Simona Bassi

Fatherhood during imatinib.

1 Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt, 2 Department of Medicine, Division of Hemato-Oncology, European Institute of Oncology, Milano, Italy, 3 Andrological Urology Unit and IVF Center, S Paolo Hospital, University of Milan, Milano, Italy, 4 Division of Medical Oncology, A Perrino Hospital and European Institute of Oncology, Brindisi and Milan, Italy and 5 Fertility and Pregnancy in Oncology Project, European Institute of Oncology, Milano, Italy

Rituximab in Lymphocyte-Predominant Hodgkin Disease

Background: Lymphocyte-predominant Hodgkin disease (LPHD) differs in biology and clinical behaviour from classic Hodgkin disease. Almost 100% of LPHD neoplastic cells express CD20 and thus rituximab could be effective; yet limited data are available. Patients and Methods: We performed a retrospective analysis on patients with LPHD who were treated with rituximab at our institution to determine the magnitude of benefit offered by this drug. Results: Seven patients were identified; 4 received the drug as single agent while the rest received it in combination with chemotherapy. All except 2 received the drug in the salvage setting. Response rate was 100% with 6 of 7 patients achieving complete remission. At a median follow-up of 2 years, 4 patients are still disease free while the rest relapsed at a median time of 27 months. Conclusion: Rituximab is effective in LPHD and should be considered; however, the optimal schedule remains to be determined.

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.

Peripheral T-lymphocyte subsets in patients treated with Rituximab-Chlorambucil combination therapy for indolent NHL.

The anti-CD20 chimeric monoclonal antibody, rituximab, is a well-established treatment for newly diagnosed or pretreated follicular non-Hodgkin’s lymphoma (NHL) patients and is able to induce molecular response in about 30% of the cases when used as single agent [1]. The addition of rituximab to chemotherapy improves the clinical and molecular remission rate and prolongs the time to treatment failure [2, 3] without any increase in infectious complications in randomized controlled trials. Prolonged rituximab treatment is associated with a depletion of circulating B cells; however, data are not available on T-cells peripheral subset after a rituximab chemotherapy combination treatment. We retrospectively investigated the effects of rituximab– chlorambucil combination therapy on peripheral blood lymphocyte subsets in 25 low-grade or follicular B-cell NHL patients (12 newly diagnosed and 13 relapsed/ refractory). The regimen [4] consisted of chlorambucil 6 mg/m daily for six consecutive weeks, in association with a standard four-weekly rituximab as induction phase. After revaluation, the responding patients received four additional cycles with chlorambucil (6 mg/m daily for 2 weeks monthly) plus rituximab (once monthly). All patients completed the planned treatment and were evaluated for response and toxicity. After induction, we observed absolute G2 and G3 lymphopenia in 13 and 6 patients, respectively. After consolidation, ten patients had G2 and five patients had G3 absolute lymphopenia. After a median of 9 months (3–30 months) from the end of treatment, six patients showed G2 lymphopenia. As expected, after the first administration of rituximab, immunophenotypic analysis showed a reduction of CD19/ 20+ positive cells below 0.1% in all the patients; that reduction was still present at revaluation after induction and consolidation therapy. As shown in Fig. 1, all the patients presented a significant CD4+ reduction (p<0.001), independent of the levels at baseline (median absolute CD4+ count, 246 cell/ μl), and this trend was maintained during the therapy (median absolute CD4+ count, 216 cell/μl). At median follow-up of 9 months in 50% of the patients, absolute CD4+ T cells had recovered within normal range. On the other hand, we observed no significant reduction of CD8+ and CD56+ absolute values. Infections were rare and none was fatal: two patients developed cutaneous HZV, one had perianal abscess, and one patient was hospitalized for HBV reactivation. To our knowledge, this is the first report on the T-cell profile in patients receiving a rituximab chemotherapy combined chemotherapy. Our experience suggests that chlorambucil–rituximab combination therapy induces a selective decrease of absolute CD4+ T cells during treatment. However, no major infection was observed; the lack of a correlation between the drop in CD4+ T cell count and an increase in infection rate could be related to the relative short period of absolute CD4+ low count. On the contrary, as recently observed by Kaplan et al. [5] in AIDSrelated lymphomas, this effect might justify the increased infectious death rates observed with rituximab-CHOP treatment. Ann Hematol (2006) 85:813–814 DOI 10.1007/s00277-006-0170-9

Intensified ChlVPP/ABVVP chemotherapy regimen and pegfilgrastim support in advanced Hodgkin lymphoma.

We present feasibility, toxicity and efficacy results of an intensified six-cycle ChlVPP/ABVVP regimen in advanced Hodgkin lymphoma (HL). From February 2004 to August 2007, 82 consecutive eligible patients were enrolled. According to the Hasenclever index, 64 patients (78%) were considered at low risk, 15 (18%) at intermediate and 3 (4%) at high risk. The most relevant toxicity was haematological: grade 3–4 neutropenia occurred in 32% of patients, grade 3–4 anaemia in 26% of patients. Severe infections and febrile neutropenia were observed in 8% of patients. With a median follow-up of 35 months (range 12–55), the three-year freedom from treatment failure (FFTF) and overall survival (OS) were 75% (95% CI 65%–86%) and 94% (95% CI 87%–99%), respectively. The intensified ChlVPP/ABVVP regimen in advanced HL is effective, does not seem to differ from standard regimens in terms of FFTF and OS and showed a favourable toxicity profile.

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