Leonard Ellman

CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications.

Clonotypic B cells circulating in patients with multiple myeloma (MM) express CD20, and it has been suggested that these cells may be clonogenic. Furthermore, 20% of patients with MM express CD20 on their bone marrow plasma cells (BMPCs). Therefore, the authors began a phase II clinical study to determine the activity of the anti-CD20 monoclonal antibody rituximab in MM patients. Nineteen previously treated MM patients received 375 mg/m 2 rituximab per week for 4 weeks. Three months after initiation of treatment, patients were assessed for response and received a second course of therapy if their disease was stable (SD) or they achieved a partial response (PR). Six of 19 (32%) patients had either a PR (n = 1) or SD (n = 5), with a median time to treatment failure of 5.5 months (mean, 10.3 months; range, 3–27+ months). All six patients who had a PR or SD had CD20 + BMPC. Overall, rituximab therapy was well tolerated. Because most patients with MM poorly express CD20 on their BMPCs, the authors evaluated agents for their ability to induce CD20 expression and thereby facilitate rituximab binding on MM cells. These studies show that interferon-gamma (IFN-&ggr;) induced CD20 expression on MM BMPCs, MM B cells, and healthy donor BMPCs. In contrast, CD20 expression on chronic lymphocytic leukemia, follicular non-Hodgkins lymphoma, healthy donor B cells, and progenitor cells was unaffected by IFN-&ggr;. Rituximab binding to the BMPCs of MM patients was also increased after culture with pharmacologically attainable levels of IFN-&ggr; (1–100 U/mL). In conclusion, these studies suggest that MM patients with CD20 + BMPCs may benefit from rituximab therapy. Furthermore, IFN-&ggr; induces CD20 expression on MM BMPCs and B cells and facilitates rituximab binding to MM BMPCs, providing the rationale for clinical trials to examine its use with CD20-directed serotherapies in MM.

Disseminated intravascular coagulation with the peritoneovenous shunt.

Coagulation data were collected before and after peritoneovenous shunting for intractable ascites in 19 shunting procedures. After insertion of the shunts, changes consistent with disseminated intravascular coagulation developed in all cases in which good flow of ascitic fluid was obtained. In cases with temporary shunt function, the coagulation variables suggestive of disseminated intravascular coagulation returned toward normal when the flow of ascitic fluid ceased. A fall in the level of fibrinogen degradation products indicated that the shunt had clotted. Bleeding attributable to disseminated intravascular coagulation alone was uncommon. Clotting of the shunts was frequent. The use of heparin improved some of the coagulation variables but did not prevent shunt clotting or clinical bleeding. We conclude that the peritoneovenous shunt induces a moderate disseminated intravascular coagulation and that measurement of fibrinogen degradation products is useful in assessing shunt function.

Diffuse large cell (Histiocytic) lymphoma of the spleen: clinical and pathologic characteristics of ten cases

Ten patients with diffuse large cell (histiocytic) lymphoma of the spleen had a characteristic clinical presentation and pathologic findings. Patients presented with left upper quadrant pain, fever, weight loss, and an elevated sedimentation rate. Imaging studies revealed an enlarged spleen with a discrete mass in all cases. Moderate to massive splenomegaly (average weight, 1025 g) was found at laparotomy; a single large mass or multiple confluent nodules with extensive central necrosis replaced 85% to 90% of the parenchyma. The tumor transgressed the splenic capsule in nine of ten cases, and either invaded or was adherent to the diaphragm, stomach, pancreas, or abdominal wall. Lymph nodes in the splenic hilum or retroperitoneum were frequently involved. Seven patients were in Ann Arbor Stage II, and three were in Stage I. Eight of the ten lymphomas were subclassified as centroblastic (large noncleaved cell) and two were immunoblastic. The B‐cell lineage of six tumors was established by the presence of monoclonal immunoglobulin. Despite combination chemotherapy, with or without radiation, three of the seven patients whose follow‐up was adequate died in less than 2 years; four are alive at 7, 12, 12, and 81 months, respectively, the last two with recurrent lymphoma. Large cell lymphoma of the spleen is a likely diagnosis in patients who present with left upper quadrant pain, fever, and radiographic evidence of a splenic mass.

Platelet autoantibody in a case of infectious mononucleosis presenting as thrombocytopenic purpura

Abstract In this unusual case acute thrombocytopenic purpura was the sole clinical manifestation of infectious mononucleosis. An antiplatelet antibody was demonstrated in the serum by two newly described technics: release of radioactive serotonin from platelets and inhibition of platelet aggregation following exposure of platelets to serum containing antiplatelet activity. The antiplatelet activity was completely inactivated by adsorption to washed platelets and was located in the immunoglobulin G (IgG) gamma globulin fraction of serum. The patients serum also reacted against her own platelets indicating that the antiplatelet factor behaved as a true autoantibody.

Hereditary antithrombin III deficiency: Effect of antithrombin III deficiency on platelet function

Antithrombin III (AT III) is the main physiologic inhibitor of thrombin, and activated factors X and IX as well. Normal levels of AT III appear to be necessary to maintain blood fluidity and to prevent thrombosis. Four families with AT III deficiency and recurrent venous thromboembolism have been reported on. We present an additional family with AT III deficiency and a high incidence of thromboembolism. AT III levels were determined by both a functional and an immunologic assay. Results of platelet function tests, not previously reported in persons with AT III deficiency, were found to be normal. Following gel filtration, the platelets were very sensitive to thrombin. Thrombin-induced platelet aggregation appears to be dependent on a balance between the amount of thrombin and AT III present.

Eosinophilia, chloromas and a chromosome abnormality in a patient with a myeloproliferative syndrome

The existence of eosinophilic leukemia remains controversial since many authors challenge the existence of this entity. We present a patient with a hypereosinophilic syndrome whose findings were consistent with a leukemic process. The patients course was marked by signs and symptoms of myeloblastoma formation and his illness terminated in an acute blastic crisis. Chromosome studies on peripheral blood leucocytes demonstrated aneuploidy and an abnormal number four chromosome with additional material on its long arm. This case appears to be an unusual example of a hypereosinophilic syndrome with both myeloblastoma formation and an abnormal leucocyte karyotype.

Uremia due to occult lymphomatous infiltration of the kidneys

An unusual case of uremia due to lymphomatous infiltration of the kidneys is described. The kidneys were of normal size and the diagnosis of lymphoma was made only at the time of open renal biopsy.

Development of a histiocytic medullary reticulosis-like syndrome during the course of acute lymphocytic leukemia.

A 54 year old woman presented with acute lymphocytic leukemia. Following an initial response to chemotherapy with vincristine and prednisone, progressive pancytopenia developed coincident with intense bone marrow infiltration by abnormal histiocytes. At autopsy two months later, no evidence of leukemia was found, but the bone marrow was replaced by abnormal histiocytes showing active erythrophagocytosis, consistent with histiocytic medullary reticulosis. Detailed morphologic, ultrastructural and histochemical studies performed throughout the course of the patients illness served to confirm the transition from leukemia to histiocytosis. Four similar cases of acute lymphocytic leukemia terminating in histiocytic medullary reticulosis have been reported. This association may represent a distinct clinicopathologic syndrome.

Cephalothin-Induced Granulocytopenia

Excerpt Since its introduction in 1962, cephalothin (Keflin®) has assumed a major role in the therapy of bacterial infection. There have been only sporadic reports of granulocytopenia caused by cep...

Prevalence of Intrinsic Factor Antibodies and Vitamin B12 Malabsorption in Older Patients Admitted to a Rehabilitation Hospital

It is possible that the commonly measured serum level of vitamin B12 may miss some cases when used to detect vitamin B12 malabsorption and deficiency in older persons. Serum levels of vitamin B12 and intrinsic factor antibody (IFAB) were determined on 250 consecutive patients over the age of 70 admitted to a rehabilitation hospital. Patients with abnormal results on either test were given the standard Schilling test when possible. Eight patients had documented B12 malabsorption. Of these, five had a low serum B12 level alone and one had a low serum B12 level and a positive IFAB level; however, two patients had positive IFAB and normal serum B12 levels. Serum IFAB level may serve as a useful adjunct to serum B12 level in detecting vitamin B12 malabsorption in older patients.