Understanding Your Blood Work Results

Transcription

1 Understanding Your Blood Work Results Carlos Besses, MD, hd Hematology Department Hospital del Mar - IMIM, Barcelona

2 Carlos Besses Disclosures Novartis Honorarium Speaker Shire Honorarium Speaker Galena Honorarium Advisory Board

3 Abnormal blood results Diagnostic process History taking hysical examination Additional tests Genetic tests Bone marrow examination

4 Blood Results Leading to Suspicion of MN Thrombocytosis ( platelets) Erythrocytosis ( red blood cells) V Leukocytosis ( white blood cells) Anemia ( red blood cells) ET Thrombocytopenia ( platelets) Any combination of the above MF

5 Work-up for a atient with Thrombocytosis latalet count 450x10 9 /L Secondary thrombocytosis ersistent unexplained thrombocytosis History taking hysical examination Additional tests Iron deficiency Infection Inflammation Surgery Cancer Splenectomy Any relative with MN or excess of blood cells? Microvascular symptoms Usually normal Genetic tests Bone marrow examination

6 Normal

7 ET

8 Workflow for Molecular Diagnosis of ET ET Suspicion JAK2 V617F ositive 50-60% Negative CALR ositive 15-35% Negative ML ositive 3-5% Essential Thrombocythemia Negative BCR-ABL1 Triple-Negative 5-25% Negative ositive CML

9 ET Clinical Case, bone marrow biopsy

10 ET

11 A B C Megakaryocyte nuclei: A. Hyperlobulation: staghorn-like B. Hypolobulation: bulbous/cloud-like C. Hyperchromatic

12 Work-up for a atient with Erytrocytosis Increased Hct/Hb History taking hysical examination Additional tests Chronic lung disease Smoking Renal disease Tumors Androgen/Epo use Sleep apnea Chest X Ray Abdominal ultrasound Oxygen saturation Carboxy hemoglobin Splenomegaly Red cell mass JAK2V617F Erythropoietin level Bone marrow examination Thrombocitosis and/or Leukocytosis

13 Normal

14 V

15 EO TO Type I cytokine receptors EOR TOR G-CSF CYTOLASM JAK2 JAK2 NUCLEUS

16 EO TO Type I cytokine receptors EOR TOR G-CSF CYTOLASM JAK2 JAK2 STAT STAT NUCLEUS Gene transcription

17 EO TO Type I cytokine receptors EOR TOR G-CSF CYTOLASM JAK2 JAK2 G>T GTC TTC Val (V) he (F) STAT STAT NUCLEUS Gene transcription

18 V

19 Work-up for a atient with Leukocytosis Increased leukocyte count History taking Secondary leukocytosis hysical examination Splenomegaly and/or lymphadenopathy Additional tests Blood film Infections Acute inflammation Corticosteroids Smoking Myeloid cells Chromosome and/or genetic studies Cell flow cytometry CT scans ET, MRI Lymphoid cells

20 What are the Cells Involved in Myeloid Diseases?

21 CLL V

22 CML

23 Work-up for a atient with Suspicion of Myelofibrosis Anemia +/- Other cytopenia +/- WBC/platelets plus Splenomegaly Genetic test eripheral blood Bone marrow biopsy +/- Cytogenetic study Mandatory JAK2V617F, CALR, ML +/- BCR-ABL1 Optional ASXL1, SRSF2, EZH2, IDH1/2 Blood film +/- Cytogenetic study Staining for: Hematoxylin-eosin Reticulin Collagen

24 MF

25 Myelofibrosis: an heterogeneous disease ET

26 Staging of Bone Marrow Fibrosis Severity in Myelofibrosis Bone Marrow Fibrosis Grading According to European Myelofibrosis Network (EUMNET) Consensus Criteria MF 0 MF 1 MF 2 MF 3 Scattered linear reticulin, no intersections 1-3 Loose network of reticulin with many intersections 1-3 Diffuse, dense increase in reticulin with extensive intersections and occasional collagen foci 1-3 Diffuse and dense increase in reticulin with extensive intersections; presence of coarse collagen bundles, often with significant osteosclerosis 1-3 With kind permission from Springer Science +Business Media: Annals of Hematology. Ref. 2, Fig Thiele J, et al. Haematologica. 2005;90: Thiele J, Kvasnicka HM. Ann Hematol. 2006;85: Michiels JJ, Thiele J. Int J Hematol. 2002;76:133

27 Reticulin fibrosis MF0 MF1 MF2 MF3

28 MF

29 WHO-Classification Thiele et al, Blood 2011;117(21):

30 A B C Megakaryocyte nuclei: A. Hyperlobulation: staghorn-like B. Hypolobulation: bulbous/cloud-like C. Hyperchromatic

31 Survival and Disease Complications in ET vs. Early/refibrotic MF Outcome ET 15-Year Cumulative Incidence (%) Early/refibrotic MF 15-Year Cumulative Incidence (%) Survival 75% 44% Leukemic transformation 2% 12% Transformation to overt myelofibrosis 9% 17% Thrombosis 22% 25% Results from 1104 patients; 891 (81%) True ET; 180 (16%) early/prefibrotic MF; 33 (3%) not evaluable Median follow-up: 6.2 years for ET; 7 years for early/prefibrotic MF Barbui et al, J Clin Oncol 2011;29(23):

32 V Suspicion ET Suspicion MF Suspicion Discard BCR-ABL JAK2V617F JAK2V617F JAK2V617F ositive Negative ositive Negative ositive Negative JAK2 exon 12 CALR CALR ositive Negative ositive Negative ositive Negative ML ML ositive Negative ositive Negative olycythemia Vera Essential Thrombocythemia rimary Myelofibrosis

33 Conclusions 1. Blood work results are important information but the diagnosis relies on the whole picture 2. Genetic studies & Bone marrow examination are essential components of the diagnosis 3. Common-sense and step-based tests are the best way to reach a well-grounded diagnosis lease, trust in your doctor!

34 Thank you for your attention