1 / 33

Adult acute lymphocytic leukemia

Adult acute lymphocytic leukemia. Jaya V.Juturi MD 5/5/2004. JM. 35 year old Hispanic male patient 2 week history of generalized malaise and pallor One week history of easy bruisability No relevant medical or surgical history No high risk behavior, non-smoker, has 8 siblings. JM.

pdrayton
Download Presentation

Adult acute lymphocytic 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. Adult acute lymphocytic leukemia Jaya V.Juturi MD 5/5/2004

  2. JM • 35 year old Hispanic male patient • 2 week history of generalized malaise and pallor • One week history of easy bruisability • No relevant medical or surgical history • No high risk behavior, non-smoker, has 8 siblings .

  3. JM • No fevers, gum bleeding, chills, • Five pound weight loss over a week to 10 days • Ecchymoses and oral thrush • Otherwise exam normal, no lymphadenopathy, hepatosplenomegaly • WBC 6.1, Hgb 3.2, Plts 4000

  4. Acute Lymphocytic Leukemia • Incidence is about 3000-4000 cases a year • 2/3 of these occur in children • 80% of children are cured • 35-40% adults with ALL survive 2 years

  5. Acute Lymphocytic Leukemia • Only 30% adults cured • Biology of the disease appears to be different • Intensive chemotherapy and CNS prophylaxis contribute to most cures! • Accurate diagnosis is crucial and an experienced hematopathologist should always be involved

  6. Kaplan-Meier Analyses of Event-free Survival (Top Panel) and Overall Survival (Bottom Panel) in 2255 Children with ALL in 13 Consecutive Studies Conducted at St Pui, C.-H. et al. N Engl J Med 1998;339:605-615

  7. Morphology VS Immunophenotype • ALL can develop from any lymphoid cell blocked from maturation • Most sensitive B-cell marker is CD 19, CD 7 for T-cell lineage, CD-13 or CD 33 for myeloid cells • Cytoplasmic CD 79a for B-cells, CD3 for T-cells and myelo peroxidase fro myeloid cells • TdT elevated in most ALL • Accurate diagnosis in 99% cases with the above described methods

  8. Morphology VS Immunophenotype • Aberrant myeloid antigen expression can be seen in about a third of the adults with ALL • 20% AML cases may have an elevated TdT • ALL • B-cell lineage 80% • T-cell lineage 10-15% • FAB classification

  9. Cellular classification (FAB) • L-1 mature appearing lymphoblasts • L-2 pleomorphic lymphoblasts • L-3 is most B-cell ALL • 95% of all acute lymphocytic leukemias except B-cell type have and elevated TdT expression (terminal deoxynucleotidyl transferase expression)

  10. Transformation of Hematopoietic Cells in the Pathogenesis of ALL Pui, C.-H. et al. N Engl J Med 2004;350:1535-1548

  11. Risk assessment • Adults • Hyperleukocytosis at presentation • Adverse cytogenetic profile • CNS or Testicular involvement at presentation • Pre-T cell leukemia and resistance to chemotherapy • Delayed early response to chemotherapy

  12. Estimated Frequencies of Specific Genotypes among Children and Adults with ALL Pui, C.-H. et al. N Engl J Med 1998;339:605-615

  13. Kaplan-Meier Analysis of Event-free Survival According to the Subtype of Leukemia in 467 Children with ALL Who Were Enrolled in Three Consecutive Treatment Protocols at St Pui, C.-H. et al. N Engl J Med 2004;350:1535-1548

  14. Proposed Risk-Classification System for ALL According to Immunophenotype and Genotype, Age, Leukocyte Count, Early Response to Treatment, and Presence or Absence of Extramedullary Disease (in B-Cell-Precursor Disease) Pui, C.-H. et al. N Engl J Med 1998;339:605-615

  15. Supportive/clinical care • At least 50% patients with Acute lymphocytic leukemia present with fever. • Often secondary to cytokines TNF, IL-1 and IL-6 • But in about a third this fever is secondary to an infection • Monitor for hyperuricemia, hyperkalemia and hyperphosphatemia in all patients----Tumor lysis syndrome

  16. Supportive/clinical care • Intravenous hydration. • Allopurinol, cytoreduction • ?Leukapheresis, hyperviscosity • Psychosocial support • Indwelling catheters • Transfusion support

  17. Treatment • Well designed clinical trials and multi-drug regimens have contributed to the cure rate • Fractionated high dose cytoxan, high dose methotrexate and cytarabine form the core of most regimens given in an intense two to eight month fashion • Most regimens also routinely include dexamethasone, vincristine, as well as asparaginase in children and anthracycline in an adult

  18. Treatment • Induction of complete remission occurs in 97-99% of children and 75-80% of the adults • Cranial prophylaxis or treatment is a must for all patients • Most induction treatments are followed by maintainance therapy long term • The role of consolidation in adults is not clear

  19. Treatment • Granulocyte colony stimulating factors hasten neutropenic recovery and thereby reduce complications of chemotherapy • They do not appear to improve or affect response to chemotherapy • Maintainance often lasts 2-3 years • 6-mercaptopurine and methotrexate are the most commonly used drugs

  20. CNS prophylaxis • CNS can be a potential sanctuary for leukemic cells • Presymptomatic therapy directed towards the CNS usually with intrathecal chemotherapy and systemic chemotherapy… • CNS relapse less than 2% with such therapy • Role of cranial irradiation not clear anymore…risk of neurotoxicity and can occasionally cause brain tumors ? • Role in high risk patients…T-cell ALL or presentation with hyperleukocytosis

  21. Treatment Strategies Associated with Improved Outcomes in Clinical Studies of ALL Pui, C.-H. et al. N Engl J Med 1998;339:605-615

  22. Allogeneic stem cell transplant • Indicated for patients who do not have a response to initial induction treatment and for those who relapse and go into a second remission • Transplantation during the first remission remains controversial • MLL gene abnormalities and BCR-ABL translocations given their unfavorable prognosis are often treated with an allogeneic transplant • HLA matched sibling transplant is ideal, but for those who lack suitable family donors a matched unrelated transplant is reasonable • Umbilical cord blood transplants are feasible in children and may not require the same degree of histocompatibility

  23. JM • Treated with Hyper CVAD/MTX-Ara-c regimen and CNS prophylaxis • Residual leukemia at the end of the first two cycles… • Primary refractory disease is being allo-transplanted in the near future • 8 siblings being typed and HLA matching in process

  24. Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia …Journal of Clinical Oncology, Vol 18, Issue 3, 2000: 547 • 204 adult ALL patients • Median age 40 yrs • T-cell disease in 17%. • Leukocytosis in 26%, • Philadelphia chromosome–positive disease in 16% • A mediastinal mass in 7%.

  25. Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia …Journal of Clinical Oncology, Vol 18, Issue 3, 2000: 547 • Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. • Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP).

  26. Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia …Journal of Clinical Oncology, Vol 18, Issue 3, 2000: 547 • 91%achieved complete remission (CR) and 6% died during induction therapy. • Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. • The incidence of CNS relapse was low (4%).

  27. Survival based on Ph + status

More Related