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Rituximab is an effective treatment for CD20+B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8–135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25–35.9%), than in autoimmune diseases (9.4–17.5%) (p<.0001). Grade 3–4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies. [ABSTRACT FROM AUTHOR]

Complementary and alternative medicine (CAM) is common in patients with cancer and its use is steadily increasing over time. We performed a multicenter survey in which the use of CAM in 442 Italian patients with chronic lymphocytic leukemia (CLL), the commonest form of leukemia in Western countries, was assessed. Data were collected by means of a face-to-face standardized questionnaire with several items. Mean age was 69 years; 258 patients (58%) were male and 184 (42%) female. Seventy-three patients (16.5%) were found to be CAM users. The most common CAM therapies were green tea, aloe formulations and high dose vitamins. Predictors of CAM use were female gender, younger age, higher education level, internet availability and newspaper reading. The reasons for CAM popularity among these patients are complex. Given the number of patients combining therapy with CAM and its possible drug interactions, doctor interest as well as patient education about CAM should be improved. [ABSTRACT FROM AUTHOR]

Current treatments for non-Hodgkin lymphomas are not optimally effective. Among new agents, bortezomib seems to play a pivotal role in the regulation of several cell pathways involved in the development of lymphomas. After results were obtained with clinical trials, we aimed to observe treatment with bortezomib in everyday clinical practice. We performed a multicenter retrospective analysis to assess the efficacy of bortezomib in heavily pretreated (median number of previous therapies 4, range 2-6) lymphoma patients in an off-label setting. Bortezomib therapy was scheduled for 4-6 cycles (1.3 mg/m2 biweekly). Data from 50 patients were collected: 22% had a complete remission, 26% obtained a partial response and the remaining 52% was non-responder. According to histotype, we observed an overall response rate (ORR) of 51.6% in mantle cell lymphomas, an ORR of 60% among follicular lymphoma patients, and an ORR of 50% in the indolent nonfollicular lymphomas. None of diffuse large B-cell lymphoma patients obtained a response. Extra-hematological toxicity was really mild, and peripheral neuropathy occurred in only 5 patients; hematological toxicity was grades 3-4 thrombocytopenia in nine patients and grades 3-4 neutropenia in only three patients. In conclusion, treatment with bortezomib as single agent resulted safe and effective in a subset of heavily pretreated lymphoma patients with usually poor outcome. New future hypotheses of investigation are indicated. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Several trials comparing the efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in elderly patients with multiple myeloma (MM) have been reported, with inconsistent results. The primary goal of our study was to evaluate the efficacy and toxicity of MP versus MPT in newly diagnosed patients with MM who were transplant-ineligible or over age 65. A total of 135 patients were enrolled. Either minimal response or better or partial response or better were more frequent with MPT treatment ( p == 0.001). After a median follow-up of 30 months, median progression-free survival (PFS) and overall survival (OS) were 33 and 52 months for MPT versus 22 and 32 months for MP, respectively. The comparison showed a significant advantage for MPT versus MP in PFS ( p == 0.02) and only a trend for OS ( p == 0.07). Severe adverse events were observed more frequently with MPT. In conclusion, our results show an improved activity of MPT at a cost of increased toxicity. We believe that MPT can be considered one of the new standard of care for elderly or transplant-ineligible patients with MM. [ABSTRACT FROM AUTHOR]

We report four patients (mean age 65 yr; range 40–77 yr) affected by acquired pure red cell aplasia (PRCA) complicating chronic lymphoid disorders and treated with anti-CD20 monoclonal antibody rituximab. Three out of four patients were given packed red cell transfusion. Steroids and recombinant erythropoietin (r-Epo) were also administered as first-line therapy without response. After a mean time of 57 d (range 23–62 d) from PRCA diagnosis, all patients received rituximab at a dosage of 375 mg/m2/wk for four consecutive weeks. First injection side effects of rituximab were minimal. All patients showed an increase in hemoglobin levels in response to rituximab, in one patient just after the first dose, in another patient after the second and in two other patients after the third dose. Three patients (75%) were considered in complete remission (CR) and one patient (25%) in partial remission 4 wk after the last rituximab infusion, despite a CR was obtained later (16 wk following the beginning of the therapy). Finally, at the last follow-up (mean 18.5 months, range 2–60 months), all patients were alive and in continue CR. Despite very limited in number, these results suggest that rituximab is very effective in the treatment of PRCA complicating B-cell chronic lymphoproliferative disorders. [ABSTRACT FROM AUTHOR]

Patients with aggressive NHL who fail initial treatment or subsequently relapse have a very poor outcome and less than 20–25% achieve a prolonged disease-free interval with salvage therapies. To improve the outcome of patients with refractory aggressive NHL not suitable for High Dose Therapy (HDT) and Autologous Stem Cell Transplant (ASCT), the efficacy of a combination of gemcitabine, vinorelbine, procarbazine and prednisone (ViGePP) were tested. Between November 1999 and September 2002, 69 patients with relapsed or refractory aggressive NHL were treated with ViGePP regimen, every 4 weeks up to six courses. At the end of planned chemotherapy patients could receive additional radiotherapy on residual masses or on sites of previously bulky disease. Sixty-six patients were available for evaluation of study end-points. Thirty patients were refractory to therapy and 36 patients had relapsed after remission obtained with previous therapy. At the end of therapy, complete remission (CR) rate was 23%, 3-year relapse free survival rate was 40% and 3-year overall survival rate was 25% for the whole series (29% and 20% for relapsed and refractory patients, respectively). Patients achieving CR with ViGePP had a significantly better survival as compared with the remaining ones ( p = 0.0003). ViGePP as used in the present setting has demonstrated a promising activity, comparable to other conventional dose regimens. Although CR was achieved only in a minority of patients, this was durable in a significant proportion of them. This regimen should be tested in less heavily pre-treated patients and probably in combination with new active agents such Rituximab. Further developments of this combination are warranted. [ABSTRACT FROM AUTHOR]

Primary breast lymphomas (PBL) are uncommon neoplasms. Seven PBL were diagnosed between March 1993 and October 2002. A lumpectomy ( n = 4) or radical mastectomy ( n = 3) was performed; 5 patients were in clinical stage (CS) II and 2 in CS IV; 6 patients received the CEOP regimen (cyclophosphamide, vincristine, epirubicin and prednisone) after surgery and 4 also had additional radiotherapy; 1 patient did not receive any treatment after local excision. Five patients (71%) achieved complete remission and 2 (29%) partial remission, with an overall response rate of 100%. All remitter patients are alive and well after a median follow-up of 75 months (range 10 – 121 months). Two patients in partial remission died of progressive disease. After a median follow-up of 99 months (range 84 – 111 months) for surviving patients, the 10 year overall and disease-free survival rates are both 71%, with 5 patients well and still free of disease. We conclude that the optimal sequence of full-dose anthracycline-containing regimens and radiation therapy should be the treatment of choice for patients with PBL. [ABSTRACT FROM AUTHOR]

OBJECTIVES:The aim of our study was to evaluate the nature of focal liver lesions detected during the ultrasound follow-up of a population (prevalently anti-hepatitis C virus [anti-HCV] positive) with chronic liver disease.METHODS:The study population consisted of 1827 consecutive newly diagnosed chronic liver disease cases without liver nodules at enrollment. Patients were screened at 4-month intervals by ultrasound and serum α-fetoprotein assessment. All lesions detected on imaging studies (except those accompanied by diagnostic α-fetoprotein levels) were subjected to biopsy (histology and cytology).RESULTS:During the 7-yr follow-up period (mean = 43.1 months), one or more solid focal lesions were found in 287 patients. α-Fetoprotein was diagnostic for hepatocellular carcinoma in 51 patients. Ultrasound-guided fine-needle biopsy was performed in the remaining 236 patients, yielding a diagnosis in 214: 198 hepatocellular carcinomas, 11 dysplastic nodules, and five B-cell non-Hodgkin’s lymphomas (all confined to the liver and all in patients with chronic HCV infection). Twenty-two patients with nondiagnostic biopsies received diagnoses of hepatocellular carcinoma (20) or dysplastic nodules (two) based on arteriography or surgical biopsy.CONCLUSIONS:Focal lesions arising in patients with HCV-related chronic liver disease can be other than hepatocellular carcinoma, and ultrasound-guided fine-needle biopsy plays an important role in their diagnosis. The prevalence of non-Hodgkin’s lymphoma in this selected population was 0.31%. The fact that all five lymphoma patients had cirrhosis related to hepatitis C strengthens the hypothesis of an etiological correlation between the latter infection and B-cell lymphoproliferative disorders. [Copyright &y& Elsevier]

Discusses the prognosis and treatment for primary central nervous system lymphoma (PCNSL) in immunocompetent adults. Combination of chemotherapy and radiotherapy for PCNSL; Review on the pharmacodynamic properties and therapeutic potential in the chemotherapy of lymphomas; Need for an optimal treatment of patients with PCNSL.

Presents a letter to the editor of the periodical 'Leukemia & Lymphoma; concerning the management of primary gastric lymphoma (PGL). Survival of patients with PGL; Clinical features; Types of treatment.

Presents a letter to the editor of the periodical 'Leukemia & Lymphoma' concerning the evaluation of CD52 expression in B-cell chronic lymphocytic leukemia. Functions of CD52; Antigenic density of CD52 on B- and T-lymphocytes; Detection of peripheral blood lymphocytes.

Presents a letter to the editor on the prevention of high-dose melphalan-induced mucositis by cryotherapy.

We report a case of Guillain-Barré Syndrome (GBS) which appeared after mobilization therapy in a patient with B-cell chronic lymphocytic leukemia (B-CLL). After obtaining a partial remission with four cycles of fludarabine at standard dose, the patient underwent to high-dose Cytoxan in order to mobilize CD34+ hematopoietic progenitor cells. During neutropenia the patient experienced fever of unknown origin (FUO) and subsequently developed GBS with normalization of his neurologic condition after 2 months. It is possible that a viral-induced activation of an antigen-specific T and B-cell clone caused a local inflammation and toxicity of Schwann cells with demyelination and axonal damage with a self-limited course. [ABSTRACT FROM AUTHOR]

This article reports the response of rituximab treatment in adults with chronic idiopathic thrombocytopenic purpura. Using the classical schedule of rituximab administration authors found that about half of patients experienced a long-lasting complete or partial response. In addition, they described two main pattern of response to rituximab. The first one with a rise of the platelet count occurring early, usually after the first antibody administration. To perform surgical ablation of breast nodule, treatment with intravenous Immunoglobulins was started with a platelet rise to 66,000/ml. An increase of platelet count was observed after the first administration of rituximab, followed by reduction to pre-treatment value.

We report an episode of severe bradycardia that occurred in a 49-year-old woman with fever and malignant jaundice during antibiotic therapy with linezolid, a new oxazolidinone with activity against Gram-positive cocci. In our case, the strict temporal dependence between bradycardia and linezolid therapy seems to provide strong evidence for a causal relationship. To our knowledge, this is the first report of linezolid-induced bradycardia. This adverse event confirms that the new antibiotic linezolid should be administered with caution in patient with jaundice and hepatic insufficiency. [Copyright &y& Elsevier]

Doxorubicin is the most effective single agent in the treatment of non-Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarily in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of nonpeghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using NPLD. Nine hundred and forty-six consecutive pts treated with R-COMP (doxorubicin was substituted with NPLD, Myocet) were collected. Median age was 74 years, the reasons for use of NPLD were: age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49.9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, and uncontrolled hypertension). Overall 687 pts (72.6%) obtained a complete remission (CR). About 5% (n = 51) of subjects developed major cardiotoxic events including heart failure (N = 31), ischemic heart disease (N = 16), acute heart attack (N = 3), and acute pulmonary oedema (N = 1). After a median follow-up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months disease free survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R-COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment., (© 2020 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Autoimmune hemolytic anemia (AIHA) is a well-known complication of chronic lymphocytic leukemia (CLL). In recent years the anti-CD20 monoclonal antibody rituximab has been used for the therapy of steroid-refractory AIHA and autoimmune thrombocytopenia, either idiopathic or in association with CLL. We report the results of rituximab treatment for 14 patients suffering from CLL-associated AIHA. They developed a direct antiglobulin test positive AIHA at a mean time of 47 months (range 0-135 months) from the diagnosis of CLL. In 3 cases AIHA was diagnosed at the same time as CLL. Only 1 patient had fludarabine-related AIHA. All patients received steroids as first-line treatment. At a mean time of 46 days (range 1-210 days) from the diagnosis of AIHA all patients received rituximab at a dosage of 375 mg/m(2)/weekly for 4 weeks. All patients except 3 (2 died of cardiac failure or sepsis soon after the third cycle and 1 HCV-positive patient experienced a rise in serum amino transferases) completed the scheduled four programmed cycles. First injection side effects of rituximab were minimal. All but 2 patients showed an increase in hemoglobin levels in response to rituximab (mean value 3.6 g/dl; range 0.7-10 g/dl) and a reduction in the absolute lymphocyte count and lymph nodes and spleen volume. Nine patients required packed red cell transfusions before starting rituximab; 5 no longer needed transfusions just after the second cycle and another patient after the fourth cycle. Three patients (22%) were considered to fully respond and 7 (50%) only responded partially. At a mean follow-up of 17 months, 8 patients were still alive, 6 of them transfusion-free. Our results prove that the anti-CD20 monoclonal antibody is an effective and well-tolerated alternative treatment for CLL-associated AIHA.