Refractory myelomatosis treated with mitoxantrone in combination with vincristine and prednisone (NOP-regimen): a phase II study

In a phase II study, patients with refractory myelomatosis were treated with a combination chemotherapy (NOP regimen): mitoxantrone (bolus injection of 4 mg/m2 on days 1-4), vincristine (continuous infusion of 0.4 mg/24 h on days 1-4) and prednisone (250 mg/d on days 1-4 and 17-20). The treatment was repeated every 4 weeks. Ninety-two patients were treated after they were found refractory to treatment with melphalan and prednisone (and occasionally vincristine) (n = 50) or more intensive treatment regimens (n = 42) including anthracyclines (n = 18). Response (greater than or equal to 50% reduction of M protein) was obtained in 23 patients and minor response (clinical improvement but less than 50% reduction in M protein) in 22 patients. The median duration of the response was 7.5 months. Equal response rates were observed irrespective of the type of previous treatment. The major toxicity was myelosuppression with severe granulocytopenia and infections. However, the frequency decreased throughout the cycles. The NOP treatment is recommended in refractory myelomatosis, especially in patients refractory to other intensive regimens. Patients in a poor clinical condition or with thrombocytopenia before treatment should have a reduced mitoxantrone dose in the first treatment cycles.     

Monoclonal antibody ratios in malignant myeloid diseases: diagnostic and prognostic use in myelodysplastic syndromes

Based on a 6 1/2-year study of bone marrows (BM) from 74 consecutive adult patients with newly diagnosed primary myelodysplastic syndromes (MDS), we have evaluated the role of immunophenotyping (IP) for subclassification purposes with a selected panel of monoclonal antibodies (Mab). Compared to normal BM IP revealed increased numbers of Mab-defined immature myeloid cells (defined by Mab MY7 [CD13] and MY9 [CD33] (P less than 0.05). Furthermore, decreased numbers of mature myeloid cells (defined by Mab NAT-9 II:3F-6F [NAT-9]) (P less than 0.001) were demonstrated in all French-American-British (FAB) subtypes except refractory anaemia with sideroblasts (RA-S). Since expression of CD13 and CD33 antigens on immature myeloid cells is variable, IP based on a single Mab was often found to be non-informative. However, the construction of myeloid antibody ratios (MAR), designed to give higher figures with increasing numbers of immature myeloid cells and/or decreasing numbers of mature myeloid cells in the BM, disclosed increasing mean ratio values with progressing FAB subtypes. More significant however, was that different prognostic subgroups based on the MAR could be identified independently of the FAB classification. We conclude that the use of IP--especially when MAR is included--is useful in prognostic scoring systems in MDS.     

Ouabain-Sensitive and Oligomycin-Sensitive Adenosine-triphosphatase Activities of Normal Human Lymphocytes

S ummary . Homogenates of highly purified normal human lymphocytes contained two different adenosinetriphosphatase (ATPase) activities. One of these activities was present in a supernatant fraction of the lymphocyte homogenates, possibly related to mitochondria. This activity was independent of the presence of monovalent cations, was insensitive to ouabain, but was inhibited by oligomycin and stimulated by 2,4 dinitrophenol. Exchange of Mg⁺⁺ with Ca⁺⁺, or addition of sodium fluoride completely inhibited this ATPase activity. A K_m-value for the substrate ATP was determined to be 0.83 m m . The specific activity of the oligomycin-sensitive, supernatant ATPase was 0.31 ± 0.13 (SD) μmoles P_i per mg protein per 30 min.
The other ATPase activity was activated by Na⁺ and K⁺ and was inhibited by ouabain. This ATPase activity was only found in the pellet fraction after centrifugation, possibly associated with the cell membranes. The specific activity of this ATPase was 0.25 ± 0.09 (SD) μmoles P_i per mg protein per 30 min. The effect of ouabain in various cation combinations of the assay is reported. Optimal ouabain-sensitive ATPase activity was found at 100 m m Na⁺, 15 m m K⁺ and 6 m m Mg⁺⁺.
Only the oligomycin-sensitive ATPase activity increased after short time stimulation of the lymphocytes by phytohaemagglutinin (PHA), and this could be inhibited by puromycin.
The increased ATPase activity of normal lymphocytes caused by the non-specific mitogen PHA suggest the possibility that the increased ATPase activity of lymphocytes from patients with malignant tumours could be due to a stimulation of the lymphocytes by tumour specific antigens in vivo.