No abstract

The thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials.

We report Guillain-Barre syndrome (GBS), developed in a patient with metastatic colon cancer, receiving oxaliplatin-based chemotherapy. The 53-year-old patient was treated with first-line chemotherapy consisting of oxaliplatin 45 mg/m2, 5-fluorouracil 450 mg/m2 and folinic acid 200 mg/m2, all given on the same day in a weekly schedule. After 13 weeks of treatment and a cumulative oxaliplatin dose of 585 mg/m2, the patient developed unsteadiness of gait, dysphagia, and weakness of both the upper and lower limbs, as well as impairment of all sensory modalities. Clinical examination, computed tomography and magnetic resonance imaging scans of the brain, blood tests, nerve conduction studies, and cerebrospinal fluid analysis confirmed the diagnosis of GBS. Intravenous immunoglobulin G was administered for 5 days and the patient recovered fully. Oxaliplatin can cause acute and delayed neurotoxicity, but this is the first report of GBS in a patient receiving oxaliplatin-based chemotherapy. Elevation of pro-inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6, induced by oxaliplatin, may represent the relevant causal links involved in the cascade of events which have led to the immune-mediated demyelination in the peripheral nervous system in this patient.

The aim of this prospective study was to determine whether treatment with a combination of GM-CSF and erythropoietin (rhEpo) can improve the anemia associated with low risk myelodysplastic syndrome (MDS), namely refractory anemia (RA), RA with ring sideroblasts (RAS), and RA with excess of blasts (RAEB) with bone marrow blasts less than 10%. Eligibility criteria included an Hb level of less than 10.5 g/dl for newly diagnosed patients, or symptomatic anemia. GM-CSF was given at a dose of 3 g/kg s.c. on days 1-2, rhEpo at a dose of 60 U/kg s.c. on days 3-5. No treatment was given on days 6-7. Patients were followed-up with full blood count on a weekly basis. The treatment was repeated for a total of 6 weeks. At that time, if a rise in Hb above 1.5 g/dl had not been achieved, the dose of rhEpo increased to 120 U/kg. Post-treatment evaluation was performed at the completion of 12 weeks. Erythroid response was defined as good (GR), if an increase in untransfused Hb values above 2 g/dl or a 100% decrease in red blood cell transfusion requirements, over the treatment period was observed, while an increase in untransfused Hb values 1-2 g/dl or a Ͼ50% decrease in transfusion requirements, were considered as partial response. Responders continued to receive the same treatment until disease progression. Nineteen patients (13 male and six female) with a median age of 69 years were enrolled in the study. The FAB subtypes were: RA one case, RAS eight cases and RAEB 10 cases. Ten of 19 patients (52.6%) responded to the treatment: 7/19 (36.8%) achieved a GR and 3/19 (15.8%) a PR. Six of eight (75%) patients with RAS, one case with RA and 3/10 (30%) of cases with RAEB responded to treatment. Pretreatment serum epo levels were generally low (less than 200 Mu/ml) in responding patients. At the completion of the initial 12 weeks, 8/12 responding patients (5 RAS, 2 RAEB and 1 RA) continued to receive the same treatment. All responding patients with RAS continued to show an erythroid response in a time period from 3 to 24 months, whilst one patient with RA and two with RAEB did not have a continuing response at 2, 4 and 12 months, respectively. The above data suggest that the combination of rhEpo and GM-CSF should be recommended in all cases with RARS. However, the clear indication of this combination for other patients with MDS remains to be determined.

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.