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The comprehensive sequencing of the complete genome of various hematological neoplasms has allowed an in-depth insight into the genomic heterogeneity and led to the discovery of new genetic aberrations, which seem to be very promising as therapeutic target structures. The molecular target structures of new therapeutic agents are, however, nearly exclusively proteins and cannot be directly identified with nucleic acid-based investigation methods. There is a great potential in investigations at the protein level that reflect an expression of the target protein and/or alterations of the signal cascade in tumor cells. In this context immunohistochemistry is a procedure that can deliver the decisive information using mutation, phosphorylation and glycosylation-specific primary antibodies. This study was carried out to comprehensively investigate the diagnostic utilization of such antibodies for hematological neoplasms. The studies summarized in this article emphasize the significance of tissue-based diagnostic approaches at the protein level and are suitable for use in patient selection for targeted treatment. A particular success of these studies was to make an essential contribution to the predictive diagnostics of multiple myeloma.

The purine analogue cladribine is a highly active cytotoxic drug for the treatment of hairy cell leukemia. The substance is easy to use and patient friendly. After preparation of a special, sophisticated formulation by a pharmaceutical cytotoxic lab, the patient might even apply the drug himself. This review points out the potential of this non-patented pharmaceutical, besides practical advices.

The hairy cell leukemia is a rare, low grade mature B-cell disease, a subtype of a Non Hodgkin-Lymphoma. The following article gives a short survey about the disease and the therapeutic options.

We describe a patient with chronic myelogenous leukemia (CML) and a patient with hairy cell leukemia being effectively treated with alpha-interferon who developed a seropositive chronic polyarthritis formally fulfilling the ACR criteria for rheumatoid arthritis. Because of its efficacy, interferon was not discontinued, and the arthritis treated with low-dose prednisolone or NSAIDS. These are the 19th and 20th case of symmetrical polyarthritis during alpha-interferon therapy fulfilling the criteria for RA. The possible mechanisms of the relatively frequent appearance of autoimmune diseases during interferon therapy are discussed.

2-chlorodeoxyadenosine (2-CDA) is very effective in the treatment of patients with hairy-cell leukaemia, with an overall response rate of 80-95%. The standard treatment is a continuous intravenous infusion for 7 days. The bioavailability of 2-CDA after subcutaneous injection is 100%, but the concentration-time profile is completely different compared to continuous intravenous administration. In the present study we compared the intravenous standard treatment (group 1, n = 22; 0.1 mg/kg/d for 7 days, civ.) with subcutaneous administration of 2-CDA (group 2, n = 62; 0.14 mg/kg/d for 5 days, s.c.) in patients with hairy-cell leukaemia. In group 1, 96% (21/22) of patients responded to 2-CDA (complete remission 73%, partial remission 23%) and in the second group 97% were responsive (complete response 76%, 47/62; partial remission 21%, 13/62). The percentage for moderate and severe infections in the trial with intravenous and subcutaneous treatment was 14% and 26% respectively (p = 0.37). We conclude that subcutaneous administration of 2-CDA in patients with hairy-cell leukaemia is feasible and economical and results in comparable responses and toxicity compared to the intravenous standard treatment.

The effect of treatment on bone marrow infiltration in hairy cell leukaemia was followed by means of MRT in five patients. A semi-quantitative method has been developed in order to judge the effect of treatment. The results correlate well with the findings on iliac crest biopsies. The method could partly replace the invasive iliac crest biopsies, which are used for therapy monitoring.

Recombinant interferon-alpha 2 (E. coli) produced a clinically significant improvement in hemoglobin, granulocytes and platelets in 7 of 8 patients with hairy cell leukemia. Response to treatment was already noticeable in the fourth treatment week. In one case without improvement after 120 days, treatment was stopped. So far only one complete remission has been documented. Because of the remarkable improvement in the peripheral blood values, the induction of a complete remission may not be the ultimate goal of interferon treatment. The side effects of this subcutaneous low-dose treatment consisted mainly of mild flu-like symptoms of short duration. The results obtained with recombinant interferon-alpha 2 confirm the initial observation by Quesada et al. with partially purified leukocyte-interferon. In our experience, these results are superior to those obtained in similar conditions with chlorambucil.

Hairy-cell leukemia has been shown to be extraordinary sensitive to treatment with alpha-interferon. In order to define clinically effective interferon doses associated with minimal toxicity two different dose regimens were applied in this clinical trial: firstly, a conventional dose schedule, and secondly, a biologically defined dose regimen. For dose finding in the latter group, neopterin, a GTP degradation product produced by macrophages under control of interferon, was chosen. Six patients (Group A) received conventional doses of recombinant interferon--alpha-2 (rIFN-alpha-2) 3 X 10(6) U/sqm/daily by the subcutaneous route. Five patients (Group B) were treated with the minimal dose of rIFN-alpha-2 which had previously been shown to induce maximum neopterin levels in urine. Already interferon doses in the range of 3 to 5 X 10(5) U/sqm2/daily administered subcutaneously proved to be sufficient for triggering maximum neopterin excretion in the urine. After six months of interferon treatment all patients were evaluable. At this time both doses regimens proved to be effective in terms of their anti-leukemic activity, but differed significantly in toxicity, which was only seen in Group A patients.