Light and electron microscopic study of cyclosporin A-induced gingival hyperplasia

Four transplant (3 kidney, 1 bone marrow) patients with cyclosporin A (CyA)-induced gingival hyperplasia are described. Light and electron microscopic findings of gingival biopsies showed in all patients that, in addition to an increase of collagen, CyA induced in the subepithelial space an enormous infiltration of morphologically normal plasma cells in different stages of maturation. These data, together with the reversibility of the lesion upon discontinuation of the drug, suggest that individual hypersensitivity is probably the most acceptable explanation of CyA-induced gingival hyperplasia. This hypothesis is also discussed in relation to the CyA-suppression of the functions of some T-lymphocyte subsets.     

Invasive fungal sinusitis: an effective combined treatment in five haematological patients

Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.     

Prospective study on the behaviour of the metalloprotease ADAMTS13 and of von Willebrand factor after bone marrow transplantation

Thrombotic microangiopathies (TMAs) are rare but serious complications of bone marrow transplantation (BMT). Clinical manifestations are similar to those of thrombotic thrombocytopenic purpura (TTP), but prognosis is generally poorer despite plasma exchange. The enzymatic activity of the plasma metalloprotease ADAMTS13, which cleaves ultralarge thrombogenic multimers of von Willebrand factor (VWF) derived from activated endothelial cells, is very low or undetectable in patients with classic TTP, and protease deficiency is thought to play a mechanistic role in the formation of platelet thrombi in the microcirculation. This is the first prospective study to evaluate the incidence of TMA in 46 consecutively recruited patients undergoing autologous or allogeneic BMT and explore in parallel the behaviour of ADAMTS13, VWF antigen and VWF multimer size. The incidence of post-BMT TMA was 6% (three of 46); all cases occurred after allogeneic BMT. Compared with baseline values plasma ADAMTS13 activity was significantly reduced in patients undergoing BMT, particularly after the conditioning regimen (mean values: 50 +/- 22 vs. 77 +/- 32%; P < 0.0001). In the three patients who developed TMA, ADAMTS13 decreased after conditioning, but was very low in one case only (8%). VWF antigen levels progressively increased after the conditioning regimen (228 +/- 75 vs. 178 +/- 76% at baseline, P = 0.002). The mean proportion of high-molecular weight VWF multimers did not change in the various stages of BMT, even though ultralarge multimers were transiently found in same cases with and without TMA. Hence, the measurements evaluated in this study are not clinically useful to predict the occurrence of post-BMT TMA.     

Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population

The main objective of this study was to investigate whether patients with chronic myeloid leukemia (CML) in treatment with long-term therapy imatinib have a different health-related quality-of-life (HRQOL) profile compared with the general population. In total, 448 CML patients were enrolled, and the SF-36 Health Survey was used to compare generic HRQOL profiles. Symptoms were also assessed. HRQOL comparisons were adjusted for key possible confounders. The median age of patients was 57 years and the median time of imatinib treatment was 5 years (range 3-9 years). The largest HRQOL differences were found in younger patients. In particular, patients aged between 18 and 39 years had marked impairments in role limitations because of physical and emotional problems, respectively: -22.6 (P < .001), -22.3 (P < .001). Patients with CML age 60 or older had a HRQOL profile very similar to that reported by the general population. Women had a worse profile than men when each were compared with their peers in the general population. Fatigue was the most frequently reported symptom. The HRQOL of CML patients is comparable with that of population norms in many areas, however, younger and female patients seem to report the major limitations.     

Reduced-intensity conditioning lowers treatment-related mortality of allogeneic stem cell transplantation for chronic lymphocytic leukemia: a population-matched analysis.

To elucidate whether reduced-intensity conditioning (RIC) decreases treatment-related mortality (TRM) after allogeneic stem cell transplantation (allo-SCT) for chronic lymphocytic leukemia (CLL), we retrospectively compared 73 RIC cases from a recent EBMT survey with 82 patients from the EBMT database who had undergone standard myeloablative conditioning (MC) for CLL during the same time period. The two populations were matched by adjusting the primary risk factor, the conditioning regimen, in a series of Cox models for age, sex, donor type, remission status at transplant and analyzed for its effect on TRM, relapse incidence, event-free (EFS) and overall survival (OS). After adjustment, a significant reduction of TRM became evident for the RIC population (hazard ratio (HR) 0.4 (95% confidence interval 0.18-0.9); P=0.03). On the other hand, RIC was associated with an increased relapse incidence (HR 2.65 (0.98-7.12); P=0.054). There was no significant difference between RIC and MC in terms of EFS (HR 0.69 (0.38-1.25); P=0.22) and OS (HR 0.65 (0.33-1.28); P=0.21). We conclude that RIC appears to favorably influence TRM after allo-SCT for CLL. This observation, as well as possible detrimental effects of RIC on relapse risk, should be confirmed by prospective studies.