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.

Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents.

BACKGROUND: Renal impairment (RI) is a common presenting complication of multiple myeloma (MM); the availability of new treatments has improved the outcomes of patients with MM; however, their impact on the survival of patients who present with RI has not been extensively studied. PATIENTS AND METHODS: We analyzed the characteristics and outcomes of 1773 consecutive unselected patients who were treated for symptomatic myeloma since January 1990. RESULTS: Although there was a significant increase in the proportion of patients of advanced age in the more recent periods, the frequency of RI as well as the proportion of patients who presented with severe RI (eGFR < 30 ml/min/1.73 m(2)) remained unchanged around 18%. Thus, after adjustment for age, there was a decrease in the risk of severe RI at presentation after 2000. Myeloma response rates (≥PR) to frontline therapy have substantially increased, and this was translated in a significant increase in the median survival. Specifically for patients with severe RI, the median OS has improved from 18 and 19.5 months in the 1990-1994 and 1995-1999 to 29 and 32 months for the periods 2000-2004 and after 2005 (P = 0.005). Severe RI was associated with a high risk of early death (12% versus 7% for patients with moderate RI versus 3% for patients with mild or no RI (P < 0.001), especially among older patients, and has remained unchanged over time. CONCLUSIONS: There has been a major improvement in the survival of patients with severe RI in the past decade, despite the increasing numbers of patients of advanced age. However, the risk of early death remains high in patients with severe RI, especially in the elderly.

High dose chemotherapy and autologous stem cell transplantation in patients with multiple myeloma: the experience of a single haematological unit.

PURPOSE: To study the toxicity of high dose chemotherapy (HDCT) in multiple myeloma (MM) patients and its impact on event free survival (EFS) and overall survival (OS), and also the impact of thalidomide maintenance therapy on EFS and OS after HDCT. PATIENTS AND METHODS: From April 1999 to November 2006 37 patients (29 males, 8 females) out of a total of 38 scheduled were treated with HDCT and autologous peripheral stem cell transplantation (APSCT), as consolidation treatment after first- or second-line chemotherapy. Their median age was 55 years (range 38-71). HDCT regimen used was melphalan 200 mg/m(2). Following HDCT thalidomide 100 mg/day was administered as maintenance therapy to 28 patients in a random fashion. RESULTS: All patients tolerated well HDCT and APSCT. There was no treatment-related mortality. The median time interval for neutrophil recovery (>500/mm(3)) was 10 days (range 8-20), while the median time interval for platelets to recover to >20.000/mm(3) was 14 days (range 9-32). Twenty (54%) patients achieved complete response (CR), 15 (40%) partial response (PR), and 2 (6%) stable disease (SD). Before receiving thalidomide as maintenance treatment 12 (42%) patients were in CR, while all the others, except one who had progressive disease (PD), were in PR. CR correlated with better EFS and probably OS. Thalidomide maintenance treatment correlated with better EFS. CONCLUSION: In our series of patients HDCT appears to be a totally feasible, safe and without treatment-related mortality procedure, even in patients older than 60 years of age. It has a major impact in terms of CR achievement, which seems to strongly correlate with a prolonged EFS and OS. The use of thalidomide as a maintenance therapy induces a greater EFS which could possibly yield an improved OS.

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.

Epoetin beta (NeoRecormon) corrects anaemia in patients with hormone-refractory prostate cancer and bone metastases.

BACKGROUND: Severe anaemia is common in patients with metastatic, hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: We evaluated the efficacy of epoetin beta in correcting anaemia and maintaining haemoglobin (Hb) levels in this group of patients. Patients with HRPC, bone metastases and anaemia (Hb < 12 g/dl) were included. Epoetin beta, 30,000 IU per week in three divided doses, was administered subcutaneously, with iron supplementation when needed. If Hb increased by < 1 g/dl during the first 4 weeks of therapy the epoetin dose was increased (increments of 5,000 IU per dose) at fortnightly intervals to a maximum of 60,000 IU per week. Patients with haematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb level > or = 12 g/dl without blood transfusions) went on to receive epoetin beta 10,000 IU once weekly for up to 24 weeks. RESULTS: All 29 evaluable patients demonstrated a haematopoietic response to epoetin beta treatment. None of the patients required blood transfusions. All patients showed improvements in quality of life (assessed using the EORTC QLQ-C30 questionnaire). Hb levels were maintained for the remainder of the trial. Epoetin beta was very well tolerated. CONCLUSION: Epoetin beta therapy resulted in a rapid and sustained improvement in Hb levels in patients with HRPC metastatic to bone.

Chronic myelogenous leukemia terminating in acute megakaryoblastic leukemia. Case report.

A case of chronic myelogenous leukemia (CML) terminating in acute megakaryoblastic leukemia (AMKL) is here presented. Megakaryoblasts were identified by the presence of platelet peroxidase in the bone marrow as well as in pleural effusion and ascites. The clinical course, morphology and immunologic studies of the blast cells are described in this report.

Aplastic anemia. Report of a case with recurrent episodes in consecutive pregnancies.

BACKGROUND: Aplastic anemia complicating normal pregnancy is a rare event, associated with increased risks for both mother and fetus. CASE: A 30-year-old woman in her fifth pregnancy experienced the complications of aplastic anemia and preeclampsia. The patient had a history of four unsuccessful previous pregnancies also complicated by aplastic anemia, but she was free of the disease in the intervals between the pregnancies. During this last pregnancy she presented at 31 weeks' gestation with symptoms and signs of severe aplastic anemia and preeclampsia. A cesarean section was performed, and a normal infant was born. Supportive therapy, growth factors, prednisolone and intravenous immunoglobulin were administered, and the patient's general condition improved two weeks after delivery. CONCLUSION: Aplastic anemia may occur during consecutive pregnancies. The gestational age at the onset of the disease and the severity of the symptoms determine the outcome of the pregnancy.

Combination therapy with recombinant human erythropoietin, interferon-alpha-2b and granulocyte-macrophage colony-stimulating factor in idiopathic myelofibrosis.

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.