Annalisa Gabriele

Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkins disease (HD) or aggressive non-Hodgkins lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET+/CT− relapsed, as compared with zero out of 29 patients in the PET−/CT− subset. Among the 41 CT+ patients, 10 out of 11 (91%) who were PET+ relapsed, as compared with 0 out of 30 who were PET−. The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET+ and PET− subsets, respectively (P=0.00001). All five patients who were PET+/CT− underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET−/CT+ (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Fludarabine-Containing Chemotherapy as Frontline Treatment of Nongastrointestinal Mucosa-Associated Lymphoid Tissue Lymphoma

Mucosa‐associated lymphoid tissue (MALT) lymphoma is a specific clinicopathologic entity with gastric and nongastrointestinal site involvement. The authors reported the clinical outcome of patients with Stage IE nongastrointestinal MALT lymphoma treated with a frontline fludarabine‐containing regimen or with a regimen containing cyclophosphamide, vincristine, and prednisone (CVP).

Extranodal Marginal Zone B-cell Lymphoma of MALT-type of the Lung: Single-center Experience with 12 Patients

The lung is a relatively rare site for mucosa-associated lymphoid tissue (MALT) lymphomas: we report the largest available single-center series of patients with this presentation. From August 1992 to October 2000, 12 patients with untreated primary low-grade MALT lymphoma of the lung were submitted either to chemotherapy alone (n =8), surgery alone (n =2) or surgery plus chemotherapy (n =2). At diagnosis, 6 (50%) were asymptomatic and 6 (50%) had nonspecific pulmonary symptoms. The most common radiologic findings were a pulmonary infiltrate (7 cases) and a mass lesion (5 cases). Histological diagnosis was obtained with transbronchial lung biopsy/bronchoalveolar lavage (BAL) (6 cases), with transthoracic needle biopsy (1 case), or an open thoracotomy (5 cases). All patients had stage IE. All 12 (100%) achieved complete remission; 3 (25%) local recurrences were observed. The global 6-year survival rate was 100% with a relapse-free survival rate of 50%. In conclusion, these data underline the diagnostic utility of BAL and the therapeutic efficacy of a chemotherapeutic strategy based on regimens such as N-CVP in the context of localized MALT lymphoma of the lung.

Value of oxaliplatin treatment in heavily pretreated patients with non-Hodgkin's lymphoma

In order to assess the efficacy and toxicity profile of oxaliplatin, a third generation platinum derivate active against several solid tumors, we carried out a study in a group of heavily pretreated patients with non-Hodgkins lymphoma (NHL). Between August 2003 and May 2004, 19 pretreated patients were enrolled in a phase II trial and were treated with oxaliplatin. The drug was administered intravenously on day 1 of a 21-day schedule, at a dose of 130 mg/m2 for a total of 6 cycles. One (5%) patient achieved complete remission (CR) and 5 patients (27%) had partial response (PR), thus giving an overall response rate of 32%. The patient in CR suffered from an aggressive B NHL. One of the 5 patients in PR had an aggressive B NHL, whereas the remaining 4 had an indolent B NHL. The treatment was well tolerated with minimal hematologic and extrahematologic toxicity. These data suggest and confirm the efficacy and low toxicity of oxaliplatin in the treatment of patients with heavily pretreated NHL. Further trials using oxaliplatin alone or in combination with other conventional drugs are needed.

High-dose therapy with autologous transplantation for aggressive non-Hodgkin's lymphoma: the Bologna experience.

Patients with aggressive non-Hodgkins lymphoma (NHL) who relapse after initial therapy have a poor prognosis and with standard dose salvage therapy the outlook remains poor. In this work we examine the patient characteristics and outcome of patients with aggressive NHL treated with HDT and autologous transplantation at our Institute from 1982 to 1999. A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for hematopietic recovery, complications of transplantation, response rates, overall survival (OS) and relapse-free survival (RFS). One hundred and thirty-four patients with aggressive NHL were treated with estimated 10-year OS and RFS rates of 50% and 66%, respectively. Disease status (sensitive vs. refractory) pre-HDT was the most powerful predictive parameter for OS and RFS, at both univariate and multivariate analysis. For the entire cohort, transplant-related mortality was only 3.5% without evidence of second malignancies. Our results confirm that HDT with autologous transplantation is associated with a durable RFS in a remarkable proportion of aggressive NHL patients with very low global early and late toxicity. Improved patient selection, transplant timing, ongoing improvements in supportive care, and selected phase III trials should increase outcomes further.

Efficacy and safety of oral fludarabine/cyclophosphamide regimen in previously treated indolent lymphomas.

The term ‘indolent’ refers to a lymphoid malignancy characterized by variable clinical presentation, high survival rate and scarce response to any therapeutic strategy. The introduction of promising new therapies, like purine analogs agents and, more recently, monoclonal antibodies has vastly increased the range of valid choices [1,2]. In particular, several reports have shown the efficacy of fludarabine in combination with mitoxantrone or cyclophosphamide in various lymphoproliferative disorders, both at diagnosis and relapse [3,4]. In addition to the IV formulation of fludarabine, a more convenient immediate-release oral formulation has been developed that shows similar efficacy and tolerability in pre-treated and untreated patients with chronic lymphocytic leukemia [5,6]. On the basis of these data, we started a monoinstitutional study with fludarabine-cyclophosphamide (FLU-CY) regimen in previously treated indolent lymphoma. Between April 2001 – October 2003, 12 patients with indolent lymphoma entered the study and were treated with fludarabine and cyclophosphamide. The main protocol requirement was that patients initially had advanced (stage III or IV) disease as defined by the Ann Arbor staging system [7], for which first-line treatment (fludarabine or other purine analogs as a prior therapy were admitted but no response was considered an exclusion criterion) had failed to produce complete response or relapse had occurred. Criteria for entry into the study included: histologic diagnosis of indolent B-cell lymphoma according to the REAL classification [8]; presence of measurable disease; normal hepatic, renal, cardiac function; radiation and chemotherapy had to be discontinued at least 6 weeks prior to treatment initiation. Informed consent was obtained from all patients in accordance with the ethical policy of the Institute. The study population included 12 patients. All the patients had recurrent, relapsed disease and none presented resistant disease. Patients’ characteristics are reported in Table I. The FLU-CY regimen schedule was: oral FLU at a dose of 40 mg m d for 3 days and oral CY at a dose of 300 mg m d for 3 days, every 4 weeks for a total of 6 cycles. Oral FLU was supplied by Schering S.p.A. (Milan, Italy). All patients received Pneumocystis carinii prophylaxis with co-trimoxazole (2 days per week) only during the entire course of therapy. Complete response (CR), partial response (PR) and no response were evaluated according to the international criteria [9]. Of the 12 patients studied, 8 (66%) fulfilled the criteria for CR and the remaining 4 patients did not respond to therapy (2 stable disease and 2 disease progression). The likelihood of response was related to the number of previous chemotherapy regimens. In fact, in the 6 patients who had previously received only one regimen, 5 CR were documented. In contrast, among the 6 patients who had received 2 or more different previous treatments, 3 CR were documented. Concerning the patients previously treated with purine analogs regimens, we observed CR in 4/4 (100%).