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

2. Section of Hematology-Oncology Summary 2 Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome

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

4. Section of Hematology-Oncology Subtleties of Neutropenia 4 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. Section of Hematology-Oncology Management of Suspected Neutropenia Fever 5 Be a decider! Mortality Rate: 5-20% >60 minute delay of antibiotics: OR:1.81 Shoot first, ask questions later… sorta

6. Section of Hematology-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) 6

7. Section of Hematology-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) 7

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

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

10. Section of Hematology-Oncology Arghh….what next? 10 Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome

11. Section of Hematology-Oncology Spinal Cord Compression Differential Diagnosis for Back Pain –Musculoskeletal disease –Spinal epidural abscess (instrumentation, IVDU) –Vertebral mets without epidural extension –Radiation myelopathy 11

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

13. Section of Hematology-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% 13

14. Section of Hematology-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 14

15. Section of Hematology-Oncology Initial Treatment: Steroids 15 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. Section of Hematology-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) 16

17. Section of Hematology-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 17

18. Section of Hematology-Oncology Cord Compression: Surgery Laminectomy: –No effective for anterior tumors –No spine stabilization –No treatment of tumor Tumor Debulking and Spine Stabilization 18 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. Section of Hematology-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 19

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

21. Section of Hematology-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 21 Howard et al. NEJM 2011

22. Section of Hematology-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 22

23. Section of Hematology-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 23

24. Section of Hematology-Oncology Who is at risk 24 Howard et al. NEJM 2011

25. Section of Hematology-Oncology Tumor Lysis Syndrome: Prevention/Treatment 25

26. Section of Hematology-Oncology Tumor Lysis Syndrome: Summary Check Tumor Lysis Labs/G6PD Aggressive hydration Start Allopurinol Consider rasburicase IF TLS Consult renal early 26

27. Section of Hematology-Oncology 60% Done!!! 27 Neutropenic Fever Spinal Cord Compression Tumor Lysis Syndrome Hypercalcemia Superior Vena Cava Syndrome

28. Section of Hematology-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) 28

29. Section of Hematology-Oncology Hypercalcemia: Treatment Hydration – Normal Saline 29 Isotonic Saline: 200-300 ml/hr UOP: 100-150 ml/hr

30. Section of Hematology-Oncology Hypercalcemia: Furosemide 30 Use only if volume overloaded

31. Section of Hematology-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 31 DrugDoseResponse Rate Pamidronate60 mg for Ca<13.5 90 mg for Ca>13.5 70% Zoledronate4 mg, reduce for CRI88%

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

33. Section of Hematology-Oncology Superior Vena Cava Syndrome 33 UTDOL

34. Section of Hematology-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 34 Airway: Extrinsic Compression Caution with Anesthesia –Airway obstruction –Cardiovascular Collapse –Facial/Neck/Cord Swelling

35. Section of Hematology-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 35

36. Section of Hematology-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 36

37. Section of Hematology-Oncology SVC Syndrome: Treatment Chemosensitive Tumor –chemotherapy Chemoresistant Tumor –XRT 37

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

39. Section of Hematology-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 39

40. Section of Hematology-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 40

41. Section of Hematology-Oncology APML on peripheral blood smear 41

42. Section of Hematology-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 42

43. Section of Hematology-Oncology Questions? 43