Chronic Myeloid Leukaemia (CML)
Haematological Pathway
for
South Wales Cancer Network
Document Control Sheet
Organisation
Specialty/Project
Document Title
Document Number
South Wales Cancer Network
Haematological Site Specific Group
Chronic Myeloid Leukaemia Haematological
Pathway
05/015
Version
Author/s
Ratified by
1.0
Dr A Goringe
Dr W Ingram
Approved by
South Wales
Haematology Cancer
Network Group
Approval date
Date of next review
12/09/14
11/09/15
Chronic Myeloid Leukaemia (CML)
NSAG Patient Care Pathway
Demographics
-
Estimated incidence of CML is 1.0-2.0 per 100,000 per year
-
Median age 65 years
-
Slight male predominance
Diagnosis
-
Characteristic blood film and differential
-
Confirmed by the identification of the Philadelphia chromosome and/or the
BCR-ABL transcripts in peripheral blood or bone marrow cells.
Required tests:
-
Full blood count and film with differential (percentage eosinophils,
basophils and blasts)
-
Bone marrow: aspirate, trephine histology, cytogenetics / FISH
-
Quantitative PCR measurement for BCR-ABL transcript
-
Measurement of spleen size (cm below costal margin)
Staging and Prognostication
Chronic Phase
-
Sokal and Hasford scores based on clinical and laboratory features
-
Requires patient age, spleen size (cm below costal margin), platelet
count and the percentage of blood basophils, eosinophils and blasts
-
Suggest using appropriate website/app such as
http://www.leukaemia-net.org/content/leukaemias/cml/cml_score/index_eng.html
-
Patients fall into low, intermediate and high risk groups
Accelerated phase
-
Persistent or increasing WBC and/or splenomegaly unresponsive to
therapy
-
Persistent thrombocytopenia (<100x109/l) unrelated to therapy
-
Clonal cytogenetic evolution in Ph+ve cells occurring after initial
diagnostic karyotype
-
>20% basophils in peripheral blood
-
10-19% myeloblasts in peripheral blood or BM.
Blast Crisis
-
Blasts >20% in peripheral blood or BM
-
Extramedullary blast proliferation
Indications to treat
-
Patients of all risk groups require active treatment
Information required at MDT
-
ICD10 v4 and morphology code
-
Sokal and Euro Hasford risk group
Treatment
Chronic Phase
Initial treatment should be with a Tyrosine Kinase Inhibitor (TKI),
-
Imatinib 400mg o.d
(Longer follow up with no emerging problems, slightly less well tolerated
with a higher incidence of low grade side effects (nausea, diarrhoea,
muscle cramps, peri-orbital oedema)
Similar cost at present – loss of patent 2016)
-
Nilotinib 300mg b.d
(Greater speed and depth of response with a small, though significant
reduction in numbers of patients progressing to accelerated/blast phase,
though no difference in mortality.
Emerging incidence of peripheral vascular side effects)
Accelerated phase (at diagnosis)
-
Imatinib 600mg o.d
-
Nilotinib 400mg b.d
Blast crisis
Treat as per AML or ALL with addition of TKI.
Aim for allogeneic BMT in first remission.
Allogeneic Stem cell transplantation
-
First remission in blast crisis
-
Patients presenting in accelerated phase who fail to achieve an optimal
response to initial TKI therapy
-
Consider 2nd line in patients resistant or intolerant to 2nd generation
TKI with high risk disease and low transplantation risk
-
Consider 3rd line in other patients with transplant option or at any stage
if patient develop TKI resistant mutations
Monitoring
Assessment of response is required at 3 months, 6 months, 12 months and 3
monthly there after (6 monthly if stable MMR is achieved). Response can be
categorised into optimal, warning or failure. Assessments are by peripheral
blood PCR and/or BM cytogenetics. The table below is taken from the 2013
ELN guidelines¹.
Mutational analysis and second line treatment should be considered in patients
with results in the warning category and is recommended in patients who have
evidence of failure. Subsequent treatment should be guided by the results of
mutational analysis. Second and subsequent lines of treatment should be
discussed at MDT. Refer to ELN guidelines for assessment of second line TKI
therapy response.
Pregnancy
TKI therapy is contraindicated in pregnancy
Discharge
-
Clinical studies are investigating the possibility of dose reduction and stopping
treatment in patients with long term MMR.
-
CML patients will generally require lifelong haematology clinic follow-up
References
1. Baccarani et al
European LeukemiaNet recommendations for the management of CML 2013
Blood 122:872-884; 2013
http://www.bloodjournal.org/content/122/6/872.short?sso-checked=true