Front
Stroke monitoring in Sickle Cell
Disease
Drug contraindicated in SCD
Sickle cell trait characteristics
Mutation sickle cell
Tactoids
Sickle cell antigen associated with
vaso-oclussive crisis
Vertebral infarction pattern in SCD
Organism aplastic crises SCD
Form of SCD that is protective
against Malaria
Standard prophylaxis TX in SCD
RBC lifespan in SCD
Average duration of aplastic crisis
Most common infectious causes of
acute chest SX
MCV in SS
Bowel Regimen in sickle cell
Max. Number of days for ketorolac
TX
Antibiotic TX in acute chest
syndrome
Empiric antibiotics sickle cell PX
Back
Transcranial Doppler ultrasonography; velocities - <170 cm/s is normal and low
risk, 170-199 conditional and moderate risk, >200 is abnormal and high risk
Ketorolac; all NSAIDs in general. Can cause AKI. Use maximum 5 days a weeks.
Around 40% of HbS, absence of anemia, inability to concentrate urine
(isosthenuria) and hematuria
Glutamate is replaced by valine in position 6 of the Hb beta chain, chromosome 11
Gel like substance that contains Hb crystals, secondary to HbS polymerization in
deoxy conditions.
VLA-4 (very late antigen 4); it interacts with VCAM-1
H vertebrae; infarction in the central portion of the vertebrae (fed by a spinal artery
branch). Outer portions are spared because of numerous apophyseal arteries.
Parvovirus B19
Only sickle cell trait HbSA; those with a homozygous HbS develop a severe form
Prophylactic penicillin before 2 months (some say for life, others recommend
cessation at age 5) + PCV13 vaccine (Pneumococcal conjugate vaccine) + at least
two doses of pnuemococcal polysaccharide vaccine (first dose <2 years)
10-20 days
10-14 days; platelets and WBCs are generally not affected
Infectious causes represent 30% of cases; most commonly Chlamydia pneumoniae
(28%), viral (22%), Mycoplasma pneumoniae (20%)
Normal, MCV is decreased with concomitant alpha-thalassemia or S beta
thalassemia and HB SC
Prevent or treat constipation secondary to opioid use; stool softeners (docusate) +
laxative (senna)
5 days a month
Broad spectrum IV Abx (cefuroxime) + oral macrolide (erythromycin, azitrhomycin)
<2 yo: cefotaxime (greater CSF penetration, young kids don’t exhibit meningeal
with fever
Normal Hb baseline in SCD
Hb elevation with packed red
blood cells
Components in cryoprecipitate
Indications for RBCs
Indications for platelets
Indications for FFP
Indications for cryoprecipitate
Transfusion reaction management
Severe neutropenia
Empiric antibiotic TX in
neutropenia
Cytarabine increases risk of
infection with...
Empiric antibiotic TX neutropenia
duration
You add antifungal in neutropenia
after...
Electrolyte abnormalities tumor
lysis syndrome
EPO during VOCs
Clinical features tumor lysis
syndrome
TX tumor lysis SX
signs); >2 years: cefuroxime
~ 7-9
HTO will raise 3% in standard adult or about 1%/ml/kg in a child; 12%/25 kg
Fibrinogen, factor VIII, vWF, XIII
Hb 7-8, decreased O2 saturation, orthostatic hypotension
<50,000 + active bleeding, prior to surgery
PX with multiple factor deficiencies and is bleeding or for thrombotic
thromobcytopenic purpura
Hypofibinogenemia, vonWillebran disease, situations calling for a “fibrin glue”
1) stop transfusion. 2) Tylenol + Benadryl. 3) maintain patent IV. 4) ABCs +
supportive symptom management. 5) if resp difficulty or severe hives, order
epinephrine at bedside
Neutrophil count <500, risk of infection is greater when <100
Broad spectrum beta-lactam with antipseudomonal activity (cefepime); additional
coverage with Vancomycin (PX with hypotension or cardiopulmonary deterioration,
PX that have received cytarabine, previous MRSA exposure); triple therapy with
metronidazole + vancomycin + 3-4 cephalosporin (patients with clinical suspicion of
tiphilitis, abdominal pain)
Alpha hemolytic streptococcus infection
48 hours, until ANC >500. ABX can be stopped if afebrile 24 hours, cultures
negative, no source of fever, marrow recovery
5 days of persistent fever
Hyperkalemia, hyperphosphatemia, hyperuricemia and hypocalcemia
EPO worsens bone pain and should be avoided in VOCs
Renal insufficiency, cardiac arrhythmias, seizures
Hydration (IV fluids with no K or phosphate), allopurinol, rasburicase (uric acid
elevation at baseline, renal impairment, Tx hyperkalemia (calcium glucanate, insulin
+ glucose, B2 agonists), phosphate binders (sevelamer, renagel)
Typhilitis
TX Typhilitis
Hyperleukocytosis
Hyperleukocytosis TX
Plain XR characteristics
osteosarcoma
Chemo agents osteosarcoma
Small round blue tumor
Bone zone osteosarcoma vs
Ewing
XR Ewing Sarcoma
Translocation Ewing Sarcoma
Chemo agents for Ewing sarcoma
Most common soft tissue sarcoma
in children
Most common pediatric
malignancy
DX bone marrow for ALL
Most common ALL
Favorable vs unfavorable
translocations in B cell ALL
Chemotherapy ALL
Auer rods are characteristic of...
Chemotherapy AML TX
Splenic sequestration
Mechanism of action hydroxyurea
in HbSS
Biggest problem of chronic
transfusions and TX
Neutropenic enterocolitis; involves distal ileum, cecum or ascending colon.
Complicated with sepsis and perforation. Associated with leukemia.
Bowel rest, IVF, ABX (cefepime + metronidazole), surgery?
AML >200,000; ALL, CML >300,000
Goal <100,000. Cytoreduction with chemotherapy, leukopheresis, exchange
transfusion, hydroxyurea
Codman’s triangle, periosteal new bone formation, “sunburst” pattern
HD MTX, doxorubicin, vincristine, ciclophosphamide, cisplatin
Ewing sarcoma
Osteosarcoma affects metaphysis, Ewing affects diaphysis
“onion skin”, erosive lesions in diaphysis
T (11;22) producing EWS-FLI1 protein
Radiation + Doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide
Rhabdomyosarcoma
Acute lymphoblastic leukemia
>25% blasts
Pre B cell ALL (70%); followed by pre B Myeloid, mature B cell, T cell
T(12;21) is favorable, T(9;22) is unfavorable
Multidrug in stages: induction, consolidation, maintenance. Vincristine, 6MP, MTX,
cyclophosphamide, 6TG, Asparag, cytarabine
AML
DCTER (dexamethasone + cytarabine + thioguanine + etoposide + rubidomycin)
Rapid enlargement of the spleen with resultant trapping of the blood elements
Increase expression of fetal Hb; preventing polymerization of HbS
Iron overload; exogenous chelator like deferoxamine (SC) or deferasirox (PO)
Chemotherapy associated with
neutropenic enterocolitis
Cell cycle non-specific chemos
S phase specific chemotherapies
M phase specific chemotherapies
Phase nonspecific vs. specific
Alkylating agents
General side effects alkylating
agents
Chemo that causes SIADH
SE specific to ifosfamide
Special considerations nitrogen
mustards
SE cyclophosphamide
Use of platinum complexes chemo
SE platinum complexes
Supportive care platinum
complexes
TX peripheral neuropathy
TX for anticipating n/v
SE nitrosoureas
Uses of nitrosoureas
SE thiotepa
Supportive care thiotepa
SE busulfan
Antitumor antibiotics
Cytosine arabinose, vinca alkaloids and doxorubicin
Alkylating agents, nitrosoureas, antitumor antibiotics, procarbazine, cisplatin,
dacarbazine
Cytosine arabinoside, hydroxyurea, 6-mercaptopurine, MTX
Vincristine, vinblastine, paclitaxel
Nonspecific exert their effect throughout the cell cycle and have a linear dose
response vs. specific phase specific beyond a certain dose, further increases in
drug dose will not result in more cell killing
Nitrogen mustards (cyclophosphamide, ifosfamide, melphalan), platinum
complexes (cisplatin, carboplatin, oxaliplatin), nitrosoureas (carmustin, lomustine),
thiotepa, busulfan
Myelosuppression (dose limiting toxicity), infertility, secondary malignancies,
alopecia, pulmonary fibrosis
Cyclophosphamide and vinca alkaloids
Fanconi SX and encephalopathy
High hydration (2x maintenance, decrease urine gravity, strict IOs), mesna (for
cyclophosphamide)
Hemorrhagic cystitis
Osteosarcoma, neuroblastoma, brain tumors, germ cell tumors
Nephrotoxicity (cisplatin, Mg and K wasting), SEVERE nausea and vomiting
(cisplatin), ototoxicity (carboplatin is less toxic), peripheral neuropathy, anemia
IVF w/ magnesium, antiemetics (ondasetron + dexamethasone + aprepitant)
Gabapentin
Loracepam; olanzapine is first line of prophylaxis in adults
Delayed myelosuppression (dose-limiting; lamustine nadir is 3-4 weeks), pulmonary
fibrosis, hepatotoxic
Brain cancer, lymphomas, multiple myeloma
Bone marrow suppression, skin rash, mucositis, transaminitis
Bath patients 3-4x a day to avoid skin breakdown due to excretion in sweat glands
Bone marrow suppression, pulmonary fibrosis, skin hyperpigmentation
Anthracyclines (daunorubicin, doxorubicin, idarubicin), bleomycin
Use anthracyclines
Toxicities anthracyclines
TX cardiotoxicity anthracyclines
Physiopathology cardiotoxicity
doxorubicin
Use of bleomycin
Toxicity bleomycin
Antimetabolites Chemo
Use of MTX Chemo
Drug interactions MTX
Toxicities MTX
Supportive care MTX
Use Cytarabine
Toxicities cytarabine
Cytarabine SX
Leucovorin rescue
TX mucositis in chemo patients
Purine analogs toxicities (6-MP)
Drug interaction purine analogs (6- Allopurinol; decreases dose by 75%. 6-MP is inactivated by xanthine oxidase
MP)
Plant alkaloids Chemo
MOA Vinca alkaloids
Toxicities vinca alkaloids
Parameter to monitor with vinca
ALL, AML, osteosarcoma, neuroblastoma, neuroblastoma, Wilms tumor, Ewings
sarcoma
Cardiotoxicity (CHF, arrhythmia, MI), n/v, mucositis, alopecia, severe vesicants
Dexrazoxane (Zinecard)
Iron binds to doxorubicin and precipitates in the heart; doses accumulate lifelong
(450 mg/m2 maximum dose in a lifetime)
Hodgkin and non-Hodgkin lymphoma
Pulmonary fibrosis, mucositis, allergic reaction, anaphylaxis, hyperpigmentation
Folic acid analogs (MTX), pyrimidine analogs (cytarabine), purine analogs (6-
mercaptopurine, 6 thioguanine, fludarabine, cladribine [oral])
ALL, NHL, Osteosarcoma
Renal elimination; careful with NSAIDS, ASA, B-lactams. Bound to plasma proteins;
careful with sulfonamides, salicylates, tetracyclines, phenytoin. Avoid PPIs.
Mucositis, myelosuppression, renal dysfunction
Leucovorin rescue, IVF with bicarbonate, antiemetics, monitor drug levels
ALL, AML, Lymphoma
Myelosuppression, mucositis, neurotoxicity, ocular (chemical conjunctivitis, keratitis,
photophobia), hepatotoxicity, cytrarabine syndrome (fever, bone pain, rash)
Infusion causes fever, bone pain and rash with chemical conjunctivitis (TX steroid
eye drops)
Administer 20-24 hours after giving MTX; cancer cells do not have receptors for
leucovorin  only healthy cells respond
Care + vancomycine (prevent gram – infections)
Myelosuppression, hepatotoxicity
Vinca alkaloids (vincristine, vinblastine, vinorelbine), topoisomerase inhibitors
[captothecins (irinotecan), epipodophyllotoxins (etoposide)]
Bind tubulin and block ability to polymerize into microtubule. Cell specific G2-M
phase
Peripheral neuropathy, hyperuricemia, vesicants, myelosuppression (vinblastine,
NOT vincristine), SIADH
Total bilirubin; adjust dose if necessary
alkaloids
Captothecins (irinotecan) toxicities
Supportive care irinotecan
Toxicities epipodophyllotoxins
(etoposide)
Neuropathy from vincristine
Chemo contraindicated intrathecal
L-asparaginase and peg-
asparaginase use
MOA L-asparaginase and peg-
asparaginase
Toxicities L-asparaginase and
peg-asparaginase
Hydroxyurea use
Special considerations
hydroxyurea
Toxicities hydroxyurea
TX Infusion reaction etoposide
Infusion reaction etoposoide
Peak incidence of malignant
abdominal masses
Malignancy depending of area of
mediastinum
Radiological signs of bone
malignancy
Percentage of hereditable vs non-
hereditable retinoblastoma
Mutation associated with
hereditable retinoblastoma
High risk features for
retinoblastoma
Most common extracranial cancer
Median age of diagnosis
Myelosuppression, diarrhea (acute and delayed; “I run to the can”), alopecia
Atropine (acute diarrhea), loperamide (delayed diarrhea), G-CSF
Cardiovascular (transient hypotension and CHF), myelosuppression, secondary
AML, hypersensitivity reactions
Sensory + motor (foot drop) + anatomic (jaw pain, constipation)
Vincristine, extremely neurotoxic. Fatal.
ALL
Inhibit protein synthesis by hydrolyzing asparagine to aspartic acid and ammonia;
G1 specific
Hypersensitivity reactions (fever, chills), hepatotoxicity, pancreatitis, coagulation
abnormalities
CML, sickle cell anemia
CBC every 2 weeks initially, then every 4-6 weeks; renal and liver function test; uric
acid
Myelosuppression, hepatotoxicity, hyperpigmentation
Stop infusion, correct blood pressure and readminister at a lower rate
Hypotension + flushing
1-5 years
Anterior – teratomas; middle – lymphomas or metastatic abdominal tumors;
posterior neurogenic tumors (neuroblastoma, ganglioneuroblastoma)
Codman triangle, sunburst pattern and onion skin appearance
Hereditable accounts for 25% of cases, nonheritable 75%
RB1 gene mutation
Choroid involvement or tumor beyond the lamina cribosa
Neuroblastoma (8% of all pediatric cancers)
19 months (0-5 years of age)
neuroblastoma
Mutation found in familial
neuroblastoma
Neuroblastoma arise from...
Most common sites for metastatic
disease of neuroblastoma and
percentage of patients
Paraneoplastic syndromes
associated with neuroblastoma
Opsoclonus myoclonus syndrome
manifestations
Vasoactive intestinal peptide
syndrome
Skin involvement of
neuroblastoma
Highly specific neuroblastoma
imaging
TX neuroblastoma in PX <1 year
of age
High risk neuroblastoma TX
Dinutuximab
Syndromes associated with
hepatoblastoma
Hepatoblastoma biomarker
Definitive cure hepatoblastoma
Mean age of diagnosis Wilms
tumor (unilateral vs bilateral)
Congenital anomalities associated
with Wilms tumor
WAGR SX
Mutations in the ALK gene; PHOX2B in 5% of cases
Adrenal glands or anywhere along the sympathetic chain
Half of patients present with metastatic disease at diagnosis; most common in
bones, bone marrow and liver
Opsoclonus myoclonus syndrome and vasoactive intestinal peptide syndrome
Myoclonus, ataxia and opsoclonus; low-stage and low-risk neuroblastoma with very
unfavorable neurologic outcomes (cognitive and motor delays)
Neuroblastoma tumors secreting VIP; presents with abdominal distention,
intractable watery diarrhea, hypokalemia and dehydration
Bluish subcutaneous nodules
I-meta-iodo-benzylguanidine (I-MIBG) scintigraphy; it is a norepinephrine analogue
that is selectively concentrated in sympathetic nervous tissue
Neuroblastoma tends to regress without treatment
3 chemotherapy phases: induction – consolidation – maintenance
Antibody Ch14.18 used in the TX of high risk neuroblastoma (improving 2-year
survival)
Beckwith/Wiedemann syndrome, familial adenomatous polyposis and trisomy 18
Alpha-fetoprotein is useful for diagnosis and monitoring; markedly elevated
suggests diagnosis (consider elevation of AFP is normal in healthy infants until 8
months of age)
Complete surgical resection
41-46 months in unilateral tumors, 29-32 months in bilateral
Beckwith-Wiedemann SX, isolated hemihypertrophy, WAGR syndrome and Denys-
Dash syndrome
Wilms tumor + aniridia + genitourinary abnormalities + mental retardation
Denys-Dash SX Nephropathy + Wilms tumor + gonadal dysgenesis
Screening of patients with Ultrasonography every 3 months until 8 years of age
increased risk for Wilms tumor
Hematologic disease acquired with 8% of patients can acquire von Willebrand factor deficiency
Wilms tumor
Staging systems for Wilms tumor Children’s Oncology Group staging system and International Society of Pediatric
Oncology
Chromosome alterations Loss of heterozygosity on chromosomes 1p and 16 q, and 1q gain
associated with poor outcomes
Wilms tumor
SE Bleomycin Pulmonary fibrosis, dermatitis, anaphylaxis
SE Busulfan VOD, rash, myelosupression
SE carboplatin and cisplatin Ototoxicity, renal dysfunction, electrolyte wasting, anaphylaxis/allergy
SE Carmustine Hepatic fibrosis, pulmonary fibrosis, CKD, dermatitis
SE cyclophosphamide Hemorrhagic cystitis, SIADH
SE Cytarabine Increased risk of strep viridans infection, anaphylaxis, dermatitis, ataxia (high
dose), conjunctivitis, stomatitis
SE Daunomycin, Doxorubicin, Pink/orange urine, arrhythmias, CHF, alopecia, stomatitis, vesicant
Idarubicin
SE dactinomycin Radiation recall, VOD/ live dysfunction
SE etoposide Stomatitis, alopecia, anaphylaxis/rash, hypotension
SE ifosfamide AKI and CKD, Fanconi SX, encephalopathy/ seizures, hallucinations, depression,
hemorrhagic cystitis
SE L’asparaginase Hepatic fibrosis, hyperglycemia, pancreatitis, coagulation defects
SE Irinotecan Diarrhea (dose limiting)
SE MTX Hepatic fibrosis, AKI, stomatitis, encephalopathy, dermatitis, anaphylaxis
SE Vincristine Constipation, jaw pain, seizures, SIADH, paresthesia, neuropathy
PRES Posterior reversible encephalopathy; clinical-radiological entity. Edema in the
posterior aspect of the brain. Signs include hypertension, seizures, altered mental
status and visual abnormalities.
Risk factors osteosarcoma P53 mutations, radiation, Paget’s disease of the bone, hereditary retinoblastoma,
Syndromes like Rothmund-Thomson, Bloom, and Werner
Risk factors ALL Down SX, chromosome fragility syndromes: Blooms, Fanconi, Anemia, Ataxia

ALL subtypes
Unfavorable factors ALL
Favorable factors ALL
Age distribution AML
Leukemia with Auer Rods
Leukemia that presents with DIC
Favorable factors AML
Unfavorable factors AML
TX APL (M3 AML subtype)
AML with eosinophilia
Cells Hodgkin Lymphoma
Age distribution Hodgkin
lymphoma
Systemic B symptoms
Age HL vs NHL
CC HL
Characteristic HL children <10 yo EBV-positive tumor genomes
Autoimmune conditions associated Nephrotic SX, AIH, ITP-like thrombocytopenia
HL
4 HL subtypes + characteristics
DDX HL
HL low prognosis “X-E-B"
TX HL
telangiectasia, NF, Klinefelter, Schwachman SX
Pre B cell (70%), pre B eel myeloid (10%), mature B cell (2-5%), T cell (16%),
<1 year or >10 years, initial WBC >50,000, hypodiploidy (<44), t(9,22), MLL
rearrangement, iAMP21, CNS or testicular disease, Minimal residual disease
>0.01%
1-10 years, WBC <50, hyperdiploidy (>50), Trisomy 4 and 10, t(12,21), MRD <0.01
Neonates, adolescence, >55 yo
AML
AML; acute promielocytic leukemia (APL)
t(15,17) in APL, NPMI Mutation, CEBPA mutation, t(8<21), inv 16
WBC >100,000, age <1 or >15, secondary AML, elevated LOH, FLT-3 ITD gene
duplications, monosomy 7
All-trans-retinoic acid (ATRA); APL has PML/RARA fusion protein
M4; characterized by inversion of chromosome 16
Reed-Sternberg cells
Bimodal; 20 years and >50 years
10% weight loss, fever 38 x 3 days, night sweats
HL in adolescents vs NHL in young children
Alcohol induced nodal pain, mediastinal involvement (upper airway SX like cough),
pruritus from cholestatic liver disease, peripheral sensory neuropathy
Lymphocyte predominance (young males, localized), mixed cellularity (age <10,
advanced disease), lymphocyte depletion (HIV patients, BM involvement), nodular
sclerosing (most common, affluent societies)
Infections (atypical mycobacteria, cat scratch disease, toxo, mono), autoimmune
(SLE, JRA, Kawasaki), oncologic (NHL, metastatic LAD, leukemia)
X for bulky disease (1/3 intrathoracic diameter, >10 c), E for extranodal disease, B
symptoms
Very radiosensitive; AVBE (adrlamycin, bleomycin, vinblastine, etoposide), MOPP
(mechlorethamine, oncovin, procarbazine, prednisone)
Ann Arbor classification
Site of presentation HL vs NHL
GI abnormality that can suggest
Burkitt’s lymphoma
Classification NHL
Staging for Burkitt Lymphoma
Subtypes of non-lymphoblastic
NHL
Deletion associated with bilateral
retinoblastoma
Indication of enucleation
retinoblastoma
Most common pediatric brain
tumors
Glial tumors
Neuronal tumors
Germ cell tumors
Choroid plexus tumors
Types of SNC pediatric tumors
Wilms vs Neuroblastoma
Genetics Wilms tumor
TX Wilms Tumor
Most common malignant brain
For HL. 1 – single lymph node region or single extralymphatic site; 2 – two or more
sites, same side of diaphragm; 3 – both sides of diaphragm or spleen; 4 – diffuse
involvement of extralymphatic sites +/- nodal disease
HL starts cervical or supraclavicular vs NHL starts in abdomen if B cell (fast
growing, with extranodal disease) or thorax if its T-cell
Intussusception in child > 5yo
1. Lymphoblastic lymphoma (immature T cell origin), indistinguishable from ALL; 2.
non-lymphoblastic (B cell origin, Burkitt’s lymphoma); 3. large cell lymphoma (large
B cell, T cell, histiocyte origin)
St. Jude/Murphy Staging System
1 Burkitt lymphoma - B cells with basophilic cytoplasm “starry sky” pattern; doubles
every 24-48 hours with high risk of TLS. 2 Sporadic – 90% present with abdominal
pain and distention, distension, intussusception, marrow and CNS involvement; 3
Endemic – equatorial Africa present in jaw, orbit, CNS, and paraspinal, EBV
genome present in 95%
13q14 deletion; inactivation of both alleles of the retinoblastoma
Large tumors (>60% of globe) with no visual potential, blind, painful eyes and/or
tumors that extend into the optic nerve
Supratentorial (60%), infratentorial (40%), medulloblastoma (25%) and astrocytoma
(18%)
Astrocytoma, oligondrendroglioma, ependymoma
Medulloblastoma, supratentorial PNET, pineoblastoma, AT/RT
Teratoma, germinoma, NCGCT
Papilloma, carcinoma
Glial, neuronal, germ cell, choroid plexus, craniopharyngioma
Wilms does not cross the midline and pulmonary mets in 10%; Neuroblastoma may
cross the midline
Chromosome 11 defect, WT1 suppressor gene
QX (nephrectomy + biopsy of contralateral kidney) + Chemo (vincristine and
actinomycin; D-doxorubicin in advance stage; radiation >stage 3
Medulloblastoma
tumor of childhood
CC medulloblastoma
DX medulloblastoma
Radiation TX for medulloblastoma
should be avoided in...
Thrombophilia Work up
Workup for patients with venous
thrombosis in atypical locations
(hepatic, mesenteric, dermal,
cerebral)
Bleeding work up
Marker for heparin induced
thrombocytopenia
Abnormal PT, normal PTT causes
Abnormal PTT, normal PT causes
Abnormal PTT + PT causes
Mutation that increases levels of
thrombin
Factors inactivated by
antithrombin
Factors inactivated by Protein C
and S
Most common genetic disorder
associated with thrombosis
Causes of hyperhomocysteinemia
K replacement
Nausea, vomiting, AMS, truncal ataxia, head titubation (bobbing), unsteady gait and
coordination, visual loss (optic nerve), diplopia with lateral gaze (abducens nerve)
Contrast enhanced MRI of brain and spine + CSF cytology
Children under 3 years old; damaging to growing CNS
Protein C (antigen + activity), protein S (antigen + activity), anti-thrombin III (level),
prothrombin gene 20210 mutation, Factor V Leiden mutation, MTFHR
polymorphism, lupus anticoagulant (cardiolipin glycoprotein IgG and IgM), D-dimer
PX should be screened for paroxysmal nocturnal hematuria. Send CD59, CD55,
WBC and RBC PNH
PT, PTT, INR, FVIII activity, vW antigen, ristocetin cofactor, vWF multimers, FIX
activity
PF4
FVII deficiency, early vitamin K defiency, oral VKA
FXII, XI, IX, VIII deficiency, Severe vWD
FX, V, II deficiency, fibrinogen, Vit K def, Oral VKA excess, liver disease
Prothrombin G20210A mutation
FIIa, FXa and FIXa
FV and FVIII
Factor V Leiden mutation (resistant to Protein C)
B6, B12 and folic acid deficiency, polymorphisms in the MTHFR gene
When K <3; replace with KCl 0.5 mEq/kg (Max: 20 mEq). Follow up K if it was <2.8;
may require a repeat replacement. PO if patient can't tolerate (IV takes 2-3 hours
and it not compatible with many other medications). REMEMBER: low Mg sets up
for low K, most calcineurin inhibitors (prograf, cyclosporine) increase Mg and K

Mg replacement
Prophylactic dosing in neutropenic
fever
Treatment dosing in neutropenic
fever
Antifungals bone marrow
transplant patients
Antivirals bone marrow transplant
patients
Hepatic Veno-Occlusive disease
(VOD)
CNS leukemia presentation
AML M4 characteristics
ABC
Increased risk of leukemia en
Down SX
Disorders associated with
increased leukemia risk
Important sites of potential
leukemia infiltration outside of
bone
Major life-threatening complication
of acute with acute leukemia
Leukemia with highest risk of
massive mediastinal
wasting
Mg <1.6; PRN IV Mg sulfate 50 mg/kg (max 2 g) infuse over 2 hours; monitor BP.
Levo, cipro or Pen VK if ANC >500; or cefepime Q12 if ANC <500
Cefepime if it’s a new fever and PX is stable; add vancomycin if patient appears
toxic, skin breakdown, presumed Gram (+) etiology, persistent fever >48 hrs on
cefepime. --- If PX is on cefepime and shows signs of deterioration start
Meropenem and Vancomycin. If PX appears septic add second gram negative
coverage (amikacin)
Micafungin Pre-BMT (during conditioning) and voriconazole or posaconazole (post-
BMT); abelcet (amphotericin B) if suspicion or history of aspergillosis or if unstable.
Nystatin topical or swish-swallow if necessary.
Acyclovir prophylaxis if CMV negative; if CMV positive or history use valganciclovir
(PO) or ganciclovir (IV) as prophylaxis (daily dosing) or treatment (BID). Based on
PCR surveillance.
Disease occurring in patients after hematopoietic cell transplantation characterized
by hepatomegaly, RUQ pain, jaundice (hyperbilirrubinemia >2 mg/dl) and fluid
retention/ascites. Generally, in pre-engraftment period.
CN palsies
Gingival infiltration with frequent skin lesions, WBC >100,000
Absolute Basophil Count; neutrophils + monocytes
15 x; 1% develop leukemia by 5 years of age
Ataxia telangiectasia, SCIDs, Fanconi anemia, Bloom SX, Klinefelter SX,
neurofibromatosis, Down SX
CNS and testes (barriers)
Overwhelming infections (sepsis, pneumonia). The risk of sepsis is correlated with
the severity of neutropenia.
T-cell ALL
lymphadenopathy
Chemotherapy phases for
leukemia
Percentage of remission of ALL in
first 4 weeks of chemotherapy
Common bone complications after
leukemia treatment
Peak incidence of ALL
Aneuploidy associated with Li-
Fraumeni
Two classes of translocations
Mutation present in infant
leukemia
Most common target genes
governing B-lymphoid
development
Percentage of B-cell vs. T-cell ALL
Most powerful leukemia prognostic
factor
Induction therapy components for
ALL
Relapse rate of children with ALL
Blinatumomab
Chemotherapy toxicity common in
adolescents with ALL
Protection against malaria sickle
cell
Inductions – intensification – maintenance
95%
Avascular necrosis, especially of the femoral head
1 to 5 years of age
Low hypodiploidy (30-39 chromosomes); associated with the presence of TP53
mutations
First: relocation of oncogenes into regulatory regions (C-Myc under control of IGH
or IGK; rearrangement CRLF2 and EPOR); Second: juxtapose of two genes that
encode a chimeric protein that has distinct functions (ETV6-RUNX1; TCF3-PBX1,
BCR-ABL1)
MLL rearrangement leukemias; they have very few additional somatic mutations
PAXX5 and IKZF1
Precursor B cell (85%) and T cell (15%)
Early response to treatment = Minimal Residual Disease (MRD) defined as 1
leukemia cell per 10,000 cells (time required to eliminate the bulk leukemic-cell
population to undetectable levels.
Glucocorticoids (prednisone or dexamethasone), vincristine, an asparaginase
preparation and an optional anthracycline (depending on risk factors) and
intrathecal therapy.
Occurs in 15-20%
Genetically modified antibody that recognizes both CD19 and CD3 (on T cells) and
therefore brings T cells into direct contact with B-cell ALL
Osteonecrosis [most commonly affects major joints (hips, knees, shoulders,
ankles)]
Only sickle cell trait is protective (heterozygous state); sickle cell disease results a
in more severe presentation
Pathophysiology sickle cell
Infectious prophylaxis for HbSS
Fever management HbSS
High-risk features for fever in
HbSS
RBC lifespan in HbSS
Infection Parvovirus B19 in HbSS
Non-specific laboratory features
during VOC
VOC indicative of poor prognosis
in HbSS
Definition of Acute Chest SX
Neurological complication HbSS
TX for acute stroke in HbSS
“Auto-transfusion” in HbSS
Splenectomy indication HbSS
TX priapism in HbSS
Surgery preparation for HbSS
patients
Lab parameter to monitor
Hydroxyurea compliance in HbSS
Age at which neutrophil
predominance occurs
Classification severity neutropenia
Valine is hydrophobic (vs. Glutamine is hydrophilic) which polymerizes in the
deoxygenated state = cells sickle repeatedly
Penicillin prophylaxis (for life vs. 5 years of age) + PCV13 + two doses of
pneumococcal polysaccharide vaccine (after 2 years of age) + meningococci
vaccine
Any fever (>38.3) is treated as an emergency – CBC + blood culture + empiric
ceftriaxone (antipneumococcal antibiotic)
WBC >30 or <5, fever >40C, “ill-appearing”
10-20 days
Aplastic crisis; due to short RBC lifespan (10-20 days), cessation of RBC
production for 10-14 days secondary to the infection leads to profound anemia
Minor decrease in Hb concentration from baseline and an increased WBC
Dactylitis, especially in infants and young children
New pulmonary infiltrate on CXR with one or more: fever, tachypnea, dyspnea,
hypoxia and chest pain
Stroke, 10% in the first 20 years (peak at 4-8 years old)
Rapid reduction of HbS percentage; RBC transfusion or exchange transfusion with
erytrhocytopheresis
RBC initially trapped in the spleen are slowly released into circulation after
transfusion (2-3 gr/dl on average); be cautious when transfusion
Commonly after second or third sequestration
Aggressive analgesia and pesudoephredrine or etilefrine (decrease vascular
engorgement of the cavernosa); aspiration and irrigation if severe
Perioperative transfusion/exchange to increase Hb concentration and decrease
HbS
Increased MCV
At puberty 70% predominance; predominant at birth, during infancy they represent
20-30%, 50% at 5 yo
Mild 1.0-1.5; Moderate 0.5-1.0; Severe <0.5
Common clinical finding in PX with
chronic sever neutropenia
Infectious pathogens in
neutropenic patients
Most common infections in
neutropenic patients
Differential for cyclic vs. Severe
congenital neutropenia
Shwachman-Diamond SX
Infectious neutropenia
Evans SX
Alloimmune Neonatal Neutropenia
Cyclic neutropenia
TX Cyclic neutropenia
Severe congenital neutropenia
Conditions associated with sever
congenital neutropenia
Gingitivits; serious infections are not common since other parts of the immune
system remain intact
Endogenous flora; S aureus, Gram negative organisms, S epidermiditis,
streptococci, enterococci
Cellulitis and abscess or furunculosis, pneumonia and septicemia
Weekly CBCs for 6 weeks
AR disease characterized by bone marrow and pancreatic insufficiency and skeletal
abnormalities (metaphyseal chondrodysplasia). Consistent with malabsorption and
neutropenia.
Most common with viral illness; during the first 24-48 hrs and lasts 3-8 days
Presence of antibodies directed against red blood cells and platelet antigens and
occasionally neutrophil antigens = pancytopenia
Transplacental transfer of maternal alloantibodies agains infant’s neutrophils –
delayed separation of umbilical cord, mild skin infections, fever, pneumonia in first 2
weeks. Recover at 7 weeks.
Regular, periodic oscillations in the number of neutrophils; neutropenia + elevated
monocyte count. Mean oscillatory period of 21 days. Mutation in neutrophil elastase
gene.
Daily rhG-CSF to reduce the 21-day interval to 9-11 days with one day of profound
neutropenia
AD, mutation in elastase gene. Arrest in myeloid maturation of the promyelocyte
stage. ANC <0.2. AR disease is called Kostmann disease.
Mouth ulcers, gingivitis, otitis media, respiratory infections, cellulitis, skin abscesses