- Email: [email protected]
57 Myelodisplastic syndromes prognostic factors in 133 patients with cytogenetic study
Prognostic Factors
Sl5
54
5.5
M~GI,OD~SPLASTIC Sk’NDRO?IIES : .-\ RETROSPECTI\‘E STID1’ OF TREATMENT RESPONE k\iD PROGNOSTIC FEATURES Iii 39 PATIENTS IN THE WESTERV REGION OF ALGEKW. XI..\ Beksdja, S. Zouani, H. Touhami. Clinic of Hematolog, University Hospital Oran, Algeria.
PROGNOSIS IN MYELODYSPLASTIC SYNDROMES WITH SPECIFIC REFERENCE TO KARYOTYPES - EXPERIENCE ON 296 PATIENTS FROM A SINGLE INSTITUTION M.Pfeilstocker, R Reisner, T.Nosslinger, H.Gniner, H.Nowotny, E Schldgl, H.TtichIer, E.Pittermann and R.Heinx 3rd Med. Deptm. and L.Boltxmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria
PRIhiwRY
The myelodysplastiz syndromes constitute: an heterogeneous group of clonal disorders of the multipotent stem cell characterised by cytopenias due ineffective hematopoiesis. R‘e studied the clinical and prognostic features in 39 patients with primary myelodysplastic syndromesnewly diagnosedin our ward from january 1988 to june 1996. The F.A.B classification was : RA 13, RARS 1, RAEB 13, RAEBT 07 , CMML 5. The median age was 38 years (15-79 yr) . The F.A.B classification, clinical and hematologic findings, Bournemouth score and treatment response were correlated with leukemic transfomation and overall surcival. Median survival for all patients was 32 months. Scoring according to the Bournemouth criteria showed significant differences in survival between groups A (45 months) , B (27 months) and C (06 months) of the separate variables. Only percentage of bone marrow blasts and haemoglobin level were prognostically significant.
A number of different prognostic risk analysis systems using clinical and morphological data have been developed for MDS New scoring systems have been proposed incorporating diagnostic and prognostic relevance of karyotype changes. This prompted us to perform a retrospective analysis on our patients to test the prognostic relevance of cytogenetic findings. We report on 296 MDS patients presenting at our institution (median age 72 years; 97 RA, 28 AISA, 56 R4EB, 3 1 RAEBT and 84 CMML according to FAB). Metapbases of bone marrow/peripheral blood cells cultured after FicolVHypaque isolation were stained using the tristaining technique for simultaneous production of R and DA-DAPI bands. Cytogenetic data at diagnosis are available from 189 patients: diploid mitoses were observed in 44%, aneuploid mitoses in 41%, in 15% no evaluable mitoses were detected. The foIIowing cytogenetically defined subgroups were found to be important for prognosis: normal, clonal aberrations involving chromosomes $7 or 8, the group of all complex aberrations and other singular aberrations not involving chromosome 7 or 8. Based on a Cox analysis we calculated a prognostic score which is able to separate groups of patients with dierent survival and likelihood of progression to acute leukemia. This score was found to be independent of others not involving cytogenetics. In addition scores combining cytogenetic, clinical and morphologic data (Lausanne-Boumemouth, Lille, International scores) were tested and compared with our cytogenetic score.
56
57
PROGNOSTIC IMPACT OF CY-I’OGENETIC INVESTIGATIONS IN WITH PRIMARY MYELODYSPLASTIC 270 PATIENTS SYNDROMES U.Germine. B. Hildebrandt, N.Gattermann, C. Aul. Dept. of Hematology, Hemrich,-Heine-University Dusseldorf, Germany
MYELODISPLASTIC SYNDROMES PROGNOSTIC FACTORS IN I33 PATIENTS WITH CYTOGENETIC STUDY G. Perez Rus, J. de1Toro, E. Prieto, J. Sanchez Fayos. P.L. Cues& Fundacion Jimenez Diaz. HGU Gregorio Maraiidn. Madrid, Spain. Forty two variables were analysed. Univariate analysis showed with predictive value for survival: FAB classification, age, systemic or anemic symptoms. hemoglobin (Hb), leucocytes, neutrophils, platelets (Plts), circulating myeloid precursors (CMP), blasts and dysgranuIopoiesis (DYSG) in peripheral blood (PB), MCV, % marrow blasts (%MB), dyshemopoiesis in more than one myeloid bone marrow cell lineages, % ringed sideroblnsts, cy@en&c abnormalities (CytA), absence of normal metaphases, complex karyotype, short evolution prior to diagnosis, development of hemorrahgic or infection symptoms during the tint six months after diagnosis, need for blood transfusions, aggravation of cytopenias and cytogenetic evolution or FAB evolution during this period. For AML evolution the predictive variables were: FAB classification, age ~40 years, anemic symptoms, leucopenia <25OOimm’, monocytopenia dOO/mm’, severe tbrombopenia, DYSG or dysthrombopoiesis and circulating blasts in PB, % MB, complex +8 or -7 karyotypes, short evolution prier to diagnosis, aggravation of cytopenias, increased %MB and need for blood transfusions during the first 6 months after diagnosis. Multivariate analysis identified the following independent prognostic factors for survival: aggravation of cytopenias, % MB, Plts, CMP and the need for blood transfusions during the first 6 months after diagnosis, From the variables present at diagnosis, % MB, Plts, CMP, age and Hb were chosen. For AML evolution the variables were high risk CytA (complex -7 +8) and FAI3 evolution during the first 6 months after diagnosis.At diagnosis, % MB, Cyt4 of high risk and anemic symptoms were shown to have predictive value.
Cytogenetic analysis was performed on bone marrow samples from 270 patients with primary myelodysplastic syndromes (MDS). 268 patients were followed up for survival and leukemic progression through Dezember 1996. 65 patients presented with RA, 44 with RARS, 74 with RAEB, 55 with RAEBfT and 32 with CMML. Clonal karyotype anomalies were found in 160 patients (40%). Complex chromosomal aberrations occurred in 21% of patients with abnormal karyotype. Chromosomal abnormalities were most frequent in RAEB (50%), followed by RAEBiT (46%). RA (43%) and RARS (34%). In contrast to other authors, 80% of our CMML patients had normal karyotypes. The most frequent abnormalities were Sq- in 14%, -7/7q- in 10% and trisomy 8 in 9% of patients with an abnormal karyotype. Patients with 5q- had the best cumulative median survival (116 mo), 2Oq- and -Y had a favourable course, too. Abnormalities of chromosome 7, 8 and complex aberrations had a poor outcome (c 12 mo). AML evolution was most frequent in patients with complex abnormalities and in trisomy 8. Based on this patient sample, we studied the prognostic value of the recently proposed International Score that include cytogenetic findings for risk evaluation. For this analysis only 181 untreated patients were considered. Results are shown in the following table: ,Chre/Riskmouos International Score A(38%) B(262) C(ZO%) 0(16%)
mo
109 48 30 8
Ion-rank
47.75
D
AMU%
7% 18% 20% 54%
Ion-tank
Q
59.18
We conclude that cytogenetic data provide valuable information and can be successfully incorporated into scoring systems.
Sl5
54
5.5
M~GI,OD~SPLASTIC Sk’NDRO?IIES : .-\ RETROSPECTI\‘E STID1’ OF TREATMENT RESPONE k\iD PROGNOSTIC FEATURES Iii 39 PATIENTS IN THE WESTERV REGION OF ALGEKW. XI..\ Beksdja, S. Zouani, H. Touhami. Clinic of Hematolog, University Hospital Oran, Algeria.
PROGNOSIS IN MYELODYSPLASTIC SYNDROMES WITH SPECIFIC REFERENCE TO KARYOTYPES - EXPERIENCE ON 296 PATIENTS FROM A SINGLE INSTITUTION M.Pfeilstocker, R Reisner, T.Nosslinger, H.Gniner, H.Nowotny, E Schldgl, H.TtichIer, E.Pittermann and R.Heinx 3rd Med. Deptm. and L.Boltxmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria
PRIhiwRY
The myelodysplastiz syndromes constitute: an heterogeneous group of clonal disorders of the multipotent stem cell characterised by cytopenias due ineffective hematopoiesis. R‘e studied the clinical and prognostic features in 39 patients with primary myelodysplastic syndromesnewly diagnosedin our ward from january 1988 to june 1996. The F.A.B classification was : RA 13, RARS 1, RAEB 13, RAEBT 07 , CMML 5. The median age was 38 years (15-79 yr) . The F.A.B classification, clinical and hematologic findings, Bournemouth score and treatment response were correlated with leukemic transfomation and overall surcival. Median survival for all patients was 32 months. Scoring according to the Bournemouth criteria showed significant differences in survival between groups A (45 months) , B (27 months) and C (06 months) of the separate variables. Only percentage of bone marrow blasts and haemoglobin level were prognostically significant.
A number of different prognostic risk analysis systems using clinical and morphological data have been developed for MDS New scoring systems have been proposed incorporating diagnostic and prognostic relevance of karyotype changes. This prompted us to perform a retrospective analysis on our patients to test the prognostic relevance of cytogenetic findings. We report on 296 MDS patients presenting at our institution (median age 72 years; 97 RA, 28 AISA, 56 R4EB, 3 1 RAEBT and 84 CMML according to FAB). Metapbases of bone marrow/peripheral blood cells cultured after FicolVHypaque isolation were stained using the tristaining technique for simultaneous production of R and DA-DAPI bands. Cytogenetic data at diagnosis are available from 189 patients: diploid mitoses were observed in 44%, aneuploid mitoses in 41%, in 15% no evaluable mitoses were detected. The foIIowing cytogenetically defined subgroups were found to be important for prognosis: normal, clonal aberrations involving chromosomes $7 or 8, the group of all complex aberrations and other singular aberrations not involving chromosome 7 or 8. Based on a Cox analysis we calculated a prognostic score which is able to separate groups of patients with dierent survival and likelihood of progression to acute leukemia. This score was found to be independent of others not involving cytogenetics. In addition scores combining cytogenetic, clinical and morphologic data (Lausanne-Boumemouth, Lille, International scores) were tested and compared with our cytogenetic score.
56
57
PROGNOSTIC IMPACT OF CY-I’OGENETIC INVESTIGATIONS IN WITH PRIMARY MYELODYSPLASTIC 270 PATIENTS SYNDROMES U.Germine. B. Hildebrandt, N.Gattermann, C. Aul. Dept. of Hematology, Hemrich,-Heine-University Dusseldorf, Germany
MYELODISPLASTIC SYNDROMES PROGNOSTIC FACTORS IN I33 PATIENTS WITH CYTOGENETIC STUDY G. Perez Rus, J. de1Toro, E. Prieto, J. Sanchez Fayos. P.L. Cues& Fundacion Jimenez Diaz. HGU Gregorio Maraiidn. Madrid, Spain. Forty two variables were analysed. Univariate analysis showed with predictive value for survival: FAB classification, age, systemic or anemic symptoms. hemoglobin (Hb), leucocytes, neutrophils, platelets (Plts), circulating myeloid precursors (CMP), blasts and dysgranuIopoiesis (DYSG) in peripheral blood (PB), MCV, % marrow blasts (%MB), dyshemopoiesis in more than one myeloid bone marrow cell lineages, % ringed sideroblnsts, cy@en&c abnormalities (CytA), absence of normal metaphases, complex karyotype, short evolution prior to diagnosis, development of hemorrahgic or infection symptoms during the tint six months after diagnosis, need for blood transfusions, aggravation of cytopenias and cytogenetic evolution or FAB evolution during this period. For AML evolution the predictive variables were: FAB classification, age ~40 years, anemic symptoms, leucopenia <25OOimm’, monocytopenia dOO/mm’, severe tbrombopenia, DYSG or dysthrombopoiesis and circulating blasts in PB, % MB, complex +8 or -7 karyotypes, short evolution prier to diagnosis, aggravation of cytopenias, increased %MB and need for blood transfusions during the first 6 months after diagnosis. Multivariate analysis identified the following independent prognostic factors for survival: aggravation of cytopenias, % MB, Plts, CMP and the need for blood transfusions during the first 6 months after diagnosis, From the variables present at diagnosis, % MB, Plts, CMP, age and Hb were chosen. For AML evolution the variables were high risk CytA (complex -7 +8) and FAI3 evolution during the first 6 months after diagnosis.At diagnosis, % MB, Cyt4 of high risk and anemic symptoms were shown to have predictive value.
Cytogenetic analysis was performed on bone marrow samples from 270 patients with primary myelodysplastic syndromes (MDS). 268 patients were followed up for survival and leukemic progression through Dezember 1996. 65 patients presented with RA, 44 with RARS, 74 with RAEB, 55 with RAEBfT and 32 with CMML. Clonal karyotype anomalies were found in 160 patients (40%). Complex chromosomal aberrations occurred in 21% of patients with abnormal karyotype. Chromosomal abnormalities were most frequent in RAEB (50%), followed by RAEBiT (46%). RA (43%) and RARS (34%). In contrast to other authors, 80% of our CMML patients had normal karyotypes. The most frequent abnormalities were Sq- in 14%, -7/7q- in 10% and trisomy 8 in 9% of patients with an abnormal karyotype. Patients with 5q- had the best cumulative median survival (116 mo), 2Oq- and -Y had a favourable course, too. Abnormalities of chromosome 7, 8 and complex aberrations had a poor outcome (c 12 mo). AML evolution was most frequent in patients with complex abnormalities and in trisomy 8. Based on this patient sample, we studied the prognostic value of the recently proposed International Score that include cytogenetic findings for risk evaluation. For this analysis only 181 untreated patients were considered. Results are shown in the following table: ,Chre/Riskmouos International Score A(38%) B(262) C(ZO%) 0(16%)
mo
109 48 30 8
Ion-rank
47.75
D
AMU%
7% 18% 20% 54%
Ion-tank
Q
59.18
We conclude that cytogenetic data provide valuable information and can be successfully incorporated into scoring systems.