CML Learning Programme for nurses & other allied health care professionals EBMT Nurses Group

1. CML Learning Programme for nurses & other allied health care professionals EBMT Nurses Group The European Group for Blood and Marrow Transplantation

2. Three different CML case studies • Transplant as therapeutic option • CML chronic phase • Palliative CML care

3. Transplant as a Therapeutic Option Courtesy of Erik Aerts, University Hospital Zürich, Zürich, Switzerland January 2012

4. Clinical Case Clinical History: • 39 year old male • Age at original diagnosis : 39 years Laboratory: Hb 8.3 mmol/l Leucocytes 32.0 - 10⁹/l Thrombocytes 247 10⁹/l Microscopic: 1% myeloblasts, 1% promyelocytes, 1% myelocytes, 8 % metamyelocytes, 21 % bars, 51% segmented nuclei, 3% basophils, 1% eosinophils, 3% lymphocytes and 4 % monocytes

5. The Patient’s Journey • Diagnosis • Allogenic Stem Cell Transplantation • Post Stem Cell Transplantation

6. Clinical Case Lifestyle considerations: - Mr. B. is 39 years old and lives alone - Truck driver - Mr. B. likes listening to country music, dancing and taking part in club activities June 2010: diagnosed with CML Translocation t (9:22) BCR/ABL positive

7. Clinical Case Mr. B.’s profile: Bone marrow: Cellularity: ++ Treatment: vincristine, dexamethasone and dasatinib

8. Clinical Case: Treatment Selection Treatment selection: Imatinib 400 mg /d from the diagnosis onwards After 6 months therapy started to have effect

9. Clinical Case Situation in May 2011: Major molecular lymphatic blast crisis: Leucocytes 8.5 g/l (32% Blasts) Hb 12.2 g/dl Thrombocytes 13 G/l BCR-ABL: 5.08 Morphology: packed with high lymphoblast infiltration Treatment: vincristine, dexamethasone and dasatinib

10. Donor Search • Generally speaking, about 25% of the patients find an HLA-matched sibling donor • Unrelated HLA-matched donor: • Worldwide registry > 8 Mio HLA-typed volunteers • Probability to find a matched donor  40-60% • For ethnic minorities under 10% • After it was found that Mr. B. did not have a sibling donor, the databank was searched for an HLA-identical donor. • It soon became clear that there was only a small chance that a donor would be found for Mr. B.

11. Decision-making Process Mr. B. and his family chose for the curative treatment option (Such decisions depend on age, co-morbidity, patient preferences and QoL indications) An HLA-identical donor was found The remissions status of the patient was CR at that time

12. Conditioning Programme On the 8th September, 2011, Mr. B. was admitted to the unit We started with conditioning cyclophosphamide, ATG and total body irradiation

13. Conditioning for HSCT On day 7 Mr. B. suffered from nausea and vomiting which we treated with several antiemetic drugs Mr. B. tolerated the first dose of ATG well. The pre-medication was prednisone and Tavegyl (anti histaminicum) In the evening, after the second dose of ATG, the patient got a fever of 38.5 ºC. After 1 g paracetamol Mr. B.’s temperature went down to 37.2 ºC

14. Conditioning for HSCT • Day 3: first of 6 TBI treatments • TBI with 6x2.2 =13.2 Gy (Lungs max 12GY) • TBI and side effects

15. Haematopoietic Stem Cell Transplantation • After the 6th TBI treatment, the patient received the stem cells from his donor • HSCT, unrelated donor, ABO-identical • The transplantation was completed without any complications

16. Haematopoietic Stem Cell Transplantation • Haematological side-effects, like mucositis and nausea, were appearing • Side-effects, combined with feelings of fear and impatience, led to the patient becoming increasingly depressed • The most significant social support • for the patient was his family

17. Post Haematopoietic Stem Cell Transplantation • 13 days after the transplant Mr. B. still • suffered from oral mucositis grade 3 • Herpetic-Stomatitis (HSV-1) • Thrombocytopenia

18. Post Haematopoietic Stem Cell Transplantation • On October 16th Mr. B. went home for a couple of days • In the afternoon Mr. B. called the ward because he had a fever (38.5 ºC) • He then returned to the ward • Mr. B. received antibiotics and prednisone

19. Discharge Day On the 18th October the patient was discharged!

20. CML chronic phase Courtesy of Thorunn Saevarsdottir, Landspitali University Hospital, Reykjavik, Iceland January 2012

21. Clinical CaseCML Chronic phase • 70 year old male, diagnosed with CML December 2008 (67 years at diagnosis) • Background information: Married with 3 grown up children and 5 grandchildren; works as hospital security guard • Presentation: Ongoing fatigue which prompted him to first consult GP. Philadelphia/BCR-ABL positive in all cells. Presented with leucocytosis, white blood cells 64 x 10E9/L, and splenomegaly • Performance status: WHO: 0; Karnofsky: 90% (where 100 is perfect health, 0 death)

22. Co morbidities • Diagnosed and operated for colon cancer 10 years earlier and treated with radiation therapy Permanent colostomy Colon cancer in complete remission 2011 • Hypertensive, on medication: darazid and amlodipine Blood pressure 120/80 mm Hg at diagnosis

23. Peripheral Blood Measurement at Diagnosis • Total White blood cell: 64.0 x 10E9/L, immature white blood cells prominent • Haemoglobin: 144 g/litre • Thrombocytes: 292 x109/L • Alkaline Phosphatase (ALP): 140 U/L • Gamma-glutamyl transpeptidase (Gamma GT): 238 U/L • Aspirate aminotransferase (ASAT): 53 U/L • Alanine transaminase (ALAT): 84 U/L • Lactate dehydrogenase (LD):1499 U/L • Creatinine : 115 µmol/L • Urea: 414 µmol/L • Carcinoembryonic antigen (CEA): 0.8 µg/L

24. Bone marrow results • Prominent hyperplasia, Philadelphia / BCR-ABL positive in all cells • t9;22 translocation in 92-97% of cells • Result: CML Chronic phase

25. Treatment • Started on imatinib 400 mg daily January 9th 2009 • Experienced a little headache, but no gastrointestinal symptoms, jaundice, or musculoskeletal symptoms Responded well to treatment: • January 28th 2009: white blood cells were 6.9 x 10E9/L • February 2009: felt better in general, less fatigue • March 2009: returned to work, strength and stamina still recovering • June 2009: Bone marrow after 6 months imatinib showed CML in complete remission Blood values normal

26. Blood measurements after treatment • 3 weeks on imatinib: Complete haematologic response • 6 months on imatinib: CML/CR (complete response) with increased reticulin in bone marrow (reticulin increase can result in dry tap) • Blood values normal ( cytogenetic/ FISH CR ) • December 2010, still on imatinib 300 mg daily • Complete haematologic response - total white blood cells 5, 7 x 10E9/L

27. Treatment toxicity • Experienced eye problems (discomfort looking into bright light), and musculoskeletal pain • Reduced dose to 300 mg imatinibdaily • Side effects decreased and has not required treatment to be revised further

28. Palliative CML care Courtesy of Arno Mank, Academic Medical Centre, Amsterdam, The Netherlands January 2012

29. Clinical Case 58 year old female (55 years old at diagnosis) Diagnosis: Philadelphia-positive CML in blast crisis phase Patient is a secretary in National Bank Lives with a friend, no children

30. Relevant history and treatment • Diagnosis +1 year: treatment with imatinib • Diagnosis + 2 year: • Myeloid blasted crisis • Induction treatment with cytarabine and idarubicin • Treatment with dasatinib • Diagnosis +3 year: allogeneic SCT with matched unrelated donor (complete remission before transplantation)

31. Relevant history and treatment Diagnosis +1 year +2 year +3 year Current situation imatinib • Blastic crisis • Induction treatment • Dasatinib • Complete remission • Allogeneic SCT with matched unrelated donor

32. Situation last year • Relapsed CML blastic phase • Treatment with Donor Lymphocyte Infusion (DLI), failed • GvHD colon and reactivation CML treated with valaciclovir • Respiration insufficient on basis of RSV-infection • Nutrition through PEG due to poor nutrition status and weight loss • Vomiting & diarrhoea

33. Situation at admission • Patient experienced nausea and vomiting for 4 weeks, with weight loss of more then 5 kg from reduced appetite • Tremendous diarrhoea - more then 5 x daily • No oral intake possible • No fever or night sweats • Red coloured skin, especially on the back • Biopsies of the colon: showed graft-versus-host disease. Treated with prednisone 40 mg per day • Multiple swellings on forehead, with aspirate blasts visible. Palliative irradiation

34. Physical examination • Weak, cachectic • Clear, appropriate, orientated to person, place and time • RR 140/100 mmHg, pulse 95/min, saturation 98% no extra oxygen, AF 18/min • Thorax: normalHeart: no soufflesAbdomen: Les peristalsis, changing tympaniExtremities: normal colour, no oedema

35. Palliative situation • No treatment options for the CML • The prognosis is unfavourable. Discussed with patient and partner who chose hospice care • Just before hospice admission the patient married in the hospital • Prednisone, calcium carbasalate, esomeprazole magnesium, loperamide and fentanyl patches will be continued, as well as enteral feeding through PEG-probe • Because of low platelet numbers, platelet transfusions will be considered if spontaneous haemorrhages occur

36. Summary • GvHD • Relapsed CML