A prior study of Hodgkin's disease (HD) incidence using national cancer survey data (1969-1980) identified unprecedented rate declines among white persons older than 40 years, and rate increases among young adults aged 15 through 39. These trends could be due to improved diagnostic accuracy. To investigate this hypothesis, the authors updated incidence rates in whites by age, sex, and histologic subtype through 1984; quantified diagnostic accuracy in corresponding detail using Repository Center for Lymphoma Clinical Studies data, which include original and expert review diagnoses on lymphoma patients; and recalculated HD incidence rates (1969-1984) corrected for diagnostic error. Updated HD incidence rates through 1984 continued to decline in older adults and showed persistent increases for young adults with the nodular sclerosis (NS) histologic subtype. The percentage of original HD diagnoses confirmed on review (confirmation rate) decreased with age and increased over time; in older adults, these patterns opposed observed incidence trends. However, for young adults, confirmation rates of NS, the most common subtype at these ages, were high and changed little over time. After adjustment for diagnostic error, incidence rates for older adults were lower than previously observed and showed no secular changes. However, young adults with NS had slightly larger rate increases than in uncorrected data. Thus, contemporary changes in HD incidence for whites primarily involve growing risk to persons at the start of adult life. These patterns are compatible with trends in suspected sociodemographic risk factors that suggest an infectious etiology for HD.
The morphologic and immunologic features of three cases of an unusual and distinct B-cell lymphoma were recently described and termed monocytoid B-cell lymphoma (MBCL) because of the striking resemblance of the neoplastic cells to reactive monocytoid B-lymphocytes. The morphologic spectrum and the clinical behavior of MBCL were investigated in a series of 21 patients. This study indicates that patients with MBCL usually present with lymphadenopathy and Stage I or II disease. MBCL also occurs at extranodal sites including the salivary gland. Because four of the patients with MBCL had Sjögren's syndrome with characteristic laboratory profiles, these results raise the possibility that there may be a relationship between MBCL and Sjögren's syndrome. Eight patients were male and 13 female (M:F = 1:1.6), and MBCL primarily involved the elderly (median age, 66 years). The most striking clinical findings were high percentages of complete remissions and long survival times indicating that MBCL is a low-grade lymphoma. Of 21 patients investigated, 18 were in complete remission at the time of completion of this study. Two patients died with the disease and one was lost to follow-up. Patients with localized MBCL may have a better survival rate than those with generalized disease. Like other low-grade lymphomas, MBCL can progress to a higher grade lymphoma of large cell type. Unlike other low-grade lymphomas, in MBCL splenomegaly, bone marrow involvement, and leukemic conversion are uncommon.
A large panel of monoclonal antibodies and polyclonal antisera were used to ascertain the immunophenotypic characteristics of 36 lymphoblastic lymphomas (LBL). Results showed that this group of lymphomas have significant immunologic heterogeneity. Of the 36 cases, 33 were positive for T-cell antigens; among these, 22 cases were classified as T-cell LBL (TLBL, Group 1) based on their expression of T-cell-restricted and T-cell-associated antigens, and five expressed the common acute lymphoblastic leukemia antigen in addition to T-cell-associated antigens (Group 2). Six cases showed strong reactivity with anti-Leu-11 antibody, which defines a specific subtype of lymphocytes considered to have a natural killer (NK) function (Group 3). Two additional cases had a "pre-B" cell phenotype (Group 4), as determined by reactivity with BA-1 and BA-2 monoclonal antibodies, which react with immature and pre-B-lymphocytes. The neoplastic cells in the remaining case showed monoclonal surface membrane immunoglobulin of the IgMD heavy chain and kappa light chain type (Group 5). Despite immunophenotypic heterogeneity, the morphologic features were essentially similar in all cases. When the clinical features for each immunologic group were compared, however, two statistically significant findings resulted: (1) the frequency of mediastinal masses was highest in TLBL (Group 1, P less than 0.01), and (2) the male-female ratio was significantly lower in patients with LBL expressing NK-associated antigens (Group 3) than in the other groups of patients (P less than 0.01). Our data indicate that LBL can be divided into several immunologic subtypes; larger, prospective clinicopathologic studies are required to determine the clinical significance of the immunophenotypic classifications of LBL.
Objective. This pilot phase 11, double-blind, placebo-controlled trial of 1 month duration, with a 2-3-month open-label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin-2 diphtheria fusion protein (DAB, in refractory rheumatoid arthritis (RA). Methods. Forty-five RA patients were enrolled in the trial, and were randomized, after a =-week diseasemodifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB,IL-2 or placebo (saline) for 5 days. A blinded, third-party observer evaluated arthritis activity. Clinical response was defined as 225% improvement in swollen and tender joints and 125% improvement in at least 2 of 6 additional parameters. The double-blind phase was 4 weeks; placebo patients could cross over to receive open-label treatment for a maximum of 3 monthly DAB,,IL-2 cycles.Results. In the double-blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open-label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB,dL3, respectively. Adverse events included transient feverkhills (45%), nausedvomiting (50%), elevated ( 1 3~ normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB,,IL-2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB-IL-2-treated versus placebo-treated patients.Conclusion. Clinical responses were noted in patients treated with DAB,,IL-2 (18%) compared with placebo (0%) in the double-blind phase. In the open-1177
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