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CLL - characteristic

Chronic Lymphocytic Leukemia (CLL) DEFINITION CLL is a neoplastic disease characterized by proliferation and accumulation ( blood, marrow and lymphoid organs ) of morphologically mature but immunologically dysfunctional l ymphocytes. CLL - characteristic.

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CLL - characteristic

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  1. Chronic Lymphocytic Leukemia (CLL)DEFINITIONCLL is a neoplastic disease characterized by proliferation and accumulation (blood, marrow and lymphoid organs) of morphologically mature but immunologically dysfunctional lymphocytes

  2. CLL - characteristic • Disease of elderly (50-60 years) • 2:1 ratio of male to female • Most common adult leukemia in Europe and USA (USA: 3/100.000 population) • In 98% of cases leukemic cells are monoclonal population of immature B lymphocytes with low-density surface immunoglobulin • Etiology unknown

  3. CLL – clinical features • Most of patients: fatigue, reduced exercises tolerance, weight loss, fever, recurrent infections, sweats, bleeding • 25% of patients: asymptomatic • 80% of patients : nontender lymphadenopaty • 50% of patients: splenomegaly • Hepatomegaly

  4. CLL - diagnostic features a) Blood test lymphocytosis ≥ 5G/l (4 weeks) b) Morphology monoconal population of small mature lymphocyte c) B-cell CLL phenotype clonal CD5+/CD19+ population of lymphocyte d) Markers of clonality κ/λ light chain restriction; cytogenetical abnormalities e) Bone marrow infiltrate > 30% of nuceated cells on aspirate f) Lymph node diffuse infiltrate of small lymphocye

  5. CLL – diagnosis (2) • Blood test • anaemia • trombocytopenia • smudge cells in peripheral blood film • Lymh node histology: diffuse infiltrate of small lymphocyte • Bone marrow histology • interstitial infiltration (30% - good prognosis) • diffuse involvement (25% - poor prognosis) • nodular involvement • Hypogammaglobulinemia • Cytogenetic abnormalities (FISH – 90%) • 13q-; 11q-; +12q; 17p-; 6q- • Molecular abnormalities • p53; bcl2

  6. CLL – clinical staging (1) RAI CLINICAL STAGING SYSTEM • Stage Clinical Features at Diagnosis Median Survival (m) ________________________________________________________________________ • Low risk • 0 Blood (> 5.000/ul. monoclonal lymphocytes) >150 • and marrow (>30%) lymphocytosis • Intermediate risk • I Lymphocytosis and enlarged lymph nodes > 101 • II Lymphocytosis and enlarged spleen and/or liver > 71 • High risk • III Lymphocytosis and anemia (Hgb < 11g/dL) > 19 • IV Lymphocytosis and thrombocytopenia (Plt < 100.000/ul.) > 19

  7. CLL – Rai stages

  8. CLL – clinical staging (2) BINET CLINICAL STAGING SYSTEM • Stage Clinical Features at Diagnosis Median Survival (m) ____________________________________________________________________ • A Blood (> 5.000/ul. monoclonal lymphocytes) > 84 • and marrow (>30%) lymphocytosis and less • than 3 areasof palpable lymphoid-tissue enlargement • B Lymphocytosis and 3 and more areasof palpable < 60 • lymphoid-tissue enlargement • C Lymphocytosis with anemia (Hgb <11g/dL; < 24 • women <10g/dL) • or thrombocytopenia (Plt <100.000/uL) • ___________________________________________________________________ An area: cervical, axillary, inguinal/femoral, spleen, liver

  9. CLL – Binet stages

  10. CLL – prognostic factors • clinical stage • marrow histology (diffuse marrow involvement - poor prognosis) • leukemia cell doubling time • CD38 expression • IgVH mutational status • ZAP-70 expression • FISH cytogenetic • low-risk: normal kariotype; isolated del(13q) • high-risk: del(17p0, del(11q), trisomy 12 • serum markers:2-microglobulin; thymidine- kinase, sCD23

  11. CLL : ZAP-70

  12. CLL – treatment (1) • Watch and wait • Monotherapy • glucocorticoids • alkylating agents (Chlorambucil, Cyclophosphamide) • purine analogues (Fludarabine, Cladribine, Pentostatin) • Combination chemotherapy • Chlorambucil/ Cyclophosphamide + Prednisone • Fludarabine + Cyclophosphamide +/- Mitoxantrone • CVP, CHOP • Monoclonal antibodies (monotherapy and in combination) • Alemtuzumab (anti-CD52) • Rituximab (anti-CD20) • Splenectomy • Radiotherapy

  13. CLL – treatment (2) • Hematopoietic stem cell transplantation • allogeneic with reduced intesity conditioning • autologous • New and novel agents • Oblimersen – bcl2-directed antisense oligonucleotide • Lenalidomide • Flavopiridol • Anti-CD23 • Anti-CD40 • Vaccine strategies • Supportive therapy(allopurinol, G-CSF, blood and platelet transfusion, immunoglobulins, antibiotics)

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