HOW WE MANAGE A PATIENT WITH CHRONIC MYELOID LEUKAEMIA WITH
POSTER 11
T315I MUTATION IN A RESOURCE RESTRICTED COUNTRY
Maduwanthi Jayaweera1, Senani Williams2 and M N Dilhani1
(1)Dr., Colombo, Sri Lanka
(2)Prof, Colombo, Sri Lanka
Introduction:
Chronic myeloid leukaemia (CML) is a BCR-ABL1 positive myeloproliferative neoplasm with
marked granulocytic hyperplasia characterized by reciprocal translocation between
chromosome 9 and 22.
We describe a 46-year-old previously healthy man who presented with abdominal fullness.
Physical examination revealed moderate splenomegaly. A complete blood count and blood
film morphology were consistent with chronic phase chronic myeloid leukaemia. BCR-ABL1
translocation detected a p210 transcript. He was treated with Imatinib mesylate 400 mg daily.
Though the initial response was good he failed treatment 6 years after diagnosis. He was
treated with Nilotinib 300 mg b.d. for approximately one year, and he remained in chronic
phase. His BCR-ABL1 quantification showed a rising trend and tyrosine kinase domain (TKD)
mutation profile revealed mutation of F359V. Next he was changed to Dasatinib 100 mg daily,
for which he re-achieved a complete haematological response (CHR), and continued for 7
months with a decreasing trend in BCR-ABL1 quantification. As he developed drug induced
recurrent bilateral pleural effusions, his dose was reduced and he he lost his CHR. A TKD
mutation profile showed a T315I mutation nine years after initial diagnosis. The F359V
mutation was also reported to as negative. He denied an allogeneic haemopoeitic stem cell
transplant (HSCT). So far, Ponatinib is not available in our country. Therefore, as salvage, he
was commenced on weekly pegylated interferon (peg IFN), 1.3 years later his leukocyte count
started to rise. A trial of Nilotinib 300mg twice a day was recommenced 4 months ago, by
which he regained the complete haematogical response. Currently he is on Nilotinib 150 mg
twice a day, having normal complete blood counts and is awaiting re evaluation of BCR-ABL1
quantification.
Discussion
A major complication of treatment of CML is TKI resistance and the acquisition of mutations.
Before defining treatment resistance, the drug compliance should be assessed and the drug-drug
interactions should be ruled out.
Our patient initially harbored F359V when he showed treatment failure to Nilotinib and later
T315I mutation. Treatment options for CML in T315I mutation are Ponatinib, Omacetaxine
and allogeneic HSCT.
In order to assess the successfulness of management of our patient, initially with α-IFN and
with Nilotinib subsequently, a TKD mutation profile and BCR-ABL1 quantification at 3 months
after Nilotinib are vital and yet to be done.
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES