Title: Oncologic Emergencies
1Oncologic Emergencies
2Oncologic Emergencies
- Presenting Emergencies
- Spinal Cord Compression
- Hyperleukocytosis
- SVC Syndrome
- APML
- Therapy-associated Emergencies
- Tumor Lysis Syndrome
- Typhlitis
- Fever and Neutropenia
3Case 1
- 2 yo previously well girl
- Two week history of difficulty walking
- No acute infectious symptoms
- Admitted to neurology service for eval.
- Initial workup including EMG, muscle bx
- Eventual MRI of spine
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5Spinal Cord Compression
- Presentation
- Back pain (50) local or radicular
- Motor deficits (70)
- Sensory deficits (30)
- Bowel/bladder dysfunction
- Hydrocephalus high cervical tumors
6Spinal Cord Compression
- Oncologic Differential
- Sarcomas (50)
- Neuroblastoma
- Lymphoma
- Leukemia
- Chemotherapy-induced transverse myelitis
7Spinal Cord Compression
- High Index of Suspicion
- Plain films abnormal 2/3 of cases
- MRI
- CT
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9Spinal Cord Compression
- Treatment
- Dont delay
- Steroids
- XRT
- Chemotherapy, Surgery
- Outcome
- Depends on duration of symptoms
- ½ who are nonambulatory never recover!
10Case 2
- 14 year old boy, previously well
- Enlarged, nontender lymph node
- Outside biopsy consistent with lymphoma
- CBC at time of biopsy with WBC 17,000
- Referred to JHH for evaluation
11Case 2
- Admission Examination
- Massive hepatosplenomegaly
- Generalized lymphadenopathy
- Admission Labs
- WBC 440,000
- BUN/Cr 50/3.2, Uric Acid 20.9, Ca 14.2
12Hyperleukocytosis
- Definition WBC gt 100,000
- Seen in 10-15 of patients with ALL or AML
- Hyperviscosity more common in AML patients
- Metabolic disturbances more common in ALL patients
13Symptoms of Hyperviscosity
- Pulmonary
- Dyspnea, hypoxemia, right ventricular failure
- CNS
- Blurred vision, confusion, headache, coma
- Other
- CNS or pulmonary hemorrhage
- Priapism
- Renal insufficiency
14Hyperleukocytosis
- Treatment
- Hydration, alkalinization, allopurinol or
Rasburicase - Transfuse for thrombocytopenia
- Avoid PRBC transfusions. Do partial exchange if
necessary - Leukapheresis transient effect
- Chemotherapy when stable
15Case 3
- 11 year old girl, previously well
- 2 week history of increasing dyspnea
- CXR in pediatricians office shows mediastinal
mass - Referred to JHH for evaluation with increasing
respiratory compromise
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17SVC/SM Syndrome
- Pathology
- Compression of SVC
- Tracheal compression by mass in superior
mediastinum - 15 of anterior mediastinal tumors, esp NHL
- Pleural/pericardial effusions
- Thromboembolism
- Increased ICP
- Decreased CO
- Respiratory Failure
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19SVC/SM Syndrome
- Symptoms
- Cough, hoarseness, dyspnea, orthopnea, chest pain
- Headache, visual changes, nausea, lethargy
- Signs
- Swelling face/neck, plethora, cyanosis of
face/neck, suffusion of conjunctiva, distended
neck and chest wall veins, diaphoresis, wheezing,
stridor
20SVC/SM Syndrome
- Diagnosis
- - CXR, CT/MRI to evaluate airway
- Tissue diagnosis by least invasive means possible
- CBC, thoracentesis, BMA/Bx, lymph node bx
- AFP, b-hCG
- Delay diagnosis if necessary to save the patient
21SVC/SM Syndrome
- Treatment
- Avoid anesthesia/heavy sedation
- XRT
- Steroids
- Chemotherapy
- Cardio-respiratory support as indicated
22Case 4
- 14 year old boy, previously well
- Increasing abdominal pain
- Abdominal mass on exam
- CT scan reveals thickened peritoneum and ascites
- Diagnostic paracentesis reveals Burkitts Lymphoma
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25Case 4
- Admission Labs
- Uric Acid 17.2
- Potassium 6.0
- Creatinine 0.9
- LDH 1582
- WBC 11,800
26Tumor Lysis Syndrome
- Chemotherapy-induced cell lysis
- Sometimes seen spontaneously, prior to
institution of therapy, especially with Burkitts
Lymphoma - Metabolic triad of
- Hyperuricemia
- Hyperkalemia
- Hyperphosphatemia (associated with hypocalcemia)
- Associated with large tumor burden, rapid
doubling time, sensitivity to chemotherapy
27Tumor Lysis Syndrome
- Hyperuricemia arises from degradation of purines
from tumor nuclei - Symptoms
- 10-15 mg/dl lethargy, nausea, vomiting, urate
crystals in urine, renal colic, hematuria - gt20 mg/dl potential renal failure, mental
status changes
28Tumor Lysis Syndrome
- Treatment of Hyperuricemia
- Decrease production allopurinol, Rasburicase
- Promote solubility alkalinization (goal urine
pH 7.0-7.5) - Reduce concentration volume expansion with IVF
29Oxidation of nucleotide precursors into uric acid
Urate
pH5.6
pH7.3
Nucleotide Precursors
X
xanthine oxidase
xanthine oxidase
X
Xanthine
Uric Acid
Hypoxanthine
Urate Oxidase
X site of action of allopurinol
Allantoin
site of action of rasburicase
30Tumor Lysis Syndrome
- Hyperkalemia arises from release of intracellular
K from dying tumor cells - Worsened by renal failure, acidosis, increased
intake (ie. From PRBC transfusions and
K-containing meds) - Remain aware of pseudohyperkalemia (RBC lysis
from venipuncture, for example) - Standard treatments (insulin/glucose, bicarb,
kayexalate, etc.)
31Tumor Lysis Syndrome
- Hyperphosphatemia/hypocalcemia
- Lymphoblasts have 4x more PO4 as normal
lymphocytes - Glomerular filtration sole means of eliminating
PO4 - Worry about calcium phosphate crystal formation
and precipitation when - Ca x PO4 gt 60 mg/dl
32Tumor Lysis Syndrome
- Treatment of Hyperphosphatemia/Hypocalcemia
- Hydration
- Diuretics
- D/C alkalinization (crystals less soluble at pH gt
6) - Correct hypocalcemia, if possible, with calcium
gluconate - Treat hypomagnesemia
- Avoid alkalosis (lowers iCa)
33Tumor Lysis Syndrome
- Management
- Frequent electrolyte monitoring (often q 2 hrs)
- Consider dialysis for
- Potassium gt 7
- Uric Acid gt 10
- PO4 gt 10
- Hypertension
- Volume overload
- Other symptomatic electrolyte abnormalities
34Standard Initial Approach to Acute Tumor Lysis
- IVF D5 1/2NS 40 meq/L NaHCO3 at 2x
maintenance - Adjust fluids to maintain urine pH 7.0-7.5
- Frequent monitoring of electrolytes (as
frequent as every 2 hours) - Allopurinol or rasburicase (there are specific
eligibility criteria for rasburicase) - Dialyze for the usual indications
- Monitor for other metabolic complications
(hyponatremia, hypomagnesemia)
35Case 5
- 15 year old girl with 3 day history of oral
bleeding following extraction of impacted wisdom
teeth on 12/23/04 - Seen at community hospital on 12/26/04, and CBC
demonstrated white blood cell count of 22,000
with 83 blasts
36Case 5
- Patient transferred to JHH PICU late at night
12/26/04 - Oncology consult 0030 12/27/04
- Peripheral blood smear found to be
morphologically consistent with APML at 0130
12/27/04 - Diagnosis confirmed by flow cytometry at 1100
12/27/04
37Case 5
- Family told of confirmed diagnosis 1200 12/27/04
and presented with options of standard care vs.
enrollment in J0442 (institutional protocol for
APML) - Family provided informed consent for J0442 1500
12/27/04 - Patient had progressive renal failure and
pulmonary failure and taken to OR for intubation
and placement of dialysis catheters at 1730
12/27/04 - Decadron therapy begun upon return to PICU
- Patient expired of uncontrollable pulmonary
hemorrhage at 0045 12/28
38What is APML?
- APMLAcute Promyelocytic Leukemia
- Characteristic t(1517) resulting in PML-RARa
fusion protein - Fusion protein is a retinoic acid-sensitive
transcription factor - Pharmacologic doses of all-trans retinoic acid
downregulate activity of transcription factor - Recognition that ATRA is effective in the
treatment of APML changed OS from 10 to 70 in
adults
39The Importance of Managing Bleeding in APML
Patients
- 3 of APML patients die of hemorrhage before
institution of specific therapy - Half of the hemorrhagic deaths seen in treated
APML patients occur within the first week of
induction - If CR rate is 90, and if 5 of patients die of
hemorrhagic complications, then half of the
patients who do not achieve remission do not
because they die of bleeding
Tallman et al., 2007
40Pathogenesis of the Bleeding Diathesis
- Most common abnormalities are hypofibrinogenemia,
elevated FDPs and D-dimer, and prolongation of PT
and TT - APML cells express Tissue Factor and Cancer
Procoagulant - They also express high levels of u-PA and t-PA,
enzymes such as elastase and chymotrypsin, and
annexin II-associated fibrinolytic activity - Bleeding exacerbated by cytolytic chemotherapy
- Depressed PAI-1 levels
- Increase levels of TNF-a and IL-1b
- Plasma elastase levels increase
41Recommended Management of the Bleeding Diathesis
- Liberal use of FFP and Cryoprecipitate to
maintain fibrinogen above 150 mg/dl - Liberal use of platelet transfusions to maintain
platelet count above 50,000/ml - The benefit of heparin, tranexamic acid or other
anticoagulant/fibrinolytic therapy remains
undetermined and should be a matter for clinical
trial investigation
Sanz et al., Blood in press
42Falanga and Rickles, Pathogenesis and management
of the bleeding diathesis in acute promyelocytic
leukaemia. Best Prac and Res Clin Haematol,
16(3) 463-482, 2003
43Case 6
- 12 year old girl with newly diagnosed ALL
- Day 11 of induction therapy
- Meds include vincristine, decadron, daunorubicin,
asparaginase, zantac - Increasing abdominal pain, RLQ
44Typhlitis
45Typhlitis
- Inflammatory cellulitis of the intestines,
especially in the cecum - Think NEC in cancer patients
- Historically seen in patients with ALL early in
therapy, but can be seen in other settings - Pancytopenia
46Typhlitis
- Presentation
- Abdominal pain
- N/V, diarrhea
- Septic Shock
- Presentation can be subtle due to neutropenia and
steroid therapy - Diagnosis
- Serial examinations
- Serial films
- Bowel wall thickening
- Mucosal edema
- Pneumatosis intestinalis
- Free Air
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48Treatment of Typhlitis
- NPO
- Surgical consultation
- Antibiotics, including anaerobic coverage
(triples) - Surgical excision of infarcted or perforated bowel
49Case 7
- 18 year old boy with metastatic osteosarcoma
- 11 days s/p chemotherapy with ifosfamide and
doxorubicin - Presents to clinic with fever to 38.9oC
- Chills
- BP 95/60
50Case 7
- Central line accessed
- Cultures drawn
- Line flushed
- Rigors and worsening hypotension (74/40)
- Volume resuscitation with crystalloid and blood
- Amikacin pushed
- Less responsive, BP 50/P, poor perfusion
51Fever and Neutropenia
- Neutropenia defined as ANC lt 500
- Falling counts just as ominous
- Fever defined as 38.5oC or 38.0oC twice in 24
hours - ALL ILL-APPEARING CHILDREN GET EVALUATED
- Signs of infection are altered by neutropenia
52Fever and Neutropenia
- History
- Date and type of last chemotherapy (usual nadir
7-14 days) - Previous documented infections
- Presence of central line
- Infectious exposures
- History of splenectomy/functional asplenia
53Fever and Neutropenia
- Symptoms
- Cough/dyspnea/chest pain
- Retrosternal pain
- Sore throat/dysphagia
- Abdominal pain
- Pain with defecation
- Vomiting and diarrhea
54Fever and Neutropenia
- Good physical examination
- - carefully note vital signs
- Include peri-rectal area
- Central line site
- Sites of previous studies
- Diagnostic Studies
- Blood cultures from all lumens (peripheral not
necessary) - Urine culture (no cath)
- Specific sites
55Fever and Neutropenia
- Treatment
- Dont Delay!
- Broad spectrum antibiotics
- Anti-pyretics
- Systemic support if necessary
- Anaerobic coverage symptom dependent
56Fever and Neutropenia
- Duration of Therapy
- Afebrile
- Well-appearing
- No source? ANC gt 200 and rising
- Source? Standard duration for that source AND
ANC gt 500 and rising
57EMPIRIC THERAPY FOR FEVER NEUTROPENIA WITHOUT
SOURCE FEVER (gt38.5, or gt38.0 twice in 24hrs)
AND NEUTROPENIA (ANC lt500 or falling)
Sources include Peri-anal disease CXR
infiltrate CVL infection Typhlitis Cellulitis Othe
rs
Clinically unstable? 1
Yes Pip/Tazo 2 Amikacin Vanc3 Consider I.D.
Consult
No
Is the patient high risk?
Yes Pip/Tazo 2 /- Vanc (48hr r/o)3
No Pip/Tazo 2
Labs Blood Cx from all central line lumens CBC
with Diff CMP UA and UCx TS /- CXR Consider
Respiratory wash
Clinical decline ? 1
Persistent fever 3-7 days or new fever after
deffervescence?
Yes Reassess risk Consider adding
amino-glycoside Add antifungal
No D/C Pip/Tazo if ANC gt200 and rising
1 Refer to Nuts and Bolts for details 2 Consider
alternative monotherapy (cefepime, ceftazidime,
carbapenems) if surveillance cultures document
history of resistant organisms, with addition of
anaerobic coverage (metronidazole) if indicated
by presence of mucositis . For PCN allergy
consider aztreonam/vancomycin. 3Coverage for
a-strep. Also consider additional anaerobic
coverage (metronidazole) for patients with risk
factors for anaerobic infections.
58High Risk Features
- Specific Clinical Situations
- Myeloablative BMT preparative regimens
- Treatment with High Dose Cytoxan
- AML induction, consolidation, intensification
- ALL relapse induction
- Intensified therapy for metastatic/recurrent
solid tumors - Acute GVHD
- Chronic GVHD
- Steroid-refractory GVHD
- Host Features
- Characteristics of an individual patient that
might make the patient high risk despite not
fitting one of the specified situations outlined
above. - Compromised mucosal or skin integrity
- Compromised or absent lymphocyte function
- Prolonged neutropenia
- Colonization with resistant organisms
- Compromised organ function (consider effects on
drug metabolism)