Lymphoblastic Leukemia Clinical and Laboratory Findings

1. Lymphoblastic LeukemiaClinical and Laboratory Findings Jason Corbeill PA-C Lock Haven University

5. Leukemia • Results from the acquired somatic mutation of a chromosome leading to proliferation of a hematopoietic progenitor cell clone

6. Leukemia • May be either acute or chronic • Hematological proliferative disorders should be thought of as being on a continuum • Accounts for 10% of all cancers • Leading cause of cancer death for those under age 35

7. Lymphoblastic Proliferative growth of the lymphoid cell line ALL 5 times more common than AML in kids Kids age 2-5 5 yr survival 78% kids, much worse in adults Myelogenous Proliferative growth of the myeloid cell line Adults > kids Leukemia

9. Unknown in majority Radiation exposure either destructive or therapeutic Benzene Phenylbutazone Arsenic Chloramphenicol RNA viruses (HTLV-1 in the caribbean) Thorotrast Chemotherapeutic agents—melphalan, chlorambucil, cyclophosphamide Congenital Immunologic deficiencies Acute Lymphoblastic Leukemia—Risk Factors

10. Acute Lympoblastic Leukemia—Risk Factors--KIDS • Downs syndrome • Neurofibromatosis • Bloom syndrome • Ataxia telangiectasia • Increased birth weight

11. Acute Lymphoblastic Leukemia-pathophysiology • Reciprocal genetic translocations involving genes that play a major role in maturation/differentiation of the progenitor cells

12. The Big Picture

14. Acute Lymphoblastic Leukemia signs/symptoms • Progressive fatigue • Due to anemia—pale, pallor MM, DOE • Infection • Due to abnormal WBC--Fevers, sweats, shakes, SOB, cough, pain, thrush, rash, zoster • Bleeding • Due to thrombocytopenia--Petechiae, purpura, bleeding gums, GI bleed, intracranial bleed, conjunctival hemorrhage, hemoptysis, easy bruising, prolonged bleeding, hematuria

15. Acute Lymphoblastic Leukemia signs/symptoms • Persistent lymphadenopathy • Epitrochlear, supraclavicular, post auricular concerning • Unchanged with abx therapy • Greater than 1cm diameter • Nontender, firm, rubbery, matted • Headache • Signs of increased intracranial pressure • Papilledema, nuchal rigidity, vomiting, lethargy • Bone pain • Due to periosteal involvement • Usually in long bones • Kids will avoid bearing weight

16. Acute Lymphoblastic Leukemia signs/symptoms • Splenomegaly • Enlarged testicle • Painless mass • Mediastinal mass • Stridor, dyspnea, SVC syndrome, chest pain

17. Acute Lymphoblastic Leukemia -diagnostic findings • WBC may be elevated, normal, or low • Anemia • Thrombocytopenia • Pancytopenia • Elevated uric acid • Hyperkalemia • Elevated LDH • Elevated PT, PTT

18. Acute Lymphoblastic Leukemia -diagnostic findings • Peripheral Blood Smear • Lymphoblasts, anemia, thrombocytopenia, leukopenia i.e. atypical cells

20. Acute Lymphoblastic Leukemia -diagnostic findings • Bone Marrow Immunophenotype analysis: • CD 19, CD 22, CD 10—B cell • CD 7 CD 3—T cell • Bone Marrow Biopsy cytogenetics: • Philadelphia (Ph) chromosome t(9;22)(q34;q11) in 30% • t(4;11) (q21;q23) t(1;19)

22. Chronic Lymphocytic Leukemia-pathophysiology • Clonal disease of immunologically incompetent long-lived lymphocytes expressing high levels of antiapoptotic proteins • I.e. they don’t function or die and end up proliferating

23. Chronic Lymphoblastic Leukemia • Most common leukemia in western countries • Very rare incidence in asia • Median age of diagnosis 70 yrs • No clear risk factors • 90% are of B-cell origin • May be familial trait in 1st order relatives • Usually presents asymptomatically • Indolent course

24. Chronic Lymphoblastic Leukemia • Patients more susceptible to infection • NK and T cells reduced • Encapsulated organisms, GNR COD in 30% • Often associated with hypogammaglobulinemia • B cells are making autoantibodies • Autoimmune hemolytic anemia, coombs +, idiopathic thrombocytopenic purpura

25. CLL-symptoms • Unintentional weight loss > 10% in last 6 mos • Fevers > 38 C (100.5F) unexplained • Night sweats • Fatigue • Recurrent infections

26. CLL--symptoms • Bleeding • Bruising • SOB • Not usually associated with CNS involvement

27. CLL-signs • Lymphadenopathy • Splenomegaly • Hepatomegaly • Skin rash • Mediastinal mass/adenopathy on CXR/CT • Involvement of other lymphoid tissue • Tonsils

28. CLL-diagnostics • CBC/diff • absolute lymphocyte count > 10000/microliter • Bone marrow biopsy • > 30% lymphocytes • Peripheral smear • 50-100 percent of leukocytes will be lymphocytes • Smudge cells present • Fragile B cells easily distorted

30. CLL-diagnostics • Agranulocytosis—decreased neutrophils/polys/segs • Low absolute neutrophil count on CBC/diff • Hypogammaglobulinemia • IgG, IgA, IgM levels low • Coombs positive • Indicated presence of autoantibody produced by malfunctioning B cell

31. CLL-diagnostics • Cytogenetics (marrow) • Unlike ALL (Ph chromosome), there is no one chromosomal abnormality diagnostic of CLL but there are patterns involving… • Del (13q14) • Del (11q) • Del(17p) • Trisomy 12, 3, 16

32. Case 1 • 73 y/o gentlemen presents to your clinic with complaint of worsening fatigue over the past month. Now, he doesn’t even feel like getting out of his chair to make himself food and his neighbor is bringing him meals. • What do you ask? • What do you look for? • What do you order? • Do you refer?

33. Case 2 • 3 yr old girl presents with limping on left leg. Had previously been worked up as knee injury but extra support/rest no help. During your exam, mom notes that she has found some lumps behind the girl’s ears. • What do you ask? • What do you look for? • What do you order? • Do you refer?

34. Summary • ALL—mostly in kids, good prognosis, (adults bad) philadelphia chromosome, persistent lymphadenopathy. • CLL—mostly in elderly people, usually slow to advance, slow to treat • For both, Cbc/diff, peripheral blood smear, bone marrow biopsy—REFER to HEMATOLOGIST