Monica Tani

Phase II Trial of Proteasome Inhibitor Bortezomib in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma

PURPOSE To determine the antitumor activity of the proteasome inhibitor bortezomib in patients with cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma unspecified (PTCLU) with isolated skin involvement. PATIENTS AND METHODS From May 2005 to June 2006 at our institute, we treated patients with previously pretreated CTCL or PTCLU using bortezomib as a single agent, at a dose of 1.3 mg/m2 intravenously on days 1, 4, 8, and 11, every 21 days for a total of six cycles. RESULTS Fifteen patients were registered, of whom 12 (10 CTCL, all mycosis fungoides, and two PTCLU with isolated skin involvement) were assessable. The overall response rate was 67%, with two (17%) complete remissions and six (50%) partial remissions. The remaining four patients had disease progression. Histologically, the responder patients were seven with CTCL and one with PTCLU with isolated skin involvement. All responses were durable, lasting from 7 to 14 or more months. Overall, the drug was well tolerated, with no grade 4 toxicity. The most common grade 3 toxicities were neutropenia (n = 2), thrombocytopenia (n = 2), and sensory neuropathy (n = 2). CONCLUSION This study suggests that bortezomib was well tolerated and has significant single-agent activity in patients with cutaneous T-cell lymphoma.

Role of [18F]Fluorodeoxyglucose Positron Emission Tomography Scan in the Follow-Up of Lymphoma

PURPOSE In lymphoma, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is routinely used for initial staging, early evaluation of treatment response, and identification of disease relapse. However, there are no prospective studies investigating the value of serial FDG-PET over time in patients in complete remission. PATIENTS AND METHODS All patients with lymphoma who achieved the first complete remission were prospectively enrolled onto the study and scheduled for serial FDG-PET scans at 6, 12, 18, and 24 months; further scans were then carried out on an annual basis. Overall, the population included 421 patients (160 patients with Hodgkins lymphoma [HL], 183 patients with aggressive non-Hodgkins lymphoma [NHL], and 78 patients with indolent follicular NHL). All patients had a regular follow-up evaluation, including complete clinical and laboratory evaluation, and final assessment of any suspect FDG-PET findings using other imaging procedures (computed tomography [CT] scan) and/or biopsy and/or clinical evolution. FDG-PET findings were reported as positive for relapse, inconclusive (when equivocal), or negative for relapse. RESULTS PET enabled documentation of lymphoma relapse in 41 cases at 6 months, in 30 cases at 12 months, in 26 cases at 18 months, in 10 cases at 24 months, and in 11 cases at more than 36 months. All 36 patients with inconclusive positive PET underwent biopsy; only 12 (33%) of 36 patients had a concomitant suggestion of positivity on CT. A lymphoma relapse was diagnosed in 24 (66%) of 36 patients. CONCLUSION Our results confirm FDG-PET as a valid tool for follow-up of patients with HL and NHL. In patients with inconclusive positive results, histologic confirmation plays an important role in identifying true relapse.

Gemcitabine as frontline treatment for cutaneous T-cell lymphoma: phase II study of 32 patients.

Based on the activity of gemcitabine in heavily pretreated patients with cutaneous T‐cell lymphoma (CTCL), the objective of the current study was to determine the role of gemcitabine in the treatment of patients with advanced, untreated CTCL.

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.

Anti-CD20 therapy for chronic lymphocytic leukemia-associated autoimmune diseases.

Rituximab is active in chronic lymphocytic leukemia (CLL) and may interfere with autoantibodies production in some immune diseases. We report the results of rituximab treatment in 7 patients with CLL-associated symptomatic autoimmune diseases refractory to standard immunosuppressive therapies: warm antibody hemolytic anemia (AHA) 4 patients, cold agglutinin disease (CAD) 1, immune thrombocytopenia (IT) I , axonal degenerating neuropathy (ADN) 1. Rituximab was given at the dose of 375mg/m2 per week for 4 weeks. One patient with AHA and one with CAD achieved complete normalization of hemoglobin levels and laboratory signs of haemolysis, with response duration (RD) of 8+ and 38+ months, respectively. In the patient with IT, complete remission was reached after the first week of treatment and RD was 6 months. The patient with ADN achieved a marked neurological improvement after rituximab therapy, with RD of 12 months. Retreatment of both patients with IT and ADN was effective. Rituximab may be an alternative agent for the treatment CLL-associated autoimmune diseases.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients

BACKGROUND A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

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).

Local chemotherapy with interferon-α for conjunctival mucosa-associated lymphoid tissue lymphoma: A preliminary report1

OBJECTIVE To evaluate the efficacy of subconjunctival interferon-alpha for the treatment of conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma. DESIGN Small, noncomparative, interventional case series. PARTICIPANTS Five patients with histologically proven conjunctival MALT lymphoma were studied prospectively. METHODS Patients were given 1,500,000 international units (IU) of interferon-alpha (IFN-alpha) (Roferon-A) subconjunctivally inside the lesion, three times a week for four weeks. If there was even a minimal response, a further cycle of 1,000,000 IU three times a week for four weeks was administered. Patients received a maintenance dose of 1 million IU, every 15 days for 4 times, after clinical resolution of the lesion. MAIN OUTCOME MEASURES Patients were followed clinically, with slit lamp examination, for evidence of tumor disappearance or recurrence. RESULTS Complete response was obtained in all patients. The lesion resolved completely by the eighth week. Four patients did not show any local recurrence with a median follow-up of 21 months (12-36 months). One patient presented with a recurrence after 11 months, in association with systemic lymphoma progression. CONCLUSIONS Local chemotherapy with IFN-alpha seems to be an effective treatment modality, alternative to radiotherapy, for conjunctival MALT lymphomas.

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.

18F-FDG PET in mucosa-associated lymphoid tissue (MALT) lymphoma

To evaluate the sensitivity of 18-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in patients with mucosa-associated lymphoid tissue (MALT) lymphoma. A total of 32 patients with a histological diagnosis of extra-nodal MALT lymphoma were referred to the PET Centers in the last 2 years (2003 – 2004) and scanned with 18F-FDG-PET following standard procedures. Overall, the results of 50 18F-FDG-PET scans performed in either active disease state or in complete remission were reviewed. Sites of primary disease included stomach, lung, parotid, skin, orbit, mandible, esophagus and uterus. This study retrospectively enrolled 26 patients with known active disease. 18F-FDG-PET was true positive (TP) in 21/26 patients and false negative (FN) in 5/26. Sensitivity of 18F FDG-PET for extra-nodal MALT was 81%. The data show that 18FDG-PET is a useful diagnostic tool in order to stage, restage or monitor disease in patients with extra-nodal MALT lymphoma.