Identification of major prognostic subgroups of patients with large-cell lymphoma treated with m-BACOD or M-BACOD

One hundred twenty-one patients with diffuse large-cell lymphoma treated with m- or M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) were evaluated for pretreatment characteristics predictive for response and survival. Two characteristics, poor performance status and massive bulky disease, were negatively associated with response rate in a multivariate analysis. These two characteristics were also negatively associated with survival in multivariate analysis, as was another factor, an increased number of extranodal sites of disease. These three pretreatment characteristics were used to construct a model containing 12 categories of patients at increasing risk for relapse and shortened survival. These categories divided naturally into three broad groups of patients with respective 5-year survival rates of 68%, 55%, and 24%.     

Lymphomas of the breast: primary and secondary involvement

BACKGROUND: The involvement of the breast by lymphoma is a rare form of extralymph node lymphoma and represents either primary disease or systemic involvement. The authors hypothesized that screening mammography may influence the detection of lymphomatous involvement of the breast. METHODS: All patients (n = 81 patients) who were diagnosed with lymphomatous involvement of the breast at the study institution between 1988 and 1999 were evaluated retrospectively. RESULTS: Clinical information was available for 73 patients who could be classified into three major groups according to their diagnosis: primary breast lymphoma (PBL) (44%), breast involvement from disseminated disease at the time of initial diagnosis (29%), and recurrence of preexisting lymphoma to the breast (27%). The majority of PBL were of intermediate or high grade, and the majority of disseminated lymphomas involving the breast were of low grade. Lymphomatous recurrence to the breast was slightly more likely to be of intermediate grade rather than low grade. In 91% of patients, the diagnosis of lymphoma was made after the evaluation of a palpable mass. All patients who were identified after the evaluation of an abnormal screening mammogram (9%) had low-grade lymphomas. Of the 32 patients with PBL, screening mammography discovered only 1. Nineteen percent of patients with PBL also had a history of an autoimmune disorder. CONCLUSIONS: These findings suggest that screening mammography has not altered substantially the detection of breast lymphoma. The clinical outcome of patients with breast lymphoma is dependent on histology and appears to parallel that of patients with lymphoma of similar histology involving other sites.     

Treatment of the blastic transformation of chronic granulocytic leukemia using high dose BCNU chemotherapy and cryopreserved autologous peripheral blood stem cells

Seven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11-46 months prior to use. Patients received 2.9 X 10(8) (1.9-7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic CGL.     

High-dose gallium imaging in lymphoma

The role of gallium-67 imaging in the management of patients with lymphoma, traditionally assessed using low tracer doses and the rectilinear scanner, was assessed when using larger doses (7 to 10 mCi) and a triple-peak Anger camera. Gallium scan results in 51 patients with non-Hodgkin's lymphoma and 21 patients with Hodgkin's disease were compared with simultaneous radiologic, clinical, and histopathologic reports. Subsequent disease course was also evaluated in light of radionuclide findings. Sensitivity and specificity of the scans were 0.90 or greater for both non-Hodgkin's lymphoma and Hodgkin's disease, and overall accuracy by site was 96 percent. Although there are insufficient numbers of pretreatment scans to allow any conclusions, our data suggest that newer approaches to gallium scanning in treated patients are (1) highly specific in all lymphomas and most sensitive in high-grade non-Hodgkin's lymphoma and Hodgkin's disease; (2) valuable in assessing the mediastinum in both non-Hodgkin's lymphoma and Hodgkin's disease; and (3) helpful adjuncts to computed tomographic scanning and ultrasonography in assessing abdominal node disease.     

Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251

BACKGROUND: The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma. METHODS: Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high-risk individuals. RESULTS: The median follow-up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P=0.001). Responses were similar, and the 3-year event-free survival rate was 0.52 (95% confidence interval, 0.38-0.65) for Cohort 1 and 0.45 (0.29-0.60) for Cohort 2. CONCLUSIONS: Intensive, short-duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma.     

Splenic enlargement and hyperfunction as indications for splenectomy in chronic leukemia.

The chronic leukemias are associated with significant morbidity from splenic enlargement and hyperfunction. Although some patients with chronic leukemia benefit from splenectomy, the indications for operation are unclear. To identify those patients who benefit most from splenectomy, nine patients with chronic lymphocytic leukemia (CLL) and eight patients with chronic granulocytic leukemia (CGL) who had splenectomy to palliate the symptoms of massive splenic bulk or to improve the hematologic sequelae of splenic hyperfunction were studied. Splenectomy for bulk symptoms provided good palliation of symptoms, but the duration of the benefit was limited by the stage of the disease. Five of eight patients with CGL with bulk symptoms died within 6 months of operation. Splenectomy for hyperfunction was limited to a short-term hematologic response. In three of four patients with CLL who were Coombs positive, the presence of autoantibodies correlated with a recurrent transfusion requirement within 3 months of splenectomy. Thus, the benefit of splenectomy for bulk symptoms must be weighed against the risk of surgery and the patient's limited life expectancy. The benefit of splenectomy for treatment of splenic hyperfunction depends on the stimulus to hyperfunction and may not be beneficial for patients with refractory autoimmune anemias.     

Single agent bortezomib in the treatment of relapsed and refractory Hodgkin lymphoma: cancer and leukemia Group B protocol 50206

Constitutive activation of nuclear factor-kappaB (NF-kappaB) has been described in patient-derived Reed - Sternberg cells and Hodgkin lymphoma (HL) cell lines and contributes to the proliferation and survival of HL. Therapeutic inhibition of the proteasome with bortezomib may inhibit over-expression of nuclear NF-kappaB by preventing degradation of IkappaB, which sequesters NF-kappaB in the cytoplasm. To evaluate this hypothesis, the Cancer and Leukemia Group B (CALGB) conducted a multi-institutional phase II trial of single agent bortezomib in patients with relapsed or refractory classical HL. Thirty patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, 11 and every 21 days for a median of 2 cycles (range, 1 - 8). Patients were heavily pre-treated with a median of four prior therapies, and 83% were previously transplanted. No responses were observed, 9 patients had stable disease, and 21 progressed. The median progression-free and overall survivals were 1.4 months [95% CI, (1.28, 1.91)] and 14.8 months [95% CI (11.2, 22.3)], respectively. Grade 3 - 4 adverse events, primarily thrombocytopenia, occurred in 15 patients. Therefore, although well tolerated, 1.3 mg/m(2) bortezomib administered biweekly has no single agent activity in relapsed/refractory classical HL.