Objectives 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 ITPDiagnosis and management of CLLDiagnosis and management of MGUSRe
1. Heme Onc ~ by someone who knows nothing about it ~ JulieAnne Gibson McGregor
2. Objectives as outlined by the retired Nate Lambert: Recognize ACS in SCD and indications for exchange transfusion
Natural history of MDS
Management of life-threatening hemoptysis due to lung cancer
Indication for splenectomy in ITP
Diagnosis and management of CLL
Diagnosis and management of MGUS
Recognize CML in chronic phase
3. Sickle Cell Disease Hemoglobinopathy characterized by a single amino acid substitution in the beta globin chain
Hemoglobin S results from the substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain
Alpha2/beta S2 poorly soluble when deoxygenated causing a marked decrease in red cell deformability and distortion into sickle shape
4. Pulmonary complications of SCD Acute and chronic pulmonary complications represent the most common cause of death in adulthood
Chronic- recurrent microvascular obstruction resulting in PHTN, endothelial dysfunction and parenchymal fibrosis
Acute- infection, fat emboli, infarction from in-situ thrombosis, pulm edema (iatrogenic)
5. Recognize Acute Chest Syndrome in Sickle Cell Disease Most common form of acute pulmonary disease in SCD, ˝ of pts.
Most frequently reported cause of death in adults
Risk factor for early mortality
6. Recognize Acute Chest Syndrome in Sickle Cell Disease New pulmonary infiltrate involving one complete lung segment (not atelectasis)
Tachypnea, Wheezing or Cough
7. Etiology of ACS (Precise etiology unclear) Pulmonary infarction (microvascular)
Chlamydia pneumonia infection
Mycoplasma pneumoniae infection
8. Clinical findings of ACS Fever
Chest and or Extremity Pain
Tenderness over the ribs or sternum
Thrombocytopenia or Thrombocytosis
Falling hemoglobin concentration
Elevated LD and Bili
9. Diagnosis of ACS No 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).
10. Management of ACS Supportive care
Community acquired pneumonia coverage
Supplemental oxygen to maintain PaO2 of > 70
Judicious use of opioid analgesics
Incentive spirometry Some data for bonchodilators
Hydration attempting to avoid pulmonary edema
RBC transfusion matched for C, E and Kell antigens
11. Indications for Exchange Transfusion Progressive infiltrates and hypoxemia refractory to conventional therapy
Reduction of the HbS level to below 30% and a Hct of 30% can lead to marked improvement in the majority of cases of ACS
12. Natural History of Myelodysplastic Syndromes MDS- series of hematologic conditions characterized by chronic cytopenias (anemia, neutropenia, thrombocytopenia) accompanied by abnormal cellular maturation
MDS leaves pts at risk for symptomatic anemia, infection, bleeding and progression to acute leukemia
13. Natural History of Myelodysplastic Syndromes Average age 65 to 70
Patients 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 required
14. Classification of MDS Refractory anemia (RA)- less than 5% BM blasts
Refractory anemia with ringed sideroblasts (RARS)- < 5% BM blasts with > 15% ringed sideroblasts
Refractory anemia with excess blasts (RAEB)- 5-19 % BM blasts
Chronic myelomonocytic leukemia (CMML)- up to 20% BM blasts + peripheral blood monocyte count >1000
RAEB in transformation- 12-30% BM blasts
15. Natural History of Myelodysplastic Syndromes Most patients with MDS die of consequences of bone marrow failure rather than transformation to AML
Low risk (blasts <5%, MCV>100): median survival 4.9 years
High risk (blasts >5%, MCV <100): median survival 0.5 years
Intermediate risk (all others): median survival 1.8 to 2.0 years
16. Management of life-threatening hemoptysis due to lung cancer Without looking this up I suppose the answer is:
Similar to management of life threatening hemoptysis in other situations
Find out code status
Attempt to intubate the lung that isn’t bleeding
Activated factor VII
Transfusion and saline to maintain blood volume
17. Management of life-threatening hemoptysis due to lung cancer Definition of massive hemoptysis is expectoration of blood exceeding 100 to 600 mL in 24 hours.
80% mortality for people with massive hemoptysis for any reason
Bronchogenic carcinoma is an infrequent cause of massive bleeding although it commonly causes nonmassive hemoptysis.
Patients with massive hemoptysis typically had large, centrally located tumors, especially squamous cell carcinoma
18. Management of life-threatening hemoptysis due to lung cancer No consensus regarding the optimal management of people with massive hemoptysis
Insure adequate airway protection, ventillation and cardiovascular function.
Reverse coagulation disorders (I didn’t think of that one, duh)
Consult pulmonary (?bronch) and thoracic surgery (?pulmonectomy) and invasive radiology (?arterial embolization).
Place the bleeding lung in dependent position to reduce spillage into healthy lung
19. Indication for Splenectomy in ITP Idiopathic thrombocytopenic purpura also known as immune thrombocytopenic purpura and ITP
Thrombocytopenia, with an otherwise normal CBC and WBC diff, including a normal peripheral blood smear
No clinically apparent associated conditions or medications that may cause thrombocytopenia
20. Indication for Splenectomy in ITP Pathogenesis of ITP is presumed to be related to the presence of platelet specific autoantibodies
Goal of treatment is to provide a safe platelet count to prevent major bleeding rather than correcting the underlying disease.
Major bleeding is rare in pts with >10,000
21. Indication for Splenectomy in ITP Spontaneous remissions are unusual in adults- one quote 9%
Often adults treated with steroids however patients with mild and asymptomatic thrombocytopenia with plts 30,000- 50,000 often have a stable and benign course
No good data on adults with ITP and spont remission, major or death from bleeding
22. Indication for Splenectomy in ITP General Treatment Goals: - treat moderate to severe thrombocytopenia who are bleeding or at risk
- limit duration of treatment unless symptoms persist
- mild, asymptomatic thrombocytopenia should not be treated.
23. Indication for Splenectomy in ITP Treatment is steroids, IVIGor anti-Rh(D) in pts whose red cells are Rh(D) +.
Splenectomy is traditional second-line treatment 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 bleeding
24. Indication for Splenectomy in ITP Splenectomy should be deferred for 4-6 weeks after diagnosis
Estimate for complete remission following splenectomy in 65%
Younger patients in general respond better to splenectomy
Risk for splenectomy increases with age, obesity and comorbid conditions
25. If you decide against splenectomy or it failed… Continuous low dose steroids
Cyclophosphamid and azathioprine
Vincristine or vinblastine
Thrombopoiesis stimulating agent
26. Diagnosis and Management of CLL CLL- one of the chronic lymphoproliferative disorders (lymphoid neoplasms); progressive accumulation of functionally incompetent lymphocytes which are monoclonal in origin
Median age 61
Age range 25 to 84
Slight male predominance
27. Diagnosis and Management of CLL Initial presenting findings- lymphadenopathy, splenomegaly, hepatomegaly, WBC >100,000, Hgb <11, Platelet <100,000
Symptoms range from totally asymptomatic to weight loss, fevers, night sweats, extreme fatigue
ALC threshold >5000 for diagnosis
28. Diagnosis and Management of CLL Peripheral blood smear- mature appearing small lymphocytes account for >50% or WBC
May also see lymphocytes which appear flattened or smudged in the process of being spread on the glass slide when looking at smear
“Smudge cells” reflect fragility of cells
29. Smudge Cells
30. Diagnosis and Management of CLL CLL lymphocytes are described as mature appearing cells but they are immature both functionally and developmentally
B-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.
31. Diagnosis and Management of CLL 1 point for each of below, 4-5 points 97% accurate
Weakly positive surface immunoglobulin stain
CD79b or CD22 weakly +
32. Diagnosis and Management of CLL- minimum dx criteria ALC in the peripheral blood >10,000 with a preponderant population of morphologically mature appearing small lymphocytes
Normo to hypercellular bone marrow with lymphocytes accounting for >30% of all nucleated cells
low levels of surface membrane immunoglobulin, expression of 1 or more B cell antigens, and expression of CD5
33. Diagnosis and Management of CLL A 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.
Major complications of CLL arise from cytopenias and immune dysfunction, anemia, and thrombocytopenia
Infections lead to 50% of deaths from CLL
34. Diagnosis and Management of CLL Depressed immune function from hypogammaglobulinemia can be improved with IVIG for patients with pattern of repeated infections, especially pneumonia and sepsis.
Sinobronchial and other bacterial infections can be treated with antibiotics alone
Acyclovir for herpes simplex and zoster
35. Diagnosis and Management of CLL Impaired T cell function can lead to opportunistic infections
In rare cases may need to use GCSF
RBC tx and epo for anemia
Thrombocytopenia- steroids, danazol and IVIG
Survival is similar to aged matched controls
36. Diagnosis and Management of MGUS Presence of a serum monoclonal protein (M-protein, whether IgA, IgG or IgM) at a concentration <3 g/dL
Fewer than 10% plasma cells in the bone marrow
Absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to the plasma cell proliferate process
37. Diagnosis and Management of MGUS Predilection for the development of multiple myeloma or a related malignancy at the rate of 1% per year
No evidence for a neoplastic plasma cell proliferative disorder or a B cell lymphoproliferative disorder
M protein detected with SPEP followed by immunoelectrophoresis or immunofixation for the identification of the M protein type.
38. Diagnosis and Management of MGUS Major reason for concern in the pt with MGUS is the risk of progression to a symptomatic plasma cell proliferative disorder
Pt with IgG or IgA MGUS may progress to multiple myeloma, primary amyloidosis or a related plasma cell disorder
Pt with IgM MGUS may progress to a lymphoproliferative disorder (lymphoma, CLL, Waldenstrom’s)
39. Diagnosis and Management of MGUS MGUS found in 1 to 2% of adults
Higher in patients over age 70
2-3 fold higher prevalence in black patients
Higher rates in men than women
40. Diagnosis and Management of MGUS In order to differentiate MGUS from a related plasma cell malignancy, pts should have a CBC, creat, Ca, and complete radiographic bone survey of the skeleton.
Abnormalities of the above should have additional tests to determine the etiology of the abnormalities and whether thany are indeed related to a plasma cell prolif. d/o.
41. Diagnosis and Management of MGUS Bone marrow aspiration and biopsy is indicated in all patients with an M proteint >1.5 gm/dL, non IgG MGUS, abnormal serum free light chain ratio and all pts with 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/u
42. Diagnosis and Management of MGUS Light chains in the urine may be found in small amount in MGUS
10% or more of plasma cells in the BM is diagnostic of MM but pts may have smoldering MM and remain stable during long term
Repeat SPEP 6 months after first abnormal one and if stable annually thereafter.
43. Recognize CML in Chronic Phase CML is shor for chronic myelogenous leukemia or chronic myelocytic leukemia or chronic myeloid leukemia
One of the myeloproliferative disorders along with PV, ET and agnogenic myeloid metaplasia now call chronic idiopathic myelofibrosis
Characterized by the proliferation of a single myeloid cell type- excess neutrophills in CML
44. Recognize CML in Chronic Phase Myeloproliferative disorders
- clonal disorders of hematopoiesis that arise 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 leuk
45. Recognize CML in Chronic Phase CML is associated with an abnormal chromosome 22 known as the Philadelphia chromosome Bcr-Abl
15-20% of cases of leukemia in adults
Median age at presentation is 50
Annual incidence of 1 to 2 cases per 100,000
Slight male predominence
46. Recognize CML in Chronic Phase Uncontrolled production of maturing granulocytes, predominantly neutrophils but also eosinophils and basophils.
3 phases of CML- chronic phase, accelerated phase, and blast crisis.
85% of pts present in the chronic phase
47. Recognize CML in Chronic Phase Chronic phase- large increase in the pool of committed myeloid progenitors leading to peripheral blood leukocytosis and often thrombocytosis
Splenomegaly, occasional hepatomegaly or adenopathy (myelofibrosis and extramedullary hematopoiesis)
48. Recognize CML in Chronic Phase Often asymptomatic
Symptoms include fatigue, malaise, weight loss, excessive sweating, abdominal fullness, early satiety, sternal tenderness, gout, and bleeding episodes due to platelet dysfunction.
49. Other phases of CML, just for fun Accelerated phase- neutrophil differentiation becomes progressively impaired and leukocyte counts are more difficult to control with myelosuppressive meds
Blast crisis- condition resembling acute leukemia in which myeloid or lymphoid blasts fail to differentiate