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

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 ill 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-a has no advantage over conventional MP plus interferon-alpha, in regard to response rate, response duration, and overall survival of patients

Hepcidin in iron overload disorders

Hepcidin is the principal regulator of iron absorption in humans. The pepticle inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin-ferroportin interaction in iron homeostasis. (c) 2005 by The American Society of Hematology

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

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. 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. 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. 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. © 2004 Elsevier B.V. All rights reserved

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

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 ill 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-a has no advantage over conventional MP plus interferon-alpha, in regard to response rate, response duration, and overall survival of patients

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