Disorders of White Blood Cells and Lymphoid Tissues

White Blood Cells
Granulocytes (i.e., neutrophils, eosinophils, and basophils)
Monocyte and macrophage lineage
Both are derived from the myeloid stem cell in the bone marrow and circulate in the blood
Lymphocytes
T lymphocytes (T cells) and B lymphocytes (B cells) originate in the bone marrow and migrate between the blood and the lymph
Hematopoiesis
White blood cells are formed partially in the bone marrow and partially in the lymph system
They are formed from hematopoietic stem cells that differentiate into committed progenitor cells
These in turn develop into the myelocytic and lymphocytic lineages needed to form white blood cells
Growth and Reproduction of White Blood Cells
The growth and reproduction of different stem cells is controlled by multiple hematopoietic growth factors or inducers
The life span of WBCs is relatively short; constant renewal is necessary to maintain normal blood levels
Conditions that decrease availability of stem cells or hematopoietic growth factors produce a decrease in WBCs
Components of the Lymphatic System
Lymphatic vessels
Lymph nodes
Spleen
Thymus

Function of the Lymphatic System
Drain lymph fluid from specific areas of the body
Filter particular matter such as bacteria and cancer cells
Causes of Neutropenia
Accelerated removal
Drug-induced granulocytopenia
Periodic or cyclic neutropenia
Neoplasms involving bone marrow
Idiopathic neutropenia occurring in the absence of other disease or provoking influence
Felty’s Syndrome
Signs and Symptoms of Neutropenia
Initially, those of bacterial or fungal infections
Malaise
Chills
Fever
Extreme weakness and fatigue
Reduced white blood cell count
Infectious Mononucleosis
Definition
Self-limited lymphoproliferative disorder
Causes and Characteristics
Caused by the B-lymphocytotropic EBV, a member of the Herpes Virus family; transmitted in saliva
Characterized by fever, generalized lymphadenopathy, sore throat, and the appearance in the blood of atypical lymphocytes and several antibodies
Highest incidence in adolescents and young adults
Treatment is symptomatic and supportive
Neoplastic Disorder of Hematopoietic and Lymphoid Origin
Represent the most important of the white cell disorders
Include somewhat overlapping categories
Lymphomas (Hodgkin’s disease and non-Hodgkin’s lymphoma)
The leukemias
The plasma cell dyscrasias (multiple myeloma)
Clinical Features of Neoplasms
Largely determined by:
Their site of origin
The progenitor cell from which they originated
The molecular events involved in their transformation into a malignant neoplasm

Symptoms of Hodgkin’s Disease
Stage A
Lack constitutional symptoms
Stage B (40% of persons with Hodgkin’s disease)
Significant weight loss, fevers, pruritus or night sweats
Advanced Stages
Fatigue and anemia
Liver, lungs, digestive tract, and CNS may be involved
Diagnosis of Hodgkin’s Disease
Reed-Sternberg cell present in a biopsy specimen of lymph node tissue
Computed tomography (CT) scans of the chest and abdomen to assess for involvement of mediastinal, abdominal and pelvic lymph nodes
A bipedal lymphangiogram to detect structural changes in the lymph nodes too small to visualize on CT scan.
A positron emission tomography (PET) imaging
A bilateral bone marrow biopsy may be performed if disease is disseminated
Categories of Non-Hodgkin’s Lymphomas
Low-grade lymphomas
Predominantly B-cell tumors
Intermediate-grade lymphomas
Include B-cell and some T-cell lymphomas
High-grade lymphomas
Largely immunoblastic (B-cell), lymphoblastic (T-cell), Burkitt’s, and non-Burkitt’s lymphomas

Staging of the NHL Disease
Bone marrow biopsy
Blood studies
Chest and abdominal CT scans
Nuclear medicine studies
Cytologic examination of the cerebrospinal fluid

Leukemias
Definition
Malignant neoplasms arising from the transformation of a single blood cell line derived from hematopoietic stem cells
Classification according to cell lineage
Lymphocytic (lymphocytes)
Myelocytic (granulocytes, monocytes)

Leukemic Cells
Are immature and poorly differentiated
Proliferate rapidly and have a long life span
Do not function normally
Interfere with the maturation of normal blood cells
Circulate in the blood stem
Cross the blood—brain barrier
Infiltrate many body organs
Classification of Leukemia Types
Acute lymphocytic (lymphoblastic) leukemia (ALL)
Chronic lymphocytic leukemia (CLL)
Both involve immature lymphocytes and their progenitors in the bone marrow, the spleen, lymph nodes, CNS, and other tissue
Acute myelogenous (myeloblastic) leukemia (AML)
Chronic myelogenous leukemia (CML)
Both involve the pluri-potent myeloid stem cells in bone marrow and interfere with the maturation of all blood cells

Warning Signs and Symptoms of Acute Leukemia
Fatigue
Pallor
Weight loss
Repeated infections
Easy bruising
Nosebleeds
Other types of hemorrhage
Criteria for Remission of ALL and AML
Less than 5% blasts in the bone marrow
Normal peripheral blood counts
Absence of cytogenetic abnormalities
Return to pre-illness performance status
Factors Affecting the Likelihood of Achieving Remission
Age (most significant prognostic variable)
Type of leukemia
Stage of the disease at time of presentation
Chronic Leukemias
Definition
Malignancies involving the proliferation of well-differentiated myeloid and lymphoid cells
Types of chronic leukemia
Chronic lymphocytic leukemia (CLL)
Chronic myelogenous leukemia (CML)
Goals of Treatment for CML
A hematological response characterized by normalized blood counts
A cytogenetic response demonstrated by the reduction or elimination of the Ph chromosome from the bone marrow
A molecular response confirmed by the elimination of the BCR-ABL fusion protein
Multiple Myeloma
Definition
A plasma cell dyscrasia characterized by expansion of a single clone of immunoglobulin-producing plasma cells and a resultant increase in serum levels of a single monoclonal immunoglobulin or its fragments
Main sites involved:
The bones and bone marrow