Haematologica 2004;89: supplement no. 6 - Supplements ...

128PostersTherefore in the propositus and his brother mutationP1337L results to be present in all the VWF subunits,which might explain their more severe phenotype incomparison with their children that carry only mutationP1337L.PO-109INTERLEUKIN-10 (IL-10) SERUM LEVELS MAY BE SYNERGISTICSWITH LOW-DOSE TACROLIMUS (FK) IN THE TREATMENT OFREFRACTORY IDIOPATHIC THROMBOCYTOPENIC PURPURAIuliano F,* Dardano A,° Levato L,* Fabiano F,*Giulino C,* Battaglia E,** Peta A, Gulletta E°*U. O. DI Ematologia,**Lab. patologia clinica A. O."Pugliese-Ciaccio", Catanzaro °Lab. patologia clinica,Università Magna grecia, Catanzaro, ItalyInterleukin-10 (IL-10) is a key cytokine that is elevatedduring systemic inflammation. The data currentlysuggest that IL-10 is synthesized by variousleukocytes and is important in regulating the productionof other cytokines (interferon-γ, TNF-β andIL-2) by TH1 cells. IL-10 has been found to inhibit theantigen presenting cell-mediated stimulation of TH1cells by inhibiting the production of inflammatorycytokines (IL-1a, IL-6, IL-8 and GM-CSF). Calcineurininhibitors, namely Tacrolimus (FK) and Cyclosporine(CsA) share similar physicochemical properties and acommon mechanism of action. FK in addition showsa strong anti-inflammatory property blocking thesecretion of pro-inflammatory cytokines and an indirectinhibitory effect on the growth and differentiationof B lymphocytes. With this background we carriedout serological studies in a consecutive refractoryITP patients receiving low-doses FK. Five patientswere enrolled in the study. Median age was 50 yrs(range 23-63), M/F=3/2, median time from diagnosiswas 4 months (range 1-24). The drug was givenorally twice a day in order to maintain blood levelsbetween 5-15ng/ml. 5/5 patients (100%) achievedCR (plts > 110 9 /L for > 12 weeks). The median time toCR was 5 months (range 1-9). In order to evaluate theresponse duration, all patients stopped FK therapyafter a median of 5 months from CR (range 2-12). 2pts relapsed after 2 and 1 patient after 3 months. Allof these patients resumed FK therapy and re-achievedCR after 2 months. 1 patient lost CR but remained inPR (plts > 40×9/L for > 8 weeks) at 10 months follow-up;1 patient showed a sustained CR (more than20 months follow up). Cytokine levels were quantifiedby enzyme-linked immunosorbent assay. Bloodfor cytokine assays was collected at day 30,60,90, insodium heparin, placed immediately in ice water, centrifugedand the resulting plasma stored in aliquotsat 80°C within 1 h of phlebotomy. IL-10 levels weremeasured in batches using an enzyme-linkedimmunosorbent assay (ELISA) technique with kitsobtained from R&D Systems (Minneapolis, MN, USA).Serum γ IFN, IL-2 and s-IL-2R levels were also quantified.All samples showed IL-10 serum high levels (>500 pg/mL, range 7.8-500 pg/mL). Interesting, serumγ IFN and IL-2 were below defined cut-off (15 pg/mland 1.2 U/ml) in all pts and serum levels IL-2 receptorwere increased (cut-off 70 pg/ml). Our data suggestthat IL-10 may be involved in limiting and terminatinginflammatory responses in ITP patients. Inthis way IL-10 may be synergistic with FK antiinflammatoryproperty. FK, on the other hand, inhibitsregulatory IL-10 effects on growth and/or differentiationof B cells.PO-110THE ROLE OF RECOMBINANT ACTIVATED FACTOR VIIA IN APATIENT WITH SEVERE THROMBOCYTOPENIA AND LIFE-THREATENING GASTROINTESTINAL BLEEDINGBenevolo G, Franceschetti S, Rossi D, Vendramin C,Conconi AUDA Ematologia, Dipartimento Scienze Mediche,Università del Piemonte Orientale "Amedeo Avogadro",Novara, ItalySevere thrombocytopenia is a common complicationin hematologic malignancies, due to a decreasedplatelet production by bone marrow involvement orto the use of intensive chemotherapeutic regimens.Platelet transfusion is the current standard treatmentfor bleeding episodes associated with severe thrombocytopenia.However, the transfusion complicationssuch as transfusion-trasmitted diseases, plateletrefractoriness, immunomodulation and difficulty toachieve a sufficient supply of platelets from donors,as well as the failure to achieve a proper hemostasisdespite transfusion, prompt the search for therapeuticmeasures that may complement platelet transfusion.Recombinant activated factor VII (rFVIIa) hasbeen shown to improve hemostasis in patients withthrombocytopenia in several studies. We report thecase of a 58-year old man who was diagnosed ashaving primary thrombocythemia in 1974.The patienthad been treated with chemotherapeutic agents,namely hydroxyurea, and later with interferon-α(INF-α) until he developed severe thrombocytopenia,mild anemia and leukocytosis in 2001. The presenceof bone marrow fibrosis, extramedullary hemopoiesisand splenomegaly suggested transformation tomyelofibrosis with myeloid metaplasia. The patientwas treated with supportive therapy until January2003, when the myeloproliferative syndrome evolvedinto acute myeloid leukemia, with monosomy ofchromosome 7.At that time, the patient also developeda thrombotic event (AMI with PTCA on righthaematologica vol. 89[suppl. n. 6]:september 2004