Prognostic value of circulating CD34+ cells in myelodysplastic syndromes.

We studied circulating (C)CD34(+) cells by flow cytometry in 96 patients with myelodysplastic syndromes (MDS) at diagnosis, and in a subset of 35 cases during follow-up. CCD34(+) counts were stratified within both International Prognostic Scoring System (IPSS) and World Health Organization (WHO) categories. Counts >10/microl were associated with poorer leukemia-free survival, a prognostic value for evolution independent from that of WHO, and a higher progression probability within intermediate-risk IPSS and WHO classes. When serial measurements were performed, counts >10/microl more frequently correlated to evolution. Separating newly diagnosed patients on the basis of 10/microl cut-off of circulating CD34(+) cells retains prognostic utility, especially in intermediate-risk MDS.

Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia.

PURPOSE: To assess life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. METHODS: The study sample consisted of 831 consecutive patients with polycythemia vera (n = 396; 4184 person-years of follow-up) or essential thrombocythemia (n = 435; 4304 person-years of follow-up). Mortality in each group was compared with the Italian population using the standardized mortality ratio (SMR) based on life expectancy data obtained from the Italian Institute of Statistics. RESULTS: The 15-year survival was 65% in patients with polycythemia and 73% in those with thrombocythemia. By Cox regression analysis, the independent predictors of death were a history of thrombosis for polycythemia (hazard ratio [HR] = 2.2; P = 0.0002) and thrombocythemia (HR = 2; P = 0.01), and male sex (HR = 1.8; P = 0.03) for thrombocythemia. Mortality compared with the general population was 1.6-fold higher (P <0.001) in patients with polycythemia but was not increased in those with thrombocythemia (SMR = 1; P = 0.8). CONCLUSION: Life expectancy of patients with polycythemia vera (especially if younger than 50 years) was reduced compared with the general population, whereas life expectancy of patients with essential thrombocythemia was not affected significantly by the disease, reflecting the more indolent nature of the proliferation. History of thrombosis was the main predictor of death in both diseases.

Risk factors for the development of bacterial infections in multiple myeloma treated with two different vincristine-adriamycin-dexamethasone schedules.

BACKGROUND AND OBJECTIVES: We evaluated bacterial infections (BIs) in patients with multiple myeloma (MM) treated with two different schedules of vincristine-adriamycin-dexamethasone (VAD). DESIGN AND METHODS: Ninety-seven patients were studied during 340 VAD cycles. VAD was given by either continuous intravenous infusion (CII) to hospitalized patients or rapid intravenous infusion (RII) to outpatients. The characteristics of patients and VAD schedules were retrospectively analyzed to detect correlations with the incidence of BI. RESULTS: By analyzing each VAD cycle, we found that profound hypogammaglobulinemia (p=0.06) and post-treatment neutropenia (p=0.08) were associated with a trend for a higher risk of infection, while renal function impairment was significantly correlated with BI risk at both univariate (p<0.02) and multivariate (p<0.002) analyses. Evaluating only the first 4 months of therapy, characterized by a significantly higher incidence of BI than the later period (p<0.0001), previously untreated disease was significantly correlated with BI risk (p<0.04), while male sex (p=0.06), CII schedule (p=0.07), and profound hypogammaglobulinemia (p=0.1) were associated with a tendency to a higher risk of infection; however, at multivariate analysis the latter two parameters independently predicted BI probability (p<0.015 and p<0.03, respectively) as did previously untreated disease (p<0.025). The high probability of CII-related infection was demonstrated to depend on the frequent development of nosocomial infections. INTERPRETATION AND CONCLUSIONS: Patients with profound hypogammaglobulinemia who receive VAD as first line treatment are at a major risk of BI up to the completion of the fourth month of therapy. In this setting hospitalization should be avoided and, if patients require admission, antibacterial prophylaxis with intravenous immunoglobulins could be appropriate and effective.

Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma.

PURPOSE: To evaluate the natural history of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), identify early predictors of evolution, and assess whether associated conditions correlate with disease progression. PATIENTS AND METHODS: A total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM (n = 127) diagnosed from July 1975 to March 1998 were included in the study. Cumulative survival probability and cumulative probability of transformation into lymphoproliferative disease were calculated by means of the Kaplan-Meier estimator. Univariate and multivariate Cox models were used to identify possible predictors of malignant evolution. RESULTS: Cumulative transformation probability at 10 and 15 years was 14% and 30%, respectively. At a median follow-up of 65 months (range, 12 to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n = 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1), Waldenström's macroglobulinemia (n = 12), non-Hodgkin's lymphoma (n = 6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of 72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt MM. A lower evolution risk was observed in MGUS than in SMM (P <.0001). Greater than 5% marrow plasmacytosis, detectable Bence Jones proteinuria, polyclonal serum immunoglobulin reduction, and high erythrocyte sedimentation rate (ESR) were independent factors influencing MGUS transformation. SMM progression correlated with greater than 10% marrow plasma cells, detectable Bence Jones proteinuria, and immunoglobulin (Ig) A isotype. Neither concomitant diseases nor immunosuppression correlated with progression. CONCLUSION: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring.