Tumor lysis syndrome occurring after the administration of rituximab in lymphoproliferative disorders: high-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Rituximab, an anti-CD20 antibody, has been recently approved for the treatment of low-grade or follicular non-Hodgkin's lymphoma (NHL). Because of its relatively benign side effect profile, it has been considered a nontoxic alternative to chemotherapy. Recently, however, tumor lysis syndrome (TLS) resulting from rituximab has been reported in a patient with chronic lymphocytic leukemia (CLL). We herein present two cases of rituximab-induced TLS. The first case occurred in a patient with high-grade NHL, while the second case occurred in a patient with CLL. We also present a summary of the literature regarding TLS induced by immunotherapies.

Adjuvant chemotherapy improves survival after liver transplantation for hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of postoperative adjuvant chemotherapy on the recurrence rate and survival of patients after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Historically, liver transplantation for HCC has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. METHODS: Twenty-five patients were placed on 6 months of intravenous fluorouracil, doxorubicin, and cisplatin after OLT. Risk factors, recurrence rates, and survival rates were analyzed and compared with historic controls. RESULTS: Overall long-term survival in the protocol patients was 46% at 3 years, improved over our historic controls of 5.8% at 3 years (p = 0.0001). Overall recurrence rate was 20% (n = 4). Possible risk factors, such as tumor size, vascular invasion, multifocality, capsular invasion, and tumor differentiation, were not found to be significantly predictive of survival. Three patients with long-term, disease-free survival had tumors > 5 cm. Side effects from chemotherapy were common, but rarely severe. CONCLUSIONS: This study suggests that adjuvant chemotherapy after transplantation for HCC can provide long-term cure and may improve survival, even in patients with stage III and IV disease.

Fatal sepsis due to a beta-lactamase-producing strain of Fusobacterium nucleatum subspecies polymorphum.

A patient with Waldenström's macroglobulinemia was treated empirically with imipenem for sepsis related to oropharyngeal infection and responded within 24 hours. When blood cultures yielded Streptococcus agalactiae, the regimen was changed to ampicillin and gentamicin. The patient's condition rapidly deteriorated, and she died 3 days later. After her death, a strain of Fusobacterium nucleatum subspecies polymorphum producing beta-lactamase (PEN-Y; group 2a) was isolated from blood cultures. A literature review revealed increasingly frequent isolation of beta-lactamase-producing strains of F. nucleatum. Thus strains of F. nucleatum isolated from blood and other specimens from patients with serious infections should be tested for beta-lactamase production.

Current treatment modalities for hepatocellular carcinoma.

OBJECTIVE: This study evaluated the currently available treatment modalities for hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: One of the most common tumors worldwide, HCC has several known risk factors. Untreated HCC typically has a dismal prognosis. Early detection remains the key to successful treatment of this malignancy. Surgical resection has been the mainstay of treatment for HCC, but newer modalities have been recently introduced. METHODS: The authors evaluated the treatment modalities for HCC. RESULTS: Surgical resection affords 5-year survival rates as high as 45% with more favorable subgroups having 1) small tumors, 2) well-differentiated tumors, 3) unifocal tumors, 4) lack of vascular invasion, 5) absence of cirrhosis, and 6) the fibrolamellar variant (FL-HCC). Resection has been limited primarily by low resectability rates and recurrent disease. Newer therapeutic modalities that appear the most promising are transarterial chemoembolization and percutaneous ethanol injection. Neither therapy has been evaluated in a prospective randomized manner. Combination chemotherapy and surgical intervention may provide the best results, but randomized controlled trials with long-term follow-up are needed. As single-treatment modalities, radiation therapy, intravenous chemotherapy, intra-arterial chemotherapy, and immunotherapy play limited palliative roles. CONCLUSIONS: Surgical resection in the form of partial or total hepatectomy is the preferred treatment for HCC. The early detection of tumors by screening high-risk populations is crucial. Randomized trials of combinations of chemotherapy and surgical resection are needed to demonstrate their potential utility for treatment.

Perioperative coagulopathy in patients undergoing primary cytoreduction.

BACKGROUND: This study was performed to determine the frequency of a perioperative coagulopathy in patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum and to identify variables that might predict this phenomenon. METHODS: A retrospective review of 90 patients undergoing primary cytoreduction for ovarian cancer or carcinoma of the peritoneum was performed at Cedars Sinai Medical Center. Univariate analysis was performed to test the relationship between 15 variables and coagulopathy status. RESULTS: Six patients (6.7%) developed a perioperative coagulopathy that was unrelated to preoperative subcutaneous heparin or dilution. Coagulation disturbances developed intraoperatively before packed erythrocyte replacement equivalent to one blood volume. Four patients (4.4%) required a repeat laparotomy due to continued postoperative bleeding unresponsive to blood component replacement. Vascular pedicles were not the cause of bleeding in any patient. Univariate analysis demonstrated a significant association between perioperative coagulopathy and the following variables: ascites volume (P = 0.009), estimated blood loss (P = 0.002), preoperative serum albumin less than 3.5 g/dl (P < 0.0001), and metastasis greater than 10 cm (P = 0.033). CONCLUSIONS: Patients undergoing primary cytoreduction who have ascites, preoperative serum albumin less than 3.5 g/dl, or metastases greater than 10 cm may be at increased risk for development of a perioperative coagulopathy.

Is liver transplantation justified for the treatment of hepatic malignancies?

Twenty-eight patients received orthotopic liver transplants for malignant disease between February 1, 1984, and December 31, 1989. Preoperative diagnoses included hepatocellular carcinoma (n = 16), cholangiocarcinoma (n = 3), other primary hepatic tumors (n = 6), and metastatic diseases to the liver (n = 3). Overall actuarial survivals at 6 months, 1 year, and 5 years were 67.3%, 51%, and 31%, respectively. Long-term survival longer than 5 years was achieved in 3 patients. The recurrence rate in patients surviving longer than 3 months is 48% (median, 7 months). Hepatocellular carcinoma and cholangiocarcinoma had the poorest survival and highest recurrence rates. Specific prognostic factors correlating with survival or recurrence could not be elucidated. These results indicate that orthotopic liver transplants can provide long-term cure and palliation for malignant disease; however, patient selection is extremely important in predicting outcome.

Adults with cyanotic congenital heart disease: hematologic management.

Hematologic management of adults with cyanotic congenital heart disease has received little recent attention. The lack of practical therapeutic guidelines prompted us to consolidate our observations on 124 cyanotic adults for general physicians, cardiologists, and hematologists who care for these patients. Specific attention focused on regulation of erythrocyte mass and concepts of compensated and decompensated erythrocytosis, symptoms of deficient tissue oxygen transport, hyperviscosity and iron deficiency, the potential relation between elevated hematocrit levels and brain injury, hemostasis, urate metabolism, and renal function. Cerebral infarction was not seen in any patient. Phlebotomy is best reserved for treatment of symptomatic hyperviscosity. Iron therapy is indicated for symptomatic iron deficient erythropoiesis. Abnormal hemostatic mechanisms are the rule. Antithrombotic medications have little or no role in treatment. Hyperuricemia is the result of abnormal renal uric acid excretion not urate overproduction, and serves as a marker of abnormal renal function. Drugs that promote urate excretion are the preferred maintenance treatment in symptomatic hyperuricemic patients.

Effects of phorbol diesters and teleocidin on normal human platelets.

Teleocidins are newly described indole alkaloid tumor promoters that are structurally distinct from phorbol diesters (PDE). We compared the effects of teleocidin and selected PDE on platelet aggregation, secretion and aspects of arachidonate metabolism. Three tumor-promoting PDE (phorbol myristate acetate (PMA), phorbol dibutyrate (PDBu) and 4-beta-phorbol didecanoate (4-beta-PDD] and a non-tumor promoting PDE (4-alpha-phorbol didecanoate (4-alpha-PDD] were used. Teleocidin and tumor promoting PDE caused platelet aggregation after a delay that was inversely related to tumor promoter concentration and also triggered secretion of alpha- and dense granules and selective release of lysosomal enzymes. Aggregation and its associated 125I-fibrinogen binding to platelets were both inhibited by Na2EDTA. 4-alpha-PDD was ineffective. Analysis of platelet aggregation responses and activation kinetics revealed that PDBu was 11.7 times less potent than teleocidin PMA, or 4-beta-PDD. Neither PDE nor teleocidin stimulated 14C-arachidonate release from normal human platelets, and both aggregated aspirin-treated platelets. These results show that representatives of two structurally distinct classes of tumor promoters, phorbol diesters and indole alkaloids, are potent activators of platelet aggregation, fibrinogen binding, and granule/lysosomal secretion, by a mechanism that bypasses arachidonate release and formation of cyclooxygenase-dependent arachidonate metabolites.

Plasma beta-thromboglobulin, platelet factor 4, fibrinopeptide A, and other hemostatic functions during improved, short-term glycemic control in diabetes mellitus.

To determine the effect of improved, short-term glycemic control on various functions of hemostasis in insulin-dependent diabetes, we measured changes in plasma fibrinogen, fibrinopeptide A (FPA), functional antithrombin III (AT-III), factor VIII:ristocetin cofactor ( VIIIRCoF ), beta-thromboglobulin (BTG), platelet factor 4 (PF4), and platelet aggregation responses to ADP and collagen in 12 patients with low or undetectable stimulated (postprandial) serum C-peptide levels during 4-8 wk (median, 6 wk) of treatment with constant subcutaneous insulin infusion. Mean plasma fibrinogen, FPA, AT-III, VIIIRCoF , and BTG at baseline were elevated compared with normal. Three patients had heightened platelet responses to ADP that did not correlate to other indicators of a hypercoagulable state; the affected patients, in fact, had significantly lower plasma BTG (25.5 +/- 5.3 [SEM] versus 44.6 +/- 4.6 ng/ml, P less than 0.05) and FPA (1.1 +/- 0.1 versus 2.5 +/- 0.5 ng/ml, P less than 0.05) than the remaining patients. Patients with clinically evident vascular disease had higher baseline plasma BTG and FPA than those without vascular disease (44.6 +/- 5.4 versus 30.2 +/- 4.6, and 2.6 +/- 0.6 versus 1.3 +/- 0.2 ng/ml, P less than 0.05, respectively). During treatment, all patients had declining blood glucose (200 +/- 18 to 102 +/- 5 mg/dl, P less than 0.001) and HbA1 (11.8 +/- 0.6 to 10.2 +/- 0.4%, P less than 0.005). No statistically significant changes in hemostatic functions were noted. During treatment, one patient had an acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases.

Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency.

Severe platelet dysfunction in hairy cell leukemia with improvement after splenectomy.

A patient with hairy cell leukemia developed purpura not attributable to thrombocytopenia. We found markedly reduced platelet aggregation responses and malondialdehyde production, decreased serotonin uptake, and depleted dense granule contents. Ultrastructural studies showed that most platelets had few or nor granules. All of the clinical and laboratory studies of platelet function and morphology improved after splenectomy. These findings indicate that qualitative defects in platelet function occurring in hairy cell leukemia may cause clinically important bleeding and that the bleeding diathesis may be ameliorated by splenectomy.