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Morphology substudy ELN low risk Registry. Aims - assess the reproducibility of diagnosis Methods - review of random selected slides from all participating countries - reviewer panel includes both „ experts “ as well as physicians in training
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Morphology substudy ELN low risk Registry Aims - assessthereproducibility of diagnosis Methods - review of randomselectedslidesfrom all participating countries - reviewerpanelincludesboth „experts“ as well asphysicians in training - description of resultsandcorrelationwith original findings - calculation of degree of discrepancyusingk-test
Methods in detail • Random selection of a total of 100 casesfrom all countries • takingintoaccounttheamount of includedpatients • (forexamplemorefrom France ascomparedto Germany • -> alreadydoneby Alex Smith • 2 marrowslides (preferably also ironstaining) and 1 blood film fromeachselectedcaseshouldbesentto Düsseldorf, wherethemorphologyreview will takeplace • > actionbycountrycoordinators
Methods in detail • Preparation of minimal requireddataset of selectedcasesnecessaryforreview, tobesenttoDüsseldorf: - ID, (Country, Hospital: onlyavailableto Alex Smith) - ageatdiagnosis - Hb, WBC, Platelets, Defferentialcount, LDH, Bilirubin, Coombs test - cytogeneticfindingatdiagnosis: necessaryfor WHO classification - no original morphologyreport -> tobedoneby Alex Smith
Morphology assessment in detail • Description of Morphologic characeristics, • to be filled in a file during the morphology meeting • Peripheral blood • - % of blasts • - % of monocytes • - signs of Dysplasia • - Anisometry of platelts? • - Macroplatelets? • - Pseudopelger? • - Hypogranulation? • - cytoplasma anomalies of erythrocytes?
Morphology assessment in detail • Description of Morphologic characeristics, • to be filled in a file during the morphology meeting • II) Marrow • Erythropoiesis • % of erythropoiesis • Clear signs of dysplasia? • Nuclear abnormalities? • Cytoplasma abnormalities? • Ring sideroblasts? (%) • Megakaryopoiesis • - Assessment of 25 megakaryocytes • Clear signs of dysplasia? (>10%) • Micromegakaryocytes ? • Mononuclear megakaryocytes? • Megas with spreaded nuclei?
Morphology assessment in detail • Description of Morphologic characeristics • Granulopoiesis • - Clear signs of dysplasia? (>10%) • Pseudopelger? • Hypogranulation? • % Medullary blast (if Erythropoiesis >50%, count blasts in the non-erythropoietic cells) • Other items • - Cellularity (Hypo vs. Normo vs. Hyper) • Plasma cells increased? • Lymphoid cells increased? • Iron load? • Other stainings available?
Morphology assessment in detail Diagnosticcategories RCUD (bicytopenia) RC RA RN MDS unclass RCUD withpancytopenia RCUD/RCMD withblasts in blood RCUD withoutdysplasia but withclonalmarker RCMD MDS with del(5q) RARS-T RAEB I RAEB II, RAEB-T, AML, CMML I, CMMLII, ICUS No MDS at all
Methods to analyse the results • Within the panel • - Discussion of cases during meeting • - Report on interobserver variation within experts • - Report on possible discrepancies between „experts“ and „non-experts“ • - description of staining techniques and quality of slides • - comparison of methods to read the slides • - correlation of WHO types with hematologic and cytogenetic findings • 2) Panel vs. Original reports • - Send list of WHO results of the morphology panel to Alex Smith • - Comparison of original reports with the results of the panel by • k-test (and/or other tests to be done my Alex Smith) to describe • amount of discrepancies • 3) Final report on • - Validation and reliability of the cases included into the ELN low risk R
Methods to analyse the results • 3) Final report on • - Validation andreliability of thecasesincludedintothe ELN lowriskRegistry tobedonewithinthepaneland Alex Smith
Morphology Panel • Chairs: Ulrich Germingand Marius MacKenzie • ProposedExperts • Argiris Symenoidis, Greece • Jaroslaw Cermak, Czech Rep. • Anna Porwit, Sweden • Teresa Valespie?, Spain • Proposed „non-experts“ • Louise deSwart, Netherlands • Judith Neukirchen, Germany • By David Bowen, UK • Others