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24 Clinical and biological profile of 55 patients with Refractory Anemia with Ring Sideroblasts
Epidemiology
and Classification
s7
24
25
CLINICAL AND BIOLOGICAL PROFILE OF 55 PATIENTS WITH REFRACTORY ANEMIA WITH RING SIDEROBLASTS. A.Richart, A.Rom&n. EArranz, E.Prieto, E.Chica, G.PCrez Rous*, CSoto, J.Outeirifio, JBenitez, J.Sanchez Fayos. Dpts. of Genetics and Hematology, Fundaci6n Jimenez Diaz,Madrid. *Dpt. of Hematology, Hospital Gregorio Maraii6n ,Madrid. Spain.
REFRACTORY ANEMIA, PURE SIDEROBLASTIC ANEMIA AND REFRACTORY CYTOPENIA WITH MULTILINEAGE. DYSPLASIA G Perez Rus, J. del Toro, T. Calabuig, J. Anguna, J. Sanchez Fayos, Fundacion Jimenez Diaz, HGU Gregorio Maraiton. Madrid, Spain. Given the exclusive presence of dyserythropoiesis (DYSE) or its association with dysgranulopoiesis and/or dysthrombopoiesis (DYSGIDYST), two types of acquired idiopathic sideroblastic anemia (AISA) have been distinguished. Similarly, for some authors, the e.xistenceof important DYSGDYST would be incompatible with the diagnosis of RA according to FAB classification. 91 patients with RA and AISA were studied to determine whether the existence of DYSGDYST leads to an outcome which justifies its differentiation from subsetswith DYSE only. Both groups of patients (DYSE only n=22, DYSG/DYST n-69) showed a median survival time not reached and 64 months respectively (p=O.122), with similar evolution to AML (14%&12%). The proportion of normal, l-2 abnormalities and complex karyotypes was similar although the latter were invariably accompanied by DYSG/DYST: patients with DYSE only 68%, 32%, and 0% and those with DYSGDYST 57%, 35% and 9%. No signiticant difference could be observed among any of these variables, nor after separateanalyses of RA (n=59) and AISA (n=32). The existence of DYSG/DYST was a well recognized prognostic factor which appeared alongside others in several scoring systems. The results of this study do not support the distinction of MDS subsets based on the presence of DYSE only, especially when it is generally admitted that in all of them there is a stem cell disorder and multiple cytopenias can present. Dysplasia limited to the erythroid series has been proposed as an earlier manifestation of the clonal process. This study shows that cytogenetic alterations may already be present in this cytologically initial stage.
Between 1978 and 1996 we have studied from a cytogenetic, hematologic and clinical point of view 55 patients with Refractory Anemia with Ring Sideroblasts (SRA) since diagnosis; 5 1 of them were primaries; 2 secundaries to chemotherapy and 2 evolutioned from RA. The mean age at diagnosis was 74 years (43-88). All cases presented anemia (80% macrocytic and 20% normocytic); 20% neutropenia ; 25 % leucopenia; 18 % trombopenia; 11% leucocitosis and 22% trombocitosis. We found cytogenetic results in 53/55 cases and abnormal karyotypes in 13 of them. Trisomy 8 was the most frequent alteration (5 cases) and three patients presented complex karyotypes (3 or more alterations). With regard to the evolution 15 patients are alive (27%); 6 evolved to leukemia (11%) and 26 dead (62 W). The mean overall survival was 32.3 months (12 months in patients with complex karywP=) Our results show the clinical/biological profile of a homogeneous group with SRA followed in our hospital during a period of 18 years and remark a group of poor prognosis in patients with complex karyotypes (5%).
27
26 ABNomaLITIsS OF EIUTHROBUUlTS M A PATImT m ,iTI,, RING SVTS. P. Acln, T. Soler, F. Sol6. C. Besses, J. woes3ner. Servei de Citologia saris-Sabrafen, 5. Gncologia 1973. Hematol~gica. Vnitat d'Hematologia i Av. Sam Antoni Maria Claret Hospital Central L'Alianga. ZOO. 08025 Barcelona. Spain.
CXSBULSIPC wrrsL.
Florensa,
Refractory anaemia with ring sideroblasts WARS) is * mvelodvsolastic svndnme characterized bv- the presence of _ _. at least 15% of ring sideroblasts in the bone n!zrrow. It is )nam that the presenct of erythroblasts with coarse unstained stippling that coexist with basophilic cytoplaamic areas in peripheral blood is indicative of ringed sideroblasts. We describe a 70-year-old woman patient who presented ~‘3 107 symptc.u of anaemia. Laboratory data: Hb 81 g/L, fL, platelet count 366X109/L, HBC 4,9x10p/L (neutrophils eosinophils 2%. basophils 2%, lylophocytes 17%, 16%. peripheral film showed monocytes 3%). The blood macrocytosis, poikilocytosis. and anisocytosis, with an abnormal erythrocytes and some erythroblasts staining showed some cytoplasmatic pattern, which with ill-defined edsea unstained areaa OccuDvin~ * variable proportion of the cyt~plasm,~ coexiatirig -with coarse basophilic stippling. Serum folate and vitamin 812 were normals A bone marrow aspirate showed a hyperccllular 61% erythroid CCllS with signs of laarrm with dvservtrowiesis. The most striking features refered to erythcoblast; with abnormalities tik pre,,. of the similar to ,thosc of the peripheral blood erythroblasts. Gr.mlocytlc cells represented 30% of the bone marrow cells. The percentage of blasts was 1%. The Prussian-bluestain showed markedly increased iron stores, and 80% of precursors were ringed sideroblasts. the erytbroid Cytogenetic studies revealed a 46,xX karyotype. of RARS was made according to the FAB A diagnosis classification. our patient began with macrocytic anaemia and the blood smear showed crythrocytes and peripheral the previously mentioned erythroblests with characteristics suspicious of the sidcroblastic phenomenon that later was demonstrated with Prussian-blue-staining. We want to emphasize how this data serves to alert haematologists of the aideroblastic phencmenom.
DOES WBC COUNT REALLY DEFINE TWO DIFFERENT SUBTYPES OF CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)? ANALYSIS OF A SERIES OF 119 PATIENTS. I. Cervera, G.F. Sam., T. ValIespi, MC. de1Caiiizo, D. Irriguible, F. LoPez, C. Sanchez-Morata,L. Larrea, A. Blanco, L. BenIIoch,A. Julia, J.F. San Miguel, M.A. Sanz. Departments of Hematology, Hospital Universitario La Fe, Valencia, Hospital Vail d’Hebron, Barcelona, and Hospital Clinieo-Universitario, Salamanca,Spain. CMML, a beterogeneonshematologicaldisorder with myelodysplasticand myeloproI&rative featmes, is classified witbin the myelodysPIastic .sydmmm. The FAB group has suggestedto segregatetwo subrypes: my&dyspIastic (MDS-CMML) and myeloprobferative (MPD-LMMC), basedon the WBC count (~13 vs. >13xlOE9/L). The aim of this study was to compare the characteristics at onset and the outcome of both subtypes in a series of 119 patients with CMML (47 MDS-CMML and 72 MPD-CMML). Hepstomegsly(P=.OS)and spleenenlargement(P=. 15) were more. common in MPD-CMML. In blood, PMN (P=.OI) and immature grsnldocyte propoition (P<.Oool), and PMN nuclear segmentstion(P-QOI), were higher in MPD-CMML, whereaslymphocyte proportion (p>.OOOl)was higher in MDS-CMML. I-Ii&r biinibii levels were noted in MPDCMML (P=.OOO3),that also show a trend to have higher IeveIsof uric acid and LDH. In marrow, MDSCMML had a lower proportion of monoc+s (P=.OOO7)and myeloid precarsors (P=.Ol), aed a bigber number of erythroid precursors (F=.OOO3)and Iympbocyres Cp=.Ol). An abnormal karyotype was present in 46% of MIX-CMML eases and in 28% of MPDCMh4L (P=NS). MDS-CMML had a somewhstshorter survivsl (MS I1 vs. I5 ino.; P=.o6). The risk of acute leukrmctransformabonwassimikrinbothsubtypes(13%and14%at2 yr. in MDS- and MPDCMML). The most important factor afF&ing survival in MFDCMML was the presenceofbIastsinblood,whereasin MDSCMML. was the pemntsge of blasts in marrow. In conclusion, although there are some clinical and biological diffbrences between the CMML subtypes defined by WBC count, overlapping predominates.A more refined definition of subtypesin CMML is required.
and Classification
s7
24
25
CLINICAL AND BIOLOGICAL PROFILE OF 55 PATIENTS WITH REFRACTORY ANEMIA WITH RING SIDEROBLASTS. A.Richart, A.Rom&n. EArranz, E.Prieto, E.Chica, G.PCrez Rous*, CSoto, J.Outeirifio, JBenitez, J.Sanchez Fayos. Dpts. of Genetics and Hematology, Fundaci6n Jimenez Diaz,Madrid. *Dpt. of Hematology, Hospital Gregorio Maraii6n ,Madrid. Spain.
REFRACTORY ANEMIA, PURE SIDEROBLASTIC ANEMIA AND REFRACTORY CYTOPENIA WITH MULTILINEAGE. DYSPLASIA G Perez Rus, J. del Toro, T. Calabuig, J. Anguna, J. Sanchez Fayos, Fundacion Jimenez Diaz, HGU Gregorio Maraiton. Madrid, Spain. Given the exclusive presence of dyserythropoiesis (DYSE) or its association with dysgranulopoiesis and/or dysthrombopoiesis (DYSGIDYST), two types of acquired idiopathic sideroblastic anemia (AISA) have been distinguished. Similarly, for some authors, the e.xistenceof important DYSGDYST would be incompatible with the diagnosis of RA according to FAB classification. 91 patients with RA and AISA were studied to determine whether the existence of DYSGDYST leads to an outcome which justifies its differentiation from subsetswith DYSE only. Both groups of patients (DYSE only n=22, DYSG/DYST n-69) showed a median survival time not reached and 64 months respectively (p=O.122), with similar evolution to AML (14%&12%). The proportion of normal, l-2 abnormalities and complex karyotypes was similar although the latter were invariably accompanied by DYSG/DYST: patients with DYSE only 68%, 32%, and 0% and those with DYSGDYST 57%, 35% and 9%. No signiticant difference could be observed among any of these variables, nor after separateanalyses of RA (n=59) and AISA (n=32). The existence of DYSG/DYST was a well recognized prognostic factor which appeared alongside others in several scoring systems. The results of this study do not support the distinction of MDS subsets based on the presence of DYSE only, especially when it is generally admitted that in all of them there is a stem cell disorder and multiple cytopenias can present. Dysplasia limited to the erythroid series has been proposed as an earlier manifestation of the clonal process. This study shows that cytogenetic alterations may already be present in this cytologically initial stage.
Between 1978 and 1996 we have studied from a cytogenetic, hematologic and clinical point of view 55 patients with Refractory Anemia with Ring Sideroblasts (SRA) since diagnosis; 5 1 of them were primaries; 2 secundaries to chemotherapy and 2 evolutioned from RA. The mean age at diagnosis was 74 years (43-88). All cases presented anemia (80% macrocytic and 20% normocytic); 20% neutropenia ; 25 % leucopenia; 18 % trombopenia; 11% leucocitosis and 22% trombocitosis. We found cytogenetic results in 53/55 cases and abnormal karyotypes in 13 of them. Trisomy 8 was the most frequent alteration (5 cases) and three patients presented complex karyotypes (3 or more alterations). With regard to the evolution 15 patients are alive (27%); 6 evolved to leukemia (11%) and 26 dead (62 W). The mean overall survival was 32.3 months (12 months in patients with complex karywP=) Our results show the clinical/biological profile of a homogeneous group with SRA followed in our hospital during a period of 18 years and remark a group of poor prognosis in patients with complex karyotypes (5%).
27
26 ABNomaLITIsS OF EIUTHROBUUlTS M A PATImT m ,iTI,, RING SVTS. P. Acln, T. Soler, F. Sol6. C. Besses, J. woes3ner. Servei de Citologia saris-Sabrafen, 5. Gncologia 1973. Hematol~gica. Vnitat d'Hematologia i Av. Sam Antoni Maria Claret Hospital Central L'Alianga. ZOO. 08025 Barcelona. Spain.
CXSBULSIPC wrrsL.
Florensa,
Refractory anaemia with ring sideroblasts WARS) is * mvelodvsolastic svndnme characterized bv- the presence of _ _. at least 15% of ring sideroblasts in the bone n!zrrow. It is )nam that the presenct of erythroblasts with coarse unstained stippling that coexist with basophilic cytoplaamic areas in peripheral blood is indicative of ringed sideroblasts. We describe a 70-year-old woman patient who presented ~‘3 107 symptc.u of anaemia. Laboratory data: Hb 81 g/L, fL, platelet count 366X109/L, HBC 4,9x10p/L (neutrophils eosinophils 2%. basophils 2%, lylophocytes 17%, 16%. peripheral film showed monocytes 3%). The blood macrocytosis, poikilocytosis. and anisocytosis, with an abnormal erythrocytes and some erythroblasts staining showed some cytoplasmatic pattern, which with ill-defined edsea unstained areaa OccuDvin~ * variable proportion of the cyt~plasm,~ coexiatirig -with coarse basophilic stippling. Serum folate and vitamin 812 were normals A bone marrow aspirate showed a hyperccllular 61% erythroid CCllS with signs of laarrm with dvservtrowiesis. The most striking features refered to erythcoblast; with abnormalities tik pre,,. of the similar to ,thosc of the peripheral blood erythroblasts. Gr.mlocytlc cells represented 30% of the bone marrow cells. The percentage of blasts was 1%. The Prussian-bluestain showed markedly increased iron stores, and 80% of precursors were ringed sideroblasts. the erytbroid Cytogenetic studies revealed a 46,xX karyotype. of RARS was made according to the FAB A diagnosis classification. our patient began with macrocytic anaemia and the blood smear showed crythrocytes and peripheral the previously mentioned erythroblests with characteristics suspicious of the sidcroblastic phenomenon that later was demonstrated with Prussian-blue-staining. We want to emphasize how this data serves to alert haematologists of the aideroblastic phencmenom.
DOES WBC COUNT REALLY DEFINE TWO DIFFERENT SUBTYPES OF CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)? ANALYSIS OF A SERIES OF 119 PATIENTS. I. Cervera, G.F. Sam., T. ValIespi, MC. de1Caiiizo, D. Irriguible, F. LoPez, C. Sanchez-Morata,L. Larrea, A. Blanco, L. BenIIoch,A. Julia, J.F. San Miguel, M.A. Sanz. Departments of Hematology, Hospital Universitario La Fe, Valencia, Hospital Vail d’Hebron, Barcelona, and Hospital Clinieo-Universitario, Salamanca,Spain. CMML, a beterogeneonshematologicaldisorder with myelodysplasticand myeloproI&rative featmes, is classified witbin the myelodysPIastic .sydmmm. The FAB group has suggestedto segregatetwo subrypes: my&dyspIastic (MDS-CMML) and myeloprobferative (MPD-LMMC), basedon the WBC count (~13 vs. >13xlOE9/L). The aim of this study was to compare the characteristics at onset and the outcome of both subtypes in a series of 119 patients with CMML (47 MDS-CMML and 72 MPD-CMML). Hepstomegsly(P=.OS)and spleenenlargement(P=. 15) were more. common in MPD-CMML. In blood, PMN (P=.OI) and immature grsnldocyte propoition (P<.Oool), and PMN nuclear segmentstion(P-QOI), were higher in MPD-CMML, whereaslymphocyte proportion (p>.OOOl)was higher in MDS-CMML. I-Ii&r biinibii levels were noted in MPDCMML (P=.OOO3),that also show a trend to have higher IeveIsof uric acid and LDH. In marrow, MDSCMML had a lower proportion of monoc+s (P=.OOO7)and myeloid precarsors (P=.Ol), aed a bigber number of erythroid precursors (F=.OOO3)and Iympbocyres Cp=.Ol). An abnormal karyotype was present in 46% of MIX-CMML eases and in 28% of MPDCMh4L (P=NS). MDS-CMML had a somewhstshorter survivsl (MS I1 vs. I5 ino.; P=.o6). The risk of acute leukrmctransformabonwassimikrinbothsubtypes(13%and14%at2 yr. in MDS- and MPDCMML). The most important factor afF&ing survival in MFDCMML was the presenceofbIastsinblood,whereasin MDSCMML. was the pemntsge of blasts in marrow. In conclusion, although there are some clinical and biological diffbrences between the CMML subtypes defined by WBC count, overlapping predominates.A more refined definition of subtypesin CMML is required.