Paola Bertazzoni

Impact of B-cell count and imaging screening in cMBL: any need to revise the current guidelines?

Impact of B-cell count and imaging screening in cMBL: any need to revise the current guidelines?

Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients.

The aim of this study was to investigate the efficacy of combined treatment with rituximab and subcutaneous cladribine in patients with newly diagnosed and relapsed chronic lymphocytic leukemia (CLL). Forty-three patients with active CLL or small lymphocytic lymphoma received rituximab 375 mg/m2 on day 1 and cladribine 0.1 mg/kg subcutaneously on days 2–6. The treatment was repeated every 4 weeks for a total of four cycles. Sixteen patients were pretreated. The overall response rate was 88% (50% complete remission and 38% partial remission). The median time to treatment failure was 37.9 months. Grade 4 neutropenia developed in 5% of patients. The data indicate that combination therapy with rituximab and cladribine is a valuable and safe treatment for patients with CLL.

Primary cardiac lymphoma with isolated parenchymal central nervous system relapse: report of two cases and review of the literature

Primary cardiac lymphoma (PCL) is a rare subset of non-Hodgkin’s lymphoma involving the heart and/or pericardium with no or minimal evidence of extracardiac involvement at presentation. Distant relapses have infrequently been observed. We report two cases of this disorder that showed isolated central nervous system (CNS) relapse. Diagnosis by endomyocardial biopsy was consistent with diffuse large B-cell lymphoma. After immunochemotherapy they achieved complete remission (CR). Eight and five weeks after, isolated CNS relapses were observed respectively. The first patient was treated with high-dose methotrexate (HD-MTX) and high-dose cytarabine, resulting in a second CR. She then went onto receive autologous stem-cell transplantation but unfortunately died shortly after because of infection. The second patient received systemic CNS prophylaxis with HD-MTX, and later she was treated with an induction chemotherapy strategy with evidencing of progressive disease after two courses of treatment. She was subsequently initiated on a salvage therapy with cytarabine, followed by whole-brain radiotherapy, and autologous stem-cell transplant (ASCT), finally achieving a complete remission. Isolated CNS relapse is a very uncommon pattern in PCL and a standard approach to treatment is not yet well established. Nevertheless, the importance of CNS evaluation, using magnetic resonance imaging (MRI) and lumbar puncture, in patients with PCL should be considered, and further studies are recommended to determine the appropriate management of this complication.

Once-weekly carfilzomib, pomalidomide, and low-dose dexamethasone for relapsed/refractory myeloma: a phase I/II study

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Secondary haematological malignancies after radioimmunotherapy

Dear Editor, Concerning the letter to the editor by Piccin et al. [1], we would like to report the experience of the Haematoncology Division of European Institute of Oncology. We recently observed two patients treated with radioimmunotherapy (RIT; 90Y-DOTATOC/Lu177-DOTATOC) because of the presence of neuroendrocrine tumours. The first patient was a male of 75 years old; he had a bowel neuroendocrine tumour with secondary liver localizations. He developed an AML with trilineage dysplasia at 2 years following RIT, with this karyotype: 59,XYY,+4,+6, +10,+11,+11,+15,+16, -9,+20,+5mar[3]/46,XY[47]. The blood count at diagnosis was WBC 2,270/mmc, platelets 44,000/mmc and Hb 8.6 g/dl. The second patient was a male, 41 years old. He had a prostatic neuroendocrine tumour with secondary lymph nodes, bone and lung localizations. He developed a secondary AML at 4 years following RIT, with this karyotype: 43∼50,XY,+1[8],del(1)(q21)[6],del(5)(q22q33) [14],+del(5)(q22q33)[9],-7[13],+8[12],+9[13],+11[12],del (12)(p12)[9],-14[14],-16[2],-17[12],-18[6],-18[3],+21[7], +22[12][cp15]/46,XY[5]. The blood count at diagnosis was WBC 18,560/mmc, blasts 76%, platelets 141,000/mmc, Hb 8.5 g/dl. The first patient received from 2005 to 2006 a cumulative dose of Y90 DOTATOC 200 mCi, then received LU 177 DOTATOC from 2006 to 2009 (with a cumulative dose of more than 300 mCi). The second patient received Y90 DOTATOC from 2006 to 2007 with a cumulative dose of 200 mCi. Both patients receiving standard induction chemotherapy for acute leukaemia (ARA-C and daunorubicin) did not achieve any remission for leukaemia showing a resistant/ refractory disease; the first patient died after 113 days following diagnosis, the second one was lost to follow-up after 58 days following diagnosis. It is well known as RIT could induce renal toxicity but is not well established the possible incidence of secondary tumours, as well as haematological malignancies, as late complications of this treatment. The presence of these complications in our patients as well as the other one presented by Piccin et al. [1] raises the issue of how to investigate the real incidence of such late complications. We suggest data collection from all patients with neuroendocrine tumours treated with RIT in a specific registry to evaluate the real incidence of haematological malignancies and solid tumours that may affect clinical results achieved in such indolent disease, using radio-labelled compounds.

Severe neuropathy in a patient with Waldenstrom disease: From a challenging diagnosis to clinical improvement by innovative therapy

Symptomatic neuropathy affects about 30 – 50% of patients with IgM monoclonal gammopathy whose prevalence in the population older than 50 years is about 100 per 100,000. Approximately one third of patients presenting with IgM monoclonal gammopathy and symptomatic neuropathy have Waldenstrom macroglobulinemia (WM) and about 15% have monoclonal gammopathy of uncertain significance (MGUS). Several forms of neuropathies have been associated with IgM monoclonal gammopathy, depending on different pathogenesis. Cranial nerve palsies and mononeuropathies have been related to direct lymphoplasmacitic infiltration of nerves, microangiopathy of vasa nervorum or amyloidosis. Neuropathies due to the reactivity of the M-protein with different neural antigens such as MAG, cytoscheletal proteins and gangliosides show an immunemediated pathogenesis and often have a homogeneous clinical presentation. This is characterized by chronic progressive, symmetric and mostly distal deep sensory involvement, gait ataxia and postural tremor in upper limbs, while motor impairment is usually less important and often presents later [1]. Treatment of these neuropathies is mainly directed against the haematological disease, which represents the pathogenetic mechanism [2]. While there is no general agreement on treatment of patients who present with MGUS associated with an immune-mediated sympthomatic neuropathy, patients with sympthomatic WM need appropriate therapy for the haematological disease: the most common worldwide treatment consists in alkylating based chemotherapy, mainly chlorambucil used alone or in combination with prednisone [3]. More recently, nucleoside analogues have been successfully used in WM patients achieving a higher and faster response rate [4]. Rituximab is a chimeric monoclonal antibody that has been successfully used in patients with indolent and aggressive non-Hodgkin’s lymphoma [5]. Since the CD20 antigen is expressed on the cell surface of Waldenstrom disease, Rituximab could represent a novel approach in symptomatic WM patients. Here, we present our experience in a 61 year-old male patient referred to our institution to investigate the IgM gammopathy. His performance status was limited by a severe peripheral neuropathy. The symptoms began in 1999 as progressive distal sensitive-motor deficit characterized by a deficiency in strength and tactile sensitivity of distal lower limbs which finally compromised the patient’s walking. The patient suffered from diabetes, and therefore it was firstly assumed that neuropathy was diabetes-related but a well balanced glycemic profile definitely excluded this hypothesis. In February 2001, he became unable to walk without crutches; therefore, two cycles of high dose i.v. Ig were delivered, but no benefit was observed. In October 2001, MNR of the brain, lumbar puncture and biopsy of the sural nerve were performed; moreover, the presence of serum auto-antibodies (MAG, SGPG, GD1b ganglioside) was investigated. None of the aforementioned analyses showed pathological results, except for the sural-nerve biopsy which revealed the