HEMATOLOGY-ONCOLOGY Saulius Girnius 07/19/2013 Hem/Onc Emergencies.
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Transcript of HEMATOLOGY-ONCOLOGY Saulius Girnius 07/19/2013 Hem/Onc Emergencies.
Section ofHematology-Oncology
Summary 2
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome
Section ofHematology-Oncology
Neutropenia Fever:Definitions 3
• What is a fever?– Single temperature >101 F– Sustained temperature >100.4 for one hour
• What is neutropenia?– ANC <500 cells/μL ANC <500 cells/μL – ANC <1000 cells/μL, with a predicted nadir of ANC <1000 cells/μL, with a predicted nadir of
<500 cells/μL over the subsequent 48h<500 cells/μL over the subsequent 48h
Section ofHematology-Oncology
Subtleties of Neutropenia
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21 yo woman with Hodgkin Lymphoma with fever on day 14 after ABVD with following CBC
WBC [L] 2.9 K/UL 4.5-11.0 HCT [L] 28.8 % 38-47 PLATELET 387 K/UL 150-400 POLY [L] 17 % 45-85 LYMPH 50 16-50 MONO [HH] 24 % 0-10 EOS 4 % 0-6 BASO [H] 5 % 0-1 ABSOLUTE POLY [LL] 0.5 K/UL
1.8-7.7
71 yo man with Non Hodgkin lymphoma with Fever on day 6 after R-CHOP with following CBC
WBC [LL] 1.0 K/UL 4.0-11.0 HCT [L] 36.6 % 40-54 PLATELET [LL] 25 K/UL 150-400POLY 64 % 45-85 LYMPH 32 % 16-50 MONO 1 % 0-10 EOS 3 % 0-6 BASO 0 % 0-1 ABSOLUTE POLY [L] 0.6 K/UL
1.8-7.8
• G-CSF does not prevent neutropenia• Time of Nadir: Commonly 10 days
Section ofHematology-Oncology
Management of Suspected Neutropenia Fever
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• Be a decider!• Mortality Rate: 5-20%• >60 minute delay of
antibiotics:• OR:1.81
• Shoot first, ask questions later… sorta
Section ofHematology-Oncology
Ask questions… sorta:Work Up while waiting for antibiotics
• Talk to patient• Physical Exam:
– Line, cellulitis, localizing symptoms– Nothing in rectum
• Blood Cultures: 1 from port, 1 from periphery• CBC + Differential• UA and urine culture• Culture Omaya• No Lumbar Puncture if circulating blasts• pCXR (I would prefer 2-V CXR)
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Section ofHematology-Oncology
Shoot:Empiric Treatment
• GNR Coverage: Within 1 hour– Cefepime 2 gm q8 hours
• (now at BMC Cefepime 500 mg q6h)
– Ceftazadime 2 gm q8h
– If PCN/Cephalosporin Allergy• Imipenem 0.5 gm q6h (do not use if Type I hypersensitivity)• Aztreonam 2 gm q8h + vancomycin 1 gm + gentamicinx1• Ciprofloxacin plus clindamycin
– Gentamicin if severe sepsis
• GPC Coverage– Skin breakdown, inflammed line/port, h/o MRSA, s/sx of
pulmonary source
– Vancomycin 15 mg/kg (usually give 1 gm)
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Section ofHematology-Oncology
Management As Outpatient?MASCC Scoring System
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• Score >21 consider outpatient monitoring, with fluoroquinolone + amox/clavulanate (or clindamycin if penicillin allergy)
JCO 2000:3038-3051; Flowers et al JCO 2013
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Section ofHematology-Oncology
Febrile Neutropenia Summary
• Must assess patient• Pan-culture• Antibiotics within 1 hour (esp GNR coverage)
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Section ofHematology-Oncology
Arghh….what next? 10
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome
Section ofHematology-Oncology
Spinal Cord Compression
• Differential Diagnosis for Back Pain– Musculoskeletal disease– Spinal epidural abscess (instrumentation, IVDU)– Vertebral mets without epidural extension– Radiation myelopathy
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Section ofHematology-Oncology
Spinal Cord Compression:Type of Cancers
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lung
breast
prostate
renal cell
NHL
Myeloma
colon, CUP,sarcoma
thoracic spinecervical spineLumbar Spine
90% of cases are due to metastatic tumor in vertebrae and are therefore anterior
Section ofHematology-Oncology
Spinal Cord Compression:Clinical Features
• Pain is present in 90% of patients• Delay in Diagnosis
– 7 weeks from onset of pain– 10 days from onset of neurologic symptoms to rx
• 3 due to patient• 4 to PMD• 4 by hospital
• Weakness – 75% of patients– Symmetric lower extremity weakness– >50% are non-ambulatory
• Loss of bladder and bowel function in 50%
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Section ofHematology-Oncology
Spinal Cord Compression:Imaging
• MRI vs Myelography• 33% will have multiple epidural tumor deposits on
scanning• At a minimum, thoracic and lumbar spine should
be imaged in addition to clinically suspicious region– will miss only 1% of cervical lesions
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Section ofHematology-Oncology
Initial Treatment:Steroids
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• High dose dexamethasone– RCT: IV Dex 100 mg vs 10 mg 16 mg PO daily– Results:
• Pain Scale: 5.2 3.8 at 3hrs 2.8 at 24hrs1.4 at 1 week
• No difference in pain, ambulation, and bladder function» Vecht et al. Neurology 1989;39(9):1255
• (Really) High Dose Dexamethasone– RCT: XRT +/- dex 96 mg IV/PO x4 day 10 day taper– Results:
• Ambulation at conclusion of therapy: 81% vs 63%
• Ambulation at 6 mos: 59% vs 33%
• No dif in OS; increased toxicity» Sorenson et al. Eur J Cancer 1994;30A(1):22
Section ofHematology-Oncology
Recommendations
• Most authorities reserve high dose treatment (100 mg IV and half dose Q3days) for paraplegic or paraparetic patients.
• Low dose (10mg IV followed by 16 mg daily) for patients with minimal neurologic dysfunction
• Lower dose reduces AE (psychosis, infection, ulcers)
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Section ofHematology-Oncology
Cord Compression:What to expect from XRT
• Radiation rays/particles only work M-F, 7 AM – 4 PM• Pain:
– 70% with improvement– 50% without spinal instability have resolution of pain
• Neurologic Function– If ambulatory 67-82% remain ambulatory– If non-ambulatory 1/3 become ambulatory– If paraplegic 2-6% become ambulatory– Duration of motor neuropathy matters
• Type of Malignancy– Radiosensitive: less likely to relapse– Radioresistant: consider SRS
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Section ofHematology-Oncology
Cord Compression:Surgery
• Laminectomy: – No effective for anterior tumors– No spine stabilization– No treatment of tumor
• Tumor Debulking and Spine Stabilization
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• Closed at interim analysis. Surgery Arm Better• Median retained ambulation: 122 vs 12 days• OR for ambulation: 6.2• If paraplegia on Dx, increased ability to walk
• 10/16 vs. 3/16
Section ofHematology-Oncology
Cord Compression:Summary
• Image entire spine immediately• Start dexamethasone
– If paraplegia: 100 mg IV and halve dose q3days– If just pain: 10 mg IV, then 4 mg q6h PO/IV
• Call Radiation Oncology and Neurosurgery
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Section ofHematology-Oncology
Is he really not even halfway through? 20
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome
Section ofHematology-Oncology
Tumor Lysis Syndrome:Pathophysiology
• Hyperuricemia: – due to catabolism of purines
• Hyperphosphatemia: – Phos concentration 4x higher in malignancy cells
• Uric acid precipitates in calcium phosphate readily– Uric acid is poorly soluble in kidneys
• Crystals deposit in renal tubules ARF
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Howard et al. NEJM 2011
Section ofHematology-Oncology
Tumor Lysis:Clinical Presentation
• Electrolyte Derangement– Hyperuricemia– Hyperphosphatemia– Hyperkalemia– Secondary hypocalcemia
• Acute Renal Failure• Symptoms
– Nausea, vomiting, diarrhea, anorexia, lethargy– Cardiac dysrhythmia, syncope– Tetany– Death
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Section ofHematology-Oncology
Tumor Lysis Syndrome:Risk Factors
• Tumor Factors– High proliferative rate– Chemosensitive disease– Tumor burden
• WBC>50K
• >10 cm diameter
• Bone Marrow Involvement
– Most commonly hematologic malignancies, not solid tumor
• Clinical Features– Serum uric acid >7.5 mg/dL or hyperphosphatemia– Nephropathy– Oliguria– Inadequate hydration
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Section ofHematology-Oncology
Tumor Lysis Syndrome:Summary
• Check Tumor Lysis Labs/G6PD• Aggressive hydration• Start Allopurinol• Consider rasburicase IF TLS• Consult renal early
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Section ofHematology-Oncology
60% Done!!! 27
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome
Section ofHematology-Oncology
Hypercalcemia:Causes of hypercalcemia
• Osteolytic metastases: 20%– Breast Cancer: mets have PTHrP local osteolysis– Multiple Myeloma activate osteoclasts
• PTH related protein: 80%– Squamous Cell Carcinoma (lung, head&neck), renal,
bladder, breast, ovarian– Affects both bone ( resorption) and kidney (
excretion)
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Section ofHematology-Oncology
Hypercalcemia:Treatment
• Hydration – Normal Saline
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Isotonic Saline: 200-300 ml/hrUOP: 100-150 ml/hr
Section ofHematology-Oncology
Hypercalcemia:“Advanced Management”• Calcitonin 4 IU/kg q12h SC/IM
– Efficacy: 48 hours– Rapid reduction– Use if corrected Ca>14 mg/L
• Bisphosphonate: pamidronate or zoledronate– MOA: analog of inorganic pyrophosphate interfere
bone absorption– Onset of Effect: 1-2 days– Max Effect: 2-4 days– Side Effects: fever, renal failure
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Drug Dose Response Rate
Pamidronate 60 mg for Ca<13.590 mg for Ca>13.5
70%
Zoledronate 4 mg, reduce for CRI 88%
Section ofHematology-Oncology
Almost done! May page myself out anyway. 32
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome
Section ofHematology-Oncology
SVC Syndrome:Clinical Presentation
• Compression of structures in mediastinum– SVC:
• collateralization of over several weeks to months
– Facial/arm swelling– Cyanosis– Flacial plethora– Coma
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• Airway: Extrinsic Compression• Caution with Anesthesia
– Airway obstruction– Cardiovascular Collapse– Facial/Neck/Cord Swelling
Section ofHematology-Oncology
SVC Syndrome:Etiology
• Non-malignancy:– Thrombosis– Fibrosing Mediastinitis– Postradiation fibrosis
• Malignancy: 60-85% of cases (60% of which are new presentations)– Lung Cancer: NSCLC (50%), SCLC (25%)– Lymphoma (25%):
• DLBCL
• Lymphoblastic lymphoma
• Primary mediastinal large B-cell lymphoma
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Section ofHematology-Oncology
SVC Syndrome:Treatment vs Diagnosis
• Immediate Treatment:– Indications
• Central Airway Obstruction
• Severe laryngeal edema
• Cerebral edema coma
– Approach: • Endovascular stenting and XRT
• If severe airway obstuction high dose corticosteroids
• Need tissue diagnosis, if possible– FNA vs Core-Needle Biopsy– Bone Marrow Biopsy– Mediastinoscopy
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Section ofHematology-Oncology
SVC Syndrome:Treatment
• Chemosensitive Tumor– chemotherapy
• Chemoresistant Tumor– XRT
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Section ofHematology-Oncology
He did what?What an xxxx! 38
• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome• Acute Promyelocytic Leukemia
Section ofHematology-Oncology
Acute Promyelocytic Leukemia:Even a heme onc fellow will come in
• Epidemiology– Hispanics>White>African Descent/Pacific Islanders– Women>Men– Age: 20s to 50s
• Clinical Presentation: variable– Hemorrhagic findings– Weakness/fatigability
• Laboratory– Leukopenia (usually)– Can have anemia/thrombocytopenia– DIC
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Section ofHematology-Oncology
APML:Why should I worry?
• Untreated DIC – pulmonary/cerebrovascular hemorrhage: 40%– Mortality rate: 10-20%
• Treated APML– CR Rate: 95-100% – 2 year PFS: 97%
» LoCoco et al. N Engl J Med 2013;369:111-21
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Section ofHematology-Oncology
APML:If Concerned
1) Check DIC panel
2) Look at PBS, especially feathered edge
3) Ask lab tech to look at smear
4) Call hematology fellow on call
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