To assess the sensitivity of primary nonHodgkin lymphoma cells to rituximabmediated cytotoxicity, we compared the potency of several rituximab-mediated killing mechanisms on fresh lymphoma cells. All lymphoma cells tested were equally sensitive to antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-mediated phagocytosis of tumor cells, and rituximab-induced apoptosis. However, they were differentially lysed by complement-dependent cytotoxicity (CDC).We found that taking into account both CD20 and complement regulatory protein expression on tumor cells could predict CDC sensitivity in vitro. Importantly, the sensitivity of lymphoma cells to CDC was consistent with the reported different clinical response rates of lymphomas: rituximab induced high CDC killing of follicular lymphoma cells, whereas mantle cell lymphoma and diffuse large cell lymphoma cells were moderately sensible to CDC, and small lymphocytic lymphoma cells were almost all resistant. We propose that CDC is a determinant mechanism of rituximab-induced killing in vivo. Poor sensitivity to CDC in vitro might predict a poor clinical response, whereas high sensitivity to CDC would only indi-

We report the results of a prospective series of 60 consecutive splenectomies for hematologic disorders performed between February 1995 and May 1996. The portal venous flow of all the patients (34 men and 26 women with a mean age of 54.1 years) was systematically studied before and after intervention with Doppler color imaging (on the day before the intervention and on the 7th and 30th postoperative days). The objective of this study were to determine the real frequency of asymptomatic portal or splenic venous thrombosis (PSVT) after hematologic splenectomy. The intervention began with exteriorization of the spleen and the tail of the pancreas; ligation of the splenic vein was performed close to its junction with the inferior mesenteric vein. Twenty-three complications (38.3%) were noted with three deaths (5%). One symptomatic PSVT (1.6%) and three asymptomatic PSVTs (6.7%) were diagnosed and treated with no deaths. Three risk factors of PSVT, recognized by all the authors, were present in these four cases: large splenomegaly, thrombocytosis, or myeloproliferative disorder. The systematic ultrasonographic (US) examinations increased the frequency of diagnosis of PSVT sevenfold during the perioperative period. Patients with marked splenomegaly associated with lymphoma, chronic lymphocytic leukemia, or myeloid metaplasia probably require systematic US monitoring during follow-up, but this must be determined by further study.

1q rearrangement is a remarkably frequent secondary chromosomal change in both non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), where it is associated with tumor progression. To gain insight into 1q rearrangement-associated disease mechanisms, we used fluorescence in situ hybridization (FISH) to search for recurring 1q breaks in 35 lymphoma samples (31 NHL patients and 4 lymphoma-derived cell lines) as well as 22 MM patients with cytogenetically determined 1q abnormalities. Strikingly, dual-color FISH analysis with chromosome 1 centromere and 1q12-specific probes identified constitutive heterochromatin band 1q12 as the single most frequent breakpoint site in both NHL and MM (39% and 89% of 1q breaks, respectively). These rearrangements consistently generated aberrant heterochromatin/euchromatin junctions and gain of 1q12 material. A further 30% of NHL 1q breaks specifically involved two other novel, closely spaced sites (clusters I and II) within a 2.5 Mb region of proximal 1q21 (D1S3620 to D1S3623). A possible association between these sites and NHL subtype was evident; the cluster I rearrangement was frequent in follicular and diffuse large cell lymphoma, whereas the cluster II rearrangement was more frequently observed in diffuse small-cell lymphoma (2/2 marginal zone lymphomas, 1/2 atypical chronic lymphocytic leukemias, and 1 lymphoplasmacytic lymphoma in this series). Candidate oncogenes bordering this interval (BCL9 and AF1Q) were not rearranged in any patient except one (AF1Q). This study provides the first evidence of involvement of 1q12 constitutive heterochromatin in the pathogenesis of NHL and MM and indicates proximal 1q21 to be of specific pathological significance in NHL.