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HEMATOLOGY-ONCOLOGY

HEMATOLOGY-ONCOLOGY. Saulius Girnius 07/19/2013. Hem/ Onc Emergencies. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome. Summary. Neutropenia Fever: Definitions. 3. What is a fever? Single temperature >101 F

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HEMATOLOGY-ONCOLOGY

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  1. HEMATOLOGY-ONCOLOGY Saulius Girnius 07/19/2013 Hem/Onc Emergencies

  2. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome Summary

  3. 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 <1000 cells/μL, with a predicted nadir of <500 cells/μL over the subsequent 48h

  4. Subtleties of Neutropenia 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 150-400 POLY 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

  5. Management of Suspected Neutropenia Fever • Be a decider! • Mortality Rate: 5-20% • >60 minute delay of antibiotics: • OR:1.81 • Shoot first, ask questions later… sorta

  6. 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)

  7. 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) DO NOT WAIT FOR CBC TO RETURN

  8. Management As Outpatient?MASCC Scoring System 29 • Score >21 consider outpatient monitoring, with fluoroquinolone + amox/clavulanate (or clindamycin if penicillin allergy) JCO 2000:3038-3051; Flowers et al JCO 2013

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

  10. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome Arghh….what next?

  11. Spinal Cord Compression • Differential Diagnosis for Back Pain • Musculoskeletal disease • Spinal epidural abscess (instrumentation, IVDU) • Vertebral mets without epidural extension • Radiation myelopathy

  12. Spinal Cord Compression:Type of Cancers 90% of cases are due to metastatic tumor in vertebrae and are therefore anterior

  13. 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%

  14. 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

  15. Initial Treatment:Steroids • 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 24hrs1.4 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

  16. 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)

  17. 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

  18. Cord Compression:Surgery • Laminectomy: • No effective for anterior tumors • No spine stabilization • No treatment of tumor • Tumor Debulking and Spine Stabilization • 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

  19. 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

  20. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome Is he really not even halfway through?

  21. 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 Howard et al. NEJM 2011

  22. 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

  23. 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

  24. Who is at risk Howard et al. NEJM 2011

  25. Tumor Lysis Syndrome:Prevention/Treatment

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

  27. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome 60% Done!!!

  28. 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)

  29. Hypercalcemia:Treatment • Hydration – Normal Saline Isotonic Saline: 200-300 ml/hr UOP: 100-150 ml/hr

  30. Hypercalcemia:Furosemide Use only if volume overloaded

  31. 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

  32. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome Almost done! May page myself out anyway.

  33. Superior Vena Cava Syndrome UTDOL

  34. SVC Syndrome:Clinical Presentation • Compression of structures in mediastinum • SVC: • collateralization of over several weeks to months • Facial/arm swelling • Cyanosis • Flacial plethora • Coma • Airway: Extrinsic Compression • Caution with Anesthesia • Airway obstruction • Cardiovascular Collapse • Facial/Neck/Cord Swelling

  35. 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

  36. 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

  37. SVC Syndrome:Treatment • Chemosensitive Tumor • chemotherapy • Chemoresistant Tumor • XRT

  38. Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome Acute Promyelocytic Leukemia He did what?What an xxxx!

  39. 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

  40. 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

  41. APML on peripheral blood smear

  42. APML:If Concerned • Check DIC panel • Look at PBS, especially feathered edge • Ask lab tech to look at smear • Call hematology fellow on call

  43. Questions?

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