No abstract

IgG-RFB4-SMPT-dgA consists of deglycosylated ricin A chain (dgA) coupled to the monoclonal antihuman CD22 antibody, RFB4. This study determined the maximally tolerated dose (MTD) of this immunotoxin (IT) administered as a continuous 8-day infusion to 18 patients with B-cell lymphoma (30% CD22+ tumor cells) over 8 days. The MTD was 19.2 mg/m2/192 h (maximum toxicity grade 1), with vascular leak syndrome (VLS) as dose-limiting toxicity (DLT) at 28.8 mg/m2/192 h (grades 3 through 5 in 7 of 11 patients). Predictors of severe VLS included serum IT concentrations greater than 1,000 ng/mL and the absence of circulating tumor cells. Decreased urine sodium excreted in 24 hours provided evidence for mild VLS without notable changes in serum albumin. Four partial responses, 3 minor responses, 6 stable disease, and 3 progression of disease were observed. The mean maximal serum concentration (Cmax) in initial courses at the MTD (19.2 mg/m2) was 443 +/- 144 ng/mL (n = 3; range, 326 to 604). At 28.8 mg/m2/192 h, the Cmax was highly variable (n = 11; mean, 1,102 +/- 702; range, 9.6 to 2,032 ng/mL). Human antimouse or antiricin antibodies developed in 6 of 16 (37.5%) patients after one course of IT. However, 10 eligible patients received multiple courses of IT. Changes in serum cytokines and cytokine receptors did not correlate with toxicity but decreased soluble interleukin-2 receptor concentrations correlated with clinical response. Comparison to a prior study with the same IT administered by intermittent bolus infusions (Amlot et al, Blood 82:2624, 1993) suggests similar clinical response, toxicity, and immunogenicity.

For Abstract see ChemInform Abstract in Full Text.

No abstract

We previously demonstrated that recombinant interferon alfa-2a (IFN-alfa) in a dose of 50 X 10(6) U million units (MU)/m2 intramuscularly (IM) three times per week has efficacy against mycosis fungoides (MF) and the Sézary syndrome (SS). However, this regimen given to patients with refractory disease was uniformly complicated by toxicities requiring major dose reductions. The present study was designed to determine if intermittent high-dose IFN-alfa would preserve efficacy and decrease toxicity in a similar patient population. Twenty-four patients with advanced disease refractory to one or more standard therapies received IFN-alfa, 10 MU/m2 IM on day 1 followed by 50 MU/m2 IM on days 2 to 5 every 3 weeks; after the first four cycles, stable and partially responding patients underwent dose escalation to twice the starting dose. One complete (CR) and six partial responses (PRs) were observed (response rate, 29%; 95% confidence interval, 13% to 51%) lasting 4 to 19 months (median, 8 months). No improvement in objective response was seen in the eight patients who received dose escalation. Dose reductions were necessary in eight of 22 patients receiving one or more cycles of therapy. Weighted mean dose rate intensity for patients on this study over the first four cycles of treatment was 65.5 MU/m2/wk compared with 73.2 MU/m2/wk over the first 12 weeks of treatment in patients from the previous study, in which all 19 patients receiving more than 1 week of treatment required dose reduction. IFN-alfa is effective against previously treated MF and the SS and is better tolerated on this intermittent schedule.

Sézary lymphoma cells respond by proliferation to IL7 plus IL2, and in some instances produce IL7. Therapeutic maneuvers should be pursued to take advantage of this potential autocrine or paracrine growth-stimulatory mechanism.

No abstract

Peripheral blood lymphocyte morphology was evaluated prospectively by light microscopy of blood smears and E rosette preparations in 160 patients with cutaneous T cell lymphoma (CTCL). Blood involvement was related to the type of cutaneous T-stage, being present in 90% of patients with erythroderma (T4), 27% of those with cutaneous tumors (T3), 9% of those with generalized (T2), and 0% of those with limited skin plaques (T1). Untreated patients with blood involvement (38 of 105) had a higher frequency of CTCL in lymph nodes and viscera and survival inferior to that of patients with normal or nondiagnostic lymphocyte morphology (P less than .001). Multivariate analysis showed skin stage and age to be the most important pretreatment risk factors for survival. Although blood involvement was not an independent risk factor for the entire group, it appeared to have some adverse influence in the T2/T3 subsets (P = .051). Both lymphocytosis and size distribution of the circulating CTCL cells at initial diagnosis influenced survival. Patients with “mixed cell” cytology (greater than 20% large [greater than 11 microns] CTCL cells), had a worse survival than those with predominantly small circulating CTCL cells (P = .009). The former were more likely to have aggressive features, including lymph node effacement by tumor (P less than .001) and visceral disease (P = .074), than were “small cell” patients. Our data indicate that detailed review of the blood lymphocyte morphology in patients with diagnosed or suspected CTCL is helpful in predicting extent of disease and prognosis.