A 10-year experience with treatment of high and standard risk Hodgkin disease: six cycles of tailored BEACOPP, with interim scintigraphy, are effective and female fertility is preserved.

Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity. A total of 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between July, 1999 and August, 2005. Patients with early unfavorable and advanced disease were eligible for the study. Patients were assigned to therapy based on international prognostic score (IPS). Those with IPS ≥ 3 received three cycles of escalated BEACOPP (EB). All others received two cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned according to early interim GA(67) or positron emission tomography (PET)/computerized tomography (CT). Four cycles of EB or SB were administered following a positive or negative scan, respectively. Complete remission rate, 10-year progression free (PFS), and overall survival (OS) were 97, 87, and 88%, respectively, at a median follow-up of 89 months (5-144). PFS and OS were similar in both groups. Fertility status was assessed in 38 females aged <40 years; 94% of females younger than 40 years preserved their cyclic ovarian function. Nineteen conceived during follow-up for 30 pregnancies, delivering 24 babies. Deliveries were reported up to 7 years from diagnosis. Predictive value of negative interim Ga(67) or PET/CT was 87 and 93%, respectively. Six cycles of tailored BEACOPP, for patients with adverse prognostic factors, provide encouraging long-term PFS and OS, and fertility is preserved in most females.

Heparin-induced thrombocytopenia with thrombotic sequelae: a review.

Heparin-induced thrombocytopenia (HIT) occurs in 1-5% of patients treated with heparin. The pathogenesis involves the formation of antibodies to heparin-platelet factor 4 complexes, and the major clinical sequelae are thrombotic. Diagnosis is based on a combination of clinical and laboratory data. Treatment consists of stopping heparin, but, insofar as the risk of thrombosis remains high, treatment by alternative antithrombotic agents is indicated. Most clinical experience has been with danaparoid sodium and hirudin. The use of low-molecular-weight heparins (LMWH) in subsequent HIT episodes has been described, but is not recommended, especially with the introduction of new agents, such as oral thrombin inhibitors and pentasaccharides, which are hoped to reduce the use of heparins and the occurrence of HIT.

Early-mid treatment C-reactive protein level is a prognostic factor in aggressive non-Hodgkin's lymphoma.

BACKGROUND: In the light of an emerging role for early-mid treatment 18 F-deoxyfluoroglucose positron emission tomography (FDG-PET) as an important prognostic indicator in aggressive non-Hodgkin's lymphoma (NHL) , we attempted to determine whether a simple parameter, such as the early-mid treatment CRP (C-reactive protein) level, could also be utilized as a significant prognostic factor in aggressive NHL. PATIENTS AND METHODS: Serum CRP levels were monitored in 55 patients with aggressive NHL. The lowest value of the early mid-term CRP levels recorded was compared with the interim PET-CT results, as well as with the clinical course and eventual outcome. RESULTS: During chemotherapy, the lowest value of early-mid treatment CRP levels significantly predicted the results of the interim FDG-PET (P = 0.04 with an odds ratio of 1.13). Patients who did not achieve an early-mid treatment CRP level of <5 mg/L, had a shorter time to disease progression or relapse (P = 0.001) as well as a reduced overall survival (OS) (P = 0.016). CONCLUSIONS: The early-mid treatment serum CRP level is a prognostic factor in aggressive NHL. Patients who do not achieve an early-mid treatment level of <5 mg/L have quicker disease progression or earlier relapse and also appear to have an inferior OS.

Risk-adapted BEACOPP regimen can reduce the cumulative dose of chemotherapy for standard and high-risk Hodgkin lymphoma with no impairment of outcome.

Therapy of Hodgkin disease (HD) is designed to prolong progression-free survival and minimize toxicity. The best regimen to achieve this has not yet been defined. A total of 108 patients with newly diagnosed HD and adverse prognostic factors were prospectively studied between 1999 and 2004. They were assigned to therapy according to defined risk stratification. Patients were defined depending on the International Prognostic Score (IPS). Those with IPS of 3 or higher received 2 cycles of escalated therapy, including bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [EB]). All others received 2 cycles of standard BEACOPP (SB). Subsequent therapy was prospectively assigned following 2 cycles according to results of early interim 67Ga or positron emission tomography/computed tomography (PET/CT). Following a positive interim scan, 4 cycles of EB were administered, whereas 4 cycles of SB were given to patients with a negative scan. The complete remission rate, the 5-year event-free survival (EFS), and overall survival (OS) rates were 97%, 85% and 90%, respectively. Relapse or progression occurred in 27% of patients with interim positive PET/CT versus 2.3% of negative scans (P<.02). Early interim fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT is a useful tool for adjustment of chemotherapy on an individual basis. Similar EFS and OS rates were observed for patients in both risk groups.

Fucoidin, an inhibitor of leukocyte adhesion, exacerbates acute ischemic renal failure and stimulates nitric oxide synthesis.

OBJECTIVES: To lessen renal ischemic injury caused by fucoidin, a substance capable of reducing tissue infiltration by neutrophils, and to seek a possible interrelationship with the nitric oxide system which may also modulate leukocyte infiltration. MATERIAL AND METHODS: Acute ischemic renal failure was induced in rats by uninephrectomy followed by 60 min of clamping of the renal artery. The rats were injected with fucoidin (25 mg/kg) or fucoidin+nitroprusside (2.5 mg/kg) before reperfusion, and urine was collected for 24 h afterwards. Serum and urine were examined for creatinine sodium and protein; creatinine clearance and fractional excretion of sodium (FENa) were calculated. The renal tissue of the sacrificed animals was examined histologically for tissue damage and histochemically for myeloperoxidase, a marker of neutrophil infiltration. The nitric oxide system was evaluated by measuring urinary nitrates and inducible nitric oxide synthase messenger RNA (iNOs mRNA). RESULTS: Renal failure was more severe in the fucoidin group than the nitroprusside group (creatinine clearance 0.11+/-0.08 ml/min for ischemia+fucoidin versus 0.26+/-0.11 ml/min for ischemia only; p<0.002). Adding nitroprusside to fucoidin lessened the decline in creatinine clearance (0.13+/-0.13 ml/min; p=NS). Fucoidin was associated with greater tubular damage, as evidenced by increased FENa (7.2%+/-2.8% vs 1.51%+/-1.96% for ischemia only; p<0.001). Nitroprusside weakened this trend. Fucoidin caused an increase in the fractional excretion of nitrates, a response accompanied by increased iNOS mRNA. CONCLUSIONS: Fucoidin failed to protect the kidney from ischemic damage and was even nephrotoxic. It also stimulated the formation of iNOS RNA.

Acute myeloid leukemia presenting as obstructive jaundice.

A 36-year-old man presented with abdominal pain and jaundice. Ultrasound examination of the abdomen showed dilatation of the intrahepatic bile ducts and a normal common bile duct. No calculi were demonstrated. A computerized tomography scan did not show any masses. A peripheral blood smear was diagnostic of acute myeloid leukemia. After remission-inducing chemotherapy, there was a complete regression of the jaundice, which had not recurred at the 12-month follow-up.

A lipid emulsion reduces mortality from clomipramine overdose in rats.

Tricyclic antidepressants are a common cause of self poisoning. Since these drugs are highly lipid soluble, we examined the interaction between imipramine and a lipid emulsion. Rats were given an iv dose of imipramine with either normal saline or a lipid emulsion as vehicle. The rats who received the lipid emulsion had a significantly lower mortality. The role of lipid emulsions poisoning therapy is reviewed.