Complete Leukemias in 1 Shot | Hematology | A Comprehensive Guide by Dr. Priyanka Sachdev

TLDR;

This video provides a comprehensive overview of leukemias, focusing on the comparison of four main types: Chronic Myeloid Leukemia (CML), Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Chronic Lymphocytic Leukemia (CLL). It explains the basics of WBC formation, the pathogenesis of each leukemia, their clinical features, lab diagnosis, treatment options, and prognostic factors.

• Understanding WBC formation is crucial for understanding leukemias.
• Leukemia involves the arrival of immature blood cell forms in the blood due to mutations.
• Each type of leukemia has distinct characteristics, including age group, mutations, and clinical presentations.

Introduction [0:01]

Dr. Priyanka introduces the session's goal: to simplify the understanding of four types of leukemia (CML, AML, ALL, and CLL). The session aims to benefit students in pathology, medicine, and those preparing for competitive exams by making leukemia a more approachable topic.

WBC Formation Basics [1:48]

Leukemia is defined as a blood cancer involving white blood cells (WBCs). There are five types of WBCs: neutrophils, eosinophils, basophils (granulocytes), lymphocytes, and monocytes (agranulocytes). All blood cells, including WBCs, are formed in the bone marrow from hematopoietic stem cells, which differentiate into myeloid and lymphoid progenitor cells. Myeloid progenitors produce red blood cells (RBCs), platelets, neutrophils, eosinophils, basophils, and monocytes, while lymphoid progenitors produce lymphocytes.

Precursors of Neutrophils and Lymphocytes [9:16]

Neutrophils develop from myoblasts through several intermediate stages: promyelocytes, myelocytes, metamyelocytes, and band forms. Lymphocytes develop from lymphoblasts via prolymphocytes. Understanding these precursors is essential for understanding leukemia.

Leukemia Explained [13:31]

In healthy individuals, immature blood cells (blasts) are confined to the bone marrow, with only mature cells circulating in the blood. Leukemia is characterized by the presence of immature forms, especially blasts, in the blood. This occurs due to mutations causing uncontrolled mitosis in blast cells, which then spill into the bloodstream. In some leukemias, these cells infiltrate organs, leading to lymphomas.

Classification of Leukemia [19:54]

Leukemias are classified based on the type of blast cell involved (lymphoid or myeloid) and whether the condition is acute or chronic. Acute leukemias are characterized by a high percentage of blast cells in the bone marrow (over 20% according to WHO criteria, or over 30% according to FAB criteria). Myeloid leukemias involve myeloid blasts, while lymphoid leukemias involve lymphoid blasts.

Morphology of Myeloblasts and Lymphoblasts [25:12]

Myeloblasts are larger with a moderate amount of cytoplasm and may contain Auer rods, while lymphoblasts are smaller with scanty cytoplasm and lack Auer rods.

Comparative Study of Four Leukemias [26:25]

The session will now compare CML, AML, ALL, and CLL based on definition, age group, pathogenesis, mutation, classification, clinical features, lab diagnosis, treatment, and prognostic factors.

Chronic Myeloid Leukemia (CML): Definition and Pathogenesis [28:39]

CML is characterized by high WBC count with immature cells, high basophil count, enlarged spleen (splenomegaly), and the presence of the Philadelphia chromosome. It typically occurs in middle-aged or older adults (after 50 years). The pathogenesis involves a translocation between chromosomes 9 and 22, resulting in the BCR-ABL fusion gene, which produces abnormal tyrosine kinase, leading to uncontrolled mitosis in myeloid precursor cells.

CML: Genetic Details and Treatment [32:19]

In CML, a portion of chromosome 9 containing the ABL gene translocates to chromosome 22, where it fuses with the BCR gene, forming the Philadelphia chromosome. This fusion gene leads to the production of abnormal tyrosine kinase, causing uncontrolled mitosis. Treatment involves targeted therapy with imatinib, an oral medication that inhibits abnormal tyrosine kinase, promoting apoptosis of cells with the fusion gene.

CML: Clinical Features and Lab Diagnosis [46:03]

Clinical features of CML include anemia, bleeding disorders, and increased susceptibility to infections due to bone marrow failure. Lab diagnosis involves blood tests, bone marrow studies, genetic analysis, and special stains. Blood tests show decreased hemoglobin and platelet counts, but a high WBC count with immature forms. A peripheral blood smear shows a "garden party" appearance with various cell types. Genetic testing confirms the 9;22 translocation. Cytochemistry reveals a reduced neutrophil alkaline phosphatase (NAP) score.

CML: Differential Diagnosis and Treatment [52:14]

The main differential diagnosis for CML is leukemoid reaction, which is an excessive increase in WBC count due to infection or other causes. Leukemoid reactions can be differentiated from CML by a lower WBC count (usually not exceeding 100,000), a predominance of mature neutrophils, a normal or increased NAP score, and the absence of the Philadelphia chromosome. Treatment for CML primarily involves imatinib, with symptomatic treatment for anemia and thrombocytopenia.

CML: Phases and Prognostic Factors [44:30]

CML has three phases: chronic, accelerated, and blast, determined by the percentage of myeloblasts. Prognostic factors are assessed using the Sokal and ELTS scores.

Acute Myeloid Leukemia (AML): Pathogenesis and Classification [1:07:48]

AML typically occurs between 15 and 40 years of age. Unlike CML, in AML, the mutation occurs only in myeloblasts, which then proliferate uncontrollably and spill into the blood. Common mutations include 15;17 translocation, 8;21 translocation, and inversion 16. AML is classified according to the French-American-British (FAB) classification into eight subtypes (M0-M7), each with distinct characteristics.

AML: FAB Classification Details [1:10:11]

The FAB classification includes: M0 (minimally differentiated), M1 (without maturation), M2 (with maturation), M3 (promyelocytic), M4 (myelomonocytic), M5 (monocytic), M6 (erythroleukemia), and M7 (megakaryoblastic). M3 is associated with disseminated intravascular coagulation (DIC). M2 often shows 8;21 translocation and chloromas. M7 is the least common and has the worst prognosis, often seen in Down syndrome.

AML: Clinical Features and Organ Infiltration [1:13:04]

Clinical features of AML include anemia, bleeding disorders, and increased susceptibility to infections. A key difference from CML is organ infiltration, where myeloblasts infiltrate organs like bone, lymph nodes, spleen, liver, and gums. Gum hypertrophy is common in M4 and M5, while chloromas (orbital infiltration) are seen in M2.

AML: Lab Diagnosis [1:15:53]

Lab diagnosis of AML involves blood tests, bone marrow examination, cytogenetics, and cytochemistry. Blood tests show decreased hemoglobin and platelet counts, with a high WBC count consisting predominantly of myeloblasts. Bone marrow is hypercellular with more than 20% blasts. Cytogenetic analysis reveals specific translocations depending on the subtype. Cytochemistry uses special stains to differentiate AML from ALL.

AML: Cytochemistry and Treatment [1:21:59]

Key cytochemical stains for AML include myeloperoxidase (MPO), Sudan black, and nonspecific esterase (NSE), which are typically positive. Periodic acid-Schiff (PAS) and acid phosphatase are negative. Treatment for AML involves bone marrow transplant or chemotherapy with cytarabine, anthracycline, and thioguanine. M3 is treated with retinoic acid due to the risk of DIC.

AML: Prognostic Factors [1:25:47]

Good prognostic factors include age less than 40, M2, M3, or M4 subtypes, blasts with Auer rods, and specific cytogenetic abnormalities like 15;17 translocation, 8;21 translocation, and inversion 16. Poor prognostic factors include extremes of age, M0, M6, or M7 subtypes, complex karyotypes, and certain chromosomal deletions.

Acute Lymphoblastic Leukemia (ALL): Pathogenesis and Classification [1:33:21]

ALL primarily affects children and involves the mutation of lymphoblasts, which then proliferate uncontrollably. ALL is classified into pre-B cell and pre-T cell types. Mutations include hyperploidy, hypoploidy, 9;22 translocation, and NOTCH1 mutations. ALL is further classified into L1, L2, and L3 subtypes based on FAB criteria.

ALL: Clinical Features and Lab Diagnosis [1:38:04]

Clinical features of ALL include anemia, bleeding disorders, and increased susceptibility to infections. Organ infiltration can occur, affecting bones, lymph nodes, spleen, liver, mediastinal lymph nodes, meninges, and testes. Lab diagnosis involves blood tests, bone marrow examination, cytogenetics, and cytochemistry. Blood tests show decreased hemoglobin and platelet counts, with a high WBC count consisting predominantly of lymphoblasts.

ALL: Cytochemistry and Treatment [1:43:04]

Cytochemistry is crucial for differentiating ALL from AML. Lymphoblasts are PAS and acid phosphatase positive, while MPO, Sudan black, and NSE are negative. Treatment for ALL involves bone marrow transplant or chemotherapy with vincristine, prednisone, daunorubicin, and L-asparaginase.

ALL: Prognostic Factors [1:45:06]

Good prognostic factors include age between 2 and 10 years, female gender, WBC count less than 50,000, and hyperploidy. Poor prognostic factors include extremes of age, male gender, CNS involvement, and hypoploidy.

Chronic Lymphocytic Leukemia (CLL): Definition and Pathogenesis [1:49:00]

CLL primarily affects older adults (over 60 years) and involves the proliferation of mature lymphocytes. Unlike other leukemias, CLL does not involve blasts in the blood. Instead, mutated mature lymphocytes accumulate. Common mutations include deletions of 11q, 13q, and 17p, and trisomy 12.

CLL: Clinical Features and Lab Diagnosis [1:52:00]

Clinical features of CLL include anemia, bleeding disorders, and increased susceptibility to infections. Lymphadenopathy, hepatomegaly, and splenomegaly can also be present. Lab diagnosis involves blood tests, immunophenotyping, and lymph node biopsy. Blood tests show decreased hemoglobin and platelet counts, with a high WBC count consisting predominantly of mature lymphocytes. A characteristic finding is smudge cells, which are ruptured lymphocytes seen on peripheral blood smears.

CLL: Immunophenotyping and Treatment [1:57:27]

Immunophenotyping shows that the lymphocytes express B-cell markers like CD19, CD20, surface IgM, and IgD, along with CD23 and CD5. Lymph node biopsy reveals pseudo follicles. Unfortunately, there is no curative treatment for CLL. Management focuses on palliative and symptomatic care.

CLL: Prognostic Factors [1:58:17]

Poor prognostic factors include 11q deletion, 17p deletion, trisomy 12, absence of somatic hypermutation, and presence of NOTCH1 mutation.

Comparative Analysis of All Four Leukemias [1:59:54]

The session concludes with a comparative analysis of CML, AML, ALL, and CLL, summarizing key differences in age group, pathogenesis, mutations, clinical features, lab diagnosis, treatment, and prognostic factors. The video emphasizes the importance of understanding these differences for accurate diagnosis and management of leukemia.