Dexamethasone, high-dose cytarabine, and oxaliplatin (DHAOx) as salvage treatment for patients with initially refractory or relapsed non-Hodgkin's lymphoma.

BACKGROUND: Dexamethasone. cytarabine (ara-C), and cisplatin (DHAP) can be used effectively to treat patients with non-Hodgkin's lymphoma (NHL). We hypothesized that substitution of cisplatin by oxaliplatin (L-OHP) could result in less toxicity and greater efficacy. L-OHP is active in patients with lymphoma. It produces mild myelosuppression and is devoid of renal toxicity. We report on a phase II study of dexamethasone, high-dose ara-C, and L-OHP (DHAOx) used to treat patients with NHL who were previously treated with chemotherapy. PATIENTS AND METHODS: Fifteen patients were given DHAOx. They had failed to achieve a CR with initial chemotherapy or had recurrent disease. DHAOx consisted of dexamethasone, 40 mg/day (days 1 to 4): L-OHP, 130 mg/m2 (day 1); and ara-C, 2,000 mg/m2 every 12 h (day 2). Treatment was repeated every 21 days. RESULTS: Patients received a median of four courses of DHAOx. Myelosuppression and transient sensory peripheral neuropathy were the most prominent toxic effects. Serum creatinine levels did not increase in patients with normal renal function, nor in patients who had renal impairment before DHAOx. The median follow-up time from the start of DHAOx treatment was 17 months. Eight patients (53%) achieved a CR, and three patients (20%) had a PR. Responses were achieved by patients with lymphomas of various histologies that included mainly the follicular subtype, and by patients with and without resistance to prior chemotherapy. None of the eight responders have relapsed from CR at 4+. 6+, 14+, 15+, 19+, 20+, 24+, and 24+ months. They had various types of therapy after DHAOx. Disappearance of molecular markers was observed in all four patients who achieved a CR and whose tumor cells carried molecular abnormalities. CONCLUSION: DHAOx possesses characteristics of toxicity which compare favorably to those reported with DHAP, and it is useful as a salvage treatment for patients with NHL. Larger studies are required to establish the therapeutic potential of the regimen.

How to stabilize the level of ionized calcium and citrate during plateletpheresis.

BACKGROUND AND OBJECTIVES: Citrate reactions are uncomfortable and potentially dangerous to apheresis donors. Reduction of citrate increases comfort, but may lead to platelet clumping. MATERIALS AND METHODS: We describe a protocol for stepwise reduction of the volume of ACD-A injected during plateletpheresis. This protocol has been carried out in 45 healthy donors with the Cobe 2997 (Cobe) cell separator, and in 35 with the Fenwal-CS 3000 (CS). RESULTS: Using this protocol, during the first hour of platelet collection, ionised calcium decreased on average by 18% for CS and by 18.4% for Cobe. During the second hour, Ca2+ and citrate ion concentration did not change with either Cobe or CS (about 65% of citrate ion load is eliminated). We observed mild signs of neuromuscular hyperexcitability in only 22% and 28% of donors with Cobe and CS, respectively. We also found a significant reduction of phosphate ions (p < 0.0001) at the end of the procedures. CONCLUSIONS: With this stepdown citrate reduction protocol, we obtained a significant reduction of injected citrate without the complication of platelet clumps.

[Relapse prevention in liver transplant patients treated for liver involvement due to hepatitis B virus]. / Prophylaxie des récidives chez les transplantés hépatiques pour atteinte hépatique due au virus de l'hépatite B.

Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success.

[Liver transplantation and the major histocompatibility complex]. / Transplantation hépatique et complexe majeur d'histocompatibilité.

We have carried out a retrospective study over 308 liver transplant patients (31 of them have had a retransplantation) in Professor Bismuth's Department at Paul Brousse Hospital. The purpose of the study was a search for the possible effect of donor/recipient major histocompatibility complex on the evolution of the transplantation. We chose to study four parameters: early acute rejection; chronic rejection; retransplantation cases and death frequency; graft survival. We observed the following: for HLA A locus: in cases of total or partial compatibility there are more moderate early acute rejections than in the case of incompatibility (p less than 0.02); for HLA B locus: in the case of total compatibility there are more chronic rejections than in cases of partial or total incompatibility (p less than 0.03); for joint A and B locus: the results are similar to those of A locus (p less than 0.03); for HLA class I: we observed no effect either on graft survival or on retransplantation cases or on death frequency; for HLA DR: we did not find any effect on the studied parameters. Considering the low statistical significance of these results and in order to confirm our analysis, we have started a prospective study in collaboration with two other European Transplantation Centers.

[Safety of donors, quality of products, how much to reduce the quantity of citrate]. / Sécurité des donneurs, qualité des produits jusqu'où diminuer la quantité de citrate.

We examined 1,053 blood samples from 48 donors, for the effect of gradual reduction of citrate. We observed that: 1--Platelet count does not show any significant variation between 1/8 to 1/18 ratio. 2--In 13.3% of the cases, platelet clumping starts at 1/18 ratio. 3--There was no significant variation of the thrombin plasma level between 1/8 to 1/16 ratio (by measuring thrombin/ATIII complex). Our results show clearly that we can reduce the citrate ratio to 1/14 without expecting any adverse effect. Therefore we designated 1/14 as the security ratio. Parallel to this we also found that the average level +/- SD of ionized calcium is 100 +/- 10 muMol at 1/14 ratio.

Alloimmune neonatal neutropenia.

In three neonates, the diagnosis of anti-NA1 alloimmune neutropenia related to maternal immunization against fetal polymorphonuclear leukocytes (PMN) antigens was achieved by serum antibody screening and PMN phenotyping. All the children were small for date and exhibited bacterial infection within days 2-13. Neutropenia persisted until days 20-50. High-dose intravenous immunoglobulin G (IVIgG) was ineffective. In one case, NA1-negative PMN collected from a normal donor were infused because of infection after thoracic surgery and resulted in a sharp but transient increase in PMN counts with resolution of infection. The natural history and the management of alloimmune neonatal neutropenia are discussed.