Human T-lymphotropic virus type I/II infections in volunteer blood donors from Northern and Western Greece: increased prevalence in one blood bank unit.

BACKGROUND: Blood donors are routinely screened for antibodies to human T-cell lymphotropic viruses type I and II (HTLV-I and HTLV-II) in the United States, Canada, Japan, and some European countries. Previous reports from our group in relatively small numbers of donors have shown a zero prevalence of HTLV-I/II markers in our region. In this study, seven blood banks in the north and west of Greece participated in order to determine whether mandatory screening of blood donations for HTLV-I/II infection should be established. METHODS: Sera from 51,714 consecutive donors were investigated for anti-HTLV-I/II using two commercially available enzyme immunoassays (EIAs). Reactive samples in one or both EIAs were repeatedly evaluated further by Western blot, which is specific for both confirmation and differentiation of HTLV-I and HTLV-II seroreactivities. Investigation for HTLV DNA was also done in all EIA-reactive donors, irrespective of the WB result, using a combination assay based on the polymerase chain reaction (PCR) and a DNA EIA. RESULTS: A total of 115 donors (0.222%; 95% CI 0.018-0.26%) were initially considered reactive for anti-HTLV-I/II by EIAs. However, only 7 of the 115 were confirmed as positive by WB (five HTLV-I and two HTLV-I/II). Thus, the prevalence of anti-HTLV-I/II in donors from northern and western Greece was 0.013% (95% CI 0.003-0.023%). Interestingly, the majority of WB-confirmed anti-HTLV-positive individuals were detected in the blood bank of Corfu (5/7, all anti-HTLV-I). This prevalence (5/15383; 0.032%; 95% CI 0.004-0.061%) was six times the prevalence found at the other blood banks combined (2/36331; 0.0055%; 95% CI 0-0.013%), but it was not statistically significant. None of the EIA-reactive donors had detectable HTLV DNA. CONCLUSIONS: The very low prevalence of confirmed anti-HTLV-I/II infection markers in northern and western Greek blood donors, together with the negative PCR results in EIA-reactive subjects, indicates that anti-HTLV-I/I routine screening is not really justified in this area of our country. However, the increased prevalence of WB-confirmed anti-HTLV-I-positive donors in the Corfu blood bank calls for further prospective and careful investigation in order to address whether this finding represents a real cluster phenomenon of HTLV infection.

Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study.

BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation after initial cytoreductive chemotherapy with the combination vincristine, doxorubicin and dexamethasone (VAD) is considered an effective therapy for many patients with newly diagnosed, symptomatic multiple myeloma. Response to initial cytoreductive chemotherapy is important for the long-term outcome of such patients. Thalidomide has recently shown significant antimyeloma activity. We studied the efficacy and toxicity of the combination of a liposomal doxorubicin-containing VAD regimen with thalidomide, administered on an outpatient basis, as initial cytoreductive treatment in previously untreated patients with symptomatic myeloma. PATIENTS AND METHODS: Thirty-nine myeloma patients were treated with vincristine 2 mg intravenously (i.v.), liposomal doxorubicin 40 mg/m(2) i.v. administered as single dose on day 1, and dexamethasone 40 mg per os daily for 4 days. Dexamethasone was also given on days 15-18 of the first cycle of treatment. The regimen was administered every 4 weeks for four courses. Thalidomide was given daily at a dose of 200 mg at bedtime. Response to treatment was evaluated after four cycles of treatment. After completion of four cycles, the patients were allowed to proceed to high-dose chemotherapy or to receive two additional cycles of the same treatment. RESULTS: On an intention-to-treat basis, 29 of the 39 patients (74%) responded to treatment. Four patients (10%) achieved complete and 25 (64%) partial response. Three patients (8%) showed minor response and seven (18%) were rated as non-responders. Major grade 3 or 4 toxicities consisted of neutropenia (15%), thrombocytopenia (15%), deep vein thrombosis (10%), constipation (10%), skin rash (5%) and peripheral neuropathy (5%). Two patients (5%) experienced early death due to infection. CONCLUSIONS: The combination of vincristine, liposomal doxorubicin, and dexamethasone (VAD doxil) with thalidomide is an effective and relatively well-tolerated initial cytoreductive treatment. Prospective randomized studies are required in order to assess the effect of this regimen on the long-term outcome of patients with multiple myeloma.

Prospective randomized comparison of vincristine, doxorubicin and dexamethasone (VAD) administered as intravenous bolus injection and VAD with liposomal doxorubicin as first-line treatment in multiple myeloma.

BACKGROUND: The combination of vincristine and doxorubicin administered as a continuous infusion via an indwelling catheter together with intermittent high-dose dexamethasone (VAD) is an effective primary treatment for patients with symptomatic multiple myeloma. In order to avoid the need for an indwelling catheter, which imposes logistic problems for outpatient administration, several phase II studies have explored the feasibility and efficacy of VAD-like outpatient regimens. We designed a prospective randomized study to compare the objective response rates of two VAD-like outpatient regimens as primary treatment for symptomatic patients with multiple myeloma. PATIENTS AND METHODS: Patients were entered in a randomized study regardless of age, performance status and renal function. One hundred and twenty-seven patients received VAD bolus, which consisted of vincristine 0.4 mg i.v., doxorubicin 9 mg/m(2) i.v. and dexamethasone 40 mg p.o. daily for four consecutive days and 132 patients received VAD doxil, which consisted of vincristine 2 mg i.v. and liposomal doxorubicin 40 mg/m(2) i.v. on day 1 and dexamethasone 40 mg p.o. daily for 4 days. The two regimens were administered every 28 days for four courses and in courses 1 and 3, in both arms, dexamethasone was also given on days 9-12 and 17-20. RESULTS: An objective response was documented in 61.4% and 61.3% of patients treated with VAD bolus and VAD doxil, respectively. Hematological and non-hematological toxicities were mild or moderate and equally distributed between the two treatment arms with the exception of alopecia, which was more common after VAD bolus, and of palmar-plantar erythrodysesthesia, which was more common after VAD doxil. CONCLUSIONS: Our multicenter trial, which included an unselected patient population, indicated that both VAD bolus and VAD doxil can be administered to outpatients and can provide an equal opportunity of rapid response in many patients with multiple myeloma.

Comparison of vincristine, carmustine, melphalan, cyclophosphamide, prednisone (VBMCP) and interferon-alpha with melphalan and prednisone (MP) and interferon-alpha (IFN-alpha) in patients with good-prognosis multiple myeloma: a prospective randomized study. Greek Myeloma Study Group.

OBJECTIVES: The purpose of the study was to evaluate, in a selected group of myeloma patients with favorable prognosis, the effect, on response and survival, of polychymotherapy compared with melphalan prednisone, plus interferon in both arms. METHODS: Eighty-nine previously untreated patients with multiple myeloma and prognostic factors indicating a good prognosis were randomized to either oral melphalan plus prednisone (MP) in combination with recombinant interferon-alpha (rIFN-alpha) or combination chemotherapy with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone (VBMCP) alternating with rIFN-alpha. The two treatment groups were comparable in terms of pretreatment characteristics. RESULTS: The overall response rate was 67.4% (2.3% complete remission, 65.1% partial response) in the MP/IFN-alpha group and 69.1% (14.3% complete remission, 54.8% partial response) in the VBMCP/IFN-alpha group (p=0.59). There were no differences also in response duration and overall survival between the two treatment groups. The median response duration was 39.1 months in the MP/IFN-alpha group and was not reached in the VBMCP/IFN-alpha group (p = 0.6). Overall survival was long in both treatment groups. The estimated 5-yr survival was 66% and 62% in the MP/IFN-alpha and VBMCP/IFN-alpha group, respectively (p=0.8). Toxicity was modest and treatments were well tolerated. Neutropenia (WHO grade 3 or 4) was higher, but not statistically significant, in the VBMCP/IFN-alpha group. CONCLUSIONS: The results of the study show that in myeloma patients with good prognosis, combination chemotherapy alternating with interferon-alpha has no advantage over conventional MP plus interferon-alpha, in regard to response rate, response duration, and overall survival of patients.

Homocysteine and C-reactive protein levels in haemodialysis patients.

BACKGROUND: Mild to moderate hyperhomocysteinemia is very common among patients undergoing haemodialysis. There is sufficient evidence that hyperhomocysteinemia is an independent risk factor for cardiovascular and or atheromatous disease in end stage renal failure patients. Vitamin supplementation such as vitamin B6, B12 or folate has been proposed to correct this metabolic disturbance and it is to be proved if this intervention benefit these patients, but there is no agreement whether oral folate supplementation is capable to normalize homocysteine levels in end stage renal failure patients. METHODS: In 53 patients, undergoing haemodialysis, homocysteine levels (Hcy), folate, vitamin B12, ferritin and C-reactive protein (CRP) were estimated before and after dialysis, without folate supplementation. Thirty voluntary blood donors were used as controls to compare homocysteine levels. After four weeks of oral folate supplementation (10 mg/24 hours) the levels of homocysteine, serum folate and intra-erythrocyte folate were estimated again. Eighteen months later the survival rate of our patients was recorded and analyzed in relation to Hcy and CRP levels. RESULTS: The results showed that haemodialysis patients exhibited, almost, fourfold higher homocysteine levels than controls (27.39 +/- 11.54 vs 7.38 +/- 3.5, t = -8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly after haemodialysis where as homocysteine levels decrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03). Fourteen (14) patients suffered from coronary heart disease (CHD) and they exhibited the higher levels of homocysteine (Hcy1 vs. CHD: z = -3.4, p = 0.0006). All estimations performed revealed a negative correlation between homocysteine levels and plasma or intra-erythrocyte folate. No other variable exhibited any significant influence upon homocysteine levels. After folate supplementation homocysteine levels in the whole number of patients were unchanged (Hcy(before) vs. Hcy(after): 27.39 +/- 11.54 vs. 26.95 +/- 8.22, z = 0.3, p = 0.7, NS). When patients with homocysteine levels higher than 24 micromol/L were selected, a significant decrease was observed (34.77 +/- 9.32 vs. 30.0 +/- 8.05, z = 2.09, p = 0.02). Forty-two patients were treated with erythropoietin for their anemia and we found a positive correlation between C-reactive protein levels and rhu-Epo dose (CRP vs. Epo: r = 0.45, p = 0.002). Homocysteine levels did not exhibit any significant influence upon short-term survival (U = -0.37, p = 0.3, NS) where as CRP levels exhibit a significant influence upon short-term survival (U = 2.15, p = 0.005). CONCLUSIONS: Homocysteine levels in haemodialysis patients are fourfold higher than healthy controls. Folate, vitamin B12 and CRP increases significantly after dialysis. Patients with coronary heart disease exhibit the highest levels of homocysteine. The homocysteine levels are inversely related with the folate levels. The exogenous folate supplementation increase the serum folate levels but decreases homocysteine only in patients with higher than mild hyperhomocysteinemia. Hcy doesn't exert any significant effect upon the short-term survival of the haemodialysis patients but CRP level is a god predictor of the short-term survival of these patients.