1 / 22

Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia. Maggie Davis Hovda 5/26/2009. Definition. Neoplastic disease which results from a mutation in a single lymphoid progenitor cell at one of several discrete stages of development B Cell or T Cell. Epidemiology. Most common childhood acute leukemia, ~80%

cormac
Download Presentation

Acute Lymphoblastic Leukemia

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Acute Lymphoblastic Leukemia Maggie Davis Hovda 5/26/2009

  2. Definition • Neoplastic disease which results from a mutation in a single lymphoid progenitor cell at one of several discrete stages of development • B Cell or T Cell

  3. Epidemiology • Most common childhood acute leukemia, ~80% • Incidence in adults ~20% • Bimodal distribution of occurrence: • Peak at age 2-5 • Second increased incidence after age 50

  4. Pathogenesis • Acquired Genetic Change in Chromosome • Change in number, ie ploidy • Change in structure • Translocations (most common) • Inversions • Deletions • Point mutations • Amplifications Changes in normal means of cell differentiation, proliferation, and survival

  5. 1 – Activation of a proto-oncogene OR creation of a fusion gene with oncogenic properties - Ph Chromosome t(9;22) 2 – Loss or inactivation of ≥ 1 tumor suppressor gene - p53 (p16 mutation) Mechanisms of Leukemia Induction

  6. Etiology • Unknown • ? Genetic Predisposition • Increased incidence amongst monozygotic and dizygotic twins • Down Syndrome • Disorder with chromosomal fragility: • Fanconi’s anemia • Bloom Syndrome • Ataxia-Telangiectasia • ? Infections • HTLV1 in T cell leukemia/lymphoma • EBV in mature B cell ALL • HIV in lymphoproliferative DO

  7. Presentation • Nonspecific Symptoms • Fatigue/decreased energy • Fever • Easy bruising • Bleeding • Dyspnea • Dizziness • Infection • Joint, extremity pains • CNS involvement

  8. Physical Exam Pallor Ecchymoses Petechiae LAD Hepatosplenomegaly Lab Abnormalities anemia wbc vary 0.1 (20-40%) - >100 k (10-16%) Platelets – usually ↓ ↑ LD, uric acid CXR: eval for thymic mass CSF to eval for involvement Clinical Presentation

  9. Diagnosis • Morphologic • French American British Classification • L1: small uniform blasts (pediatric ALL) • L2: larger, more variable sized blasts (adult ALL) • L3: uniform cells with basophilic and sometimes vacuolated cytoplasm (mature B cell ALL)

  10. Immunophenotyping From: Jabbour, E. et al. Adult Acute Lymphoblastic Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527

  11. Cytogenetic Abnormalities From: Jabbour, E. et al. Adult Acute Lymphoblastic Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527

  12. Classification of ALL From: Harrison’s Principles of Internal Medicine, 16th ed. 2005. Chapter 97, Malignancies of lymphoid cells.

  13. Differential Diagnosis • ITP • Aplastic Anemia • Infectious mononucleosis • Rheumatoid Arthritis • Rheumatic Fever • Collagen Vascular Disease

  14. Treatment • 1 – Remission Induction • 2 – Intensification (Consolidation) Therapy • 3 – Maintenance Therapy • 4 – CNS Prophylaxis • 5 – Allogeneic Stem Cell Transplant

  15. Treatment • Remission Induction • Goals: restore normal hematopoiesis, induce a complete remission rapidly in order to prevent resistance to drugs • Standard induction regimen • 4 or 5 drugs: vincristine, prednisone, anthracycline, L-asparaginase, +/- cyclophosphamide • Intensification • High doses of multiple agents not used during induction or re-administration of the induction regimen

  16. Treatment • Maintenance Therapy • Daily po 6MP, weekly MTX, monthly pulses of vincristine and prednisone for 2-3 yrs • CNS Prophylaxis • Given during induction and intensification • Intrathecal: MTX, Cytarabine, corticosteroids • Systemic: high dose mtx, cytarabine, L-asparaginase • +/- Cranial Irradiation

  17. Treatment • Stem Cell Transplant • Done during first CR • Indications: • Ph Chromosome • t(4;11) mutation • Poor initial response to induction therapy • Other • Adolescents benefit significantly from pediatric ALL regimens vs. adult regimens

  18. Relapse & Prognosis • Relapse • Most occur during treatment or within the first 2 years • Bone Marrow is the most common site • Poor prognostic factors in patients previously treated: • Relapse on therapy • Short initial remission after intense therapy • T-cell immunophenotype • Ph Chromosome • Circulating blasts • High leukocyte count at relapse

  19. Prognosis • Overall better in children than in adults • In adults, worse outcomes with: • Increasing age, >60 • Increased wbc count at presentation

  20. Sources • Jabbour, E. et al. Adult Acute Lymphoblastic Leukemia. Mayo Clinic Proc. 2005;80(11):1517-1527 • Xavier, T. Chemotherapy of acute leukemia in adults. Expert Opin. Pharmacother. (2009) 10(2):221-237 • Williams Hematology, 6th ed. 2001. Chapter 97, Acute Lymphoblastic Leukemia. • Harrison’s Principles of Internal Medicine, 16th ed. 2005. Chapter 97, Malignancies of lymphoid cells.

More Related