M. Bendandi

Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients.

PURPOSEnTo evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine antimetabolite with a low-toxicity profile and activity in several solid tumors, in patients with relapsed or refractory cutaneous T-cell lymphomas.nnnPATIENTS AND METHODSnBetween May 1997 and February 1999, 44 previously treated patients with mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU) with exclusive skin involvement (n = 14) were enrolled onto a two-institution, phase II trial and treated with gemcitabine. This drug was given on days 1, 8, and 15 of a 28-day schedule at a dose of 1,200 mg/m(2) intravenously over 30 minutes for a total of three courses.nnnRESULTSnOf the 44 patients, five (11. 5%) achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the remaining 13 showed no benefit from the treatment. Two of the CRs were histologically confirmed. The CR and PR rates were the same for patients with MF and those with PTCLU, respectively. No difference in terms of overall response rate was observed between relapsed and refractory patients. The median durations of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15 months), respectively. Treatment was well tolerated; hematologic toxicity was mild, and no nausea/vomiting or organ toxicity was recorded.nnnCONCLUSIONnThe results of the present phase II study show activity of gemcitabine as a single agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that use gemcitabine alone or in combination with other drugs in earlier stages of the disease are needed.

The role of positron emission tomography (PET) in the management of lymphoma patients

BACKGROUNDnTreatment of both Hodgkins disease (HD) and aggressive non-Hodgkins lymphoma (NHL) with abdominal presentation at the time of diagnosis is often followed by detection of residual masses by computed tomography (CT). However, CT is usually unable to discriminate between residual tumor and fibrosis/necrosis. We investigated the ability of fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to differentiate between residual active tumor tissue and fibrosis.nnnPATIENTS AND METHODSnForty-four patients with HD or aggressive NHL presenting abdominal involvement (41% with bulky mass) were studied with CT and PET at the end of chemotherapy +/- radiation therapy.nnnRESULTSnAfter treatment, seven patients had negative PET and CT, and none of them relapsed. The remaining 37 patients all had positive CT (abnormalities < or = 10%). All of the 13 who also had positive PET relapsed (100%). By contrast, there was only 1 (4%) relapse among the 24 patients who were positive at CT but negative at PET. The two-year actuarial relapse-free survival rate was 95% for those with negative PET compared with 0% for positive PET patients (P < 0.000000).nnnCONCLUSIONSnIn lymphoma patients with abdominal masses who present CT positivity at restaging, PET should be considered the noninvasive imaging modality of choice for differentiating early recurrences or residual disease from fibrosis.

Therapy with gemcitabine in pretreated peripheral T-cell lymphoma patients

BACKGROUNDnGemcitabine 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.nnnPATIENTS AND METHODSnWe 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.nnnRESULTSnOf 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.nnnCONCLUSIONSnIn 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.

Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients.

PURPOSEnDuring the last few years, the application of CD30 monoclonal antibodies has led to the identification of a new lymphoma entity, termed anaplastic large cell lymphoma (ALCL). This tumor includes four distinct histologic subtypes, among which the Hodgkins-like/Hodgkins-related one (ALCL-HL) shares morphologic and phenotypic features with Hodgkins disease (HD).nnnPATIENTS AND METHODSnFrom September 1988 to October 1993, 90 ALCL patients were treated with third-generation chemotherapy regimens (either vincristine, cyclophosphamide, fluorouracil, cytarabine, doxorubicin, methotrexate with leucovorin, and prednisone [F-MACHOP] or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]) during the course of an Italian multicentric randomized trial on high-grade non-Hodgkins lymphomas (HG-NHL). In particular, 47 patients had ALCL of the common type (ALCL-CT) and 43 ALCL-HL. Null phenotype was the most common (39.8%), while T-cell, B-cell, and hybrid forms accounted for 35.5%, 22.2%, and 2.5%, respectively.nnnRESULTSnComplete remission (CR) was achieved in 66 of 90 (73.5%) patients (33 of 47 [70%] with ALCL-CT and 33 of 43 [77%] with ALCL-HL). The majority of the patients in CR (56.5%) were alive and well at a median follow-up time of 38 months; no significant differences were observed between the two histologic groups, with the rate of complete responders being 49% and 65% in ALCL-CT and ALCL-HL, respectively. The probability of relapse-free survival (RFS), projected at 63 months, was 67% for ALCL-CT and 82% for ALCL-HL. The risk of lower CR and RFS rates was associated with the presence of bulky disease, advanced stage, and B symptoms.nnnCONCLUSIONnThe data of the present study confirm that ALCL responds to third-generation chemotherapy regimens similarly to other aggressive malignant lymphomas in terms of both CR and RFS rates.

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.

Fludarabine treatment in resistant Waldenstrom's macroglobulinemia

Abstract: Fludarabine (FLU) is a fluorinated purine analogue with a promising antineoplastic activity in lymphoproliferative disorders. In this study, we evaluated the efficacy of FLU in 12 previously treated (primary refractory and refractory relapse) patients with Waldenstroms macroglobulinemia. All patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days for a total of six courses. Of the 12 patients, 5 (41%) achieved partial response (PR), and the remaining 7 showed no benefit from the treatment. An increased response rate was obtained in the 4 primary refractory patients in which 2 PR were documented. Treatment was well‐tolerated and there were no Fludarabine‐related fatalities. With a mean follow‐up of 10 months, only 1 PR patient has relapsed. Fludarabine is an interesting new salvage agent effective against recurrent/resistant Waldenstroms macroglobulinemia and should be evaluated in further studies in untreated patients with Fludarabine in monochemotherapy or in combination with other active modalities.

Fludarabine-mitoxantrone combination-containing regimen in recurrent low-grade non-Hodgkin's lymphoma

BACKGROUNDnThe promising results of fludarabine (FLU) in chronic lymphocytic leukemia have prompted its extensive evaluation in low-grade non-Hodgkins lymphoma (LG-NHL). Its different mechanisms of action make FLU an attractive partner for combination with other cytostatic agents.nnnPATIENTS AND METHODSnWe used a three-drug combination of FLU (25 mg/m2 i.v. on days one to three), mitoxantrone (10 mg/m2 i.v. on day one) and prednisone (40 mg given orally on days one to five) (FMP) to treat 48 patients with recurrent LG-NHL.nnnRESULTSnOf the 48 patients, 17 (35%) achieved complete responses (CR), 23 (48%) partial responses, while the remaining 8 (17%) showed no benefit from the treatment. The risk of lower CR rate was significantly correlated with the presence of advanced stage (IV) (P = 0.01), the number of previous regimens (> or = 3) (P = 0.006), and the follicular histologic subtype (P = 0.02). The major toxic effects observed were neutropenia and infections; there was only one fatality, due to drug-related side effects.nnnCONCLUSIONSnThese data confirm the significant efficacy of the FMP fludarabine-mitoxantrone combination regimen in obtaining a good remission rate with moderate toxicity in a particular subset of recurrent LG-NHL.

Nongastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas: Clinical and therapeutic features of 24 localized patients

BACKGROUNDnPeripheral B-cell lymphoma of the marginal zone (MALT, low-grade), presenting as localized, extranodal disease, usually affects the elderly. The gastrointestinal tract is the most frequently involved extranodal location, representing 70% of all MALT lymphomas. Recently, numerous other extranodal sites involved by MALT lymphomas have also been described.nnnPATIENTS AND METHODSnFrom January 1990 to October 1995, 24 patients with untreated nongastrointestinal low-grade MALT lymphoma were submitted to treatments ranging from the local approach of radiotherapy and local alpha-interferon (alpha-IFN) administration to chemotherapy. The tumours were located in the lung (seven cases), conjunctiva (four cases), lachrymal gland and orbital soft tissue (four cases), salivary glands (three cases), skin (three cases), breast (two cases), and thyroid (one case). All patients had low-grade stage IE tumours.nnnRESULTSnChemotherapy was administered in 11 patients (six with lung, three with salivary gland, one with breast, and one with thyroid locations); radiation therapy was employed in seven patients (three with lachrymal gland, three with skin, and one with breast locations); local alpha-IFN administration was administered in five patients (four with conjunctival, and one with lachrymal gland sites); and surgery was employed in one patient with a lung tumour. All patients achieved complete remissions; three local recurrences and two relapses in other sites were observed. The global five-year survival rate was 100% with a relapse-free survival rate of 79%.nnnCONCLUSIONSnThese data confirm the significant efficacy of different therapeutic approaches to specific sites inbes obtaining a good remission rate for nongastrointestinal localized low-grade MALT lymphomas.

Adult Lymphoblastic Lymphoma: Clinical Features and Prognostic Factors in 53 Patients

Lymphoblastic lymphoma (LBL) in adult patients is recognized as a particular entity in the high-grade non-Hodgkins lymphoma (HG-NHL) group with characteristic clinical and prognostic features. Initially, polychemotherapy normally used in HG-NHL failed to produce long-term relapse-free survival because of progression disease in the CNS and in the bone marrow. Subsequently, the intensification of therapy using multimodality aggressive acute lymphoblastic leukemia (ALL) treatments led to an increase in long-term relapse-free survival. We analyzed retrospectively 53 adult patients with LBL according to the Kiel classification and the criteria by Nathwani et al. Therapeutic modifications depended upon the different times of diagnosis. Twenty-one patients received the modified L17 regimen, 13 patients were treated with the L0288 regimen, and 19 patients were submitted to the L20 protocol. There was no significant differences in CR rates among the three protocols: 48% vs 54% vs 63%, respectively. Nineteen of 29 patients who achieved CR were alive and relapse-free at a median follow-up of 84 months. Ten of the CR patients underwent autologous bone marrow transplantation (ABMT) to consolidate the first response and 7 of them are alive and relapse-free. Early stage of disease, age < 30 years, low LDH levels, the absence of leukemic phase at diagnosis, and, in particular the attainment of CR were all features of patients with good prognosis. Our study confirms the role of intensive polychemotherapeutic regimens including CNS prophylaxis, the significance of a score model of prognostic factors, and of the role of ABMT (or allogeneic bone marrow transplantation) in the treatment of adult LBL.

Efficacy of fludarabine and mitoxantrone (FN) combination regimen in untreated indolent non-Hodgkin's lymphomas

PURPOSEnIn the last years, fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of previously treated low-grade non-Hodgkins lymphomas (LG-NHL). The aim of this study was to define the therapeutic efficacy and toxicity of a combination of FLU and mitoxantrone (FN regimen) in untreated LG-NHL.nnnPATIENTS AND METHODSnWe used a two-drug combination of FLU (25 mg/m2 i.v. on days 1 to 3) and mitoxantrone (10 mg/m2 i.v. on day 1) to treat 27 previously untreated patients with LG-NHL, Chemotherapy was repeated every four weeks for a total of six cycles. Among 27 patients, 17 (63%) were diagnosed with follicular, 6 (22%) with small lymphocytic, and 4 (15%) with immunocytoma subtypes.nnnRESULTSnOf the 27 patients, 18 (67%) achieved complete response (CR) and 6 (22%) partial response, while the remaining 3 (11%) showed no benefit from the treatment. Regarding histology, in the follicular subtype we observed an overall response rate of 94%, with a 76.5% CR rate. The estimated two-year relapse-free survival was 83%, and overall survival was 92%. Hematologic grade 3-4 toxicity was seen in only five (3.3%) patients; no opportunistic infections or deaths were associated with the administration of the FN regimen.nnnCONCLUSIONSnThese preliminary data show that the FN regimen is a very active, well-tolerated combination chemotherapy for untreated patients with advanced LG-NHL.