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Hematologic Malignancy for Internist 2014

Hematologic Malignancy for Internist 2014. Chinadol Wanitpongpun MD. Cancer treatment. Chemotherapy & Targeted therapy Radiotherapy Surgery Other : Bone Marrow transplantation (BMT) / Tumor vaccine. BSA. BSA = √Ht X BW /3600 Actual BW (JCO2012) Overweight (conditioning regimens)

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Hematologic Malignancy for Internist 2014

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  1. Hematologic Malignancy for Internist 2014 Chinadol Wanitpongpun MD.

  2. Cancer treatment • Chemotherapy & Targeted therapy • Radiotherapy • Surgery • Other : Bone Marrow transplantation (BMT) / Tumor vaccine

  3. BSA • BSA = √Ht X BW /3600 • Actual BW (JCO2012) • Overweight (conditioning regimens) • Actual > 40% IDW : Adjust BW • Adjust BW = IBW + 0.5(Actual-Ideal) • Male 50 + 2.3 X (inch > 60) • Female 45 + 2.3 X (inch > 60)

  4. Hematologic Malignancy • Myeloid Neoplasms • Lymphoid Neoplasms • Histiocytic & Dendritic neoplasms

  5. The Must Known • Acute Leukemia especially M3 • MPNs : PV / ET / CML / AMM • Lymphoma : HD / DLBCL / BL • Multiple Myeloma

  6. Scope for each Diseases • Criteria Diagnosis • Clinical features or manifestations • Classification • Staging • Prognostic score • Treatment

  7. Myeloid Neoplasms

  8. Myeloid Neoplasms

  9. AML (1) • FAB classification : morphology M0-M7 • WHO classification : cytogenetic • Acute marrow failure within 8 weeks • Hepatosplenomegaly rare in de novo • WBC usually high (leukemic profile) except aleukemic or hypoplastic leukemia

  10. AML (2) • Diagnosis by Blast > 20% in PBS and BM except t(8;21) / t(15;17) / inv(16) t(16;16) or erythroleukemia Flow cytometry : blast gate >20% M0-M7 by CD marker Mass biopsy : Granulocytic sarcoma • DDX : ALL

  11. AML-M6 • 2 forms • Pure erythroid leukemia • Erythroid > 80% minimal myeloblast • Acute erythroid/myeloid leukemia • Erythroid > 50% • Blast > 20% of all non erythroid cell

  12. Flow Cytometry for AML 1. Blast gate : Acute Leukemia 2. AML / ALL : MPO / TdT / CD19 / CD 34 / CD117 3. M3 / Non M3 : CD34 - & HLADR – 4. M6 (GPA) / M7 (CD41/61) 5. M4/M5 (CD11c / CD14 / CD64) 6. M0-2 (MPO / CD15) -/-, +/-, +/+

  13. AML (3)

  14. AML (4)

  15. AML (5)

  16. ALL

  17. Cytogenetic in AML

  18. Normal Cytogenetic AML

  19. AML (6)

  20. AML (7) • Mutation associated with prognosis • Favorable + c-kit mutation = intermediate • Normal karyotype + NPM1 = favorable • Normal karyotype + CEBPA = favorable • Normal karyotype + FLT3/ITD = unfavorable

  21. AML (8) • Treatment 2 phases • Induction : 3+7 regimen (Idarubicin 3 + Ara-C 7) • Post remission therapy or consolidation depend on cytogenetic Favorable : CMT (HDAC 3-4 cycles) Intermediate / Unfavorable : ALBMT

  22. Cytarabine (Ara-C) SE • Neutrophilic Eccrine Hydradenitis • Pyoderma Gangrnosum • Keratitis / Conjunctivitis • Cytarabine syndrome : seizure & cerebellar toxicity

  23. APL (1) • Acute promyelocytic leukemia • Abnormal promyelocyte

  24. APL (2) • Present with bleeding (DIC) or BM failure • Diagnosis by PBS / BMA • Abnormal promyelocyte or blast > 30% • 2 subtypes • Hypergranular or Typical : Low WBC • Hypogranular (Microgranular) : High WBC

  25. APL (3)

  26. APL (4) • Flow cytometry dual low or absence expression of HLA-DR and CD34 and bright expression of CD33 • Cytogenetic : t(15;17) • Other : t(5;17) or t(11;17) poor response to ATRA just only t(11;17) associated PLZF-RARA

  27. APL (5) • Treatment • APL with PLZF-RARA treat as AML non M3 • 3 phases • Induction : Idarubicin + ATRA • Consolidation • 1st and 3rd cycle : Idarubicin + ATRA + Ara-C • 2nd cycle : Idarubicin + Mitoxanthone • Maintenance : 6-MP + MTX + ATRA 2 yr.

  28. Ara-C in Consolidation • Depend on risk group • High risk • Initial WBC > 10,000 • Initial Platelet < 40,000

  29. APL (6) • ATRA side effects • Differentiation syndrome : fever + weight gain + dyspnea + pleural effusion and ascites + leukocytosis treat by stop ATRA + IV steroid • Hepatitis • Pseudotumor cerebri • Dry mouth

  30. APL (7) • ATO3 • SE as ATRA • QTc prolong • Hypokalemia / Hypomagnesemia

  31. MDS (1) • Subacute to chronic cytopenia • Elderly • 80% involve erythroid (anemia) • No organomegaly • Dysplastic features > 10% of lineage • Diagnosis by PBS + BMA + Chromosome

  32. DDX. Erythroid Hyperplasia • Acute Blood loss • Hemolysis • Megaloblastic anemia • Myelodysplastic syndrome (MDS) • AML-M6

  33. MDS (2) • Dysplastic features • Erythroid : nucleus-multiple / budding Ring sideroblast (>15% erythroid series) • Myeloid : bilobed / Pelger-Huet Incease myeloblast • Megakaryocyte : micro-hypolobated • Cellularity mostly increase with eythroid hyperplasia

  34. MDS (3) • WHO Classification • RA / RCMD + RS • RN / RT • 5q- syndrome • RAEB-I / RA EB-II • MDS/MPD • AML • Unclassified

  35. MDS (5) • Treatment • Transfusion / Iron chelation • 5q- syndrome : lenalidomide RR 67% • Hypoplastic / HLADR-15 / PNH : treat as AA • RN / RT : hypomethylating agent • IPSS score • Low risk : Growth factors EPO + G-CSF • High risk : BMT / Hypomethylating agent

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