Summary. About 30% of patients with severe aplastic anaemia (SAA) unresponsive to one course of immunosuppressive (IS) therapy with antithymocyte or antilymphocyte globulin can achieve complete or partial remission after a second IS treatment. Among various second-line treatments, rabbit ATG (r-ATG) could represent a safe and effective alternative to horse ALG (h-ALG). In a multicentre study, 30 patients with SAA (17 males and 13 females, median age 21 years, range 2±67) not responding to a ®rst course with h-ALG plus cyclosporin (CyA) and granulocyte colony stimulating factor (G-CSF), were given a second course using r-ATG (3´5 mg/kg/d for 5 d), CyA (5 mg/kg orally from day 1 to 180) and G-CSF (5 mg/kg subcutaneously from day 1 to 90). The median interval between ®rst and second treatment was 151 d (range 58±361 d). No relevant side-effects were observed, but one patient died early during treatment because of sepsis. Overall response, de®ned as transfusion independence, was achieved in 23/30 (77%) patients after a median time of 95 d (range 14±377). Nine patients (30%) achieved complete remission (neutrophils >2´0´10 9 /l, haemoglobin >11 g/dl and platelets >100´10 9 /l). The overall survival rate was 93% with a median follow-up of 914 d (range 121±2278). So far, no patient has relapsed. Female gender was signi®cantly associated with a poorer likelihood to respond (P 0´0006). These data suggest that r-ATG is a safe and effective alternative to h-ALG for SAA patients unresponsive to ®rst-line IS treatment.
Summary. We administered the anti-angiogenic drug thalidomide to 21 patients (12 men) with myelofibrosis with myeloid metaplasia (MMM), who were not responsive to standard treatment. Patients received thalidomide at an escalating dose from 100 to 400 mg/d. Administration of the drug was discontinued before the planned 6 months of treatment in 19 patients (90´5%), mainly because of somnolence and/or fatigue, neurological symptoms or neutropenia. Of the 13 evaluable patients (who received more than 30 d of therapy), anaemia improved in three out of seven (43%) who were treated because of anaemia; thrombocytopenia improved in two out of three (66´6%) who were treated because of thrombocytopenia; splenomegaly was reduced in four (30´8%). Undesired increases in white blood cell and platelet counts were observed in three (23´1%) and five (38´5%) patients respectively. A severity score, indexed on haematological and clinical parameters, improved in two patients (15´4%), but worsened in five (38´5%). In conclusion, standard-dose thalidomide in MMM patients is burdened with a high rate of side-effects, which prevent prolonged treatment. Because the drug is effective in improving anaemia and thrombocytopenia and in reducing splenomegaly, lowdose therapy warrants evaluation. The unexpected observation of leucocytosis and thrombocytosis suggests biological studies and better criteria for selection of patients for treatment.
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