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

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

The European Group for Blood and Marrow Transplantation Transplant as a Therapeutic Option Courtesy of Erik Aerts, University Hospital Zürich, Zürich, Switzerland January 2012

The European Group for Blood and Marrow Transplantation Clinical Case Clinical History: 39 year old male Age at original diagnosis : 39 years Laboratory: Hb 8.3 mmol/l Leucocytes ⁹ /l Thrombocytes ⁹ /l Microscopic: 1% myeloblasts, 1% promyelocytes, 1% myelocytes, 8 % metamyelocytes, 21 % bars, 51% segmented nuclei, 3% basophils, 1% eosinophils, 3% lymphocytes and 4 % monocytes

The European Group for Blood and Marrow Transplantation The Patient’s Journey Diagnosis Allogenic Stem Cell Transplantation Post Stem Cell Transplantation

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Clinical Case Mr. B.’s profile: Bone marrow: Cellularity: ++ Treatment: vincristine, dexamethasone and dasatinib

The European Group for Blood and Marrow Transplantation Clinical Case: Treatment Selection Treatment selection: –Imatinib 400 mg /d from the diagnosis onwards After 6 months therapy started to have effect

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation 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. Donor Search

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Conditioning Programme On the 8 th September, 2011, Mr. B. was admitted to the unit We started with conditioning cyclophosphamide, ATG and total body irradiation

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Conditioning for HSCT Day 3: first of 6 TBI treatments TBI with 6x2.2 =13.2 Gy (Lungs max 12GY) TBI and side effects

The European Group for Blood and Marrow Transplantation Haematopoietic Stem Cell Transplantation After the 6 th TBI treatment, the patient received the stem cells from his donor HSCT, unrelated donor, ABO-identical The transplantation was completed without any complications

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Post Haematopoietic Stem Cell Transplantation 13 days after the transplant Mr. B. still suffered from oral mucositis grade 3 Herpetic-Stomatitis (HSV-1) Thrombocytopenia

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Discharge Day On the 18 th October the patient was discharged!

The European Group for Blood and Marrow Transplantation CML chronic phase Courtesy of Thorunn Saevarsdottir, Landspitali University Hospital, Reykjavik, Iceland January 2012

The European Group for Blood and Marrow Transplantation Clinical Case CML 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 10E 9 /L, and splenomegaly Performance status: WHO: 0; Karnofsky: 90% (where 100 is perfect health, 0 death)

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Peripheral Blood Measurement at Diagnosis Total White blood cell: 64.0 x 10E 9 /L, immature white blood cells prominent Haemoglobin: 144 g/litre Thrombocytes: 292 x10 9 /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

The European Group for Blood and Marrow Transplantation Bone marrow results Prominent hyperplasia, Philadelphia / BCR-ABL positive in all cells t9;22 translocation in 92-97% of cells Result: CML Chronic phase

The European Group for Blood and Marrow Transplantation Treatment Started on imatinib 400 mg daily January 9 th 2009 Experienced a little headache, but no gastrointestinal symptoms, jaundice, or musculoskeletal symptoms Responded well to treatment: January 28 th 2009: white blood cells were 6.9 x 10E 9 /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

The European Group for Blood and Marrow Transplantation 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 10E 9 /L

The European Group for Blood and Marrow Transplantation Treatment toxicity Experienced eye problems (discomfort looking into bright light), and musculoskeletal pain Reduced dose to 300 mg imatinib daily Side effects decreased and has not required treatment to be revised further

The European Group for Blood and Marrow Transplantation Palliative CML care Courtesy of Arno Mank, Academic Medical Centre, Amsterdam, The Netherlands January 2012

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation 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)

The European Group for Blood and Marrow Transplantation Relevant history and treatment Diagnosis+1 year+2 year+3 yearCurrent situation imatinibBlastic crisis Induction treatment Dasatinib Complete remission Allogeneic SCT with matched unrelated donor

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation 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: normal Heart: no souffles Abdomen: Les peristalsis, changing tympani Extremities: normal colour, no oedema

The European Group for Blood and Marrow Transplantation 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

The European Group for Blood and Marrow Transplantation Summary GvHD Relapsed CML