HEMATOLOGY-ONCOLOGY

HEMATOLOGY-ONCOLOGYSaulius 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


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


Subtleties of Neutropenia4

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


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


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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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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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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Febrile Neutropenia Summary• Must assess patient• Pan-culture• Antibiotics within 1 hour (esp GNR coverage)

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Arghh….what next? 10



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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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


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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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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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


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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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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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


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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Is he really not even halfway through? 20



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


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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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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Who is at risk24

Howard et al. NEJM 2011


Tumor Lysis Syndrome:Prevention/Treatment

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Tumor Lysis Syndrome:Summary• Check Tumor Lysis Labs/G6PD• Aggressive hydration• Start Allopurinol• Consider rasburicase IF TLS• Consult renal early

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60% Done!!! 27



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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Hypercalcemia:Treatment• Hydration – Normal Saline

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Isotonic Saline: 200-300 ml/hrUOP: 100-150 ml/hr


Hypercalcemia:Furosemide

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Use only if volume overloaded


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 RatePamidronate 60 mg for Ca<13.5

90 mg for Ca>13.570%

Zoledronate 4 mg, reduce for CRI 88%


Almost done! May page myself out anyway. 32



Superior Vena Cava Syndrome33

UTDOL


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


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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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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SVC Syndrome:Treatment• Chemosensitive Tumor

– chemotherapy• Chemoresistant Tumor

– XRT

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He did what?What an xxxx! 38

• Neutropenic Fever• Spinal Cord Compression• Tumor Lysis Syndrome• Hypercalcemia• Superior Vena Cava Syndrome• Acute Promyelocytic Leukemia


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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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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APML on peripheral blood smear41


APML:If Concerned1) Check DIC panel2) Look at PBS, especially feathered edge3) Ask lab tech to look at smear4) Call hematology fellow on call

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Questions?43

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