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

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

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 A man of 39 years old is examined by the haematologist because he suffers from fatigue, weight loss and pain on the left side of the upper abdomen. After physical examination it is found that the man has an enlarged spleen. The laboratory study has the following results: Hb 8.3 mmol/l Leucocytes 32.0 - 10⁹/l Thrombocytes 247 10⁹/l Microscopic : 1% myeloblasts, 1% promyelocytes, 1% myelocytes, 8 % metamyeloyctes, 21 % bars, 51% segmented nuclei, 3% basophils, 1% eosinophils, 3% lymphocytes and 4 % monocytes Further, 5 erythroblasts were found per 100 leucocytes. The erythrocytes showed anisopliae and were slightly mesochromatic. The granulocytes were morphologically normal.

The Patient’s Journey Diagnosis Allogenic Stem Cell Transplantation Post Stem Cell Transplantation This case study presents one patient`s journey from the time of this diagnosis, through his stem cell transplantation, to his post-transplantation recovery.

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 Mr. B. is 39 years old, worked as a truck driver and is supported by his employer. He lives alone with his cat in a house that is inhabited by multiple families. Mr. B. lost his mother at a young age and his father suffered from schizophrenia. As a result, Mr. B. was forced to become independent early in life. In 2008 he lost his wife after she had an accident in the Swiss Alps. Mr. B. is still close to his mother-in-law, who is also the family`s contact point. Mr. B. likes listening to country music, dancing and taking part in club activities. In June 2010, Mr. B was diagnosed with a CML. Translocation t (9:22) BCR/ABL positive The performance status according Karnofsky is 100%.  

Clinical Case Mr. B.’s profile: Bone marrow: Cellularity: ++ Treatment: vincristine, dexamethasone and dasatinib Here you see an overview of Mr. B‘s profile The bone marrow was cellular, and myelopoiesis predominant. During a number of months the CML remained stable; Mr. B. was treated with vincristine, dexamethasone and dasatinib. Nevertheless, his leucocytes concentration increased greatly in a short period of time, to over 120 10⁹/l. The CML progressed to an accelerated phase which was directly followed by a blast crisis of the CML. The blood contained 47% myeloblasts with a concentration of leucocytes of 22.1 10⁹/l. The bone marrow was very cellular and contained 65% myeloblasts.

Clinical Case: Treatment Selection Imatinib 400 mg /d from the diagnosis onwards After 6 months therapy started to have effect Mr. B. had an intermediate risk (CML-score 1191.4) and was treated with imatinib 400mg/d from diagnosis onwards. After 6 months the therapy started to have effect.

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   In May 2011 the patient`s condition quickly worsened. Situation in May 2011: Major molecular lymphatic blast crisis: Leucocytes 8. 5 g/l (32% Blasts) . Hb 12.2 g/dl Tc 13 G/l BCR-ABL: 5.08 Morphology: packed with high lymphoblast infiltration. Treatment: vincristine, dexamethasone and dasatinib. After 3 months complete hematological, cytogenetic and molecular genetic remission in his blood. It was decided to try and find a donor for Mr. B.

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.

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 There was much talk about the options - palliative or curative. Mr. B. and his family chose the curative treatment option. Such decisions depend on age, co-morbidity, patient preferences and QoL indications. Since an HLA-identical donor was found, the haematologists decided together with the patient to transplant with a matched unrelated donor (MUD). The remissions status of the patient was a CR at that time.  

Conditioning Programme On the 8th September, 2011, Mr. B. was admitted to the unit We started with conditioning cyclophosphamide, ATG and total body irradiation We started with the Conditioning Cyclophosphamide, ATG and total body irradiation. In some centres all the allogeneic transplantation patients have to take gut decontamination medications each day, which can reduce the severity of acute GvHD. Before admission every transplant patient has a talk with their primary nurse who has responsibility for their care from admission to discharge.   Also, patients and their loved ones come into contact with other multi-disciplinary carers and the whole team meets once a week to discuss the patient’s treatment programme (of the patient), with an exchange of information between all services. This meeting is led by the nurse manager. Decisions depend on age, co-morbidity, preferences and QoL indications. Since an HLA-identical donor was found, the haematologists decided together with the patient to transplant with a matched unrelated donor (MUD). The remissions status of the patient was a CR at that time.

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  

Conditioning for HSCT Day 3: first of 6 TBI treatments TBI with 6x2.2 =13.2 Gy (Lungs max 12GY) TBI and side effects     On the morning of day 3 the patient went to the department for radiology accompanied by a nurse for the first of 6 TBI treatments. TBI with 6x2.2 =13.2 Gy (Lungs max 12GY) After the second TBI Mr. B .suffered from nausea and swollen salivary glands. This was treated with anti-emetics. The salivary glands were locally treated with lemon juice. On the 13thSeptember the leucocytes were decreasing and the patient was in aplasia. On day -1 the patient complained about a slight pain in his mouth. The oral cavity showed small blisters. It was then decided to start with acyclovir i.v.

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

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 longer the aplasia continued the more “typical” haematological side-effects, like mucositis and nausea, were appearing. The consequence was that the patient received a lot of morphine and anti-emetic therapy. In combination with fear and impatience, this led to the patient becoming increasingly depressed. The spiritual worker and psychologists visited the patient many times. Mr. B. was open for discussions with the psychologists. The most significant social support for the patient was his family, who provided an important role filtering stress, sadness and other negative emotions.

Post Haematopoietic Stem Cell Transplantation 13 days after the transplant Mr. B. still suffered from oral mucositis grade 3 Herpetic-Stomatitis (HSV-1) Thrombocytopenia     Mr.B.’s psychological condition was under control. He had become used to the isolation and kept himself busy with his laptop (e-mail and Facebook). He was also visited daily by friends and family. On the 30th September, (day + 14 after the transplant) his leucocytes concentration increased and the isolation was lifted. The Oral Mucositis complaints decreased and the morphine was reduced to 15 mg/24h. On the 13th September the leucocytes were decreasing and the patient was in aplasia. Because of decreasing thrombocytes Mr. B. had a light epistaxis which was treated with a thrombocyte transfusion. To stop the bleeding a tamponade for the nose was used.  

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   On October 16th Mr. B. went home for a couple of days. He could not stand being on the ward any longer and he was also curious to see if he could manage at home. In the afternoon Mr. B. called the ward because he had a fever: 38.5 ° C He then returned to the ward. Mr. B. received antibiotics and prednisone.

Discharge Day On the 18th October the patient was discharged!   On the 18th October the patient was discharged!   Under the circumstances 41 days after SCT the patient feels well. He is coping with the side effects of the transplantation and feels thankful that he is still alive. He considers his quality of life to be very good. He is able to work.

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

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 10E9/L, and splenomegaly Performance status: WHO: 0; Karnofsky: 90% (where 100 is perfect health, 0 death)

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 Darazid= drug to treat hypertension Amlodipine: calcium channel blocker, used to treat hypertension also for example Norvasc, which is amlodipine besylate.

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

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

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

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

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

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

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 29

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)

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

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

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

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

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

Summary GvHD Relapsed CML