Hematological malignancies are not very common. About 150 cases of acute myeloid (AML), 70-80 cases of acute lymphatic (ALL), 110-120 cases of Hodgkin´s lymphoma, and 750-800 cases of non-Hodgkin´s lymphomas are diagnosed annually in Finland. However, their economic and human impacts are greater than could be anticipated based on their incidence rates. This is because they often affect young people. The patients can often be cured of their malignancies, but the treatments cause severe acute and late toxicity and may also expose the patient to a risk of treatment-related death. The treatments are also very resource-intensive due to the expensive medications required, such as chemotherapeutics and growth factors, and often also due to long inpatient periods needed for the treatment of the acute side effects of the cancer treatments. Moreover, for a partly unknown reason, the incidence of non-Hodgkin´s lymphomas seems to be rising at a rate of three percent annually in the developed western countries (Bierman et al. 1996). For years the classification of hematological malignancies have possesed a challenge to pathologists and hematologists. Currently they are classified according to the WHO II classification. (Jaffe et al.2001)
However, biologically distinct diseases exists even within each certain subgroup. Some biological features imply a more aggressive disease with an enhanced likelihood of advanced disease, while not necessarily interfering with the response to treatment. Factors interfering with the therapeutic response and predictive factors also imply a need for more aggressive treatment. The treatments of hematological malignancies range from short-course, moderate-dose chemotherapy with local radiotherapy to high-dose treatments with autologous or allogeneic stem cell transplantation. Usually, the more intensive treatments offer the best probabilities for cure while they simultaneously also expose the patient to an increased risk of treatment-related toxicity (Philip et al. 1995, Diehl et al. 1997, Gobbi et al. 1998, Gustaffson et al. 1998). This calls for good predictive factors that could be used to individually assess the patient’s risk of relapse and to tailor the therapy to maximize the curative potential while minimizing toxicities.
Most hematological malignancies are already widely disseminated at the time of the diagnosis and can seldom be cured with local treatment modalities, such as surgery or local radiotherapy. For this reason, the development of modern chemotherapeutic modalities was revolutionary in the treatment of hematological malignancies, as they offered a possibility to cure these diseases, which had previously been inevitably fatal. However, chemotherapeutics possess unselective cytotoxic effect and also attack many normal cells, which leads to severe side effects. During the past few decades, there has been active research going on in the field of malignant diseases to clarify their basic biological behavior. Accumulation of such biological data has made it possible to develop more specific medications with fewer side effects. Most of these new, more specific and selective drugs, including metalloproteinase inhibitors and angiogenesis inhibitors, are still under phase I and II development, but a tyrosin kinase inhibitor, imatinib mesylate, has already shown its remarkable activity in the treatment of chronic myeloid leukemia. Despite these achievements, much basic research still needs to be performed before oncologists and hematologists have safe and effective treatments to be offered to the majority of their patients.
Knowledge about the biological and clinical role of gelatinases in solid malignancies is rapidly increasing. In the field of hematological malignancies, however, the data consist mainly of cell culture data, while clinical data are missing. The need for this data is further underlined by the fact that first MMP inhibitor drugs are in clinical trials.