LLA 2011 - J.R. Passweg - Diagnosis and treatment in leukaemia


Published on

Published in: Health & Medicine, Technology
  • Be the first to comment

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

LLA 2011 - J.R. Passweg - Diagnosis and treatment in leukaemia

  1. 1. ESO Leukemia Lymphoma 2011<br />Diagnosis and treatment in leukaemia<br />Prof Jakob R Passweg<br />
  2. 2. Case 1<br />A 27-year-old woman is admitted with fever and thoracic pain. During the last week she experienced general fatigue and dyspnea during mild to moderate physical exertion.<br />The physical examination, including cardiovascular and pulmonary examination was normal. There was no lymphadenopathy, splenomegalyor hepatomegaly<br />
  3. 3. Hematology Lab<br />
  4. 4. Scattergram<br />PEROX: two major cell populations, large peroxidase positive cells (Neutr), and small to medium sized peroxidase negative cells (peroxidasenegative blasts and normal lymphocytes)<br />BASO: nuclear shape. The predominant cell population is mononuclear<br />
  5. 5. Peripheral blood smear<br />smallblastswithscantcytoplasm, condensednuclearchromatinandindistinctnucleoli, andlarger blastswithmoderate cytoplasm, smallcytoplasmicvacuolesand a distinctnucleoli. Noprimarygranulesor Auer rods<br />35% blasts = acuteleukemia<br />
  6. 6. BM Cytology<br />no marrow fragments but an adequate number of free marrow cells, predominance of small to medium sized blasts. <br /> Sudan Black staining: blast cells are negative. <br /> <br />PAS staining: blast cells are negative. <br /> <br />Morphologic diagnosis: acute peroxidase negative leukemia. Suggestive for an ALL. <br />
  7. 7. BM Histology<br />Giemsa stain: densely infiltrated marrow, blasts monomorphicwith prominent nucleoli and narrow cytoplasm. <br /> <br />Immunostaining, dim positive for TdT, strongly positive for CD10, and negative for CD20, CD3, CD117. (CD10 is shown)<br /> <br />CD34 neg, (endothelial cells positive, (internal positive control)).<br /> <br />The histological diagnosis is acute B-cell lymphoblastic leukemia<br />
  8. 8. Flow Cytometry<br />Blasts: intracellular CD22, CD79a, IgM, and dimly TdT. Surface markers: CD19, CD10, and HLA-DR.<br /> <br />Blasts:negative for immuno-MPO, CD34, surface IgM and for all myeloid and T-cell markers analyzed.<br /> <br />The flowcytometric analysis demonstrates the B-lymphoid precursor cell phenotype of the acute leukemia. Diagnosis: acute B-cell ALL. <br /> <br />Expression of cytoplasmic but not surface IgM allows to subclassify the leukemia as pre-B-cell ALL, without aberrant myeloid or T-cell markers <br />
  9. 9. Classification according to EGIL<br />mature <br />B Cell neoplasms<br />Mature B<br />Common B<br />Pre-B<br />pro B <br />AUL <br />TdT<br />CD19<br />CD10<br />cIgM<br />sIgM<br />IgG/IgD/ Kappa/Lambda<br />
  10. 10. MolecularGenetics<br />Multiplex RT-PCR screening for 28 fusion transcripts. Eight multiplex RT-PCR amplifications, containing each, primers for a house keeping gene as well as primers for 4 to 5 fusions transcripts are included. <br /> additional gene product: suggesting the existence of an abnormal fusion transcript. <br />split out: abnormal band, corresponding to the fusion transcript E2A/PBX1.<br /> <br /> Conventional cytogenetics:<br /> 46, XX, del(9)(q?12q32), del(11)(p?11.2),del(11)(q22q23) [6]<br />46, XX [11]<br /> <br /> Definitive diagnosis<br /> Pre-B-ALL with E2A/PBX1<br />  <br />General Remarks<br /> The fusion transcript E2A/PBX1 corresponds to a genetic translocation type t(1;19)(q23;p13). This translocation has not been found with conventional cytogenetics, probably cryptic. However, other complex cytogenetic anomalies are found on chromosome 9 and 11. <br /> pre-B-cell ALL associated with t(1;19) and/or E2A/PBX1 fusion transcript.<br /> unfavorable prognosis<br />
  11. 11. Treatment on GRAALL <br />Steroid prephase<br />Chemosensitivityevaluation d+8<br />Double induction<br />R – Rituximabif CD20+<br />R – HyperCVADvsconventional<br />Monitor MRD / B-cellreceptorgenerearrangement / flow / fusiontranscripts<br />
  12. 12. Treatment on GRAALL<br />Transplant in CR1 ?<br />WBC > 30G/L<br />CNS involved<br />B-ALL: CD10-; t(4;11); t(1;19)<br />Complexcaryotype (>5); haploid ornear triploid<br />Corticoresistance<br />Chemoresistance<br />No CR1 after induction<br />
  13. 13. Case 2<br />A 51-year-old gentleman, admitted for thoracic pain. During the last three weeks the patient presented non productive cough, fever, shortness of breath and petechiae.<br />On physical examination: body temperature was 38.4 C° and moderate hepatomegaly could be observed. <br />Conventional chest radiograph was normal, but on computed tomography two opacified pulmonary nodules, suggestive of fungal infection were observed in the lung periphery.<br />
  14. 14. Hematology lab<br />
  15. 15. Scattergram<br />Perox: majority of rather small, peroxidase positive cells, distributed over three regions, the neutrophil (Neutr), monocyte (Mo) and eosinophil (Eo) corresponding to blast cells, and + residual neutrophils. <br /> <br />Baso: The predominant cell population has a mononuclear nucleus (MNC). Only few cells a polymorphonuclear.<br /> <br />This scattergram demonstrates, that the blast cells are strongly peroxidase positive -> AML.<br />
  16. 16. Peripheral Blood<br />small blast with a thin rim of basophilic cytoplasm. The residual mature neutrophils show homogenous pink colored cytoplasm. Long Auer rods are found in the blast cells as well as in mature neutrophils. <br /> <br />A blast proportion above 20%, with some of the blasts containing an Auer rod -> acute myeloid leukemia.<br />
  17. 17. MarrowCytology<br />increased cellularity , mostly large blasts abundant cytoplasm, prominent Golgi. Blasts with very large granules, (pseudo Chediak-Higashi). Mature neutrophils with prominent and sharp Auer rods. <br /> <br />Most of the blast cells stain moderately to strongly for peroxidase. The Chediak-Higashi granules as well as the Auer rods show strong peroxidase positivity.<br /> <br />The diagnosis based on morphology: AML with maturation (M2). Some of the morphologic characteristics are suggestive for an AML with t(8;21)(q22;q22)/AML1//ETO.<br />
  18. 18. Histo<br />cellularity markedly <br />increased (60-70%) <br />blasts infiltration. <br />pleomorphic blasts <br />abundant cytoplasm. <br /> <br />Blasts strongly <br />positive for immunoperoxydase, CD34 <br />CD117 dim.<br /> <br />Histological diagnosis: acute myeloid <br />leukemia (AML) with maturation <br />
  19. 19. Flow<br />Blasts, gated on CD45 dim, <br />myeloid immunophenotype; <br />positive for MPO, CD33, CD13, <br />and express markers of <br />immaturity (CD34, HLA-DR, <br />CD117). Additionally they express a <br />B-cell (CD19) and a NK-marker (CD56).<br /> <br />The flowcytometric analysis confirms the myeloid phenotype of the acute leukemia. The aberrant marker expression of CD19 and CD56 are typically found in AML with translocation t(8;21) and/or AML1/ETO<br />
  20. 20. Diagnosis<br />Molecular genetics and Cytogenetics<br />  <br />Using a Multiplex RT-PCR System for genotyping leukemia that screens for 28 different fusion transcripts, the blast cells are positive for the fusion transcript AML1/ETO.<br /> <br />conventional cytogenetics, karyotype :<br /> 45, XX, -Y, t(8;21)(q22;q22) [13]<br /> <br /> <br />Definitive Diagnosis<br /> Acute myeloid leukemia with t(8;21)(q22;q22); (AML1/ETO)<br />
  21. 21. Treatment (HOVON SAKK 102 30/09)<br />
  22. 22. Case 3<br />A 53-year-old man seen for follow-up 10 years after autologous stem cell transplantation for follicular lymphoma.<br /> <br />Follicular lymphoma of the tonsils. Cervical radiotherapy with 36 Gy. Relapse 5 years later follicular lymphoma IIIB treated by chemotherapy followed by autologous HSCT (CBV conditioning). <br /> <br />Excellent general condition, no pain or fever, no weight loss and no night sweats. The physical examination, including cardiovascular examination was normal. Absence of palpable lymphnodes, spleen or liver. <br />
  23. 23. Hem Lab values<br />
  24. 24. Peripheral Blood<br /> <br />Minor morphologic changes: platelets, with size variability, and neutrophils with granulation defect. Few pseudo-Pelgerneutrophils. No blast cells.<br /> <br />
  25. 25. MarrowCytology<br />The marrow aspirate is moderately hypercellular. Erythropoiesis without dysplastia, except for few erythroblasts with cytoplasmic vacuoles (). Myelopoiesis slightly increased with few immature forms. Megakaryocytes with dysplastic changes, hypolobular.<br /> <br />On iron staining a few ringed sideroblasts. <br /> <br />
  26. 26. Histology<br />marrow biopsy: moderately hypercellular marrow, restructured topography with clusters of erythroblasts and immature myeloid cells. Few abnormal megakaryocytes, with hypolobulated nuclei. <br /> <br />Conclusions<br /> <br />Suspicion of therapy related myelodysplastic syndrome (t-MDS).<br />
  27. 27. Follow-up 6 monthslater<br />No complaints, no treatment proposed<br />6 months later: fatigue, no fever, no bleeding. <br />
  28. 28. Hem Lab follow-up<br />
  29. 29. Blood Smear @ FU<br />Evident dysplastic changes of all three cell lines. <br />RBC: remarkable anisocytosis and poikilocytosis. <br />Platelets marked size variability and abnormal granulation <br />Neutrophils have hypogranulation and nuclear hyposegmentation. <br />
  30. 30. MarrowCytology<br />Marrow aspirate of poor quality, dysplastic changes of all three cell lines are evident. <br />Erythroid hyperplasia, with important dyserythropoiesis. <br />Increased number of megakaryocytes (small, hypolobulated nucleus). <br />Few immature cells with abnormal chromatin pattern, but overall the number of blasts is below 5%. In iron staining, the proportion of ringed sideroblasts has increased, and is > 15% of all erythroblasts. <br />
  31. 31. Histology<br />Densely hypercellular marrow, complete replacement of fat, trilineage hyperplasia. <br />Marked proliferation of immature myeloid cells, abnormal localization, hypolobularmegakaryocytes, increased reticulin and secondary marrow fibrosis. <br />Immunostains for CD34 shows some positive endothelial cells, few immature hemopoietic cells. The overall proportion of CD34-positive blasts is <5%. <br />
  32. 32. Genetics<br />Only 5 metaphases:<br /> <br />45, XY, add(5)(q11.2), dic(17;20)(p11.2;p112.2) [4]<br />46, XY [1]<br />Conclusions<br /> <br />Therapy related myelodysplastic syndrome (t-MDS)<br />refractory cytopenia with multilineage dysplasia<br />with ringed sideroblasts<br />and cytogenetic anomalies<br />
  33. 33. Another 6 months down theroadfatigue ++, petechiae ++<br />* transfused<br />
  34. 34. Cytogenetics<br />12 metaphases:<br />  <br />45, XY, add(5)(q11.2), dic(17;20)(p11.2;p112.2) [1]<br />45, idem, del(7)(q22) [1]<br />45, idem, del(7)(q22),del(12)(p11.2),-21,+r [10]<br /> <br /> <br />Definitive diagnosis<br /> <br />Therapy related acute myeloid Leukemia (t-AML)<br />Alkylating agent related<br />with complex cytogenetic anomalies <br />
  35. 35. Comments<br /> <br />Typical case of a therapy related MDS/AML, presenting initially with discrete morphologic changes, progressing than to a MDS type refractory cytopenia with multilineage dysplasia and evolving eventually to an AML. <br /> <br />“alkylating agent” related MDS/AML, occuring 5-6 years following exposure to mutagenic agents. In the present case, mutagenicity can be due to the alkylating agents and to radiotherapy.<br /> <br />Cytogenetically “alkylating agent” related MDS/AML present typically unbalanced translocations or deletions of chromosomal material. <br /> <br />Alkylating related t-MDS/AML are associated with unfavorable outcome<br />
  36. 36. Case 4<br />50-year old female patient<br />Progressive fatigue since 4 months<br />Diffuse upper abdominal pain <br />No history of radiotherapy / drug exposure <br />Slight splenomegaly<br />blood count<br />
  37. 37. Blood count<br />
  38. 38. Peripheral blood smear<br />
  39. 39. At this step what is the most probable diagnosis ?<br />SeverebacterialInfection<br />Myeloproliferativedisorder (MPD)<br />Chronicmyeloidleukemia (CML)<br />MPD / MDS<br />None oftheabove<br />
  40. 40. What is typical for CML?<br />Leukocytosis <br />Neutrophilia with pathologic left shift<br />Increased number of myelocytes/metamyelocytes<br />Thrombocytosis<br />Anisocytosis of platelets<br />Increased number of eosinophils<br />Increased number of basophils<br />
  41. 41. What is absolutely necessary to confirm the diagnosis<br />Flowcytometry<br />Bone marrow histology including immunohistchemistry<br />Cytogenetics<br />Molecular genetics<br />Bone marrow cytology<br />
  42. 42. Molecular genetic result<br />Bcr/abltranscript positive b2a2<br />Do we still needconventionalcytogenetics?<br />
  43. 43.
  44. 44. Why do we need morphology in CML patients ?<br />Confirmation of the diagnosis of CML<br />Define the stage of the disease<br />To complete the diagnosis <br />To recognize possible atypical forms of CML or MPD<br />For treatment decision<br />
  45. 45. Bone marrow cytology<br />
  46. 46. Bone marrow histology<br />Hematoxylin-eosin stain<br />Gömörri stain (silver stain)<br />
  47. 47. Immunohistochemistry (anti CD34)<br />40x<br />20x<br />
  48. 48. Stages of the CML<br />Atdiagnosis<br />Chronicphase<br />Acceleratedphase<br />Blast crisis<br />Myeloid blast crisis<br />Lymphoid blast crisis<br />Duringfollow-up<br />Remission<br />Hematological<br />Morphological<br />Cytogenetic<br />Major Molecular<br />CompleteMolecular<br />Chronicphase<br />Acceleratedphase<br />Blast crisis<br />
  49. 49. Additional information<br />Bonemarrowcytology<br />Blasts 1.5%, Basophils1%<br />Bonemarrowhistology<br />CD34 positive cells 2.5%<br />Cytogenetics<br />46,XX,t(9;22)(q34;q11)[20]<br />
  50. 50. What is the stage of the disease at diagnosis?<br />Myeloid blast crisis<br />Hematological remission<br />Chronic phase <br />Accelerated phase<br />None of the above<br />
  51. 51. Diagnostic criteria (WHO)<br />for CML in accelerated phase<br /><ul><li>Blasts 10-19% in bloodand/orbonemarrow
  52. 52. Peripheralbloodbasophils> 20%
  53. 53. Persistent thrombocytopenia (<100x109/l) unrelatedtotherapy
  54. 54. orthrombocytosis (>1000x109/l) unresponsivetotherapy
  55. 55. Increasingspeensizeandincreasing WBC unresponsivetotherapy
  56. 56. Cytogeneticevidenceofclonalevolution</li></li></ul><li>Diagnostic criteria forCML-blast crisis<br />Blasts ≥ 20% of PB and/or BM<br />Extramedullary proliferation of blasts (myelosarcoma)<br />Large aggregates and clusters of blasts in the BM-biopsy<br />Immunophenotype of Blast crisis<br />70% myeloid blasts, 30% lymphoblasts<br />
  57. 57. Final diagnosis<br />Chronic myeloid leukemia (CML)<br />t(9;22)(q43;q11)/BCR-ABL positive<br />in chronic phase<br />
  58. 58. How would you treat this patient?<br />
  59. 59. Take home messages<br /><ul><li>The diagnosis of CML depends on the presence of the characteristic t(9;22) or its respective BCR-ABL fusion transcript
  60. 60. Morphology of bone marrow is needed for definition of the stage of the disease
  61. 61. The classification in chronic, accelerated and blast phase is based on a combination of clinical, morphological and genetic findings</li></li></ul><li>Case 5<br />79 year old man with absolute lymphocytosis<br />Accidental finding<br />Patient in good general health<br />Clinical finding<br /><ul><li>No lymphadenopathy
  62. 62. No enlarged spleen or liver</li></li></ul><li>Peripheral blood count<br />
  63. 63. Peripheral blood smear<br />
  64. 64. Diverse mature lymphoid neoplasms<br />B-CLL<br />Hairy cell leukemia<br />Sezary‘s Syndrome<br />Follicular lymphoma<br />T-LGL leukemia<br />Prolymphocytic leukemia<br />
  65. 65. Flow cytometric pattern of mature B-cell lymphoid neoplasms<br />
  66. 66. What is the next step ?<br />Minimal diagnostic program<br /><ul><li>Coombs test, Immunoglobulin levels
  67. 67. Immunophenotyping from peripheral blood</li></ul>Results<br /><ul><li>Coombs test negative
  68. 68. Immunoglobulin levels normal
  69. 69. no monoclonal fraction
  70. 70. Immunophenotyping (FACS)</li></li></ul><li>What is here the aim of immunophenotyping<br />Distinction between neoplasm & reactive lymphocytes<br />Light chain monoclonal lymphocytes<br />Distinction between mature & precursor cell lymphoid neoplasm<br />lymphoma / CLL: mature neoplasms<br /> ALL/ lymphoblastic NHL: Precursor cell neoplasms<br />Distinction between B-, T- & NK-cell neoplasms<br />Defining subtypes of lymphoid neoplasms<br />
  71. 71. Immunophenotyping results<br />
  72. 72. Algorithm of mature B-cell neoplasms<br />Monoclonal B-cells<br />+<br />-<br />CD5<br />+<br />+<br />-<br />-<br />CD23<br />CD10<br />others<br />CLL<br />MCL<br />FL<br />
  73. 73. Complete result of the immunophenotyping<br />Kappa-monoclonality<br />Cells are positive for <br />CD19+, CD20+, CD5+, CD23+<br />Negative or dim positive for<br />sIgM dim, CD79b-, FMC7-, CD10-, CD103- <br />Immunophenotypic conclusion<br />Mature B-cell neoplasm, Type B-CLL<br />CLL score (matutes score) 5/5<br />
  74. 74. Final diagnosis<br />Mature B-cell lymphoid neoplasia, type B-CLL<br />Rai 0, Binet A<br />asymptomatic <br />No autoimmune phenomena<br />In an elderly patient (79-years old)<br />No genetic information available<br />
  75. 75. What will be the treatment strategy?<br />Watch and wait<br />Regular follow-up (every 6 months)<br />Constitutional symptoms<br />Organomegaly<br />Peripheral blood count<br />Why is it acceptable to restrict diagnostics to a minimal program?<br />elderly patient <br />no intention of curative therapy<br />asymptomatic patient <br />no treatment required<br />
  76. 76. Case 5b<br />45 year old man<br /><ul><li>Check-up taking out insurance
  77. 77. No symptoms</li></ul>Clinical findings<br /><ul><li>No lymphadenopathy
  78. 78. No hepatomegaly, no splenomegaly
  79. 79. Five years previously, normal blood count and differential count</li></ul>Family history of CLL - aunt, mothers side<br />
  80. 80. Peripheral blood count<br />
  81. 81. Confirmation of the B-CLL<br />Complete Immunophenotype<br />Lymphocytes positive for<br />CD19, CD20dim, CD23, CD5, kappa, sIgM dim<br />Lymphocytes negative for:<br />FMC-7, CD79b, CD103, CD10<br />
  82. 82. How to define management strategy<br />Young patient with B-CLL<br />Rai 0, Binet A<br />Considerations for management strategy<br />Age of the patient<br />Age - not an independent risk factor in CLL<br />Younger patients are more likely to die from CLL<br />Stage of the disease: early stage is due to <br />early stage with undefined prognosis <br />or good prognosis CLL – smoldering disease<br />We need more information<br />
  83. 83. Clinical prognostic factors in CLL<br />Symptomatic CLL; B-symptoms<br />Fever, night sweat, weight loss<br />Disease stage<br />Rai or Binet<br />Lymphocyte count<br />> 50 x109/L<br />Doubling time of absolute lymphocyte count<br />< 12 months<br />
  84. 84. Genetics -> Prognosis<br />interphase FISH<br />Good prognosis<br />Isolated del 13q14<br />Intermediate<br />Trisomy 12<br />Normal karyotype<br />Poor prognosis<br />del 11q<br />del17p<br />del 11q<br />
  85. 85. Mutational status of IgVH genes in B-cell CLL<br />Two phases in B-cell development<br />Antigen-independent phase<br />Bone marrow<br />Gene rearrangement<br />Lymphoid follicle (follicular mantle)<br />Unmutated B-cells<br /> naïve B-cells<br />Antigen-dependent phase<br />In lymphoid follicle (germinal centre)<br />Somatic hypermutation<br /> mutated B-cells<br />Memory cells<br />
  86. 86. Biological surrogate markers for mutational status<br />Mutational status not routinely available<br />CD38 expression on B-cells<br />Poor prognosis: <br />positive ( 30%)<br />No good correlation with mutational status<br />ZAP70 expression on B-cells<br />Poor prognosis: <br />positive (>20%)<br />Better correlation <br />
  87. 87. ZAP-70 expression by flow cytomtery<br />ZAP-70 positive B-cells<br />ZAP-70 negative B-cells<br />
  88. 88. Interpretation of the global situation and next steps<br />Early stage, high risk B-CLL in a young patient<br />CLL asymptomatic<br />Rai I / Binet A stage, lymphocyte count<br />FISH del(11q); ZAP-70 positive, CD38 positive<br />Watch and wait as long as asymptomatic<br />In particular cases option of experimental therapy<br />HLA-typing of the family<br />if no sibling donor available, consider unrelated donor<br />Close follow-up of the patient<br />Three monthly<br />
  89. 89. Take home message<br />More complete diagnosic workup is needed, when therapeutic intervention is an option<br />Distinction between different lymphoid neoplasms<br />Determination of prognostic factors<br />New biological prognostic markers do not directly determinate the time of treatment<br />They may have an impact on the long term treatment strategy<br />Clinical staging still plays a essential role <br />
  90. 90. Case 6History/ Clinicalfindings<br />53 year old, female <br />Presenting a transient ischemic attack (TIA) <br />Brachiofacialhemiparesis<br />Risk factors, dyslipidemia, and cigarette smoking<br />Weight loss of 7kg with 5 months<br />Discrete splenomegaly<br />
  91. 91. Initial blood counts<br />
  92. 92. What is the most relevant change in peripheral blood?<br />Leukocytosis <br />Macrocytic anemia <br />Thrombcytosis<br />Regenerative anemia<br />Pancytopenia<br />
  93. 93. Peripheral blood<br />
  94. 94.
  95. 95. What do the changes in peripheral blood suggest?<br />Status post-spenectomy <br />Hemolytic anemia <br />Marrow fibrosis<br />Myeloproliferative disease <br />Acute myeloid Leukemia<br />
  96. 96. Bone marrow:dry tap<br />
  97. 97. Bone marrow Histology<br />
  98. 98.
  99. 99.
  100. 100.
  101. 101.
  102. 102.
  103. 103. Summary of morphology<br />Aspiration: Punctio sicca <br />Hypercellular, maturating marrow without increased blasts<br />Clustered Megakaryocytes with variable size<br />Reticulin fibers moderately augmented<br />Dilated sinusoids with prominent intracellular megakaryocytes<br />Stainable iron<br />Lymphoid follicles<br />
  104. 104. What is the diagnosis at this stage?<br />Essential thrombocythemia (ET)<br />Chronic myeloproliferative disease (MPD)<br />Chronic idiopathic myelofibrosis (CIMF)<br />Chronic myeloproliferative disease and suspicion for Non-Hodgkin-Lymphoma<br />CML<br />No diagnosis possible, further staining required<br />
  105. 105. Do we need additional investigations?<br />Immunocytochemistry: CD34 staining<br />Cytogenetics and BCR-ABL fusion transcript<br />Colony forming assay<br />JAK2 mutational status<br />All of them<br />
  106. 106. Results of additional investigations<br />Immunohistochemistry<br />no CD34-positive cells, no increase of blasts<br />Genetic analysis<br />46,XX[20]<br />BCR-ABL negative<br />JAK2-V617F mutated<br />Colony forming assay<br />No erythroid independent BFU’s<br />
  107. 107.
  108. 108.
  109. 109. Definitive diagnosis<br />Chronicidiopathicmyelofibrosis (CIMF)<br /> in earlyfibroticstage<br />no blast increase<br />reactivelymphocyticinfiltrate<br />Goodprognosticfeatures<br />fewconstitutionalsymptoms<br />nocytopenia (except a mild anemia)<br />no blast excess<br />nocytogeneticanomalies<br />Thromboemboliccomplications (TIA)<br />
  110. 110. Treatment?<br />
  111. 111. ThankYou<br />