1st Lecture in Hematology PDF

Senior Specialist in Internal Medicine Assistant Professor , Internal Medicine Department , College of Medicine, UST 1 Dr.Ameen Dabwan Anemia Definition: According to the World Health Organiza...

Senior Specialist in Internal Medicine Assistant Professor , Internal Medicine Department , College of Medicine, UST 1 Dr.Ameen Dabwan Anemia Definition: According to the World Health Organization (WHO), anemia is defined as a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal. Specifically, it is characterized by: Hemoglobin levels less than 13 grams per deciliter (g/dL) in men Hemoglobin levels less than 12 g/dL in women Hemoglobin levels less than 11 g/dL in pregnant women 2 Dr.Ameen Dabwan Page 1 of 14  Clinical Features History Symptoms of anemia include fatigue, headache, light-headedness, malaise, weakness, decreased exercise tolerance, dyspnea, palpitations, dizziness, tinnitus, and syncope. Consider acute vs. chronic causes, bleeding, systemic illness, diet (iron, B12 sources), alcohol use, and family history. Menstrual history: menorrhagia, menometrorrhagia Rule out pancytopenia: recurrent infections, mucosal bleeding, easy bruising. Physical Signs HEENT: Pallor in mucous membranes and conjunctiva at Hb 50 × 10⁹/L) not caused by malignant transformation of a hematopoietic stem cell. It can result from a variety of causes, particularly other cancers or systemic infection. Usually, the cause is apparent, but apparent benign neutrophilia can be mimicked by chronic neutrophilic leukemia or chronic myeloid leukemia. Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial 14 and lymphaticDr.Ameen systems. Dabwan Page 7 of 14  3 15 Dr.Ameen Dabwan Classification of Hematological Malignancies Hematological malignancies are primarily classified into three major categories: A. Leukemias 1. Acute Lymphoblastic Leukemia (ALL) Rapidly proliferating cancer primarily affecting lymphoblasts. Most common in children but can occur in adults. Subtypes: B-cell ALL (most common), T-cell ALL. Clinical Features: Fatigue, fever, bleeding (petechiae, purpura), and lymphadenopathy. 2. Acute Myeloid Leukemia (AML) Affects myeloid cells; characterized by the presence of immature myeloid cells. More common in adults, with several subtypes based on cell lineage. Subtypes: M0 through M7, including acute promyelocytic leukemia (APL, M3). Clinical Features: Fatigue, anemia, frequent infections, easy bruising, and bleeding. 16 Dr.Ameen Dabwan Page 8 of 14  Classification of Hematological Malignancies cont. 3) Chronic Lymphocytic Leukemia (CLL) Slow-growing cancer characterized by the accumulation of mature lymphocytes. Primarily affects older adults. Subtypes: Unmutated and mutated CLL. Clinical Features: Often asymptomatic initially; may present with lymphadenopathy, splenomegaly, and recurrent infections. 4) Chronic Myeloid Leukemia (CML) Involves the proliferation of myeloid cells and is often associated with the Philadelphia chromosome (BCR-ABL fusion). Typically occurs in middle-aged adults. Subtypes: Chronic phase, accelerated phase, and blast crisis. Clinical Features: Fatigue, splenomegaly, weight loss, night sweats, and a high white blood cell count. The disease can progress from a chronic phase to an accelerated phase and ultimately to blast crisis. 17 Dr.Ameen Dabwan Classification of Hematological Malignancies cont. B. Lymphomas: Cancers of the lymphatic system. B. Hodgkin Lymphoma (HL) Characterized by the presence of Reed-Sternberg cells; more common in young adults and adolescents. Subtypes: Classical HL (with variants like mixed cellularity, nodular sclerosis, lymphocyte-rich, and lymphocyte-depleted) and Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL). Clinical Features: Painless lymphadenopathy, B symptoms (fever, night sweats, weight loss), pruritus, and mediastinal mass symptoms. C. Non-Hodgkin Lymphoma (NHL) A heterogeneous group of lymphoid malignancies; includes B-cell and T-cell lymphomas. Subtypes: Includes B-cell lymphomas [Diffuse Large B-cell Lymphoma (DLBCL), follicular lymphoma, Burkitt Lymphoma] and T-cell lymphomas [Peripheral T-cell Lymphoma (PTCL), Anaplastic Large Cell Lymphoma (ALCL)]. Clinical Features: Symptoms vary based on subtype; common features include lymphadenopathy, splenomegaly, fever, and night sweats. DLBCL often presents with rapidly enlarging lymph nodes, while follicular lymphoma may be more indolent. 18 Dr.Ameen Dabwan Page 9 of 14 Classification of Hematological Malignancies cont. C. Myelomas 1. Multiple Myeloma Cancer of plasma cells; characterized by excessive production of monoclonal immunoglobulins. Clinical Features: Bone pain (especially in the back), anemia, renal insufficiency, hypercalcemia, and recurrent infections. 2. Monoclonal Gammopathy of Undetermined Significance (MGUS) A precursor condition that can progress to multiple myeloma; typically asymptomatic. Clinical Features: No specific symptoms, but regular monitoring for progression to multiple myeloma or other related disorders is needed. 19 Dr.Ameen Dabwan Investigations of Hematological Malignancies 1) Blood Tests: a. Complete Blood Count (CBC): Identifies abnormalities in red and white blood cell counts and platelets. b. Peripheral Blood Smear: Assesses morphology of blood cells to detect leukemic cells or abnormal lymphocytes. c. Additional Tests in Multiple Myeloma:  Serum Protein Electrophoresis (SPEP): Detects monoclonal protein (M-protein) in the blood.  Urine Protein Electrophoresis (UPEP): Identifies light chains in urine, especially in light chain myeloma. 2) Bone Marrow Biopsy: Essential for diagnosing leukemias and myelomas; assesses cellularity, presence of malignant cells, and any chromosomal abnormalities. 3) Imaging Studies: a. X-rays: Identify lytic bone lesions. b. CT Scans: Evaluate lymphadenopathy, organ involvement, and splenic size. c. MRI or CT Scans: Evaluate bone marrow infiltration and detect lesions not visible on X-rays in multiple myeloma. d. PET Scans: Assess metabolic activity of lesions and help in staging lymphomas. 20 Dr.Ameen Dabwan Page 10 of 14 Investigations of Hematological Malignancies cont. 4) Cytogenetic and Molecular Studies: a. FISH (Fluorescence In Situ Hybridization): Purpose: FISH is used to detect specific chromosomal abnormalities in cells. It's particularly useful in identifying genetic changes associated with certain cancers (e.g., BCR-ABL in CML). b. Next-Generation Sequencing: Purpose: NGS allows for comprehensive genetic profiling by sequencing large amounts of DNA quickly and accurately. It can identify mutations across multiple genes simultaneously and provides detailed genetic profiling for targeted therapy options. 21 Dr.Ameen Dabwan Treatment Approaches Hematological Malignancies 1) Chemotherapy: Standard first-line treatment for acute leukemias and aggressive lymphomas, often involving multi-drug regimens tailored to the specific type. 2) Targeted Therapy: a. Tyrosine Kinase Inhibitors (TKIs): e.g., Imatinib for CML; these target specific mutations or pathways involved in the malignancy. b. Monoclonal Antibodies: e.g., Rituximab for CD20-positive B-cell lymphomas; these enhance immune response against cancer cells. 3) Immunotherapy: a. CAR T-Cell Therapy (Chimeric Antigen Receptor T-cell therapy): A promising treatment for certain aggressive leukemias and lymphomas, involving re- engineering the patient’s T cells to target cancer cells. b. Immune Checkpoint Inhibitors: These enhance the body’s immune response against tumors by blocking proteins that normally inhibit immune responses, allowing T cells to attack cancer cells more effectively. Used in some lymphomas and multiple myeloma. 22 Dr.Ameen Dabwan Page 11 of 14 Treatment Approaches Hematological Malignancies 4) Stem Cell Transplant: Considered for high-risk patients or those who relapse; can be autologous (using the patient's own cells) or allogeneic (from a donor). 5) Supportive Care: Management of symptoms and complications, including antibiotics for infections, blood transfusions for anemia, and medications for pain management. Prognosis Survival Rates: ALL: 5-year survival ~90% in children; lower in adults. AML: 5-year survival ~27%, with variations based on age and cytogenetics. NHL: 5-year survival ~72% overall; highly variable based on subtype. Multiple Myeloma: 5-year survival ~54%, improving with new therapies. 23 Dr.Ameen Dabwan Bone Marrow Transplantation Definition Bone marrow transplantation (BMT) is a medical procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Types of Bone Marrow Transplants 1) Autologous Transplant Patient’s own stem cells are collected and reinfused after high-dose chemotherapy/radiation. 2) Allogeneic Transplant Stem cells are sourced from a compatible donor (related or unrelated). 3) Syngeneic Transplant Stem cells are obtained from an identical twin. 24 Dr.Ameen Dabwan Page 12 of 14  Bone Marrow Transplantation Indications for BMT: 1) Hematologic Malignancies a. Leukemia: Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). b. Lymphoma: Hodgkin and non-Hodgkin lymphoma. c. Multiple Myeloma: Plasma cell disorders requiring high-dose therapy. 2) Non-Malignant Conditions a. Aplastic Anemia: Severe bone marrow failure resulting in reduced blood cell production. b. Inherited Blood Disorders: Sickle cell disease and thalassemia, which require gene therapy. c. Myelodysplastic Syndromes: Disorders caused by poorly formed or dysfunctional blood cells. 3) Genetic Disorders Immunodeficiencies: Congenital immune disorders where the body cannot fight infections effectively. 25 Dr.Ameen Dabwan Bone Marrow Transplantation The Transplant Process: 1) Pre-Transplant Evaluation: Comprehensive assessment including blood tests, imaging, and psychosocial evaluation. Donor matching through HLA typing. 2) Conditioning Regimen: High-dose chemotherapy or radiation therapy to eliminate diseased bone marrow and suppress the immune system. 3) Stem Cell Infusion: Healthy stem cells are infused into the patient's bloodstream, akin to a blood transfusion. 4) Post-Transplant Care: Close monitoring for complications, including infections and organ function, and support for recovery. 26 Dr.Ameen Dabwan Page 13 of 14  Bone Marrow Transplantation Complications: 1) Immediate Complications a. Graft-versus-Host Disease (GVHD): Occurs in allogeneic transplants where donor immune cells attack recipient tissues. Can be acute or chronic. b. Infection: Patients are at high risk due to immunosuppression, necessitating prophylactic antibiotics and vigilant monitoring. c. Organ Toxicity: Potential damage to organs (liver, lungs, kidneys) from chemotherapy or radiation therapy. 2) Long-term Complications a. Relapse: Risk of the original disease returning, particularly in malignancies. b. Secondary Malignancies: Increased risk of developing new cancers due to previous treatment regimens. c. Endocrine and Cardiovascular Issues: Possible hormonal imbalances, cardiac issues, and metabolic syndrome. d. Psychosocial Effects: Anxiety, depression, and adjustment challenges post- transplant. 27 Dr.Ameen Dabwan 28 Dr.Ameen Dabwan Page 14 of 14