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M&M 12-5-2001

M&M 12-5-2001. Presented by: Michael Greene, M.D. Do you think the ARS will work today?. All signs point to YES Probably Maybe Unlikely No way. 37 y.o. woman with acute leukemia Ambulatory Presentation. Persistent URI symptoms: Treated with several courses of PO Antibiotics

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M&M 12-5-2001

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  1. M&M 12-5-2001 Presented by: Michael Greene, M.D.

  2. Do you think the ARS will work today? • All signs point to YES • Probably • Maybe • Unlikely • No way

  3. 37 y.o. woman with acute leukemiaAmbulatory Presentation • Persistent URI symptoms: • Treated with several courses of PO Antibiotics • Associated with profound progressive fatigue • CBC reveals: WBC 30 with peripheral blasts and PLT 38

  4. 37 y.o. woman with acute leukemiaAmbulatory Presentation • Bone Marrow Biopsy performed: • Suspicious for AML. • Directly admitted to DHMC for further evaluation and treatment.

  5. 37 y.o. woman with acute leukemiaPresentation to DHMC • HPI : • Persistent URI symptoms. • Pain: L shoulder, R ankle, L thigh • New non-pruritic rash on buttocks • 6-7 lb weight loss over last 6 weeks • No bleeding or bruising • No N/V/D • No neurologic symptoms

  6. Presentation to DHMC • Medications • Recent antibiotics, prednisone taper, and NSAIDs • PMH • NSVD times three

  7. Presentation Physical Exam • Gen: friendly, young, healthy appearing WF • VS: 37.1 85-105 110/70 20 wt:68.1 kg • HEENT: NCAT, EOMI s nystagmus, sclera anicteric, OP clear • Neck: supple, shotty cervical adenopathy R • Lungs: CTA-B • CV: RRR s MRG • Abd: Soft, NTND, +BS, no HSM • Ext: without c/c/e • Neuro: CN II-XII intact, Str 5/5 all groups, sensory intact and symmetric • Skin: acneform pustular rash on buttocks, non-palpable petechiae on shins B • M/S: without joint swelling

  8. Presentation Labs 8.4 136|100 | 11 / C 8.9 30.4 38 3.7| 25 |0.6 \ M 0.87 N2, B8, L23, M26,Blasts 51 % P 3.2 PT 13.5 INR 1.1 PTT 34 TT 21 D-Dimer 0.5 Tbili:0.4, Dbili:0.1, AP: 237, AST:61, ALT: 98 U.A. 3.7, ALB: 3.5

  9. Initial Assessment • Labs c/w AML • obtain outside marrow for review • peripheral blood flow cytometery and cytogenetics • Begin preparation for definitive treatment • triple lumen groshong catheter • allopurinol & IV hydration • baseline echocardiogram • BID DIC screen and tumor lysis labs • Acne rash likely 2’ to steroids • Consider LP to assess CNS involvement

  10. Initial Work-Up • Baseline echo: • EF 65-70% with mild TR • Flow analysis: • CD33, CD 34, CD 117, and HLA-B positive • Cytogenetics: • inv16 positive • Bone Marrow Biopsy:

  11. Marrow #1 • Acute mylogenous leukemia • Prominent eosinophilic component. • Consistent with M4E

  12. Which of the following is NOT a favorable prognostic factor in AML • Inv 16 • MDR-1 positive phenotype • Prior MDS • Younger age • 2 and 3

  13. Initial Notes: • Chaplancy Service: • Receptive to pastoral care. • Received anointing of the sick. • Social Work: • “Patient’s primary concern is for her three children and her husband.” • “Patient is optimistic regarding her life in general.”

  14. Initial Notes: • Attending Note: • “Talk again today [of] specific risks of IDA and ARA-C including heart, GI, infectious, hair loss, kidney, and explained the possibility of death. Patient understands the seriousness of the situation.”

  15. Hospital Course • HD 2- 4 • Induction chemotherapy initiated. • Progressive nausea. • New resprophasic CP without cough. • CXR shows questionable RUL infiltrate.

  16. Hospital Course • HD 5-9 • Febrile Neutopenia: • Ceftazidime initiated • Tobramycicn added HD 7 • Vancomycin added HD 9 • New pleural effusions. • TPN initiated 2’ to prolonged nausea. • Red man syndrome.

  17. Hospital Course • HD 10- 20 • Vaginal bleeding at time of expected menses. • Continued resprophasic CP. • Spiral CT negative for PE or infiltrate. • LE dopplers negative. • Continued fevers. • Cultures NGTD. • Abd/pelvis CT for evaluation of fever. • Clindamycin added for anerobic coverage (HD 17) • Ampho B initiated and ID consulted (HD 20) • New Rash.

  18. ID Consult • Antibiotics to date: • day 18 ceftazadime • day 15 aminoglycoside • day 13 vancomycin • day 4 clindamycin • day 2 Amphotericin B • Rash likely secondary to ceftaz • Change to Imipenim as single agent • Continue Ampho B

  19. Hospital Course, Continued • HD 21- 26 • BM bx • Immature marrow without leukemia cells • Fever breaks (HD 24) • All cultures negative • D/C home • F/U CBC and BM Bx in 1 wk

  20. Which of the following is NOT a criteria of complete remission (CR)? • Normal Hg, ANC, PLT count for >30 days. • No blast clusters/collects on BMBx • Normal cellularity and maturation on BM aspirate. • <5% blasts in BM • Absence of previously detected clonal cytogenetic abnormality.

  21. Admission for Consolidation • Consolidation Therapy • f/u marrow shows no residual disease. • #1 HiDAC • unremarkable except for nausea and continued pain complaints. • total hospitalization: 6 days

  22. Hospitalization #3 • Readmitted for pancytopenia and diarrhea. • 0.5 \ 6.7 / 3 / \ • Transfused PRBCs and platelets. • Diarrhea resolved with supportinve care, likely chemo effect. • Total hospital days: 7

  23. Hospitalization #4 • Admitted for menorrhagia. • 0.3 \ 8.7 / 54 / \ • Received PRBC and PLT transfusions. • Started on monophasic premarin. • Total hopsitalization: 7 days

  24. Hospitalization # 5-12 • Ongoing treatment complications: • HiDAC x 3 cycles completed. • Neutropenic fever 5 times, once requiring DHART transport from local hospital to ICU on pressor support for sepsis syndrome. • LLE DVT: coumadin started. • Impaired renal K handling believed 2’ to multiple courses empiric of Ampho B. • Menorrhagia despite premarin: changed to norethindrone 5 mg QD.

  25. Hospitalization # 5-12 Continued • Relapse 5 months after induction. • Reinduction with mitoxandrone and VP-16 for relapse leukemia. • New DVT despite therapeutic on coumadin, changed to lovenox 1.5 mg/kg QD • BM Bx at discharge w/o residual leukemia. • Total days hospitalized since dx: 146/519 days

  26. Second Relapse • BM bx at discharge without evidence of residual leukemia • Second relapse following 4 months of remission with mitoxantrone and VP16.

  27. Treatment Options • Relapse following 4 months of remission after mitoxantrone. • Myelotarg re-induction for 2 cycles. • BMT discussed and sought. • Sib 5/6 match • Unrelated donor 6/6 match

  28. Which of the following is NOT true of Gemtuzumab (Mylotarg)? • Monoclonal antibody directed against CD33. • Serious side-effects include: anaphylaxis, hepatic vein thrombosis and ARDS. • More effective than chemotherapy for first relapse in AML. • FDA approved for first relapse of AML for those > 60yo • I have NO idea!

  29. Continued Treatment • Re-induction complicated by neutropenic fever. • Patient moved into near-by apartment with sister-in-law to allow seeing children without having to live with them. • Treatment for depression • Follow-up BM Bx performed. • Hypocellular marrow with residual blasts

  30. Re-Induction Marrow • Hypocellular marrow with excess blasts.

  31. Persistent Leukemia • Pt’s disease relapsed despite multiple chemotherapies. • Pt insistant that she wants to continue toward transplant.

  32. Would you recommend continued attempts at therapy? • Definitely • Probably • Not sure • Probably not • No

  33. Reinduction #3 • HiDAC reinduction initiated. • BM Bx obtained after therapy. • show

  34. Multiple Re-induction Bone Marrow • Aplastic Bone Marrow • No neoplastic cells identified. • No hematopoiesis seen.

  35. Working toward Transplant • 3 month hospitalization. • Transfusion dependent. • Numerous bouts of fever. • Enterococcal bacteremia • C. difficile colitis • Ongoing and escalating pain. • Dilaudid PCA

  36. Working toward Transplant • New pulmonary nodules seen on CT • Bronchoscopy with BAL • Needle bx->open lung bx->RUL lobectomy • Negative for bacteria, AFB, nocardia or aspirgillus, PCP, legionella • Respiratory difficulty prompted greenfield filter placement • Audiology consult obtained showing severe sensineural hearing loss 2’ to aminoglycoside use

  37. Working toward Transplant • Transfer to University of Massachusetts for transplant on HD 92. • Persistent aplastic anemia. • Afebrile.

  38. What are her chances for successful engraftment? • Very good • Better than 50% • 50/50 • Unlikely • Slim to none

  39. Return to DHMC • Pt became febrile after transportation to U Mass. • Transplant cancelled • She was transferred back to DHMC

  40. Pneumonia with empyema • Confirmed pneumonia and empyema. • vanco/aztreonam/flagyl • chest tube drainage • Pain continues to be problematic despite dilaudid PCA. • Family discussion again obtained.

  41. Family Meeting • Minimal likelihood for cure. • Data free zone. • Patient and patient’s family want to pursue more treatment options.

  42. Treatment Options • Decision to pursue “mini-allogeneic” transplant. • Functional improvement required. • Pt transferred to New England Medical Center for mini-allo. on HD 25 • Total days in hopsital since dx: 262/610 • Hospital costs to date $ 1, 906,294.90

  43. Transplant • Patient underwent 2 transplants without engraftment. • Remains hospitalized at NEMC. • Currently infected. • They are working to get her home.

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