This article contains biological, epidemiological and clinical data on multiple myeloma and the role of proangiogenetic cytokines in the development of this neoplasm. The role of angiogenesis in the transformation and development of multiple myeloma is a topic which is presently readily studied in leading scientific centres in many parts of the world. Serum and bone marrow levels of cytokines such as VEGF, b-FGF, IL-6, sIL-6R, HGFare raised in patients with multiple myeloma as compared to healthy subjects; their values correlate with the severity of disease and are presently recognised as prognostic factors. Thalidomide has anti-inflammatory, immuno-modulating and antiangiogeneic properties but the mechanism of its action is not yet completely understood. Thalidomide is presently used in therapy of patients with resistant and relapsed multiple myeloma with very promising results.
The treatment of adults with Philadelphia-negative acute lymphoblastic leukaemia (ALL) depends on the presence of risk factors including age, white blood cell count, immunophenotype and time to complete remission. In recent years, status of minimal residual disease (MRD) has been postulated as an additional risk criterion. This study prospectively evaluated the significance of MRD. Patients were treated with a uniform Polish Adult Leukemia Group (PALG) 4-2002 protocol. MRD status was assessed after induction and consolidation by multiparametric flow cytometry. Out of 132 patients included (age, 17-60 years), 116 patients were suitable for analysis. MRD level >/=0.1% of bone marrow cells after induction was found to be a strong and independent predictor for relapse in the whole study population (P < 0.0001), as well as in the standard risk (SR, P = 0.0003) and high-risk (P = 0.008) groups. The impact of MRD after consolidation on outcome was not significant. The combination of MRD status with conventional risk stratification system identified a subgroup of patients allocated to the SR group with MRD <0.1% after induction who had a very low risk of relapse of 9% at 3 years as opposed to 71% in the remaining subjects (P = 0.001). We conclude that MRD evaluation after induction should be considered with conventional risk criteria for treatment decisions in adult ALL.
Due to its high efficacy, imatinib (IM) has become the treatment of choice for patients with chronic myeloid leukemia (CML). However, there is still a substantial group of patients who need higher doses of IM or alternative therapy. The resistance to IM led to development of 2 nd generation tyrosine kinase inhibitors (TKI). Higher doses of IM or 2 nd generation TKI are used to overcome the resistance to therapy. There are several factors that need to be considered in the treatment choice decision making process in IM-resistant patients, who failed or achieved only suboptimal response, such as compliance and the type of underlying mechanism of resistance. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is used currently as subsequent treatment line in patients who failed therapy with 2 nd generation TKI and progressed to
A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients.Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment.Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004).In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit.
