HemeOnc~bysomeonewhoknowsnothingaboutit~

1、Heme Onc by someone who knows nothing about it JulieAnne Gibson McGregorObjectives as outlined by the retired Nate Lambert:Recognize ACS in SCD and indications for exchange transfusionNatural history of MDSManagement of life-threatening hemoptysis due to lung cancerIndication for splenectomy in ITPD

2、iagnosis and management of CLLDiagnosis and management of MGUSRecognize CML in chronic phaseSickle Cell DiseaseHemoglobinopathy characterized by a single amino acid substitution in the beta globin chainHemoglobin S results from the substitution of a valine for glutamic acid as the sixth amino acid o

3、f the beta globin chainAlpha2/beta S2 poorly soluble when deoxygenated causing a marked decrease in red cell deformability and distortion into sickle shapePulmonary complications of SCDAcute and chronic pulmonary complications represent the most common cause of death in adulthoodChronic- recurrent m

4、icrovascular obstruction resulting in PHTN, endothelial dysfunction and parenchymal fibrosisAcute- infection, fat emboli, infarction from in-situ thrombosis, pulm edema (iatrogenic)Recognize Acute Chest Syndrome in Sickle Cell DiseaseMost common form of acute pulmonary disease in SCD, of pts.Most fr

5、equently reported cause of death in adultsRisk factor for early mortalityRecognize Acute Chest Syndrome in Sickle Cell DiseaseNew pulmonary infiltrate involving one complete lung segment (not atelectasis)Chest PainT 38.5Tachypnea, Wheezing or Cough Etiology of ACS (Precise etiology unclear)Pulmonary

6、 infarction (microvascular) Fat embolismChlamydia pneumonia infectionMycoplasma pneumoniae infectionViral infection Mixed infectionsOther pathogensClinical findings of ACSFeverChest and or Extremity PainDyspneaNonproductive coughTenderness over the ribs or sternumLeukocytosisPulmonary consolidationT

7、hrombocytopenia or ThrombocytosisFalling hemoglobin concentrationElevated LD and BiliDiagnosis of ACSNo currently laboratory or radiographic finding permits the differentiation of ACS from other acute pulmonary manifestations of SCD, including pneumonia and infarction from large vein thrombis (PE).

8、Management of ACSSupportive careCommunity acquired pneumonia coverageSupplemental oxygen to maintain PaO2 of 70Judicious use of opioid analgesics Incentive spirometrySome data for bonchodilatorsHydration attempting to avoid pulmonary edemaRBC transfusion matched for C, E and Kell antigensExchange tr

9、ansfusionIndications for Exchange TransfusionProgressive infiltrates and hypoxemia refractory to conventional therapyReduction of the HbS level to below 30% and a Hct of 30% can lead to marked improvement in the majority of cases of ACSNatural History of Myelodysplastic SyndromesMDS- series of hemat

10、ologic conditions characterized by chronic cytopenias (anemia, neutropenia, thrombocytopenia) accompanied by abnormal cellular maturationMDS leaves pts at risk for symptomatic anemia, infection, bleeding and progression to acute leukemiaNatural History of Myelodysplastic SyndromesAverage age 65 to 7

11、0Patients who evolve to AML from MDS are less reponsive to standard treatment than is de novo AML. Mainstays of therapy- RBC and platelet transfusions as needed and amtibiotic supportive care when requiredClassification of MDSRefractory anemia (RA)- less than 5% BM blastsRefractory anemia with ringe

12、d sideroblasts (RARS)- 15% ringed sideroblastsRefractory anemia with excess blasts (RAEB)- 5-19 % BM blastsChronic myelomonocytic leukemia (CMML)- up to 20% BM blasts + peripheral blood monocyte count 1000RAEB in transformation- 12-30% BM blastsNatural History of Myelodysplastic SyndromesMost patien

13、ts with MDS die of consequences of bone marrow failure rather than transformation to AMLLow risk (blasts 100): median survival 4.9 yearsHigh risk (blasts 5%, MCV 10,000 Indication for Splenectomy in ITPSpontaneous remissions are unusual in adults- one quote 9%Often adults treated with steroids howev

14、er patients with mild and asymptomatic thrombocytopenia with plts 30,000- 50,000 often have a stable and benign courseNo good data on adults with ITP and spont remission, major or death from bleedingIndication for Splenectomy in ITPGeneral Treatment Goals: - treat moderate to severe thrombocytopenia

15、 who are bleeding or at risk - limit duration of treatment unless symptoms persist - mild, asymptomatic thrombocytopenia should not be treated. Indication for Splenectomy in ITPTreatment is steroids, IVIGor anti-Rh(D) in pts whose red cells are Rh(D) +. Splenectomy is traditional second-line treatme

16、nt in adults with ITP who fail to achieve a safe platelet count with initial prednisone therapy.Splenectomy no appropriate in mild or mod thrombocytopenia and minor bleedingIndication for Splenectomy in ITPSplenectomy should be deferred for 4-6 weeks after diagnosisEstimate for complete remission fo

17、llowing splenectomy in 65%Younger patients in general respond better to splenectomyRisk for splenectomy increases with age, obesity and comorbid conditionsIf you decide against splenectomy or it failedContinuous low dose steroidsRituxCyclophosphamid and azathioprineVincristine or vinblastineDanazolA

18、minocaproid acidThrombopoiesis stimulating agentOther Diagnosis and Management of CLLCLL- one of the chronic lymphoproliferative disorders (lymphoid neoplasms); progressive accumulation of functionally incompetent lymphocytes which are monoclonal in originMedian age 61Age range 25 to 84Slight male p

19、redominance Diagnosis and Management of CLLInitial presenting findings- lymphadenopathy, splenomegaly, hepatomegaly, WBC 100,000, Hgb 11, Platelet 5000 for diagnosisDiagnosis and Management of CLLPeripheral blood smear- mature appearing small lymphocytes account for 50% or WBCMay also see lymphocyte

20、s which appear flattened or smudged in the process of being spread on the glass slide when looking at smear“Smudge cells” reflect fragility of cellsSmudge CellsDiagnosis and Management of CLLCLL lymphocytes are described as mature appearing cells but they are immature both functionally and developme

21、ntallyB-CLL- low levels of surface membrane immunoglobulin, expression of B cell antigens (CD19, CD21, CD 23 ect), and expression of CD5 a T cell associated antigen.Diagnosis and Management of CLL1 point for each of below, 4-5 points 97% accurateWeakly positive surface immunoglobulin stainCD5 +CD23+

22、CD79b or CD22 weakly +FMC7 negativeDiagnosis and Management of CLL- minimum dx criteriaALC in the peripheral blood 10,000 with a preponderant population of morphologically mature appearing small lymphocytesNormo to hypercellular bone marrow with lymphocytes accounting for 30% of all nucleated cellsl

23、ow levels of surface membrane immunoglobulin, expression of 1 or more B cell antigens, and expression of CD5Diagnosis and Management of CLLA series of 25 cases of T cell CLL has been reported but many of these cases have been reclassified and suggestion was made to discard this diagnosis entirely.Ma

24、jor complications of CLL arise from cytopenias and immune dysfunction, anemia, and thrombocytopeniaInfections lead to 50% of deaths from CLLDiagnosis and Management of CLLDepressed immune function from hypogammaglobulinemia can be improved with IVIG for patients with pattern of repeated infections,

25、especially pneumonia and sepsis. Sinobronchial and other bacterial infections can be treated with antibiotics aloneAcyclovir for herpes simplex and zoster Diagnosis and Management of CLLImpaired T cell function can lead to opportunistic infectionsIn rare cases may need to use GCSFRBC tx and epo for

26、anemiaThrombocytopenia- steroids, danazol and IVIGSurvival is similar to aged matched controlsDiagnosis and Management of MGUSPresence of a serum monoclonal protein (M-protein, whether IgA, IgG or IgM) at a concentration 1.5 gm/dL, non IgG MGUS, abnormal serum free light chain ratio and all pts with

27、 abnormal CBC, creat, Ca or bone survey. BM bx can be deferred in elderly asymptomatic pts with a small IgG monoclonal protein who have f/uDiagnosis and Management of MGUSLight chains in the urine may be found in small amount in MGUS10% or more of plasma cells in the BM is diagnostic of MM but pts m

28、ay have smoldering MM and remain stable during long termRepeat SPEP 6 months after first abnormal one and if stable annually thereafter. Recognize CML in Chronic PhaseCML is shor for chronic myelogenous leukemia or chronic myelocytic leukemia or chronic myeloid leukemiaOne of the myeloproliferative

29、disorders along with PV, ET and agnogenic myeloid metaplasia now call chronic idiopathic myelofibrosisCharacterized by the proliferation of a single myeloid cell type- excess neutrophills in CMLRecognize CML in Chronic PhaseMyeloproliferative disorders - clonal disorders of hematopoiesis that arise

30、in a hematopoietic stem cell or early progenitor cell - characterized by dysregulated production of a particular lineage of mature myeloid cells with fairly normal differentiation - variable tendency to progress to acute leukRecognize CML in Chronic PhaseCML is associated with an abnormal chromosome 22 known as the Philadelphia chromosome Bcr-Abl15-20% of cases of leukemia in adultsMedian age at presentation is 50Annual incidence of 1 to 2 cases per 100,000Slight male predominenceRecognize CML in Chronic PhaseUncontr