Exam 2, deck 2 Flashcards
Ratio of Sickle cell trait
1:12 Black Americans
1:150 Hispanic Americans
300,000 babies born each yr with Sickle cell disease globally
2,000 babies with SCD born in US
SCD has a problem on what chromosome. What happens?
Chromosome 11
Point mutation for Hemoglobin S
Substitutes Glutamine for Valine
SCD is autosomal _____
Recessive
must have 2 abnormal copies to result in disease
Hemoglobin Genotypes for SCD
AA: Normal hemoglobin
AS: Sickle cell trait
SS: Sick cell disease
Other beta globin Traits
C trait (AC)
B0 trait (AB0)
B+ trait (AB+)
You have a mom and dad who both have Sickle Cell trait what are your genetic possibilities?
Genetic possibilities for mom with Beta Thalassemia trait (AB) and dad with Sickle cell trait (AS)
Genetic possibilities for mom with hemoglobin C trait (AC) and dad with Sickle cell trait (AS)
labs that show intravascular and extravascular hemolysis in SCD
Increased LDH
Increased bilirubin
Sickle RBC lives how long vs normal
8-21 days vs 120 days
polymerization of hemoglobin S leading to membrane rigidity
SCD
What type of anemia is seen in SCD
Normocytic anemia
what type of anemia is seen in SB and SC
microcytic anemia
target cells on smear
Hemoglobin SC
general preventative care for SS and SB0
Penicillin by 6 weeks of age
(spleen is impacted and not as effective to prevent infection - functional asplenia)
<3 years - 125 mg BID
>=3 years - 250 mg BID
Transcranial Doppler Ultrasound (TCD) by age 2 and at least annually until unable to obtain values - looking at cerebral blood flow to see who is at high risk for stroke
All types of sickle cell genotypes preventative care
Fever precautions: 101 is a med emergency
pneumococcal and meningococcal vaccines
annual influenza vaccine
Annual retinopathy screening starts at 10 years
annual screening for proteinuria begins at age 10 yrs
Genetic counseling for parents and adolescents
Folic acid supplementation if live outside US
most common cause of death in children with SCD
infection
SCD is at higher risk for what infections
pneumonia
Osteomyelitis which can be difficult to discern from Vaso-occlusive pain (VOP) on imaging
most common complication in SCD
Vaso-occlusive pain crisis
Pain in a vaso-occlusive pain crisis is what type of pain
Ischemic due to tissue infarction
Vaso-occlusive pain crisis may be precipitated by
dehydration
temp extremes
A pulmonary emboli in SCD is from
bone marrow breaking off
Defined as a new lung infiltrate, chest pain or resp sx +/- fever
Acute chest syndrome
Any fever in sickle cell disease requires
blood cultures
antibiotics
+/- chest x ray
vascular flow out of spleen blocked due to occlusion. Spleen starts blowing up like a balloon
splenic sequestration
symptoms of splenic sequestration
Acute and painful splenomegaly
irritability
pallor
+/- fever
Hgb below baseline +/- thrombocytopenia
transfusions in splenic sequestration
small aliquots of RBC transfusions, even though Hgb may be dramatically low. Non-sickled blood helps to release trapped native RBCs in spleen
After you have had splenic sequestration, do you have to worry about it happening again
yes
Unwanted, painful erection in SCD
Priapism
Early intervention may prevent what in priapism
irreversible penile fibrosis or impotence
Treatment for Priapism
Short episodes managed at home: increase fluids, warm bath, frequent urination, analgesics +/- pseudoephedrine
If > 2 hrs, needs medical attention
Potential Urinary catheterization
consult urology
hemoglobin severely below baseline with reticulocytopenia which can happen in any hemolytic anemia
Aplastic crisis
(in SCD lecture)
What illness is associated with Aplastic crisis
Parvovirus B19
Aplastic crisis recovery/treatment
spontaneous recovery within 7-10 days
may need transfusion support until recovery
Common symptoms of stroke in SCD
Hemiparesis
Seizures
Gait dysfunction
Speech Defects are common
imaging for stroke in SCD
initial non-contrast CT
then MRI +/- MRA
Treatment for stroke in SCD
Emergent exchange transfusion. Donor must not have Sickle cell trait!
Untreated stroke in SCD
20% mortality and 70% with permanent motor/cognitive defects
screening tool to determine children at increased risk of stroke
TCD
Abnormal TCD value
> 200 cm/s
when do you screen for TCD
begins at age 2 until at least 16 years old
If you have an abnormal TCD, what happens
start chronic transfusion therapy every 4 weeks to prevent stroke.
chronic complications of sickle cell disease and preventative measures
Neurocognitive abnormalities
-Neuropsychological eval for delays or declining school performance
Retinopathy
-Annual eye exams at age 10
Lung disease
-PFTs for those with pulmonary symptoms
Cholelithiasis
-Bilirubin stones in childhood or early adolescence
Leg ulcers
-more common in tropical climates
Avascular necrosis
Growth delay
-linear and puberty
Pulmonary HTN
Cardiomegaly with Left ventricular hypertrophy
Proteinuria and nephrotic syndrome
-avoid nephrotoxic drugs and contrast dye when possible
Treatment for SCD
Curative - Bone marrow transplant
-only for patients with severe disease or stroke
-Best prognosis with HLA matched sibling donors
working on gene therapy but not there yet
Transfusions in SCD
Leukoreduced
Sickle neg units
C, E, Kell matched units
Increased risk of alloimmunization, autoantibodies
Avoid overtransfusion, no need to achieve a normal Hgb
Avoid targe hgb >10 gm/dl in non-chronically transfused patients
Can have hemolytic transfusion reactions
transfusion calculation
Quick and dirty: Weight: kg x (goal hgb - current hgb) x 3.75 = mL of PRBCs
SCD med treatments
Hydroxyurea (Hydrea)
Voxelotor (Oxbryta)
Crizanlizumab ((Adakveo)) - monthly infusion
L glutamine (Endari)
which SCD treatment does not require lab monitoring
Voxelotor (Oxbryta)
Oldest SCD treatment
Hydroxyurea
SCD treatment that is an infusion
Crizanlizumab (Adakveo)
Medications that are FDA approved for SCD, What are the ages?
Hydroxyurea (Hydrea) - >=2 yrs
Voxelotor (Oxbryta) >= 12 years
Crizanlizumab ((Adakveo)) - monthly infusion - >= 16 years
L glutamine (Endari) - >= 5 years
Hydroxyurea (Hydrea) activates
Hemoglobin F
what type of genetic disorder is hemophilia
X- linked recessive bleeding disorder.
Hemophilia is caused by deficient or defective
Factor VIII (Hemophilia A) or Factor IX (Hemophilia B)
Hemophilia is a disorder or secondary hemostasis meaning that
fibrin clot formation is too unstable to adequately stop bleeding
what happens in hemophilia
Normally there is an injury to a vessel, both intrinsic and extrinsic pathways of clotting activated, leads to stabilization of platelet plug so bleeding is contained. When there is a Factor VIII or IX deficiency (these are responsible for stabilization of platelet plug by forming fibrin clot. So Secondary hemostasis is prevented (jelly like and unstable). This leads to delayed clotting and spontaneous bleeding.
Hemophilia B is often referred to as
Christmas disease
which type of hemophilia is most common
Hemophilia A
If a mom has a family history of hemophilia, what is important during birth
no use of forceps or vacuum extraction
Differential Dx for conditions that affect fibrin clot formation
Hemophilia
Von Willebrand disease
Systemic lupus erythematosus
Factor XII deficiency
Vit K deficiency
Liver disease
DIC
Heparin
Warfarin
In Hemophilia you would expect PTT to be
Platelet count
prolonged
normal platelet count
normal PT
normal fibrinogen
normal bleeding time
what tests look at Hemophilia
Assays for Factor VIII and IX
initial dosing for hemarthrosis in pt with factor VIII deficiency
dose for next day?
25-50 units/kg of Factor VIII concentrate
20 units/kg the following day
additional doses based on treatment response
initial dosing for hemarthrosis in pt with factor IX deficiency
dose for next day?
40-80 units/kg of factor IX concentrate followed by
20units/kg the following day
additional doses based on treatment response
total dose of factor VIII in units formula
= desired rise in plasma factor VIII activity x body weight in kg x correction factor of 0.5
formula of dose for correction of Factor IX
desired rise in factor IX activity times the body weight in kg
half life of factor VIII and factor IX
VIII - 8-12 hours
IX - 12-24 hrs
Joint aspiration generally avoided in Hemophilia except hip hemarthrosis due to associate with
avascular necrosis of femoral head
supportive care in hemophilia for joint bleeding
ice application
compressive dressing
resting the joint
elevating it
muscle hemorrhage can lead to
contractures
muscle atrophy
pseudotumor formation
In hemophilia pt, the development of _____ hemorrhage is particularly dangerous and can result in severe morbidity
Iliopsoas
life threatening bleeding in Hemophilia
bleeding into the CNS, into and around the airway and into the peritoneal cavity
The goal for treating life threatening hemorrhage in hemophilia
to maintain near normal levels of clotting factor for a min of 14 days and then prophylaxis doses to ensure resolution of hemorrhage.
in hemophilia, after intracranial hemorrhage the patient should be treated with prophylaxis for at least
6-12 months
Treatment in mild to moderate hemophilia A
desmopressin acetate (DDAVP) either IV or intranasally.
0.3 mcg/kg for 3 doses→ if bleeding does not respond, supplemental factor VIII concentrate can be given
DO NOT give to pts with severe hemophilia.
treatment in severe hemophilia
frequently treated with prophylactic infusions of factor VIII or factor IX concentrates to prevent bleeding into joints and other tissues.
-May result in alloimmunization and the development of autoantibodies that inhibit the function of the infused factor concentrates.
Suspect pt has autoantibodies when unabated bleeding despite administration of adequate doses of factor concentrate
Bleeding in the presence of an inhibitory antibody is difficult to control and requires administration of drugs that bypass the necessity for factor VIII or IX activity→ recombinant activated factor VII or activated prothrombin complex
Ultimate goal is to get rid of autoantibodies with immune tolerance induction therapy→ administer very large doses of factor VIII in an effort to tolerize the pt against the exogenous factor. Success rate is 50-70%
what race is twice as likely to develop inhibitory antibodies to the factor in hemophilia
African Americans
what type of precautions are used in hemophiliac patients before surgery or an invasive procedure
avoid NSAIDS and products containing ASA for 1-2 weeks prior to procedure
recombinant clotting factor concentrate to achieve 100% replacement immediately preceding procedures
-Factor VIII concentrate - 50units/kg parenterally
maintenance 25 units/kg
Factor IX - 75-100units/kg parenterally
maintenance 35-50 units/kg
assess pt for presence of any inhibitors
post op administration of factor concentrate at maintenance doses for at least 3 weeks or until no further bleeding symptoms remain
what medications do hemophilia pt have to avoid bc it inhibits platelets or coagulation factors
NSAIDS
ASA
Anticoagulants
Certain abx such as
Carbenicillin
PCN G
Hemophilia pt should be evaluated annually for
annual evaluation at an HTC for
infectious diseases and other blood borne pathogens
Vaccinations recommended against Hepatitis A and B
contraindications (lifestyle) in hemophilia
no contact sports
ITP < 3 months from diagnosis
Newly diagnosed ITP (Immune Thrombocytopenia)
Idiopathic thrombocytopenia purpura is now called
Immune Thrombocytopenia (ITP)
ITP 3-12 months from diagnosis
Persistent ITP
ITP > 12 months from diagnosis
Chronic ITP
Thrombocytopenia that occurs due to a destruction in peripheral circulation due to inappropriate platelet0directed antibody development
(platelet production is not the problem)
Immune Thrombocytopenia
ITP ages
Peak ages 2-4 years but can occur at any age
rapid onset of petechiae, purpura, bruising, mucocutaneous bleeding
ITP
Triggers for ITP
usually 1-2 weeks after
viral illness
Live virus Immunization (MMR)
Allergic reaction
what vaccine has been related back to ITP
MMR
greatest incidence of ITP season
fall
MPV is the counterpart of ___
what does it tell you
MCV
tells you how big your platelets are
MPV in ITP
higher…Platelets typically bigger
ITP is a diagnosis of
exclusion
diagnostic criteria of ITP
diagnosis of exclusion
Physical exam normal except platelet type bleeding (mucous membranes, bruising)
No sig lymphadenopathy
No sig splenomegaly (tip palpable in 10%)
CBC otherwise normal unless explained by infection
50% of pt present with platelets less than 20k
In lipincott - diagnostic is <100,000; large platelets on smear
Sudden onset of bruising, mucocutaneous bleeding, petechiae
50% of ITP pt present with platelets less than
20K
Patho of ITP
Autoantibodies (IgG) against platelet antigens
Platelets are flagged with autoantibodies
Destroyed by spleen
+/- Decreased platelet production
Platelet transfusion in ITP
Contraindicated. Adding fuel to the fire.
limited role in life threatening bleeding
Treatment in ITP
IVIG 1gm/kg/day (prevents destruction of antibody coated platelets)
Steroids - first line at many centers (prednisone, Methylpred, Dexamethasone)
Anti-RhD immune globulin (WinRho SDF) (works similarly to IVIG) - only in Rh positive patients
Thrombopoietin-R agonists (TPO agonists) - tells body to make more platelets -
-Eltrombopag (Promacta) -daily, oral
Romplostim (N-Plate) - Weekly, subcutaneous
adverse effects of IVIG
n/v
headache
fever
Rare
alloimmune hemolysis infection transmission
IVIG is derived from
human plasma
IVIG cost
$1000/gm at TCH
Anti-RhD immune globulin (WinRho SDF) can only be used in patients who are
Rh +
Have a spleen
used in ITP
dosing for Anti-RhD immune globulin (WinRho SDF)
75 mcg/kg IV x 1
Anti-RhD immune globulin (WinRho SDF)
contraindicated if they have what infection
mono
active EBV infection
adverse effects Anti-RhD immune globulin (WinRho SDF)
fever
chills
n/v
effects lessened by premedications
Corticosteroid therapy in ITP takes a min of how many days to work
3-5 days
Romplostim (N-Plate) - takes how long to work
weeks to months for effect
Treatment with Life threatening Bleeding in ITP
Platelet infusions/drip
Emergent splenectomy (sometimes does not fix)
IV Methylprednisolone
IVIG
Recombinant FVIIa
Antibodies that coat platelets in ITP
IgG, IgA, IgM
common pediatric hematologic malignancies
Acute lymphocytic leukemia
Acute myeloid Leukemia
Hodgkins lymphoma
Non-Hodkins lymphoma
Common pediatric solid tumor malignancies
Medulloblastoma brain tumor
Astrocytoma brain tumor
Craniopharyngioma brain tumor
Ependymoma brain tumor
Neuroblastoma
Osteosarcoma bone tumor
Ewing’s Bone tumor
Wilm’s tumor
Rhabdomyosarcoma
Retinoblastoma
most commonly diagnosed cancer in peds 0-14 years
- Leukemia
- Brain tumors
- Lymphoma
most commonly diagnosed cancer in peds 15-19 years
- Hodgkin
- Thyroid
- Brain tumors
syndromes that predispose to cancer (inherited genetic mutations that predispose them)
Trisomy 21
Fanconi anemia
Neurofibromatosis 1
Tubular sclerosis
Beckwith-Wideman Syndrome, Isolated hemihypertrophy
Von Hippel Lindau
Li Fraumeni
Familial adenomatous polyposis
common childhood illness symptoms that present with oncology
fever
infections that dont resolve
joint pain
rash
n/v/d
physical exam findings - oncology
Pain
Joint or bone swelling, masses
Hepatosplenomegaly
Diplopia
nystagmus
exotropia
gait changes
ataxia
petechiae
oncology workup
labs:
CBC diff
platelets
electrolytes
BUN
Creatinine
Calcium
magnesium
phosphorus
uric acid
LDH
liver enzymes
Coag panel
Urinalysis
Diagnostic imaging depends on differential
Chest x ray
CT scan
PET
MRI
US
Invasive procedures
-biopsy
-bone marrow aspiration and biopsy
-lumbar puncture (if pt has neuro symptoms, you need an MRI before the LP)
most common site of metastasis in solid tumor cancers
lungs
Neoadjuvant chemotherapy purpose
used in solid tumors to reduce size of tumor. Make it more sizeable for surgical resection. Also tests response to chemotherapy. When they take out the tumor. We can see what percentage of the tumor is alive and what percentage is dead. Helps guide therapy
Staging cancer
Low, intermediate and high risk
local or metastatic
not same system in pediatrics as adults
classifications of chemotherapeutic agents
Cell cycle specific agents
G1: RNA synthesis begins
S: DNA is replicated
G2: RNA synthesis is complete
M: Mitosis (cell division) occurs
Cell cycle nonspecific agents
-bolus dosing
Cell cycle
Immunotherapy in Oncology
augment, modify or restore aspects of the normal immune response to control cancer cells
Monoclonal antibodies - attach to surface markers and cause cell death
Checkpoint inhibitors- block protein receptors on cell surfaces that inhibit cell death
Targeted therapies in oncology
Targets specific pathways involved in cancer growth
-Tyrosine kinase-enzyme that binds phosphates to other amino acids. functions as an on-off switch for cellular functions
Targeting specific antigens of cancer cells
Chimeric antigen receptor (CAR) T cells: patients engineered T cells to recognize, attach to and kill antigens on the tumor cells (adoptive cell transfer tharapies)
High energy particles to break strands of DNA preventing cell replication and kill the tumor
radiation
dividing the total dose into smaller fractions to allow for tumor kill and sparing of normal tissue during radiation
Fractionation (proton)
what emergent oncological presentations that might warrant radiation as emergent use with chemo
Superior cava syndrome
airway compromise
spinal cord compression
also in
palliative care/pain control
Radiation is not for children < ____ yrs
3 years age d/t underdeveloped nervous system
types of radiation
Proton beam
Brachytherapy - radioactive implants (used frequently in infants)
Radiopharmaceuticals (iodine given in bloodstream to target tumor)
-MIBG therapy for neuroblastoma
what radation used frequently in babies
Brachytherapy - radioactive implants (used frequently in infants)
Radiopharmaceutical used in neuroblastoma
MIBG therapy
Side effects of radiation
Based on target area
Fatigue
N/v
diarrhea
Xerostomia
Erythema, darkening of skin or excoriation
Pneumonitis
Pericarditis or effusion
Radiation nephritis
Radiation cystitis
Growth hormone def
Hypothyroidism
Hypopituitarianism
Gonadotropin defi
ACTH deficiency
Neruopathies
Musculosk
-Osteochondromas
-Arrest of growth plates
Side effects of radiation
Based on target area
Fatigue
N/v
diarrhea
Xerostomia
Erythema, darkening of skin or excoriation
Pneumonitis
Pericarditis or effusion
Radiation nephritis
Radiation cystitis
Growth hormone def
Hypothyroidism
Hypopituitarianism
Gonadotropin defi
ACTH deficiency
Neuropathies
Musculosk
-Osteochondromas
-Arrest of growth plates
After your neutrophils respond, what is your next cell to respond
Monocytes migrate to liver, spleen and become macrophages and dendritic cells
cell that displays Ag fragments on cell surface and present to lympocytes
Monocytes
messengers between innate and adaptive immune response
Monocytes
surface markers on lymphocytes (used in targeted therapies and monoclonal antibodies)
Stem cells: CD34
T cell markers: CD3, CD4, CD5, CD7, CD8
B cell markers: CD10, CD19, CD20, CD22
NK cell marker: CD56
CD= cluster of differentiation
Lab testing for surface markers on lymphocytes
flow cytometry or immmunophenotyping
impact of chemotherapy on hematopoiesis
7-10 days - neutropenia, anemia, thrombocytopenia (Count nadir)
14-21 days - counts start to recover - if recovered -> next chemo course
if not, wait
ANC formula
Normal values
Absolute neutrophil Count (ANC) = WBC x % neutrophils or segs + % bands
> = 1000 - normal
<1000 - neutropenia
200-500 - moderate neutropenia
<200 severe neutropenia
Neutropenic precautions
strict handwashing
social isolation
Call for temp 100.4
Immediate ER visit for blood cultures and broad spectrum antibiotics within 1 hour
No rectal temps or suppositories
assess oral mucosa, all skin, peri-rectal area
pain may be only one sign/symptom. unable to demonstrate inflammatory response ( no redness or pus)
PJP prophylaxis for oncological
Bactrim
Pentamidine
Atovaquone
Dapsone
Antibiotic Prophylaxis for onc
Levofloxacin
vaccines in onc
NO vaccines until off chemo for 6 months
Influenza vaccine to patients, family members
no covid vaccine
vaccines in BMT
none until 1 year post BMT and off immune suppression. Only attenuated vaccines
Live virus vaccines at 2 years post BMT
Siblings - no varicella vaccine. MMR okay
No influenza vaccine to patients or family early post BMT or active graft vs host disease
COVID vaccine hold while on steroids
Fever and Neutropenia in Hemoc empiric abx
Outpatient low risk: Ceftriaxone/Cefepime with oral fluoroquinolone (Cipro or Levo) x 7 days
inpatient low risk - ceftriaxone
High risk such as neutropenia or with focal findings such as cellulitis, pneumonia, mucositis, tunneled line infections:
Cefepime +/- Vancomycin (concern for strep/staph; skin barrier breakdown) +/- Metronidazole (Flagyl) (concern for intraabdominal process/GI barrier breakdown)
In bolick what infections are associated with ITP
measles
mumps
chicken pox
infectious mononucleosis
common cold
H. pylori
Hepatitis C
Onc patient with no identified infectious source that have persistent fever after 4-7 days of broad spectrum abx. What should be considered
fungal etiology
Granulocyte colony stimulating growth factors. What do these do. What are some agents we use
Enhance neutrophil recovery
-Neupogen - SQ, IV once daily
-Neulasta - pegfilgrastim
-SQ 0 once per chemo cycle, 24-72 hours after chemo
-typically used in solid malignancies
-risk of exacerbating blasts
<10kg we use Neupogen over Neulasta for tighter control
Engraftment period for BMT
14-21 days
what happens <3 months post BMT
Impaired neutrophil function on immunosuppressive treatment
impaired lymphocyte function
3 mos - 1 yr post BMT
T4:T8 inversion
delayed production of immunoglobulins
1-2 year post BMT
naïve but strengthening lymphocyte immunity
Oncologic emergencies
Anaphylaxis
Septic shock (CLABSI, peri-rectal or other abscess, pneumonia, bacterial translocation in gut)
increased ICP
Spinal cord compression
Superior vena cava syndrome
Tumor lysis (Hyperkalemia, hypocalcemia, hyperuricemia)
Typhilitis
Pancreatitis
SIADH
HTN
DVT
Capillary leak syndrome (specific to T cell immunotherapy)
peak onset of leukemia
2-10 years old
uncontrolled proliferation of immature white blood cells in blood forming tissues of the body
leukemia
chronic leukemia
Chronic myelogenous leukemia (CML)
Acute Leukemias
Acute lymphoblastic leukemia (more common)
Acute myelogenous leukemia
ages associated with poor outcomes in leukemia
<12 mos
>12 yrs
most common leukemia
Acute lymphoblastic leukemia (ALL)
s/s leukemia
fatigue
bone pain
fever
recurrent infections
anorexia
weight loss
pallor
gingival bleeding
bruising
hepatosplenomegaly
what lab findings are we looking for in leukemia
anemia
thrombocytopenia
elevated WBC with blasts and low neutrophils
Elevated LDH
tumor lysis (hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia)
treatment in leukemia
Chemotherapy +/- radiation
Relapse - chemo, radiation, BMT
length of treatment for leukemia
2 1/2 years
race higher risk for ALL
Hispanic followed by
white
CML develops due to
translocation of chromosomes 9 and 22 that produce the Philadelphia chromosome→ results in BCR-ABL1 chimera mRNA that allows for growth of leukemia cells
Testes and CNS are important sites to check for leukemia …..why?
very hard to treat
localized masses of leukemic cells
Chloromas
small, colorless to blue/purple nodules under the skin which are signs of leukemic infiltrates (most common in infants with congenital leukemia)
Leukemia cutis
Hgb requirement to go for radiation
at least 10
new dx of ALL/AML, when would you start allopurinol, rasburicase and aggressive IV fluid management
WBC>100,000 or in acute tumor lysis syndrome
Which is higher risk for leukocytosis
AML (more cell lines affected)
induction therapy for ALL lasts approx
4-6 weeks with goal of eliminating leukemia
chemo and meds for induction therapy for ALL
Vincristine
Corticosteroids
Asparaginase (PEG)
If high risk they will add in
anthracycline
What is done at end of induction therapy for ALL to help guide treatment plan
BMA + LP using flow cytometry
phases in ALL treatment
Induction phase
consolidation phase
maintenance phase
Goal of consolidation phase
eliminate submicroscopic levels of leukemia
meds used in consolidation phase
High dose methotrexate
Oral mercaptopurine
Asparaginase (PEG)
Vincristine
Decadron
high risk add
Anthracycline
Cytarabine
Cyclophosphamide
why do males get longer maintenance therapy
testes being a sanctuary site for leukemia to hide
ALL with CNS involvement, do you need to add radation
yes
CD 19 CAR T cells serious AE
tumor lysis syndrome
Cytokine release syndrome
encephalopathy
(all reversible but dangerous and can occur in the weeks following)
Cancer of the blood and blood-forming organs, such as the bone marrow, lymph nodes, and spleen.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 834). Wolters Kluwer Health. Kindle Edition.
leukemia
leukemia is classified by
the cell line affected and level where differentiation has been interrupted
inherited conditions that predispose patients to ALL
Fanconi anemia, trisomy 21, ataxia telangiectasis, Klinefelter syndrome, and Shwachman–Diamond syndrome.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 834). Wolters Kluwer Health. Kindle Edition.
increased incidence to AML with previous exposure to ______ and what inherited conditions
exposure to chemotherapy and inherited conditions, including trisomy 21, Diamond–Blackfan anemia, Fanconi anemia, Li–Fraumeni syndrome, paroxysmal nocturnal hemoglobinuria, and neurofibromatosis.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 834). Wolters Kluwer Health. Kindle Edition.
which leukemia is associated with chromosomal translocation known as philadelphia chromosome
CML
CML may progress after a variable amount of time to the accelerated phase and blast crisis which resembles
acute leukemia
In ALL very high WBC may cause
Leukostasis
what leukemia tend to appear more ill and why
AML,
cytopenias are more significant, ecchymoses, petechiae, epistaxis and other bleeding
Chloromas seen in
AML
what leukemia is often symptomatic and is often diagnosed incidentally
CML
In leukemia what is diagnostic
Bone marrow aspirate is diagnostic when blasts comprise >25% of the marrow space
LP is done to determine if CNS is involved
Hyperleukocytosis Is a WBC >
100,000
Hyperleukocytosis results in
increased blood viscosity (may result in neurologic, pulmonary, or cardiac sequelae) and is a medical emergency.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 836). Wolters Kluwer Health. Kindle Edition.
Therapy for Hyperleukocytosis
aggressive hydration, correction of metabolic disturbances, and prevention of tumor lysis syndrome. May require leukopheresis or exchange transfusion.
Transfusion may be indicated
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 836). Wolters Kluwer Health. Kindle Edition.
Treatment for CML
Current therapy is tyrosine kinase inhibitor (imatinib mesylate) while in chronic phase. The only curative therapy for CML is HSCT from an allogeneic donor; indicated if the patient does not tolerate or fails to achieve or maintain a remission with imatinib mesylate.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 837). Wolters Kluwer Health. Kindle Edition.
side effects of chemotherapy and radiation
n/v
alopecia
mucositis
anorexia
pancytopenia
s/s lymphoma
fixed and non tender lymphadenopathy
B-symptoms
-fever
-drenching sweats
-Unintentional weight loss
Lymphoma typically occurs in what age
15-35
what virus is believed to have an association with lymphoma
EBV
Children with immunodeficiencies are at greatest risk for what type of lymphoma
Hodgkin lymphoma
which lymphoma spreads faster
Non Hodgkin lymphoma
is the result of proliferation of T, B, or indeterminant-cell origin lymphocytes,
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 838). Wolters Kluwer Health. Kindle Edition.
Non Hodgkin lymphoma
spreads more slowly and orderly, typically to adjacent lymph nodes and possibly involving the liver, spleen, bone, bone marrow, lungs, or brain.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 838). Wolters Kluwer Health. Kindle Edition.
Hodgkin lymphoma
Non Hodgkin lymphoma symptoms
Lymphadenopathy may be present. If abdomen is involved, palpable mass may be present and associated with pain, nausea, vomiting, abdominal distension, hepatosplenomegaly, changes in bowel habits, or hematochezia. Mediastinal involvement may present as superior vena cava syndrome, facial/neck swelling, snoring, dysphagia, or chest pain. Systemic symptoms may include fatigue, fever, malaise, weight loss, anorexia, and night sweats. Pancytopenia and related complications may be present if the bone marrow is involved.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (pp. 838-839). Wolters Kluwer Health. Kindle Edition.
What differentiates NHL from HL
Reed sternberg cells
presence ->HL
absent -> NHL
Tumor of lymphocytes
Lymphoma
what “better” to have
HL
NHL
HL
Reed-Sternberg cells have the appearance of
an owls eye
3 types of NHL
Lymphoblastic lymphoma
Anaplastic large cell lymphoma
Mature B cell lymphoma (Burkitt, primary mediastinal B cell lymphoma, and diffuse large B cell lymphoma)
risk for developing NHL
-Congenital and acquired immunodeficiencies
-Solid organ transplants are 200-300xs more likely
-EBV
oncological process
Contains 2 cell types: Neuroblasts and Schwann cells
Neuroblastoma
most frequently diagnosed malignancy in infancy
Neuroblastoma
Med diagnosis age for Neuroblastoma
19 mos
Most common race for neuroblastoma
white
neuroblastoma can develop anywhere within
the sympathetic nervous system
-most found chest, abd, pelvis
50% of neuroblastoma arise from
adrenal medulla
s/s neuroblastoma
asymptomatic
Edema - large masses can alter venous return from lower extremities
abd involvement: tenderness, distention, hepatosplenomegaly
Lesion in upper thoracic spine or posterior mediastinum -> superior vena cava syndrome due to vascular compression
Spinal cord compression: motor weakness, sensory loss, difficulty urinating/pooping
Oncological emergency: steroids, chemo, with possible radiation or surgery
Cervical mass: Horner syndrome = unilateral ptosis, myosis, and anhidrosis
Most common sites for metastatic disease: lymph node, liver, bone, bone marrow, skin (rarely metastasize to lung or brain)
spinal cord compression symptoms
motor weakness, sensory loss, difficulty urinating/pooping
emergency!
spinal cord compression syndrome treatment
steroids
chemo
possible radiation or surgery
Cervical mass symptoms
horner syndrome: Unilateral ptosis, myosis, anhidrosis
Most common sites for metastatic disease of Neuroblastoma
lymph node
liver
bone
bone marrow
skin
(rare for it to metastasize to lung or brain)
Opsoclonus-myoclonus ataxia syndrome (OMA) in Neuroblastoma
Myoclonic jerking, nystagmus, cerebellar ataxia
Tx: surgical resection, glucocorticoids, IVIG
Elevated LDH and ferritin in Neuroblastoma may suggest
more aggressive disease
Urine vanillylmandelic acid and homovanillic acid are elevated
in
Neuroblastoma
what is preferred test to check for metastatic disease in neuroblastoma
metaiodobenzylguanidine (MIBG)
what test is needed to confirm neuroblastoma
Biopsy
chemo treatment phase in neuroblastoma
Induction – multi agent chemo
Local control – surgical resection of tumor and radiation to tumor bed
Consolidation – high dose, myeloablative chemo followed by autologous stem cell rescue
Maintenance – eradicate any residual, circulating tumor cells
2nd most common abd malignancy
Wilms Tumor (Nephroblastoma)
3 most common gene involvement: WT 1 loss, WNT signaling pathway activation, and IGF2 overexpression
Wilms Tumor (Nephroblastoma)
Well-demarcated from renal tissue and surrounded by a fragile, gelatinous capsule
Wilms Tumor (Nephroblastoma)
median age of dx for Wilms Tumor (Nephroblastoma)
3.5 years
Smooth painless abd mass that does not cross midline most often found during bath or well child ecam
Wilms Tumor (Nephroblastoma)
what should you be careful with during exam when you suspect Wilms tumor?
when there is concern the patient has wilm’s tumor, care should be taken to avoid deep or repetitive and palpation because there is risk for capsular rupture (impacts staging and therapy)
why is biopsy contraindicated in Wilms tumor
capsular spillage ->advances pt stages and would require chemo and radiation as a part of plan
treatment for Wilms tumor
Goal: complete ureteronephrectomy with lymph node sampling before chemo (unless you have bilateral disease)
Bilateral: chemo and nephron-sparing surgery
Radiation if patient has stage III or IV, anaplastic histology, or to the lungs if metastases
85-95% survival rates
in this onc, lab findings may include acquired vWD or polycythemia
Wilms tumor
in wilms tumor, always assess for
Global Devlopmental Delay, aniridia, macroglossia, hemihypertrophy, overgrowth, history of omphalocele, or genitourinary abnormalities
Neoplasm from the sympathetic nervous system, most common extracranial solid tumor of childhood, typically disease of infants and young children.
Kline, Andrea M.; Haut, Catherine. Lippincott Certification Review: Pediatric Acute Care Nurse Practitioner (p. 840). Wolters Kluwer Health. Kindle Edition.
Neuroblastoma
Benign counterpart of neuroblastoma
Ganglioneuroma
In Neuroblastoma, MYCN gene amplification is associated with
poorer prognosis
Neuroblastoma, DNA index of ___ is associated with poorer prognosis
1
In neuroblastoma ages >= ______ is associated with poorer prognosis
12-18 mos
abdominal mass who presents with palpable mass, constipation and refusal to walk
Neuroblastoma
Neuroblastoma with metastatic disease may also present with
bone pain
malaise
fever
raccoon eyes (periorbital ecchymosis)
Blueberry muffin spots (metastasis to subcutaneous tissue)
Fastest growing tumor in pediatric oncology
Burkitt’s (Non-Hodgkin Lymphoma)
Fast growing tumor often presents with bowel perf
Burkitt’s (Non-Hodgkin Lymphoma)
which type of lymphoma that effects deeper lymph nodes
NHL
type of lymphoma that effects superficial lymph nodes
HL
lymphoma that more commonly affects children 15-19
HL
lymphoma that more commonly affects children <14
NHL
Treatment time for HL and NHL
HL 6 months
NHL - 3+mos but can be long 2.5 years like leukemia
most common solid tumors in children
brain tumors
60% of Brain tumors are located
Infratentorial (cerebellum)
40% are in the anterior 2/3 or brain mainly in the cerebrum (Supratentorial)
s/s brain tumors
depends on location and size
Headaches (usually in the AM)
lethargy
n/v
visual changes
polydipsia
personality or academic changes
Physical exam
Nystagmus
diplopia
ataxia
cranial nerve defects
Cranial nerves
I olfactory
II optic
III oculomotor
IV Trochlear
V trigeminal
VI Abducens
VII facial
VIII vestibulocochlear
IX Glossopharyngeal
X vagus
XI Accessory
which cranial nerves are for eye movement
III, IV, VI
which cranial nerves
sensation of face, biting, chewing
V
Which cranial nerves
facial muscles of face
VII
Which cranial nerves
Hearing and balance
VIII
Which cranial nerves?
oral, taste
IX
Which cranial nerves? brainstem, parasympathetic control of heart, lungs, GI tract
X
Which cranial nerve?
Shoulder elevation
XI
Which cranial nerve tongue movement
XII
Cerebellar tumors you will see changes in
gait
coordination issues
may present with increased ICP symptoms
Treatment for brain tumor
Surgical resection
Radiation
Chemo
Length ranges from 6mos to 1 year
IN tumor lysis syndrome, hyperurecemia is due to the breakdown of
nucleic acids
symptoms of tumor lysis syndrome
n/v/d
muscle weakness
if hypercalemic -> Trousseau’s sign and Chvostek’s sign
tumor lysis syndrome can cause
AKI
cardiac arrhythmias
seizures
lactic acidosis
what elevated labs coorelate with increased risk of tumor lysis syndrome
WBC
LDH
Treatment in tumor lysis syndrome
for Hyperkalemia -> calcium gluconate, insulin + dextrose, polystyrene sulfonate
for hyperphosphatemia -> phosphate binders
Hyperuricemia -> Allopurinol - inihibits
Rasburicase breaks it down
Renal dialysis
Serial cardiac monitoring
