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Since the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha2 (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2–47 weeks) were induced by phythemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.

We describe a human acute unclassified leukemia with a unique t(4;17) translocation that coexpresses T-lymphoid and myeloid surface antigens after in vitro culture in the presence of the tumor promoter, TPA. Under these conditions, the joining regions of the immunoglobulin heavy chain and T-cell receptor gamma and beta chain complexes remained in germ line configuration. A T-cell receptor beta chain variable gene probe, however, revealed the presence of rearrangements in the V beta M3-2 gene region after bilineage differentiation. These results may be pertinent to the interrelationship of T-cell receptor gene rearrangements and the control of T-cell antigen surface expression.

52 patients entered a study for remission induction and intensified consolidation in AML. Group I (age less than or equal to 50 years) received a combination of DNR, ara-C and VP16-213 for induction and early consolidation and HDara-C/DNR for late consolidation. Of 34 evaluable patients (25 first diagnosis, 9 first relapse), 27 achieved CR. 13 patients received 1-2 courses of HDara-C/DNR. Toxic symptoms of HDara-C/DNR were severe myelosuppression, infections, skin reactions, diarrhea and hepatotoxicity. CNS toxicity was not observed. 2 patients died from infection. The duration of granulocytopenia (less than 500/microliter) was 7-43 days (range) and of thrombocytopenia (less than 25,000/microliter) 5-34 days (range). Patients of group II (age greater than 50 years) received a modified regimen with reduced toxicity. Their number is too small for evaluation as yet.

Summary. For further analysis of their lineage affinity the differentiation capacity of five cases of acute unclassified leukaemias were studied in vitro using 5 nm 12-O-tetradecanoyl-phorbol-13-acetate as an inducing agent. After 4 d in vitro a co-expression of both myeloid and early B-lymphoid or myeloid and early T-lymphoid antigens on the same population of cells was found. While ultrastructural analysis of the blasts prior to culture revealed the morphology of undifferentiated blasts without any specific endogenous peroxidase activity, the cultured blasts displayed monoblastic features and myeloperoxidase activity after 4 d in vitro. Since this type of peroxidase is highly specific for the myelomonocytic lineage the data indicate myelomonocytoid differentiation of all five cases studied. The co-expression of lymphoid as well as myeloid antigens and myeloperoxidase by the same blasts after culture could be indicative of bilineage differentiation capacity characterizing the original blasts as bipotential progenitor cells.

In a small percentage of acute leukemias the lineage specificity of blasts remains undetermined after morphologic, cytochemical, and immunologic analyses. Some of these cases may coexpress markers of different cell lineages, suggesting their origin from a multipotent precursor cell or an aberrant gene expression [1–3].

The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB Ll, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of β-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data (1) support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and (2) confirm the value of Ig gene analysis as marker for cellular clonality.