Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma.

Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.

Erythropoietin in cancer: the new face of an old friend.

During the last decade, anemia, a very common situation in patients with malignant diseases, either associated with chemotherapy or not, is being treated with recombinant erythropoietin (rEPO). Recent experimental findings have elucidated the role of EPO as a strongly anti-apoptotic agent in multiple non-erythroid and neoplastic tissues. The discovery of probably functional EPO receptors (EPOR) on malignant cells, hinting that EPO may act as a tumor growth factor, raised embarrassing thoughts regarding the routine administration of erythropoiesis-stimulating agents (ESAs). In addition, the results of a few clinical trials showing a negative impact on overall survival of rEPO-treated cancer patients, although strongly criticized for several methodological pitfalls, led the FDA to force a "black label" warning concerning the use of rEPO and to recommend that physicians should use the lowest possible dose of ESAs in chemotherapy-treated cancer patients. This recommendation comes in accord with the recent guidelines of European Organisation for Research and Treatment of Cancer (EORTC) which are reviewed in this paper, along with the structure of EPO and EPOR, the role of EPO on normal and malignant cells and the clinical applications of EPO.

Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or refractory multiple myeloma patients.

PURPOSE: The purpose of this study was to assess the efficacy and toxicity of DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin), as third-line regimen in relapsed or refractory multiple myeloma (MM) patients. PATIENTS AND METHODS: Twelve patients (11 men, 1 woman, aged 38-73 years, median 58) with relapsed or refractory MM received 28 cycles of DCEP. Eleven out of 12 patients had already failed 4-6 cycles of VAD (vincristine, doxorubicin, dexamethasone), 7/12 had received 2 or more lines of prior therapy and one of them had high-dose therapy with stem cell support. Seven out of 12 patients were candidates for megatherapy with autologous peripheral blood stem cells transplantation (ASCT) either as consolidation or as salvage treatment. Each cycle of DCEP consisted of cyclophosphamide 400 mg/m(2)/daily, cisplatin 15 mg/m(2)/daily and etoposide 40 mg/m(2)/daily as a 24h infusion, all three drugs administered on days 1-4; plus dexamethasone i.v. bolus 40 mg daily, days 1-4. The dose of cisplatin was adjusted in case of renal impairment. G-CSF was administered daily from day +5 to recovery. The course was repeated every 28 days or was delayed 5-10 days according to the patient's clinical condition. RESULTS: The regimen was well tolerated with no major adverse reactions, except for grade 3 or 4 myelotoxicity of short duration. Responses were assessed using the EBMT criteria after the second cycle. Two out of 12 patients achieved complete remission (CR) and 5/12 partial remission (PR), while 5/12 had no response (NR). The overall response (OR) was 58.3% with a median response duration 9 months (range 4-36). Four patients proceeded to successful peripheral blood stem cell mobilization and transplantation. CONCLUSIONS: DCEP is an effective and safe salvage treatment for relapsed or refractory MM patients which also offers the possibility for a successful peripheral blood stem cells collection in patients eligible for high-dose therapy and ASCT.

Prevalence of autoantibodies (ANA, anti ds-DNA, ENA, IMF) and rheumatic syndromes in patients with lymphoproliferative diseases.

PURPOSE: In the development of rheumatic syndromes as well as of lymphoproliferative disorders it is probable that there are common genetic, environmental and immunoregulatory pathogenetic mechanisms. The purpose of this study was to determine the frequency of simultaneous presentation of both lymphoma or other lymphoproliferative diseases, and rheumatic syndromes. PATIENTS AND METHODS: In this study included were all patients with lymphoproliferative diseases (1920 patients) followed at our hospital during the last 5 years. 312/1920 (16.2%) patients presented with non-Hodgkin's lymphoma (NHL), 645/1920 (33.5%) had myeloma, 558/1920 (29%) had leukemia and miscellaneous other hematological malignancies (Hodgkin's lymphoma, cryoglogulinaemia etc) had 405/1920 patients (21%). Antinuclear antibodies (ANA), ribosome P and intermediate filament antibodies (IMF) were measured by immunofluorescence (IF). Anti-double-stranded DNA (ds-DNA) antibodies and extractable nuclear antigens (ENA: Sm, RNP, SSA, SSB, Scl70) were measured by ELISA and the rheumatoid factor (RF) by nephelometry. RESULTS: 388/1920 (4.6%) patients were ANA positive (antibody titres>1/160). On the other hand, clinical symptoms attributed autoimmune diseases (arthralgias, morning stiffness etc) plus autoantibodies other than ANA were present only in 8/312 (2.56%) patients with NHL, among them one with anti-cardiolipin antibodies. It is interesting that from these 8 patients, 3 had MALT lymphoma and 3 diffuse B-cell large cell lymphoma. Also, we detected anti-IMF and IgM and lgG anti-CMV antibodies in 2/312 (0.42%) patients with NHL. CONCLUSION: We conclude that the simultaneous presence of lymphoproliferative diseases and rheumatic syndromes are more frequent among lymphoma patients than in other lymphoproliferative diseases. Therefore, the screening of antibodies in NHL patients may be useful for the discovery and the treatment of an underlying autoimmune disease.

Candidemia in patients with acute leukemia.

PURPOSE: To present the clinical course and laboratory results of leukemic patients with candidemia and to comment on the incidence and clinical findings of mycoses in this particular patient population. PATIENTS AND METHODS: From 2002 to 2005 in the Department of Hematology of our institution 53 leukemic patients with clinical signs of infection and severe neutropenia after intensive chemotherapy presented 127 febrile episodes during which blood cultures were taken, both from central venous catheters and from peripheral veins with a sterile method as described elsewhere. RESULTS: 4/53 (7.5%) of neutropenic patients presented disseminated candidiasis with positive blood cultures with different species of Candida (C) according to the EORTC criteria. Two patients had strains susceptible to all or most antifungal agents, 1 had dose-dependent sensitivity and 1 had C. krusei resistant to all agents. Two patients died probably because of disseminated candidiasis, 1 survived and 1 died of unrelated cause. CONCLUSION: Fungal infections are not uncommon in patients with hematological malignancies, but they are rarely microbiologically documented. A fast and reliable means of diagnosis of invasive fungal infections is urgently needed.