Patrizia Albertini

Nongastrointestinal Low-Grade Mucosa-Associated Lymphoid Tissue Lymphoma: Analysis of 75 Patients

PURPOSE Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma. PATIENTS AND METHODS From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient). RESULTS Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported. CONCLUSION Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites.

Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients

BACKGROUND Gemcitabine is a novel nucleoside analogue which has shown promising results in most solid tumors; like the arabinosylcytosine analogue, gemcitabine may be an active drug in lymphoproliferative malignancies. We tested it in pretreated peripheral T-cell lymphoma patients with isolated skin involvement. PATIENTS AND METHODS We performed a phase II study with the drug in 13 pretreated patients with peripheral T-cell lymphoma, five of whom had advanced-stage mycosis fungoides (MF), and eight peripheral T-cell lymphoma unspecified (PTCLU). Patients were treated on days 1, 8, and 15 of a 28-day schedule at the dosage of 1200 mg/m2 for a total of three courses. RESULTS Of the 13 patients, one achieved complete response (CR) and eight achieved partial responses (PR); the remaining four showed no benefit from the treatment. Among the responders, one CR and four PR were documented in the PTCLU patients and four PR in MF patients. Treatment was well tolerated; hematologic toxicity was mild and no nausea/vomiting or organ toxicity was recorded. CONCLUSIONS In view of its significant activity and its modest toxicity profile, the role of gemcitabine deserves further evaluation in the management of pretreated patients with peripheral T-cell lymphoma.

Isolated Central Nervous System Relapse in Aggressive Non-Hodgkin's Lymphoma: the Bologna Experience

Isolated central nervous system (CNS) relapse was evaluated in terms of incidence, risk factors, and outcome in a consecutive cohort of 175 patients with aggressive non-Hodgkins lymphoma in which no case of lymphoblastic or Burkitts lymphoma was encountered. All these patients had obtained a complete remission with first-line treatment and none had received prophylactic CNS treatment at diagnosis. Nine patients (5.2%) developed isolated CNS relapse after a median of 8 months from diagnosis. CNS involvement was documented by cerebrospinal fluid (CSF) cytology in 4 patients and on the basis of radiologic and clinical features in 5 others. Factors significantly associated with a greater likelihood of CNS relapse were advanced stage, B symptoms, bone marrow involvement, and high LDH levels in univariate analysis with only advanced stage being of significance in multivariate analysis. All relapsed CNS lymphoma patients died within a median time of 4 months from the disease recurrence, confirming the poor prognosis after CNS relapse and stressing the need to develop new treatment strategies for patients at high risk of CNS recurrence.

Clinical implications of serum levels of soluble CD30 in 70 adult anaplastic large-cell lymphoma patients.

PURPOSE In the last few years, the search for new biologic markers in high-grade non-Hodgkins lymphomas has provided important results. In particular, soluble CD30 (sCD30) levels were elevated in most patients with Hodgkins disease (HD) and anaplastic large-cell lymphoma (ALCL). PATIENTS AND METHODS From September 1988 to October 1993, treatment was completed in 70 previously untreated patients with ALCL, of whom 38 had the common type (ALCL-CT) and 32 had the Hodgkins-like subtype (ALCL-HL). Serum sCD30 levels were measured at the time of diagnosis and after induction polychemotherapy in all patients; in addition, the initial sCD30 levels were compared with those obtained from 50 stage-matched patients with HD. RESULTS Pretreatment levels of sCD30 were highly elevated in the stage-matched group of HD patients compared with healthy controls; median sCD30 levels in patients with ALCL-CT and ALCL-HL were 18 and seven times higher, respectively, than in patients with HD. The sCD30 level normalized on achievement of complete response (CR). The risk of lower relapse-free survival was associated with bulky disease, advanced stage, and high pretreatment sCD30 levels; the risk of lower overall survival was associated with advanced stage and pretreatment levels of sCD30 in both univariate and multivariate analysis. CONCLUSION The results of this study suggest that sCD30 is a specific prognostic indicator of the risk for lower complete response rate and relapse-free expectancy for patients with ALCL.

Advantages of Positron Emission Tomography (PET) with Respect to Computed Tomography in the Follow-up of Lymphoma Patients with Abdominal Presentation

For abdominal lymphoma patients, fluorine-18 fluorodeoxyglucose positron emission tomography (PET) provides unique information on the presence of residual active disease. We provide an update on the largest reported cohort of patients whose management following induction therapy was based on routine PET and computed tomography (CT) restaging. Fifty-nine patients with Hodgkins disease or aggressive non-Hodgkins lymphoma presenting abdominal involvement (35% with bulky disease) were studied with both PET and CT following combined chemotherapy/radiation treatment. After treatment, 3/3 (100%) patients who were PET+/CT- relapsed, compared with 0/7 patients in the PET-/CT- subset. Among the 49 patients who were CT+, six of the 10 (60%) who were PET+ relapsed, as compared with only two of the 39 (5%) who were PET-. The actuarial relapse-free survival (RFS) rates were 0 and 100% in the PET+/CT- and PET-/CT- subsets, respectively. In the PET+/CT+ subset, RFS was 94% at 5 years. PET restaging is very valuable for the identification of patients who would need appropriate second-line therapy because of the presence of residual active abdominal disease and should be made widely available in combination with CT.

Cytotoxic Combination of Loxoribine with Fludarabine and Mafosfamide on Freshly Isolated B-Chronic Lymphocytic Leukemia Cells

Fludarabine has shown a definite clinical activity in B-cell chronic lymphocytic leukemia (B-CLL). Recently it has been demonstrated that loxoribine, a guanine ribonucleotide derivative, is able to increase the cytotoxicity of fludarabine in B-CLL cells, in vitro. We have here extended these findings by testing the activity of loxoribine in combination with fludarabine and mafosfamide. As we have previously demonstrated, loxoribine enhances the activity of fludarabine at all concentrations, while only lower doses of mafosfamide seem to be positively affected by loxoribine. The combination of fludarabine and mafosfamide is synergistic on CLL cells, and the cytotoxic activity is increased by the addition of loxoribine. We have also evaluated the pro-apoptotic activity of each drug, both alone and in combination; these results are concordant with the cytotoxicity data, thus demonstrating that, even though loxoribine is more active in combination with fludarabine than with mafosfamide, the efficacy of the triple combination is higher than that obtained with any other agent alone or in double combination.

MACOP-B Regimen Followed by Involved-Field Radiation Therapy in Early-Stage Aggressive Non-Hodgkin's Lymphoma Patients: 14-Year Update Results

A single-center, retrospective study was conducted to evaluate therapeutic results of the MACOP-B third-generation chemotherapy regimen followed by involved-field radiation therapy in a stage I-II aggressive non-Hodgkins lymphoma (NHL) patients. From 1986 to 1995, 118 consecutive patients with the diagnosis of aggressive NHL, stage I-IE or II-IIE, with or without bulky disease were treated with MACOP-B regimen followed, when appropriate, by 30–36 Gy involved-field radiation therapy The complete response (CR) rate was 95% after the combined modality treatment (97% for stage I-IE and 93% for stage II-IIE). Patients with bulky disease had a CR rate of 92%. Treatment was well tolerated and no deaths occurred from acute toxicity. After a median follow-up of 68 months, 24 (21%) patients relapsed. The 14-year projected relapse-free and overall survival rates were 78% and d 69%, respectively. MACOP-B regimen with/without involved-field radiation therapy provides a safe and effective combined modality treatment for early-stage aggressive NHL, with the possibility to definitively cure two thirds of the patients

ABVD and radiation therapy as first-line treatment in advanced Hodgkin's disease.

The purpose of this study was to evaluate the efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and radiotherapy in advanced Hodgkins disease. In addition, to evaluate whether patients with slow responding tumors could profit from the early change of treatment regimen [MOPP (mechloretamine, vincristine, procarbazine, and prednisone)] followed by radiation therapy or autologous bone marrow transplantation (ABMT). Finally, to evaluate treatment options for patients with both early and late relapses. A total of 78 patients with previously untreated stages IIA bulky, IIB, III (A and B), and IV (A and B) Hodgkins disease were treated with the ABVD regimen followed by radiotherapy. Patients with stages IIIB and IV (A and B) were re-staged after 4 ABVD courses of the treatment: slow responders (response less than 70%) underwent second-line treatment (MOPP) and eventually ABMT. Relapsed patients with a long initial complete response (> or = 12 months) were treated with second-line conventional treatment and those patients with a short initial complete response (< 12 months) underwent ABMT. The complete response (CR) rate was 91% after ABVD and radiation therapy. An additional 5 stage IIIB and IV patients whose therapy was switched after 4 cycles because of a slow response obtained a CR (3 after 2 MOPP courses plus radiotherapy and 2 after 2 MOPP courses followed by ABMT). Including these additional CRs, the overall CR rate was 97%. No episodes of clinical cardiopulmonary toxicity were observed. With a median follow-up time of 42 months, the 4-year relapse-free survival was 87%. The 4-year overall survival was 96%. Ten cases relapsed: all but one obtained a second CR with different approaches depending on the timing of relapse. The ABVD regimen appears to be effective and well tolerated confirming the validity of this four-drug regimen in the treatment of advanced Hodgkins disease. In addition, therapeutic choices based on the timing of the relapse and the use of re-staging after 4 cycles in order to identify slow responders can play an important role in increasing the number of cured patients.