- Email: [email protected]
16 Epidemiology of myelodysplastic syndromes in a French general hospital
Epidemiology
and Classification
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EPIDEMIOLOGY OF MYELODYSPLASTIC SYNDROMES IN A FRENCH GENERAL HOSPITAL. F. Bauduer L. Ducout. C. Capdupuy. M. Renoux, Centre Hospitalier de la C&e -. Basque, Bayonne, France Up to now, few studies of descnpttve epidemiology based on population observation have been published concerning myelodysplasttc syndromes (MDS) The annual incidence of MDS reported in the LJK (1984-86 penod) was 3.6/1OOCOO/year(Carhwight, 1990) Thts parameter was very similar with 4.1/100000 in Diisseldorf (Aul et d, 1992) and about 1/100000 m Japan (Shimizu et cd. 199%. Nevertheless, a study performed in a population of one English district general hospital during a IO-year period found a markedly bieher incidence rate of 12.6/100000 ~Williamsott et al. 1994). , The aim of this work was to compare wr own experkw with these above data The Centre Haspitalier de la C&e Basque representsa structure with 1197 beds which serves a pqdation of 29OOCfJindividuals. Most of the inhabitants are in a rural entirottnement while few of them live in little urban areas. Twenty % of the populatiott are aged over 65. The data wera collected from the results of bone marrow studies performed on a 4-year pxtod (1993-1996) at the Laboratory of Haematology of our institution. patients (pts) being seropositive for HIV were excluded from this shuiy. During these 4 years, 90 new cases of MDS were tegiskted. Repartition among FAB subtypes wb(: refrwtoty anaetttias @.A): 27 cases(30 %). RA with ring sidamblasts(RARS): 21 (23.3 %), RA with excessof blarts (RAEB) and in transfomtatiott (RAE&T): 22 (24.4 %), chronic myelomoncqtic leukaemia (CMML): 10 (11. I %), unclassifted: IO (1 I. I %). Folty five pts were male and 45 wre female. The age distribution vaned between 23 and 96 (meati 74.3) Thirty-seven % of the pts were 80 year or older. A detailed occupaional or therapeutical past history wts not wadable tn each case Catycqpe analysis were not performed systematically. The calculated imiden~ of MDS was 7.7 cased100000/year in the whole population and bmeased to 31.4/1OOOOO/yearfor people over 65. MDS representedan important part of our out-patient unit activity especially for transfusions We conclude that MDS are more cmtmmn diseases than previously repotied by university centers perhaps becausethe majority of cases are managed m general hospitals. The incidence of hlDS being related to age, these diseasesrepresenta major public health issue in terms of care and cost for OUTdeveloped countries in which a significant prolongation of bfe duration has been obtained. Large registries are necessary to establish the real epidemiologic characteristics of these entities
MYELODYSPLASTIC SYNDROMES IN THA[LAND: A RETROSPECTIVE PATHOLOGIC AND CLiNXAI. ANALYSIS OF 1I7 CASES. Tanin Intmaumtrmt&ai,’ Wichai Pmycomviwat,’ Lkatatts Swasdikul,’ Nipha suwanwla. BoonsomChaimongkol,’Smgsura Jwtar,’ Kanchaw Chansun8,6 SupomCbmcharuaee,’ Apichsi Leelasiri, * Yatam Yoshida.’ ‘Chulalonpkom Universitv. ‘Ramon&utkl~ Homital. ‘Rankihi Hosoital. ‘Chisnamai Universw.,. ‘Mahid University, 6KonkaenLkiversity, llmiland.“Kyoto University. Japan. Backgmund. Most dsta of myelodysplasticsyndromes(MDS) is derived &cm studyin the westemcmmies. hdormationregardingthe Asian patientsmostly tised from studyconductedby Japanesemvestigators.Data of the diva~e ss occurredin southcnst Asian is scnrcclyavailable.We thereforewnducted a nationwide MDS studycomprised of five major tertmry-caremedical centersin various regionsof Thailand in order to gainmore insight into the un-ing of the diseaseas wxrriq in this country. Methods. A retmspect~veanalysison the bonemarrow, peripheral blood smearsand cliical kshues was cncductedin patients(age> 15 years)diagnosedas MDS during Jrmusty I992-Dccembu 19% at the five psrticipatiq centers.Central reviewers (Drs. LX, NS. WP and YY) examinedall pathologicalspecimensand classitied the disease accordingto the FAB classification. Results. There was a total of II7 cases.The medianageof the patrentswas $6 years (rsnge,lS-86). Thirty-two percentof the patientswere youngerthan 40. Malcfemale WBSi:l. The frequencyof the FAB subtypeswss RAW, 56% (65 cases),RAEB, 24% (28 cases),CMML, 9% (11 cases)andRAEB-T, 11% (13 cases).Anemia, tbe mmt commonsymptom,presentedin 84% of the patients:the mediandurstion of which was 2 months(range,0.2-72). ThemeanHhvahteof thetotal9”tientswas6.9B/dl. WBC. 9.1 x 10%. ANC, 4.7 x 10% and platelet count. 74 x IO /l Compsrablelevel of Hb and WEICwere observedamongeachsubtypeexcept for CMh4L where a higha Hb and WBC were sem (Hb. 9.0 &ll. WBC, 43x IO’fl). Tmnsfksionswere the main tbempcuticmodality in 86% of the pabents.Kaplan-Meier analysisrevealeda 5-year survival rate of 31% for the whole groupwith a mediansurvival of 24 months.At a medianfollow-uptimeof 6 months, 20patimtlhadpr0grasiv.z disease(15 as AML, 5 as RAEEZ-T).The mediantime ta disease-~ssicm was 57 months.The median survivalforRAandRARs,RAEB,CMMLandRAEB-Twac58,24.11Md9months respectively( P < 0.001 by lqrank test). Univariate and the stepwis Cox re@wsion revealedthe FAB subtypess the only psrametersi&kanly correlatedwith survival and time to progression. Conclusion. The ageof Thai patientswith MDS is lessthan what has teen rqorted in the westerncountries.The Gequencyof the FAB subtypessad the survival of tix patmts are similar. However, the major prognosticfeatureslie in the FAB subtypes rather than the de&meof the observd cytopenias.
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MORPHOLOGKAL FBATURJZS OF ,MYELODYSPLASI.A AFTER AUTOLOGOCS TRANSPLANTATION M. L. Ami o C. del Cahiro, M.A. Garcia. R. Revilla, J.F. San ?cQK+ ervicro de Hematologia. Hospital clinico Universitario Salamanca. Spain.
MYELODYSPLASTIC SYNDROME AFTER AI’TOLOGOliS STE&I CELL ‘TR.~NSPLANTATlON L.Laurentj, A.Di Mano. G.d’Onofrio, G.Zmr. SSica, PSalutari, C Rumi, G.Lsone. S.Cicconi, P.Chiusolo. N. Piccirillo, Hematology Dpt -Catholic University-Rome-Italy
In order to determine the influence of autoiogous transplantation in the development of myelodysplasia, we have reviewed retrospectively bone marrow samples (pre and post-transplantation) of 31 patients who underwent autologous transplantation in our cenw searching for myelodysplasia features. I9 patients who had persistent peripheral blood cytopenia (hematocrit < 306. WBC count < 4 x IO’ or platelet count < 100 x IO’) at 6 and/or 12 months after trasplantatlon were selected for this study. None oi the patients included in the study received any further treatmenr after transplantation and all were disease free at the moment of the analysis. Bone marrow slides were evaluated according to a semiquantitative score based on the percentage of dysplastic erythroblasts, granulocytes and megakaryocytes. Final punctuation is obtained by the sum of all these values. Results are shown in table. No differences were found in morphological evaluation of dysplastic features pre and postransplantation. In two patients with oersistent cvtooenia after transulantation. clonal cvtoeenetic &normalities h&e been detected w’hch suggests the emerge&e of a Secondary Mvelodvsdastic Syndrome. In neither case bone marrow evahtation showed differ&es from the rest of the group. Myelodysplastic semiquantitative score Stand. Deviation SE. Mean N Mean 0.91 Pre-transplant. 19 L. 0.21 2.89 1.20 m----m-transplant. 19 In summary, our data indicate that t’ttyelOdy8plaStiC morphological characteristics are not increased after autologous transplantation.
I.
1
I
I
A high mcidence (2-7Oo~of myelodysplastic syndromes (MDS) in pts submitted to autologous bone marrow (ABMT) or peripheral blood progenitor cell (PBPCT) transplant has been recently reported. We evaluated the occurrence of morphological dysplasia in BM and PB, the blood count parameters, immunological subtypes of circulatmg lymphocytes and cytogenetic findings in 25 patients; 11 NHL, 8 HD and 6 MM, submitted to ABMT (I pt) , APBPCT of unselected cells (I7 pts), ABMT plus APBPCT (2 pts) immunoselected CD34- ceils (5 pts) in remission (PR or CR). Median follow-up after PBPCT was I7 months (range 8-72). Specific criteria for hematopoietic dysplasia were defined according to FAB classification for MDS. Normal WBC and RBC count, normal differential CBC and no alterations of MCV and MPXI were found. Seven out of 25 pts have Hgb < 12 g/dL; RDW was > 15% in 81’25pts and HDW was > 3.2 &IL in 8i25 pts. Platelet count were < 150x109/L in S/25 pts. The median retyculocyte count was 1,560/bof RBCs (range 0.76-2.97%) with 16,15% (range 8,3-29”o) immature retyculocytes (HFR). The BM examination revealed minor dysplastic changes: Jolly bodies, karyorrhexis and n/c asincromism in erythroid series; nuclear neutrophils; binucleated hypolobularity, hypogranular megakaryocytes and micromegakaryocytes. No cytogenetic abnormalities were observed so far. A persistent reduction of CD4CD8 ratio 0.5 (n.v. l.l-1.8), a reduction of CD4- cells 472/mmc=:2 I%; (n.v. 670-950/mmc=42-52%), an increase of CDS- cells 933immc=45% (n.v. 505-695=29-38%) and an increase of NK 26C/mmc=l4?6: (n.v.70-190/mmc=4-I 1%) and activated Tcells258i’mmc=I2%(n v.40-155/mmc=2-9%).
and Classification
s5
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EPIDEMIOLOGY OF MYELODYSPLASTIC SYNDROMES IN A FRENCH GENERAL HOSPITAL. F. Bauduer L. Ducout. C. Capdupuy. M. Renoux, Centre Hospitalier de la C&e -. Basque, Bayonne, France Up to now, few studies of descnpttve epidemiology based on population observation have been published concerning myelodysplasttc syndromes (MDS) The annual incidence of MDS reported in the LJK (1984-86 penod) was 3.6/1OOCOO/year(Carhwight, 1990) Thts parameter was very similar with 4.1/100000 in Diisseldorf (Aul et d, 1992) and about 1/100000 m Japan (Shimizu et cd. 199%. Nevertheless, a study performed in a population of one English district general hospital during a IO-year period found a markedly bieher incidence rate of 12.6/100000 ~Williamsott et al. 1994). , The aim of this work was to compare wr own experkw with these above data The Centre Haspitalier de la C&e Basque representsa structure with 1197 beds which serves a pqdation of 29OOCfJindividuals. Most of the inhabitants are in a rural entirottnement while few of them live in little urban areas. Twenty % of the populatiott are aged over 65. The data wera collected from the results of bone marrow studies performed on a 4-year pxtod (1993-1996) at the Laboratory of Haematology of our institution. patients (pts) being seropositive for HIV were excluded from this shuiy. During these 4 years, 90 new cases of MDS were tegiskted. Repartition among FAB subtypes wb(: refrwtoty anaetttias @.A): 27 cases(30 %). RA with ring sidamblasts(RARS): 21 (23.3 %), RA with excessof blarts (RAEB) and in transfomtatiott (RAE&T): 22 (24.4 %), chronic myelomoncqtic leukaemia (CMML): 10 (11. I %), unclassifted: IO (1 I. I %). Folty five pts were male and 45 wre female. The age distribution vaned between 23 and 96 (meati 74.3) Thirty-seven % of the pts were 80 year or older. A detailed occupaional or therapeutical past history wts not wadable tn each case Catycqpe analysis were not performed systematically. The calculated imiden~ of MDS was 7.7 cased100000/year in the whole population and bmeased to 31.4/1OOOOO/yearfor people over 65. MDS representedan important part of our out-patient unit activity especially for transfusions We conclude that MDS are more cmtmmn diseases than previously repotied by university centers perhaps becausethe majority of cases are managed m general hospitals. The incidence of hlDS being related to age, these diseasesrepresenta major public health issue in terms of care and cost for OUTdeveloped countries in which a significant prolongation of bfe duration has been obtained. Large registries are necessary to establish the real epidemiologic characteristics of these entities
MYELODYSPLASTIC SYNDROMES IN THA[LAND: A RETROSPECTIVE PATHOLOGIC AND CLiNXAI. ANALYSIS OF 1I7 CASES. Tanin Intmaumtrmt&ai,’ Wichai Pmycomviwat,’ Lkatatts Swasdikul,’ Nipha suwanwla. BoonsomChaimongkol,’Smgsura Jwtar,’ Kanchaw Chansun8,6 SupomCbmcharuaee,’ Apichsi Leelasiri, * Yatam Yoshida.’ ‘Chulalonpkom Universitv. ‘Ramon&utkl~ Homital. ‘Rankihi Hosoital. ‘Chisnamai Universw.,. ‘Mahid University, 6KonkaenLkiversity, llmiland.“Kyoto University. Japan. Backgmund. Most dsta of myelodysplasticsyndromes(MDS) is derived &cm studyin the westemcmmies. hdormationregardingthe Asian patientsmostly tised from studyconductedby Japanesemvestigators.Data of the diva~e ss occurredin southcnst Asian is scnrcclyavailable.We thereforewnducted a nationwide MDS studycomprised of five major tertmry-caremedical centersin various regionsof Thailand in order to gainmore insight into the un-ing of the diseaseas wxrriq in this country. Methods. A retmspect~veanalysison the bonemarrow, peripheral blood smearsand cliical kshues was cncductedin patients(age> 15 years)diagnosedas MDS during Jrmusty I992-Dccembu 19% at the five psrticipatiq centers.Central reviewers (Drs. LX, NS. WP and YY) examinedall pathologicalspecimensand classitied the disease accordingto the FAB classification. Results. There was a total of II7 cases.The medianageof the patrentswas $6 years (rsnge,lS-86). Thirty-two percentof the patientswere youngerthan 40. Malcfemale WBSi:l. The frequencyof the FAB subtypeswss RAW, 56% (65 cases),RAEB, 24% (28 cases),CMML, 9% (11 cases)andRAEB-T, 11% (13 cases).Anemia, tbe mmt commonsymptom,presentedin 84% of the patients:the mediandurstion of which was 2 months(range,0.2-72). ThemeanHhvahteof thetotal9”tientswas6.9B/dl. WBC. 9.1 x 10%. ANC, 4.7 x 10% and platelet count. 74 x IO /l Compsrablelevel of Hb and WEICwere observedamongeachsubtypeexcept for CMh4L where a higha Hb and WBC were sem (Hb. 9.0 &ll. WBC, 43x IO’fl). Tmnsfksionswere the main tbempcuticmodality in 86% of the pabents.Kaplan-Meier analysisrevealeda 5-year survival rate of 31% for the whole groupwith a mediansurvival of 24 months.At a medianfollow-uptimeof 6 months, 20patimtlhadpr0grasiv.z disease(15 as AML, 5 as RAEEZ-T).The mediantime ta disease-~ssicm was 57 months.The median survivalforRAandRARs,RAEB,CMMLandRAEB-Twac58,24.11Md9months respectively( P < 0.001 by lqrank test). Univariate and the stepwis Cox re@wsion revealedthe FAB subtypess the only psrametersi&kanly correlatedwith survival and time to progression. Conclusion. The ageof Thai patientswith MDS is lessthan what has teen rqorted in the westerncountries.The Gequencyof the FAB subtypessad the survival of tix patmts are similar. However, the major prognosticfeatureslie in the FAB subtypes rather than the de&meof the observd cytopenias.
18
19
MORPHOLOGKAL FBATURJZS OF ,MYELODYSPLASI.A AFTER AUTOLOGOCS TRANSPLANTATION M. L. Ami o C. del Cahiro, M.A. Garcia. R. Revilla, J.F. San ?cQK+ ervicro de Hematologia. Hospital clinico Universitario Salamanca. Spain.
MYELODYSPLASTIC SYNDROME AFTER AI’TOLOGOliS STE&I CELL ‘TR.~NSPLANTATlON L.Laurentj, A.Di Mano. G.d’Onofrio, G.Zmr. SSica, PSalutari, C Rumi, G.Lsone. S.Cicconi, P.Chiusolo. N. Piccirillo, Hematology Dpt -Catholic University-Rome-Italy
In order to determine the influence of autoiogous transplantation in the development of myelodysplasia, we have reviewed retrospectively bone marrow samples (pre and post-transplantation) of 31 patients who underwent autologous transplantation in our cenw searching for myelodysplasia features. I9 patients who had persistent peripheral blood cytopenia (hematocrit < 306. WBC count < 4 x IO’ or platelet count < 100 x IO’) at 6 and/or 12 months after trasplantatlon were selected for this study. None oi the patients included in the study received any further treatmenr after transplantation and all were disease free at the moment of the analysis. Bone marrow slides were evaluated according to a semiquantitative score based on the percentage of dysplastic erythroblasts, granulocytes and megakaryocytes. Final punctuation is obtained by the sum of all these values. Results are shown in table. No differences were found in morphological evaluation of dysplastic features pre and postransplantation. In two patients with oersistent cvtooenia after transulantation. clonal cvtoeenetic &normalities h&e been detected w’hch suggests the emerge&e of a Secondary Mvelodvsdastic Syndrome. In neither case bone marrow evahtation showed differ&es from the rest of the group. Myelodysplastic semiquantitative score Stand. Deviation SE. Mean N Mean 0.91 Pre-transplant. 19 L. 0.21 2.89 1.20 m----m-transplant. 19 In summary, our data indicate that t’ttyelOdy8plaStiC morphological characteristics are not increased after autologous transplantation.
I.
1
I
I
A high mcidence (2-7Oo~of myelodysplastic syndromes (MDS) in pts submitted to autologous bone marrow (ABMT) or peripheral blood progenitor cell (PBPCT) transplant has been recently reported. We evaluated the occurrence of morphological dysplasia in BM and PB, the blood count parameters, immunological subtypes of circulatmg lymphocytes and cytogenetic findings in 25 patients; 11 NHL, 8 HD and 6 MM, submitted to ABMT (I pt) , APBPCT of unselected cells (I7 pts), ABMT plus APBPCT (2 pts) immunoselected CD34- ceils (5 pts) in remission (PR or CR). Median follow-up after PBPCT was I7 months (range 8-72). Specific criteria for hematopoietic dysplasia were defined according to FAB classification for MDS. Normal WBC and RBC count, normal differential CBC and no alterations of MCV and MPXI were found. Seven out of 25 pts have Hgb < 12 g/dL; RDW was > 15% in 81’25pts and HDW was > 3.2 &IL in 8i25 pts. Platelet count were < 150x109/L in S/25 pts. The median retyculocyte count was 1,560/bof RBCs (range 0.76-2.97%) with 16,15% (range 8,3-29”o) immature retyculocytes (HFR). The BM examination revealed minor dysplastic changes: Jolly bodies, karyorrhexis and n/c asincromism in erythroid series; nuclear neutrophils; binucleated hypolobularity, hypogranular megakaryocytes and micromegakaryocytes. No cytogenetic abnormalities were observed so far. A persistent reduction of CD4CD8 ratio 0.5 (n.v. l.l-1.8), a reduction of CD4- cells 472/mmc=:2 I%; (n.v. 670-950/mmc=42-52%), an increase of CDS- cells 933immc=45% (n.v. 505-695=29-38%) and an increase of NK 26C/mmc=l4?6: (n.v.70-190/mmc=4-I 1%) and activated Tcells258i’mmc=I2%(n v.40-155/mmc=2-9%).