182PostersPO-196EPRATUZUMAB/SAPORIN-S6: A NEW ANTI-CD22 IMMUNOTOXINWITH A POTENT ANTITUMOUR ACTIVITYPolito L, Farini V, Zinzani PL,° Stirpe F, Bolognesi ADipartimento di Patologia Sperimentale, Universitàdi Bologna, Bologna, Italy; °Istituto di Ematologia eOncologia medica “L. & A. Seràg<strong>no</strong>li”, Università diBologna, Bologna, ItalyThe use of mo<strong>no</strong>clonal antibodies as anti-cancertherapies has been widely explored since their initialdevelopment by Kohler and Milstein. 1 In contrast tochemotherapy and radiotherapy specific antibodiescan preferentially bind tumor cells over <strong>no</strong>rmal tissues.The vascular nature of most lymphomas suggeststhat they may represent a favorable setting forthis treatment modality. In fact, the first successfuluse of antibodies as treatment for cancer wasdemonstrated in lymphoma, and these agents have<strong>no</strong>w been employed to benefit thousands of patientswith <strong>no</strong>n-Hodgkin's lymphomas (NHL). 2 CD22 isexpressed at high levels on <strong>no</strong>rmal mature B-cellsand on a large proportion of B lymphoma cells. Thehumanized anti-CD22 antibody Epratuzumab (hLL2)was used in clinical trials giving good anti-tumoractivity. It was well tolerated, 16% of the patientsresponded and one third of them achieved CR in aPhase I/II trial. 3 Better results could be obtained couplingthis mAb to a toxin to obtain a chimeric protein,defined immu<strong>no</strong>toxin. 4,5 In our studies we linkedEpratuzumab to the RIP saporin-S6.RIPs are planttoxins with RNA N-glycosidase activity, which cleaveone or more adenine molecules from ribosomal RNA,thus damaging ribosome in an irreversible manner. 6The effects of Epratuzumab-saporin-S6 were evaluatedas inhibition of protein synthesis on five targetB-lymphoma cell lines: BJAB, REH, D430B, Raji andRamos. Time-course and dose-response experimentswere performed to extrapolate the kinetics of proteinsynthesis inhibition and the concentration ofimmu<strong>no</strong>toxin giving 50% inhibition (IC50). Conjugationwith Epratuzumab enhanced saporin-S6 cytotoxicityon target cells by at least 3 logs, with IC50in the pM range. No protein synthesis inhibition wasinduced by free mAb. Protein synthesis of CD22-negativeJurkat cells was <strong>no</strong>t affected by the immu<strong>no</strong>toxinat concentrations up to 10 nM. These resultswere confirmed by a<strong>no</strong>ther cytotoxicity assay, basedon MTS. We further demonstrated the killing efficiencyof the immu<strong>no</strong>toxin using a very sensitivelumi<strong>no</strong>metric method, measuring the ATP producedby surviving cells, in time- and dose-response experiments.Moreover, as the final target of an antitumourtherapy is to completely eradicate the disease,the clo<strong>no</strong>genic growth of target cell lines wasdetermined after exposure to anti-CD22 immu<strong>no</strong>toxin.A complete elimination of BJAB clones wasreached after a short time (3 h) exposure to the conjugate,at 10 nM concentration vs a 15% inhibitio<strong>no</strong>f clo<strong>no</strong>genic growth reached with saporin-S6 alone.References1. Kohler G, Milstein C. Eur J Immu<strong>no</strong>l 1976;6:511-519.2. Forero A, Lobuglio AF. Semin Oncol 2003;30:1-5.3.Leonard JP, Coleman M, Ketas JC, et al. Clin Oncol. 2003;21:3051-9.4.Kreitman RJ, Pastan I. Adv Drug Deliv Rev 1998;31:53-8.5.Bolognesi A, Polito L. Mini Rev Med Chem <strong>2004</strong>;4:563-85.6.Barbieri L, Battelli MG, Stirpe F. BBA 1993;1154:237-82.haematologica vol. <strong>89</strong>[suppl. n. 6]:september <strong>2004</strong>
VIII Congress of the Italian Society of Experimental Hematology, Pavia, September 14-16, <strong>2004</strong>183PosterLYMPHOMAS AND LYMPHOPROLIFERATIVEDISORDERS IIPO-197HHV-8 POSITIVE PEL IN A HIV-POSITIVE WOMAN FROMCENTRAL AFRICA WITH AGGRESSIVE KAPOSI SARCOMAAscoli V,* Natale ME,* Giannakakis K,* Dell'Isola S,°Mastroianni CM,° Calabrò ML, # Buffoli<strong>no</strong> S, §Floriddia G, § Cimi<strong>no</strong> G §*Dipartimento di Medicina Sperimentale e Patologia,°Dipartimento di Malattie Infettive e Tropicali,§Dipartimento di Biotec<strong>no</strong>logie Cellulari ed Ematologia,Università La Sapienza, Rome; # Dipartimento diScienze Mediche e Chirurgiche, Università di Padova,Padova, ItalyHuman herpesvirus 8 (HHV-8) associated primaryeffusion lymphoma (PEL) and Kaposi sarcoma (KS)are diseases primarily affecting men. HHV-8 is highlyprevalent in many African countries, wherein it isas common in women as in men. Since the epidemicof HIV, KS has become relatively more frequent inwomen and it can be aggressive and devastating(N<strong>no</strong>ruka et al. Int J Dermatol 2003). We herein reportthe case of a HHV-8-positive PEL in a HIV-positive26-year-old black woman. She was born and livedfor 22 years in Cameroon, central Africa, then 4 yearsin Italy. The patient was graduated student whodenied intrave<strong>no</strong>us drug abuse and declared heterosexualunprotected intercourse. Her past medical historywas negative except for malaria during childhood/adolescence.In July 2003 she became symptomaticwith progressive malaise. In August she developeda febrile syndrome associated with Shigella flexineri,and received a blood transfusion because ofsevere anemia (Hb 7.0 g/dL). Serologic test for HIVwas positive (HIV-RNA 5300 copies); CD4 8%; CD494/mm 3 ; CD8 61%. She underwent highly anti-retroviraltherapy. Nonetheless, the patient developedrecurrent pleural effusions, high fever and widespreadlymphoade<strong>no</strong>patic, visceral and mucocutaneous KS.The course of disease was aggressive and deathoccurred in November. Effusions contained largeatypical lymphoid cells that were <strong>no</strong>t numerous inthe first fluid but increased in number in the subsequentsamples. HHV-8 DNA sequences, but <strong>no</strong>t EBV,were detected by PCR in peripheral blood mo<strong>no</strong>nuclearcells, saliva and in the pleural sediment. Antibodiesto the latent nuclear antigen (LNA-1) ORF 73revealed nuclear staining in atypical lymphoid cells.PCR analysis of the pleural sediment disclosed <strong>no</strong>clonal rearrangements of the Ig heavy chain gene.The failure of Ig PCR in PEL has been reported previously(Fais et al. Leukemia 1999; Hamoudi et al.Leukemia Research <strong>2004</strong>). Sequencing of the ORF K1gene is in progress to document the HHV-8 strain.This case is an example of HHV-8 associated PEL inan African woman with HIV-related immu<strong>no</strong>deficiency.Few papers have described PEL in women: 6HIV-negative cases (Said et al. Blood 1996; Carboneet al. Br J Hematol 1996; Codish et al. Am J Hematol2000; Niitsu et al. Ann Hematol 2000; Boulanger etal. Am J Hematol <strong>2004</strong>) and 1 HIV-positive case inwhich, however, the proof of HHV-8 infection is lacking(Valencia et al. AIDS 1999). To our k<strong>no</strong>wledge,PEL has never been reported in Africans. In Cameroon,HHV-8 seroprevalence is high (28-62%; up to 55%in pregnant women), HHV-8 infection takes placeduring childhood by <strong>no</strong>n-sexual casual routes, and KSwas relatively frequent also before the spread of HIVinfection epidemic (8/1000 men) (Gessain et al. Int JCancer 1999).PO-198EFFECT OF DEXRAZOXANE ON TOTAL PLASMA ANTIOXIDANTCAPACITY AND ON QT DISPERSION IN LYMPHOMA PATIENTSDURING ANTHRACYCLINE-BASED CHEMOTHERAPYCervetti G,* Franzoni F,° Galetta F,° Cecconi N,*Rossi A,* Femia FF,** Fazzi R,* Regoli F,** Santoro G,°Petrini M**Department of Hematology, °Department of InternalMedicine, University of Pisa, Pisa, **Institute ofBiology and Genetics, University of Ancona, ItalyAnthracyclines are widely used in the treatment oflymphomas but their clinical efficacy can be limitedby acute and chronic toxicity, in particular cumulativecardiac damage. Several approaches have beenattempted to reduce cytotoxicity of these antineoplasticagents, such the use of drugs with potentialcardio-protective action. Dexrazoxane clorhydrate(Cardioxane®), a synthetic bisdiketopiperazine tworingedcompound which hydrolyzes to an EDTA analog,seems to be able to reduce cardiac toxicity bybinding to free and bound iron, thus reducing theformation of anthracycline-iron complexes and thegeneration of free radicals which are toxic to cardiactissue. In daily practice, parameters of systolic function(left ventricular ejection fraction or fractionalshortening) are employed to detect cardiotoxicity, butthese methods are <strong>no</strong>t able to identify acute cardiacdamage. The determination of QT dispersion mayidentify patients at risk of the development of earlyheart failure. The main purpose of the present studywas to assess the effect of epirubicin-based chemotherapy(PROMECECytaBOM) on plasma free radicalhaematologica vol. <strong>89</strong>[suppl. n. 6]:september <strong>2004</strong>
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62PostersPosterACUTE MYELOID LEUKEM
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64Postersone course of CI-FLA. Ther
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68Posterstion until optimal VPA pla
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70Posterseffective biotechnological
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72Postersdirectly to maintenance th
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74PostersPosterACUTE LYMPHOID LEUKE
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76Postersformed in half the patient
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78Posterspatients correlating data
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80Postersleukemia-related and thus
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82PostersCD33/CD16, CD13/CD16, CD45
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84PostersIn myelodysplastic syndrom
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86Postersin our series of 376 conse
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88PostersPO-041FUNCTIONAL ANALYSIS
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90PostersPO-044FISHING NUP98 INVOLV
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92Postersof AML blasts to RA. In su
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94Postersafter 72-96 h treatment wi
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96PostersPosterMOLECULAR HEMATOLOGY
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98Postersanalyse the transcribed HU
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102Postershowever, been reported in
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104Postersand the intrinsic apoptot
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106Postersferentation by BM stromal
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108PostersPO-075NONMYELOABLATIVE AL
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112PostersPosterMULTIPLE MYELOMA II
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114Posterssion, the immunomodulator
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116Posters(p-ERK1/2) levels in myel
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118PostersPO-092ROLE OF THE MEVALON
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120Postershis study evaluates the p
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122PostersPosterNON-ONCOLOGICAL HEM
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124PostersPO-101A WHOLE BLOOD FLOW
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126Postersthat ITP DCs, after pulsi
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128PostersTherefore in the proposit
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130Postersods and early effective a
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