Acute Leukemias Slides PDF

Leukemias and overview of management Dr Lawrence Ng Consultant Department of Haematology Singapore General Hospital Scope • Basic anatomy • Diagnosis • Leukemias: - Acute myeloid leukemia - Acute lymphoblastic leukemia - Chronic myeloid leukemia - Chronic lymphocytic leukemia • Stem cell transplan...

Leukemias and overview of management Dr Lawrence Ng Consultant Department of Haematology Singapore General Hospital Scope • Basic anatomy • Diagnosis • Leukemias: - Acute myeloid leukemia - Acute lymphoblastic leukemia - Chronic myeloid leukemia - Chronic lymphocytic leukemia • Stem cell transplantation Basic anatomy Diagnosis Acute Myeloid Leukemia (AML) • Heterogenous clonal stem cell malignancy in which immature hematopoietic cells proliferate and accumulate in bone marrow, peripheral blood and other tissues. • results in inhibition of normal hematopoiesis, characterized by neutropenia, anaemia or thrombocytopenia • 90% of all acute leukemias in adults. • Annual incidence ~3.5 per 100,000 in US • Overall survival in adults remain poor. Acute myeloid leukemia • FAB subtype: M0 - M7 • WHO 2016 classification • Most have no apparent cause • Most common risk factor is previous exposure to radiation or chemotherapy. • Environmental risk factors: benzene and ionizing radiation. • Inherited bone marrow failure (Fanconi Anaemia etc) • Genetic disorders: Down syndrome • MDS/MPD Acute myeloid leukemia Flow cytometry analysis Acute myeloid leukemia Acute Myeloid Leukemia European Leukemia Network 2022 Indications for allogeneic HCT: Acute myeloid leukemia AML (treatment) • Most important prognostic indicators: age, cytogenetics, molecular genetics. • Treatment: - Chemotherapy: -> Idarubicin/Daunorubicin + cytarabine 3+7 regimen -> Consolidation with HIDAC - Allogeneic stem cell transplantation for intermediate and poor risk disease. - Targeted therapy – FLT3 inhibitor, CD33 inhibitor (Gemtuzumab Ozogimicin) - Supportive care AML in patients less than 60 years of age. Jacob M. Rowe, and Martin S. Tallman Blood 2010;116:3147-3156 ©2010 by American Society of Hematology AML: survival from relapse by age. Jacob M. Rowe, and Martin S. Tallman Blood 2010;116:3147-3156 ©2010 by American Society of Hematology HSCT in Acute Myeloid Leukemia (AML) 16 Acute myeloid leukemia Complications Acute promyelocytic Leukemia • Unique subtype • Leukemia cells have a balanced reciprocal translocation between chromosomes 15 and 17. • Exquisitely sensitive to ATRA, anthracyclines and arsenic trioxide. • Cure rates high • May be complicated by life threatening coagulopathy Acute Lymphoblastic Leukemia • Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. • Arise from a lymphoid progenitor cell that has sustained multiple genetic damage. • 20% of adult acute leukemias. • As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated. Acute lymphoblastic leukemia • Precursor lymphoid neoplasm -> B lymphoblastic leukemia/lymphoma -> T lymphoblastic leukemia/lymphoma ALL (treatment) • Multiagent chemotherapy - induction - consolidation-intensification - Maintenance • Cure rates of adult remain inferior compared to children • AlloSCT improve survival in subset of patients. Indications for allogeneic HCT: Acute lymphoblastic leukemia HSCT in Acute Lymphoblastic Leukemia (ALL) Prognostic factor Indication for allo-HSCT if Age >40 years High WBC count at diagnosis >30 × 10^9/L in BCP-ALL >100 × 10^9/L in T-ALL Poor-risk cytogenetics Ph chromosome t(4;11)(q21;q23) t(8;14)(q24.1;q32) Complex karyotype Low hypodiploidy/near triploidy ALL subtypes with poor prognosis Early T-cell precursor ALL (Ph-like ALL) (limited data, pending trials) High risk genetics IKZF1 deletion in B precursor ALL (NOTCH1/FBXW7; N/K-RAS; PTEN genetics in T-ALL (Trinquand et al. 2013)) (limited data, pending trials) Failure to attain CR Within 4 weeks of therapy Minimal residual disease >1 × 10−4 after two courses of therapy Reappearance of MRD marker (no MRD marker at initial diagnosis) Ph +ve ALL Outcome of patients with acute lymphoblastic leukemia (ALL) by genetic risk group. Anthony V. Moorman Haematologica 2016;101:407-416 ©2016 by Ferrata Storti Foundation Chronic myeloid leukemia • Chronic myelogenous leukemia is a pluripotent hematopoietic stem cell neoplasm characterized by the BCR-ABL1 fusion gene, derived from balanced translocation between the long arms of chromosomes 9 and 22. • 15-20% of leukemia cases in adults. • Slight male predominance. Chronic myeloid leukemia Chronic lymphocytic leukemia • Incidence increases with age • Median age 70 years old • Presents with lymphocytosis • Presents with symptoms referable to lymphadenopathy, splenomegaly, or anaemia, fatigue, recurrent infection • B symptoms in a minority • A diagnosis can be established from the peripheral blood. Bone marrow biopsy is not required for diagnosis. Diagnosis (flow cytometry) The End • Questions? Stem cell transplantation Types of Hematopoietic cell transplants Thank you