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Long-term survivors in chronic granulocytic leukaemia: a study by the International CGL Prognosis Study Group. Italian Cooperative CML Study Group.

The purpose of the present work were to identify the initial characteristics associated with long-term survival in chronic granulocytic leukaemia (CGL) and to analyse the accuracy of prognostic models in identifying long-term survivors. 813 Philadelphia (Ph) chromosome-positive, nonblastic CGL patients from six American and European institutions, the majority treated conventionally, with a minimum follow-up > 10 years, were studied. Stepwise logistic regression was performed to ascertain the association between the initial clinicohaematological variables and survival > or = 8 years, and a prognostic index was derived. The usefulness of both Sokal's and the new prognostic index to identify long-term survivors was assessed by calculating their positive and negative predictive accuracies, sensitivity and specificity. Median survival of the series was 45 months (range 1-255), with 784 patients (96.4%) having died and 109 (13.4%) surviving 8 years or longer. Younger age, smaller spleen, platelets < or = 600 x 10(9)/l, and lower blood blast percentage were associated with survival > or = 8 years; platelets < or = 600 x 10(9)/l and lower blood blast percentage were the predictive factors in patients 50 years old or younger. Two-thirds of long survivors belonged to Sokal's low-risk group, but the positive predictive accuracy and specificity for prolonged survival of Sokal's index were very low. This was also the case for the new predictive index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Specific suppression of MLC and CML by anti-idiotypic antibodies in the mouse.

Rabbit antisera directed against idiotypic determinants of alloreactive mouse CBA anti-C57BL/6 T blasts were raised in the following manner: first, a rabbit serum directed against nonspecific CBA blasts cells was prepared by injecting CBA concanavalin A blasts three times at monthly intervals into a rabbit. Second, specific CBA anti-C57BL/6 T lymphoblasts were induced in a mixed lymphocyte culture (MLC), were purified by gravity sedimentation through a fetal calf serum gradient, and, finally, were incubated with the anti-blast serum from the first step. During this incubation, presumably all epitopes of the blast cell population were blocked by anti-blast antibodies, except for the greatly amplified set of CBA anti-C57BL/6 alloreactive idiotypes. The mixture was then injected into fresh rabbits, which were boosted with similar mixtures after 3 and 6 weeks. Blood samples were removed 10 days after each injection. Such sera, when used together with complement, inhibited specifically the stimulation of CBA cells by C57BL/6 antigens in MLC and the CBA anti-C57BL/6 killer cells.

Animals↗

Genetics of cell-mediated lympholysis (CML) in man.

Human cytotoxic lymphocytes (CTL), developed in responder-stimulator combinations incompatible for only one HLA-B antigen, have been used to study the specificity and genetics of target cell determinants. We were able to develop specific CTLs directed against HLA-B7, B8, B27 and Bw44, as defined by standard serological reagents. CTL-anti-B5 and CTL-anti-Bw35 gave a number of false positive reactions. In addition, we have found that specific cytotoxic effector cells can be generated against B27 by sensitization of cells from a B7 donor and vice versa; B7 and B27 can in this way be recognized easily. The data support the view that HLA-B is the target antigen. In addition, population and family studies revealed that extra reactions with CTLs developed in female (parous) responder-male stimulator combinations were due to HLA-restricted H-Y antigen killing. These findings suggest that by selecting responder-stimulator pairs differing for only one antigen at a locus, it should be possible to develop CTLs which will allow recognition of other specificities at the HLA-B locus and other loci.

Family↗

Human B-blast specific target determinants in CML: a panel study.

The B blast specific target determinant phenotype defined by cytotoxic lymphocytes and the HLA-DR phenotype was tested for correlation in two panel studies. First, CTL reagents with B blast specificity were selected from CTLs educated between HLA-A, B, (C) identical unrelated donors giving no cytotoxicity with specific T blasts, resulting in free selection of panel B blasts used as targets. Second, CTLs educated between HLA non-identical unrelated donors giving cytotoxicity against specific T as well a B blast targets could be seen with negative reactions against T blasts but positive reactions against B blasts of selected panel members giving, in this set up, a free selection of donors cocultured for education of CTLs. These panel studies showed that HLA-DR associated B blast specific target determinants can be identified by CTLs, indicating that the HLA system codes for these determinants either through gene products of a locus closely linked to or identical with the HLA-DR locus.

B-Lymphocytes↗

Human B-blast specific target determinants in CML: a family study.

Human B blast specific target determinants, selectively identified on PWM stimulated purified B lymphoblasts by in vitro generated CTLs, have previously been studied in the population and showed association to and inclusion of HLA-DR geneproducts. This report indicates that B blast target determinants are products of genes which in a codominant mendelain way segregate with the HLA haplotypes in 4 selected families. Furthermore tests of families with HLA-B/D, DR and HLA-D, DR/GLO recombinations show that human B blast specific target determinants are coded from loci (locus) in the HLA-D region, between HLA-B and GLO.

B-Lymphocytes↗

Y chromosome duplication: a minor route evolutive pattern in CML.

2 patients have been investigated, in which Y chromosome duplication occurred during blastic transformation of chronic myelocytic leukaemia. Comparison of cytogenetic findings and survival data in our cases and in previously reported individuals, suggests preliminary conclusions about the prognostic significance of this aneuploidy. Y chromosome gain does not seem to represent per se an unfavourable event, unless it is associated with additional chromosome change.

Aneuploidy↗

Automated measurement of cell destruction: the Patimed system in comparison with conventional HLA typing and the cell mediated lympholysis test (CML).

The key role of HLA polymorphism in the pathogenesis of many diseases and in determining compatibility in transplantation makes it desirable to employ automated systems for identifying HLA polymorphism. For more than one year we have used the photometer system Patimed commercially available from the Leica company. We compared the results of the conventional cell-mediated lympholysis test and conventional serological HLA typing with the results obtained by the Patimed system. Despite some good preliminary results it would be premature, in our opinion, to recommend the Patimed system for routine assessment of killer cell activity whereas we can definitely recommend the Patimed system to define HLA class I and class II molecules serologically for research or routine purposes.

HLA Antigens↗