In a previous study, we showed that patients undergoing allogeneic hemopoietic stem cell transplantation (HSCT) who had cytomegalovirus (CMV) antigenemia with more than 4 CMV antigen-positive cells/200,000 have a high transplant-related mortality (TRM) rate, despite treatment with ganciclovir or foscarnet. In an attempt to reduce TRM, 32 allogeneic HSCT recipients, between the ages of 16 and 55 years (median, 35 years), with CMV antigenemia (> or = 5 positive cells) developing at a median interval from HSCT of 49 days, were given combination treatment with foscarnet and ganciclovir for 15 days. The prescribed dose was 180 mg/kg/day of foscarnet and 10 mg/kg/day of ganciclovir: the median administered dose in the first 15 days, after adjusting for creatinine levels and peripheral blood counts, was 64% for foscarnet and 53% for ganciclovir. Maintenance was given with foscarnet and ganciclovir on alternate days for an additional 2 weeks. Thirty-one of 32 patients were on cyclosporine, 30 were on systemic antibiotics, and 9 were on intravenous amphotericin. Median laboratory values on days 1 and 15 of treatment were 1.0 and 1.1 mg/100 ml creatinine, 5.7 x 10(9)/L, and 4.1 x 10(9)/L white blood cells, and 78 x lO(9)/L and 72 x 10(9)/L platelets. All patients cleared CMV antigenemia by day +15, although CMV antigenemia recurred in 5 patients on maintenance therapy and in 14 patients off maintenance therapy: the dose of foscarnet (but not ganciclovir) received in the first 15 days was significantly lower in patients in whom antigenemia recurred within 30 days (P=0.0002). Six patients died, one with interstitial pneumonia, one with multiorgan failure, and four with infections. Twenty-six patients survived 119-1051 days after transplant. The actuarial TRM rate at 1 year is 23%. Eighteen patients who had received unmanipulated bone marrow transplants from HLA-identical siblings were compared with 15 matched controls who had been treated with a single drug (either foscarnet or ganciclovir) for CMV antigenemia (> or = 5 cells): the actuarial 1 year TRM rate was 13% for patients receiving combined treatment, compared with 47% for controls receiving a single drug (P=0.02). This study shows that combined foscarnet-ganciclovir is one therapeutic option for allogeneic HSCT recipients who develop CMV antigenemia with a high number of CMV antigen-positive cells. Treatment can be given together with cyclosporine and antibiotics with appropriate dose reductions. It produces prompt clearing of CMV infection, and may reduce TRM rates in comparison to single-agent therapy.

Although in recent years the use of purine analogues has increased the percentage of long-term complete response the effect on overall survival of patients with hairy cell leukemia (HCL) is not yet clear. This study aimed to evaluate the long-term outcome (mean follow up of 92 months) of 64 patients receiving IFN as first-line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty-one patients (63%) received IFN 3 MU/ wk as maintenance therapy. The 10-yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non-responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p <0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population.

In vitro priming of T cell with horse antilymphocyte globulin (HALG) results in cytokine release, and this has been associated with its clinical efficacy in patients with severe aplastic anaemia (SAA). Rabbit antithymocyte globulin (RATG) has been studied less extensively. In this study we compare the in vitro priming effect of HALG and RATG on purified normal marrow T cells: end‐points of the study were 1) levels of TNF‐alpha (TNF‐α), IFN‐gamma (IFN‐γ) GM–CSF in T cell supernatants, and 2) effect of T cell supernatants on colony formation with or without exogenous GM–CSF. TNF‐α, IFN‐γ and GM–CSF levels were comparable for HALG, RATG and phytohaemagglutinin (PHA). T cell supernatants showed comparable enhancement of colony formation in the presence of recombinant human GM–CSF (rhGM–CSF) and supported colony forming unit granulomacrophage (CFU–GM) growth in the absence of growth factor. This study shows that horse and rabbit derived ALG/ATG and PHA have a comparable in vitro priming effect on T cells: both agents should probably be tested for their clinical efficacy in SAA patients.

No abstract

No abstract