Case studies_Chronic Myeloid Leukaemia (CML) Learning Programme.ppt

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

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

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

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

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

Clinical Case:
Treatment Selection
• Treatment selection:
– Imatinib 400 mg /d from the diagnosis
onwards
After 6 months 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

• 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

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

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

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

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

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

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

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

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

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

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

Case studies_Chronic Myeloid Leukaemia (CML) Learning Programme.ppt

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