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

86Postersin our series of 376 consecutive MDS patients, to correlatethe defect with peculiar morphological features,to determine whether the breakpoints of theinterstitial deletion, the presence of one additionaldefect and an increased medullary blast count affectedoverall survival (OS) and event-free survival (EFS).Cytogenetic analyses were carried out at diagnosis onbone marrow cells with a trypsin-Giemsa bandingtechnique. Metaphase cells were obtained fromshort-term unstimulated cultures. Whenever possibleat least twenty metaphases were analysed and tenfully karyotyped. An isolated del(5q) was discoveredin a 32 patients, while a del(5q) plus one additionaldefect in 13.The median age of single del(5q) patientswas 60 years (35-80 years). Male to female ratio was1:1, but it changed to 1:1.7 when only refractory anemia(RA) and refractory anemia with ringed sideroblast(RARS) were examined. Twenty patients wereclassified as RA and RARS, 8 as refractory anemiawith excess of blasts (RAEB), 2 as RAEB in transformationand 2 as chronic myelomonocytic leukemia(CMML). The 20 patients with less advanced MDSshowed erythroid hypoplasia and hypolobulatedmegakaryocytes as their most prominent morphologicfeatures. In particular the former morphologicalfinding was discovered in about 50% of patients.Considering del(5q) plus one additional defect fourpatients were classified as RA, 4 as RAEB, 2 as RAEBtand 2 as CMML. The median survival for patientswith an isolated del(5q) was 138 months, while thatof patients with an increased medullary blast countor with del(5q) plus one additional abnormality was38 and 50 months respectively. When we comparedpatients with an isolated del(5q) versus those withdel(5q) plus one additional defect death rates were7.5 (95% confidence intervals, CI=2.9-19.8) vs 25.6(95% CI=12.2-53.9) with an hazard ratio of 0.2 (95%CI=0.1-0.8) and death/progression rates were 11.5(95% CI=5.1-25.8) vs 33.6 (95%CI=17.5-64.6) withan hazard ratio of 0.3 (95%CI=0.1-0.8). Patients withsingle del(5q) presented a significantly better OS andEFS in comparison to those with del(5q) plus oneadditional defect (p values= 0.01 and 0.02). No differencein OS and in EFS was seen in relation eitherto the different breakpoints of the interstitial deletionor to the amount of dysplasia. Death occurred in 8patients with an isolated del(5q) and in 7 patientswith del(5q) plus one additional defect, whileleukemic evolution occurred in 11 and in 9 patientsof each group respectively. In addition we could notsegregate patients with single del(5q) from thosebelonging to the good-risk cytogenetic category asdefined by the International Prognostic Scoring System(IPSS). In fact OS and EFS for both patient groupswere similar. The same occurred when patients withdel(5q) plus one additional defect were compared tothose belonging to the IPSS intermediate-risk cytogeneticscategory. In conclusion our study strengthensthe WHO definition of del(5q) as a separate entitywithin MDS subgroups but also suggests thatpatients with an otherwise typical 5q-syndrome butwith an increased blast count or with additionaldefects should not be included within this entity.PO-039PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTSDISPLAY HIGH FREQUENCY OF CIRCULATING T LYMPHOCYTESEXPRESSING ACTIVATING ISOFORMS OF INHIBITORY SUPER-FAMILY RECEPTORSNegrini S, #$ Zocchi MR, & Massaro AM, #& Gargiulo L,*Serra M,* Notaro R,* Luzzatto L,* Poggi A ##Laboratory of Immunology, Istituto Nazionale per laRicerca sul Cancro, Genova; $ Laboratory of ClinicalImmunology, Dipartimento di Medicina Interna,University of Genoa, & Laboratory of Tumor ImmunologyIstituto Scientifico San Raffaele, Milan, Italy;*Laboratory of Human Genetics, Istituto Nazionaleper la Ricerca sul Cancro, Genova, ItalyRecently, it has been reported that a minor subsetof T lymphocytes express at the cell surface KIRand/or CLIR members of the Inhibitory ReceptorSuperfamily (IRS). These T cells would representchronically stimulated memory cells expanded duringviral infection or autoimmune responses. Paroxysmalnocturnal hemoglobinuria (PNH) is a clonal disorderof the hematopoietic stem cell (HSC) characterized bydeficiency of glycosylphosphatidylinositol (GPI) membrane-linkedproteins. It has been proposed that normalHSC are selectively eliminated by autoreactive Tcells, while PNH HSC can escape this killing and thussurvive and expand. The identity of autoreactive Tcells and their target are still elusive. We have analyzedthe surface expression and function of IRSmembers in T cells of PNH patients. We found thatthe proportion of KIR + or CLIR + cells within CD3 + cellswas consistently higher in PNH patients than inhealthy donors. In addition, the ratio betweenCD3 + KIR + and CD3-KIR + or CD3-CLIR + and CD3-CLIR +was >1 in 8 out of 12 PNH patients, whereas thisratio was >1 only in 3 out of 30 healthy donors. Thisindicates that, beside by the increase of CD3 + IRS +cells, PNH patients are characterized by a decrease ofCD3-IRS + Natural Killer cells. A minor fraction ofCD3 + IRS + T cells express TCR γδ (belonging to the Vδ2subset) and the remaining large fraction of these cellswas TCR αβ + . PNH CD3 + IRS + T cells were characterizedby a powerful cytolytic activity when triggeredthrough the engagement of KIR or CLIR receptors.This indicates that CD3 + IRS + T cells express IRSbelonging to the activating type. Clonal analysisrevealed that in the large majority of T cell cloneshaematologica vol. 89[suppl. n. 6]:september 2004