Does thrombopoiesis in multiple myeloma patients depend on the stage of the disease?

PURPOSE: Infiltration of the bone marrow by neoplastic plasmocytes in multiple myeloma (MM) patients might impair megakaryocytopoiesis. The aim of the study was to evaluate stage-dependent platelet count (PLT) and thrombopoietin (TPO) concentration in comparison to the control group. We also wanted to establish whether TPO might be recognized as a marker of the stage of the disease. MATERIAL/METHODS: The study group consisted of 41 patients (mean age 67.7) with newly diagnosed MM prior to treatment and categorized according to the Durie and Salmon diagnostic classification. The control group consisted of 30 healthy subjects (mean age 65.5). PLT, WBC, RBC and Hb were measured with the use of the haematological analyser. TPO was assayed with the use of ELISA and albumin with the use of the immunonephelometry method. The number of plasma cells in the bone marrow was evaluated in bone marrow smears under light microscopy. RESULTS: PLT was not statistically different as compared the control groups, but was stage-dependent. Thrombocytopenia was observed in the III stage of MM. TPO median was significantly higher in study group than in healthy subjects and it was increasing considerably with the stage of the disease. TPO concentration was negatively correlated with albumin and PLT. AUC for TPO was 0.9764. The number of plasma cells in the bone marrow was considerably increasing with the stage of the disease. CONCLUSIONS: PLT and TPO in MM patients were stage-dependent. Elevated TPO concentration in MM patients might be an unfavourable marker of the stage of the disease.

Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG).

OBJECTIVES: The addition of cladribine to the standard regimen consisting of daunorubicin and cytarabine has been reported to increase the efficacy of induction therapy in acute myeloid leukemia (AML). The goal of this study was to determine the effect of this modification on the incidence and spectrum of infectious complications. METHODS: Case report forms of 309 patients with newly diagnosed AML who had been enrolled in the prospective, randomized 'DAC-7 vs. DA-7' trial were reviewed. The frequency, etiology, localization, severity, and outcome of infections were compared for patients receiving only daunorubicin and cytarabine (DA-7) and those additionally treated with cladribine (DAC-7). RESULTS: A total of 443 febrile episodes were reported with no significant difference between the treatment groups. A trend towards a higher frequency of bacteremias was observed among DA-7 patients compared to those in the DAC-7 group (31% vs. 21%; p=0.08). The treatment arms did not differ in terms of the distribution of the isolated Gram-positive, Gram-negative, fungal, and viral organisms. However, when bacteremias were considered, Gram-positive blood cultures tended to be more frequent in the DA-7 compared to the DAC-7 group (16% vs. 8.5%; p=0.07). This difference reached statistical significance when major blood bacteremias were analyzed separately (13% vs. 5%; p=0.02). Complete recovery from infections was observed in the majority of patients across both treatment arms and no significant difference was noted regarding infection-related mortality. CONCLUSIONS: The addition of cladribine to standard induction chemotherapy has no impact on the incidence and spectrum of infectious complications in newly diagnosed AML patients.

Assessment of circulating proteasome chymotrypsin-like activity in plasma of patients with acute and chronic leukemias.

OBJECTIVE: We evaluated whether the proteasomal chymotrypsin-like (ChT-L) activity is increased in plasma of patients with acute lymphoblastic (ALL), acute myeloblastic (AML) and chronic lymphocytic (CLL) leukemias. METHODS: The activity was assayed using the fluorogenic peptide substrate in the presence of an artificial activator sodium dodecyl sulfate (SDS) in the plasma of healthy donors (n=15) and ALL (n=15), AML (n=28) and CLL (n=22) patients. RESULTS: The activity was significantly (P<0.001) higher in the plasma of ALL and AML patients at the diagnosis than in healthy subjects and decreased after therapy or remained unchanged or rose during relapse. By contrast, in CLL patients at the diagnosis, the activity did not differ significantly from the healthy controls. In each group, the activity positively correlated with the serum lactic dehydrogenase activity. CONCLUSIONS: Plasma proteasome ChT-L activity can be a useful bio-marker for patients with acute leukemia at the blast stage.

Cladribine in a weekly versus daily schedule for untreated active hairy cell leukemia: final report from the Polish Adult Leukemia Group (PALG) of a prospective, randomized, multicenter trial.

Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may shorten potentially long-term survival in hairy cell leukemia (HCL). In search of the optimal mode of 2-CdA administration, 132 patients with untreated HCL were randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of 6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment response confirmed similar complete remission rates, overall response rates, progression-free survival, and overall survival in both 2-CdA protocols. However, we did not observe lower toxicity in the weekly schedule. Of special interest, no significant differences were found in the rate of grade 3/4 infections (18% for daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI] -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion, HCL treatment with weekly 2-CdA infusions is equally effective but no safer than the standard 5-day 2-CdA protocol.