Pediatric Hematology/Oncology: Anemia, Leukemia, and Lymphoma

hematocrit, 2, hemoglobin, thalassemia, systemic, marrow, large, B12, loss, destruction, DIC

Anemia: Background

-Quantitative Definition → any hemoglobin or __________ value that is _ standard deviations below the mean for age and gender

-Hypochromic, microcytic → inadequate production of ____________

• Iron deficiency anemia, ___________, and lead intoxication

-Normochromic, normocytic → usually associated with ________ illnesses that impair _________ synthesis of RBCs

• Malignancy, renal failure, inflammatory diseases

-Macrocytic → ______ RBCs

• Vitamin ____ deficiency, folic acid deficiency, hypothyroidism, recent blood _____

-Hemolytic → caused by disorders intrinsic or extrinsic to the RBC that increases cell ____________

• Hemoglobinopathies, G6PD deficiency, ____, HUS, TTP

jaundice, family, murmur, exercise, fatigue, purpura, growth

Anemia: History and Exam

-History → blood loss, history of _________ or pallor, dietary history, _______ history (especially anemia and chronic diseases), systemic complaints (chronic illness)

-Exam → tachycardia, systolic flow _________, poor ________ tolerance, headache, excessive sleeping or ________, irritability, syncope, jaundice or petechiae/________, ______ failure or poor weight gain

CBC, RBC, increased, decreased, bone marrow, destroyed

Anemia: Work-Up and Reticulocyte

-Initial Work-Up → ____ with diff, reticulocyte count, and blood smear

-Further Work-Up → based on initial results

• Whether ____ production is adequate or inadequate and if the cells are microcytic, normocytic, or macrocytic

-Reticulocyte Counts

• Elevated reticulocyte count → _________ RBC production (hemolysis or blood loss)

• Normal reticulocyte count → _________ or ineffective production of RBCs for the degree of anemia

• Decreased reticulocyte count → ______ ________ hasn’t had time to respond, reticulocytes are being __________ in the marrow, or bone marrow is present

milk, large, decreased, 6, 6-24, menstruating, asymptomatic, pallor, dizziness

Iron Deficiency Anemia: Background and Symptoms

-Etiology/Epidemiology

• Infants < 1 y/o who are fed cow’s ______

• Toddlers who are fed ______ amounts of cow’s milk leading to decreased intake of food

• Menstruating adolescents

• Chronic inflammatory diseases

• Rarely seen in children <_ months

• Most commonly seen between __-___ months or in _________ adolescents

-Symptoms

• Can be ___________ if mild

• ______, fatigue, irritability, delayed motor development, headache, _________, and pica in moderate to severe

microcytic, anisocytosis, elevated, low, low, elevated, elemental iron, 3-5, 4-6

Iron Deficiency Anemia: Labs and Treatment

-Labs

• RBCs → _______, hypochromic with ___________

• MCV → low

• RBC distribution width → ________

• Hemoglobin → low

• Absolute reticulocyte count → ____

• Serum iron → low

• Ferritin → ____

• TIBC → _________

• Transferrin saturation → low

-Treatment

• _________ _____ 3-6 mg/kg/day in 3 divided doses

• Reticulocyte count usually increases within __-__ days and hemoglobin follows

• Anemia typically resolved within __-__ weeks

hypochromic, iron, lead, >, irritability, personality, headache, convulsions

Lead Poisoning (Plumbism): Background and Symptoms

-Associated with __________, microcytic anemia because most have ____ deficiency as well

-Etiology → _____ exposure

• Living in older home (built before 1980) with lead based paint

• Toxic effects likely if _ 0.5mg of lead/day absorbed

-Symptoms → weakness, ________, weight loss, vomiting, _________ changes, ataxia, constipation, ___________, abdominal pain

-Can progress to mental retardation, __________, and coma

basophilic, iron, 5, severe, 100

Lead Poisoning: Labs

-CBC → _________ stippling common

-Iron studies → associated with ____ deficiency anemia

-Blood lead levels

• >_ mcg/dL leads to diagnosis

• >10 mcg/dL leads to more ______ symptoms

• >____ mcg/dL leads to encephalopathy

remove, Succimer, 45, symptomatic, 70, iron

Lead Poisoning: Treatment

-________ exposure

-Chelation therapy

• __________ → initiated in asymptomatic children at blood lead levels > __ mcg/dL

• Dimercaprol and calcium disodium EDTA → considered in ___________ children or levels > __ mcg/dL

-Correction or _____ deficiency

African, SS, anemia, deoxygenated, morphology, decreased, viscosity, hypoxia, fever

Sickle Cell Disease: Background and Pathogenesis

-Epidemiology

• Most common in _______ descent

• Part of the newborn screen in the US

-Sickle Cell Syndromes

• Hemoglobin __ (Sickle Cell anemia, which is the most severe)

• Hemoglobin S-C, hemoglobin S-Beta 0 thalassemia, hemoglobin S-Beta + thalassemia, rare variants

• Sickle Cell _______ is the most common sickle cell disease

-Pathogenesis: ____________ blood/hemoglobin → Hgb crystallizes and RBC __________ distorted → _________ red cell life span (hemolytic anemia) → increased blood __________ → vaso-occlusion

• Sickling exacerbated by ______, acidosis, _____, hypothermia, and dehydration

pallor, spleen, strep pneumoniae, enlargement, Hgb, shock, Parvovirus B19, dactylitis, pain, fever

Sickle Cell Disease: Symptoms

-Hemolytic Anemia → ______, fatigue, jaundice

-Splenomegaly

• Congestion of _____ → splenic dysfunction/infarction → susceptible to infection (____ __________)

-Splenic sequestration crisis (life threatening)

• Sudden ____________ of the spleen with pooling of red cells → drop in ____ → exacerbates anemia → can lead to ______ and death

-Aplastic crisis

• Viral infection (_________ ____) of RBC precursors in marrow → transient RBC aplasia with reticulocytopenia → exacerbated anemia

-Vaso-Occlusion and Tissue Ischemia

• _______ aka hand and foot syndrome (often 1st presentation)

• Bone/extremity ____

• Abdominal pain

• Acute chest syndrome (_____, pleuritic chest pain, pulmonary infiltrates)

• Stroke

electrophoresis, PCN, cultures, hydration, analgesia, anemia, failure, hydroxyurea

Sickle Cell Disease: Diagnosis and Treatment

-Diagnosis → Hemoglobin __________ to identify the type of hemoglobin

-Treatment

• Prophylactic ___ (especially in HbSS and HbS-beta 0 thalassemia)

• Immunizations

• If febrile, order bacterial _______, close observation, broad spectrum antibiotics

• Vaso-occlusive episodes → __________, correction of acidosis, ________, maintenance of oxygen saturation, and treatment of any infection

• Red cell transfusion → exacerbation of ______, stroke, acute chest syndrome, organ _________

• ___________ → decreases hemolysis and reduces painful events by increasing fetal hemoglobin. Start if > 9 months old

ALL

What is the most common childhood cancer overall?

>, Down Syndrome, B, 2-5, older, >, immature, lymphoblasts, marrow

Acute Lymphoblastic Leukemia (ALL): Background

-Most common childhood cancer overall

-Etiology → mostly unknown; thought to have genetic and environmental factors

-Epidemiology

• Caucasian _ AA

• Increased incidence in individuals with ______ _________

• B-precursor cell ALL is most common → peaks between __-__ years old and most cases before the age of 15. Slightly more common in males

• T-cell ALL → ______ age of onset (adolescents), male _ female

-Pathogenesis: composed of ________ B or T cells called __________ → replace normal _______ → disrupts normal function

->25% of malignant blasts on a bone marrow aspirate

fevers, pallor, pain, petechiae, splenomegaly, tachypnea, palsies

ALL: Symptoms and Physical Exam

-Symptoms

• Intermittent ______ → cytokine induced by the leukemia or due to secondary infections from leukopenia

• Bruising

• ________

• Bone ______ (pelvis, vertebral bodies, legs)

-Physical Exam

• Can be normal

• Pallor, _________, purpura, hepatomegaly/___________, lymphadenopathy

• Mediastinal adenopathy → may cause SVC syndrome

• Mediastinal mass → __________ and orthopnea

• Leukemic infiltration of cranial nerves → cranial nerve _________

decrease, neutropenia, low, >, blasts, teardrop, infiltration, blasts, small, no

ALL: Diagnosis

-CBC with differential

• _________ in at least one cell type but often more (_________, thrombocytopenia, anemia)

• 50% have ____ or normal WBC count with neutropenia

• 30% have WBC count between 10,000-50,000

• 20% have WBC count _ 50,000

-Peripheral Blood Smear → ______ among normal lymphocytes, ________ RBCs

-Bone marrow aspiration

• Homogenous __________ of leukemic ______ replacing normal marrow

• Blasts → ______, scant cytoplasm, __ nucleoli or one indistinct nucleolus

-Immunophenotyping by flow cytometry

-Histochemical stains

widening, xray

ALL: Imaging

-CXR → mediastinal __________ or anterior mediastinal mass

-Abdominal US → intra-abdominal adenopathy

-_____ of long bones and spine → demineralization, periosteal elevation, growth arrest lines, compression of vertebral bodies

2-3, remission, intrathecal, CNS, methotrexate

ALL: Treatment

-Lasts between __-__ years

-Induction Phase

• >95% of patients will enter __________ in this phase

• Oral prednisone/dexamethasone, IV vincristine/danurubicin, IM or IV asparaginase and intrathecal methotrexate

-Consolidation Phase

• _________ chemo and continued systemic therapy. This is important because systemic chemo can’t penetrate ____ or testes very well

• Possibly cranial radiation

-Intensification Phase

• Intensive chemo for several months

-Maintenance Phase

• Daily oral mercaptopurine, weekly oral __________, and monthly vincristine and oral steroids, and intrathecal chemo every 2-3 months

fever, cultures, bactrim, varicella, 72, acyclovir

ALL: Treatment

-Monitor for drug toxicities and complications such as infection

• _____ in these patients need worked up (blood cultures, treated with broad spectrum antibiotics)

-Prophylaxis against pneumocystis jiroveci (______)

-Those who are not immune to ________ must get VZIG within __ hours of exposure and treatment with IV ________ for active infection

neonatal, adolescence, >, oncogenic, blasts, failure

Acute Myeloid Leukemia (AML): Background

-Accounts for 20% of leukemia cases

-Epidemiology

• Incidence is higher in the ________ period then drops and stabilizes until _________ where there is a slight increase that continues into adulthood

• Males = females

• Hispanic and AA _ Caucasian

-Pathogenesis

• Acquired _________ mutation → impairs differentiation → accumulation of immature myeloid ______ in the marrow and other organs → marrow ________ and complications (anemia, thrombocytopenia, neutropenia)

pallor, hematuria, purpura, stasis, lungs, 7, platelets, >

AML: Symptoms and Labs

-Symptoms

• _______, fatigue, easy bleeding (epistaxis, bleeding gums, __________), ecchymosis, ________, petechiae, fevers, frequent infections

• Venous _____/sludging in vessels that leads to hypoxia, hemorrhage, infarction (most often in ______ and CNS)

-Diagnosis

• CBC with differential

• Hgb around _

• _________ < 50,000

• WBCs _ 100,000

• Neutrophils < 1000

aggressive, stem cell, pneumocystis, acyclovir

AML: Treatment

-Need more ________ chemotherapy because it is less responsive

-_____ ____ transplant following remission if matched donor or continued chemotherapy in those who don’t

• Recommended in all patients

-Monitor, evaluate, and treat possible infections promptly

-__________ prophylaxis with bactrim

-VZIG within 72 hours of exposure to varicella or IV ________ for active infection

children, extranodal, unpredictable, Burkitt, EBV, neoplasm, 5, >

Non-Hodgkin Lymphoma: Background

-More common that Hodgkin Lymphoma in _________

-Diffuse and highly malignant

-Arises at ________ sites and spread in an ___________ manner

-Types

• Mature B-cell NHL/_______ lymphoma are most common

• Lymphoblastic lymphoma

• Large cell lymphoma

-Risk Factors → ___ infection, congenital and acquired immunodeficiency, and previous __________

-Epidemiology → increases with age (uncommon before _ years old)

• Males _ females

translocations, oncogene, pain, mass, LAD, sweats

Non-Hodgkin Lymphoma: Patho and Symptoms

-Pathogenesis → Chromosomal ____________ result in unregulated or increased expression of an _________ that drives malignant transformation

-Symptoms

• Abdominal _____, vomiting, abdominal _____ (possible), cough, SOB, ___ (neck, underarm, stomach, groin), fever, night _______, weight loss

LDH, CT, biopsy, PET, chemotherapy

Non-Hodgkin Lymphoma: Diagnosis and Treatment

-Diagnosis

• CBC, LFTs, serum electrolytes, ___, uric acid, CXR and ___

• _______ of involved lymph node is diagnostic

• Bone marrow evaluation and ____ scan for staging

-Treatment → systemic ______________

single, contiguously, sclerosis, EBV, adolescent, young

Hodgkin Lymphoma: Background

-Arises in a ______ chain of lymph nodes and spreads ___________

-Common Types

• Nodular ________ (adolescents/young adults)

• Mixed cellularity and nodular lymphocyte predominant (younger children)

-Risk Factors

• ___ infection, immunodeficiency, autoimmune lymphoproliferative syndrome

-Epidemiology

• Peaks in __________/young adults and again after 50

• Males > females in ______ children

• Male = female in adolescent/young adult

painless, LAD, contiguous, cervical, cough, loss

Hodgkin Lymphoma: Symptoms

-_________, firm ____ confined to 1-2 ___________ lymph node areas (supraclavicular and ________ nodes most affected)

-_______ and/or shortness of breath

-Fever

-Night sweats

-Unintentional weight _____

ESR, biopsy, Reed-Sternberg, chemotherapy, surgery

Hodgkin Lymphoma: Diagnosis and Treatment

-Diagnosis

• CBC, ____, electrolytes, uric acid, LDH, CXR

• _______ of involved lymph node is diagnostic. Will see characteristic _____-__________ cells

• PET scan for staging

-Treatment

• 4-6 courses of ___________

• Radiation if needed

• Stage I: _______ alone may cure