient TPI showed a normal kinetic pattern with markedly reduced heat instability.Immunologic studies demonstrated no cross reacting material in proposita leukocytes and a normal molecular specific activity. These studies suggest that molecular instability might cause both enzymatic and antigenic degradation of the TPI molecule and, therefore, TPI deficiency in our patient.