Pediatric Hematology and Oncology Nursing Practice Review

Pediatric Cancer Epidemiology and Overview

• Leading Cause of Death: Cancer is the leading cause of death by disease in children in the United States.
• Statistics:     * Over $15,000$ cases are diagnosed in children and adolescents annually.     * Over $1700$ cancer-related deaths occur annually.
• Demographics: Childhood cancer affects all ethnic, gender, and socio-economic groups.
• Gender: Males are affected more than females.
• Survival: $85\%$ of children diagnosed with cancer today will survive more than $5$ years.
• Commonality: Leukemias are the most common childhood cancer (specifically Acute Lymphoblastic Leukemia, or ALL), followed by CNS tumors.
• Classification of Childhood Cancers:     * Hematologic Malignancies:         * Leukemia: Cancer of the blood.         * Lymphoma: Cancer of the immune system.     * Solid Tumors: Cancer involving bone, organs, and tissues.
• Cellular Behavior in Pediatric Cancer:     * Cells divide and grow rapidly with little or no control.     * Growth is rapid enough to destroy healthy cells and invade different body parts.
• Etiology:     * In most cases, the cause is unknown.     * It is not caused by actions or failures of the parents or child.     * Often related to periods of peak growth.     * Environmental Agents: May include electromagnetic fields, chemicals/pesticides, and viruses.

Genetic Mutations and Cellular Changes

• DNA Mutations: Result in clinical manifestations through specific cellular changes:     * Lack of Cell Differentiation: Cells remain immature (blasts) and fail to perform the work of normal cells.     * Loss of Contact Inhibition: Unlike normal cells that stop dividing when touching other cells, cancer cells continue to divide.     * Unregulated Growth: Cancer cells multiply out of control due to a lack of normal feedback mechanisms.     * Cellular Immortality: A failure of apoptosis (intrinsic suicide program).
• Genetic Predisposition and Syndromes:     * Down Syndrome (Trisomy 21): Carries a $10\%$ to $20\%$ risk for developing leukemia.     * Li-Fraumeni Syndrome: A rare hereditary condition increasing the risk for sarcomas, osteosarcomas, leukemias, and brain tumors. Associated with a loss of the $p53$ tumor suppressor gene.     * Neurofibromatosis 1 (NF1): Linked to various cancer developments.     * Retinoblastoma Gene (RB1): If the $RB1$ gene cannot make the functional protein, cells cannot regulate division. Associated with retinoblastoma, small-cell lung cancer, and osteosarcoma.
• Immunodeficiency Factors:     * Congenital or acquired (e.g., AIDS, organ transplant drugs, immunosuppression after HPCT) increase cancer risk.
• History of Cancer: Previous treatment increases the risk for a second malignancy.

Myelodysplastic Syndrome (MDS) and Hematopoietic Stem Cells

• Hematopoietic Stem Cells (HPSC): Give rise to lymphoid and myeloid cells.     * Myeloid Cells: Red blood cells, white blood cells, and platelets.
• MDS Definition: Occurs when blood-forming cells in the bone marrow become abnormal; often referred to as "pre-leukemia."
• Pathophysiology: Ineffective hematopoiesis with dysplasia starting in one cell line, progressing to pancytopenia and bone marrow failure.
• Triggering Agents: Common agents include alkylating agents like Cyclophosphamide (CPM) and Ifosfamide (IFOS); approximately $1/3$ of cases develop into AML.

Blood Cell Types and Function

• White Blood Cells (WBCs): Functional infection fighters.     * Granulocytes: Neutrophils, Basophils, and Eosinophils.     * Monocytes: Enter tissues to become macrophages, digesting germs and helping lymphocytes recognize pathogens.     * Lymphocytes: Main cells of the lymph tissue/immune system, comprising B cells (antibody production) and T cells (killing foreign agents).

Leukemia: General Concepts and Diagnosis

• Prevalence: Most common childhood cancer with a $90\%$ survival rate.
• Lineage Types:     * Acute Lymphoblastic Leukemia (ALL): $75-80\%$ of cases.     * Acute Myelogenous Leukemia (AML): $15-20\%$ of cases.     * Chronic Myeloid Leukemia (CML): $< 5\%$ of cases.
• Diagnostic Tools:     * Morphology: Microscopic description of cell appearance (cellularity, cell lines, blast percentage).     * Immunophenotyping: Identifies markers on blast cells to differentiate between ALL and AML.     * Cytogenetics: Chromosomal analysis (translocation, inversion, deletion, ploidy).     * Clinical Features: Presence of leukocytosis, pancytopenia, etc.
• Pathophysiology of Blasts: Immature blood cells grow uncontrollably and crowd out normal cells. Typically, $1 \text{ trillion}$ blast cells are present at diagnosis.

Acute Lymphocytic Leukemia (ALL)

• Definition: Originates from early lymphocytes.
• Presentation and Assessment:     * Fever and abnormal CBC.     * Neutropenia: Increased risk of infection; necessitates monitoring Absolute Neutrophil Count (ANC).     * Anemia: Leads to malaise, fatigue, pallor, dizziness, palpitations, and dyspnea.     * Thrombocytopenia: Results in gingival, cutaneous, or nasal bleeding and petechiae.     * Other signs: Splenomegaly, lymphadenopathy, bone pain (marrow infiltration), painless testicular swelling, and frequent URIs.     * CNS Disease: Uncommon but includes headache, vomiting, blurred vision, and increased Intracranial Pressure (ICP).
• Subtypes:     * B-cell: Most common; typical in preschoolers. Mature B-cell (Burkitt) is a rare subtype that responds poorly to standard therapy.     * T-cell: Common in adolescent males; high WBC count and often associated with a mediastinal mass.
• Cytogenetics in ALL:     * Hyperdiploid: Extra copies of chromosomes ($20\%-30\%$ of cases); usually a favorable prognosis.     * Hypodiploid: Missing copies ($2\%-3\%$ of cases); always an unfavorable prognosis.
• Diagnostic Procedures: Bone marrow aspiration and biopsy (looking for $> 20\%$ blasts).

Acute Myelocytic Leukemia (AML)

• Characteristics: Most aggressive leukemia; originates from myeloid cells. Survival is lower than ALL, and the relapse rate is up to $50\%$
• Presentation: Bone marrow failure and organ infiltration. Symptoms include gingival hypertrophy, leukemia cutis, sore throat, recurrent infections, and anorexia.
• FAB Classifications:     * M0: Undifferentiated.     * M1: Minimal maturation.     * M2: With maturation; Favorable prognosis (translocation between 8 and 21).     * M3 (APL): Acute Promyelocytic Leukemia; Favorable (translocation between 15 and 17).     * M4: Myelomonocytic.     * M4 eos: Myelomonocytic with eosinophils.     * M5: Monocytic.     * M6: Erythroid.     * M7: Megakaryoblastic.
• APL Specifics (M3): Blasts release procoagulants, causing severe coagulopathy and Disseminated Intravascular Coagulation (DIC). Treated with Arsenic and ATRA (All-Trans Retinoic Acid, a Vitamin A derivative). Survival is $> 80\%$

Chronic Myeloid Leukemia (CML)

• Details: Very rare in children. Cells look normal but function abnormally.
• Presentation: High WBC ($> 100,000/mm^3$). Commonly positive for the Philadelphia chromosome ($Ph+$), involving the $BCR/ABL$ translocation.
• Treatment: Tyrosine Kinase Inhibitors (TKIs).     * Examples: Imatinib mesylate (Gleevec®), dasatinib, nilotinib, bosutinib.     * Administered orally daily. Side effects include GI issues and skin rashes.

Nursing Management of Leukemias

• Nursing Assessments: Monitor for Tumour Lysis Syndrome (TLS), DIC, and Hyperleukocytosis (if WBC $> 200,000$).
• Interventions:     * IV hydration with alkalinization.     * Allopurinol administration for uric acid buildup.     * Strict Intake/Output (I&O).     * Prompt administration of blood products and chemotherapy.

The Lymphatic System and Lymphoma

• Lymph System Components: Vessels, nodes (filter debris/infection), thymus, spleen, tonsils, stomach, small intestines, and skin.
• Lymph Node Chains: Pre-auricular, occipital, cervical, supraclavicular, axillary, mediastinal, mesenteric, iliac, inguinal, popliteal.
• Lymphoma Overview: Third most common childhood cancer. Predisposition includes EBV (Epstein-Barr Virus) infection or immune conditions.
• Hodgkin Lymphoma:     * More common in adolescents; starts in B lymphocytes.     * Presence of Reed-Sternberg Cell: (Owl-looking appearance under microscopy).     * Symptoms: Painless nodal swelling, itchy skin, and "B symptoms" (Fever $> 38^{\circ}C$, drenching night sweats, $> 10\%$ weight loss in 6 months).     * Subtypes: Nodular sclerosis (most common), Mixed cellularity, Lymphocyte rich, Lymphocyte depleted.     * Markers: CD30+, CD15+, CD20-.
• Non-Hodgkin Lymphoma (NHL):     * Most common in younger children. Rapid growth of lymphoblasts.     * Lymphoblastic Lymphoma: $> 20\%$ of NHL; $85\%$ T-cell; $70\%$ associated with mediastinal mass.     * Burkitt Lymphoma: $40\%$ of NHL; presents in the abdomen; associated with translocation $t(8;14)$. Endemic form common in Africa/New Guinea is EBV+.     * Diffuse Large B-cell (DLBCL): $> 15\%$     * Anaplastic Large Cell Lymphoma (ALCL): $10\%$ of NHL; CD30+; ALK+; often involves skin lesions.
• Nursing for NHL: Monitor for emergencies like Superior Vena Cava (SVC) Syndrome or Intussusception (abdominal tumors).

Central Nervous System (CNS) Tumors

• Prevalence: Most common solid tumor in children ($17.2\%$ of cases) and most common cause of death from disease. Overall survival is $75\%$
• Risk Factors: Li-Fraumeni ($p53$), NF1, Retinoblastoma, Cranial radiation, paternal/maternal age.
• Symptoms by Location:     * Cerebellum: Balance, posture, ataxia.     * Brainstem: Involuntary functions (Cranial Nerves V-XII).     * General ICP signs: Morning headache/vomiting, widened pulse pressure, decreased heart rate, increased head circumference in children $< 4$ years.
• Gold Standard Imaging: MRI of the brain.
• Medulloblastoma:     * Most common embryonal tumor; arises from the cerebellum. Small round blue cells.     * Highly malignant; peak incidence at $4-7$ years.     * Post-operative risk: Posterior Fossa Syndrome (Mutism).
• Gliomas:     * Astrocytoma: Most common glioma ($50\%$ of brain tumors). Grade I (Pilocytic) is often cystic/low grade. Grade IV (Glioblastoma Multiforme) and DIPG (Diffuse Intrinsic Pontine Glioma) are high grade and rapidly fatal.     * Brain Stem Gliomas: Often inoperable; $< 10\%$ survival past $18$ months.     * Ependymomas: Line ventricles; Grade I-III. Can often be cured by surgery alone if it hasn't spread.
• Craniopharyngioma: Located above the pituitary; causes endocrine and vision (optic nerve) issues.

Neuroblastoma

• Definition: Cancer of the sympathetic nervous system (nerve cells). Usually develops in the adrenal gland, chest, or abdomen.
• Prevalence: Most common malignancy of infancy.
• Clinical Presentation: Raccoon eyes (periorbital ecchymosis), Blueberry muffin spots (skin nodules), Horner's syndrome (ptosis/miosis), hypertension, and abdominal mass.
• Diagnosis: MIBG scan (iodine-absorbing tumor), elevated urine HVA/VMA (catecholamines).
• Genetics:     * N-myc (MYCN) Amplification: Indicates advanced stage/poor prognosis.     * TrkA Expression: High TrkA is favorable.     * Ploidy: Hyperdiploid is favorable.

Bone Tumors: Osteosarcoma and Ewing's Sarcoma

• Osteosarcoma:     * Most common bone cancer; peak incidence in adolescents during growth spurts.     * Locations: Distal femur, proximal tibia, proximal humerus.     * Presentation: Pain with activity, limp, mass. $20\%$ metastatic at diagnosis.     * Radiology: Codman’s triangle on X-ray. Increased Alkaline Phosphatase (Alk Phos) and LDH.     * Surgery: Limb salvage, wide resection ($> 5\,mm$ margin), or amputation.
• Ewing's Sarcoma:     * Second most common bone cancer; originates from neural crest cells. Infiltrates soft tissue.     * Locations: Pelvis and leg bones ($87\%$     * Diagnosis: Small round blue cell tumor. Often associated with translocations ($t(11;22)$, etc).

Wilms Tumor (Nephroblastoma)

• Definition: Rapidly growing vascular renal tumor with a fragile gelatinous capsule.
• Prevalence: $75\%$ diagnosed by age $5$. Higher incidence in African Americans.
• Presentation: Asymptomatic abdominal mass (does not cross midline). CRITICAL: DO NOT PALPATE THE ABDOMEN to prevent capsule rupture.
• WAGR Syndrome: Wilms, Aniridia (no iris), GU anomalies (cryptorchidism/hypospadias), Mental Retardation.
• Staging: Stage V indicates bilateral renal disease.

Rhabdomyosarcoma and Retinoblastoma

• Rhabdomyosarcoma:     * Cancer of skeletal (voluntary) muscle. Bimodal peaks at $2-5$ and $15-19$ years.     * Linked to Li-Fraumeni and Beckwith-Wiedemann (large tongue, hemihypertrophy).     * Subtypes: Embryonal (favorable) vs. Alveolar (unfavorable).
• Retinoblastoma:     * Malignant retinal tumor; $95\%$ diagnosed by age $5$.     * Presenting Sign: Leukocoria ("white pupil"), strabismus, and vision changes.     * Treatment: Enucleation (eye removal) or specialized chemotherapy.

General Hematology: Anemia

• Anemia Definition: Reduction of RBCs or Hemoglobin ($Hgb$). Normal range for children ($6-12$ years) is $11.2$ to $14.5\,g/dL$.
• RBC Lifespan: $120$ days.
• Management:     * Leukocyte Reduced Transfusion: Decreases viral infection/alloimmunization.     * Irradiated Transfusion: Inactivates T cells to prevent Graft vs. Host Disease (GVHD).
• Specific Anemias:     * Autoimmune Hemolytic Anemia: Positive Coombs test; treated with steroids, Rituximab (CD20+), and IVIG.     * Thalassemia: Autosomal recessive. Alpha (4 gene mutation = hydrops fetalis) vs. Beta (Cooley’s). Requires chronic transfusions and chelation therapy (Exjade, Jadenu, Desferal) for iron overload.     * Sickle Cell Disease (SCD): Mutation to $Hgb\,S$. Crisis triggered by infection, dehydration, or temperature extremes. Management: Hydroxyurea (increases $Hgb\,F$), TENS, and screening for Acute Chest Syndrome.     * G6PD Deficiency: X-linked. Triggers for hemolysis include ASA, Sulfa drugs, Rasburicase, Fava beans, Henna, and naphthalene (mothballs).     * Hereditary Spherocytosis: Spherocytes are destroyed by the spleen. Treated with folic acid and splenectomy.     * Fanconi Anemia: Inherited bone marrow failure. Skeletal anomalies (absent thumb/radius). High risk for MDS/AML.

Neutropenia and Thrombocytopenia

• Neutropenia:     * ANC levels: $< 1000$ in infants; $< 1500$ in children. Severe risk if $< 500$.     * $ANC = \text{WBC} \times (\%\text{segs} + \%\text{bands})$.     * Fever in Neutropenia: An oncologic emergency; antibiotics within $1$ hour.
• Thrombocytopenia:     * Natural platelet lifespan: $8-10$ days. Normal count: $100,000-150,000$.     * Watch for active bleeding if count $< 20,000$; neurological concern if $< 10,000$.
• ITP (Immune Thrombocytopenia Purpura): Autoimmune destruction post-viral illness. Peak age $2-5$.

Bleeding Disorders: Hemophilia and von Willebrand Disease

• Hemophilia: X-linked. Prolonged PTT, normal PT.     * Type A: Factor VIII deficiency ($80\%$ of cases).     * Type B: Factor IX deficiency.     * Treatment: DDAVP (for Factor VIII) and replacement factors.
• von Willebrand Disease (vWD): Most common autosomal dominant bleeding disorder. Deficiency in vWf (platelet adhesion).     * Symptoms: Mucosal bleeding, heavy menses, epistaxis.

Miscellaneous Hematologic Disorders

• Shwachman-Diamond Syndrome: Pancreatic insufficiency, short stature, neutropenia. Genetic sweat test used for diagnosis.
• Evans Syndrome: Simultaneous AIHA and ITP (affects $> 2$ cell lines).
• PNH (Paroxysmal Nocturnal Hemoglobinuria): $PIGA$ gene mutation. Loss of $CD55$ and $CD59$ protective proteins.
• HUS (Hemolytic Uremic Syndrome): Anemia + Thrombocytopenia + AKI following diarrhea/shiga-toxin.
• Diamond-Blackfan Anemia: Macrocytic anemia with low reticulocyte count (red cell aplasia).

Clinical Trial Phases and IRB Process

• Phase I: Safety, toxicities, and Maximally Tolerated Dose (MTD). Pediatric starting dose is $80\%$ of adult MTD.
• Phase II: Determines efficacy in specific diseases.
• Phase III: Compares new treatment to standard (Large number of patients).
• Phase IV: Post-commercialization long-term safety/late effects.
• Protocols: Every hospital must have IRB (Institutional Review Board) approval. Informed consent is obtained from parents; Assent is obtained from children of appropriate age.

Nursing Professional Performance and Ethics

• Communication Models:     * SBAR: Situation, Background, Assessment, Recommendation.     * I-PASS: Illness Severity, Patient Summary, Action List, Situation Awareness, Synthesis.
• Compassion Fatigue: Indirect trauma from helping others. Symptoms: apathy, hopelessness.
• Moral Distress: Inability to act correctly due to constraints (poor staffing, futile care). Treated with the 4 A's: Ask, Affirm, Assess, Act.
• Belmont Report Principles (1979):     * Respect for Persons: Informed consent and protection of vulnerable populations.     * Beneficence: Maximize benefits, minimize risks.     * Justice: Fair distribution of research burdens and benefits.
• Five Rights of Delegation: Right task, right circumstance, right person, right directions/communication, and right supervision/evaluation.