PMID- 30923102
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 1592-8721 (Electronic)
IS  - 0390-6078 (Print)
IS  - 0390-6078 (Linking)
VI  - 104
IP  - 11
DP  - 2019 Nov
TI  - MR4 sustained for 12 months is associated with stable deep molecular responses in 
      chronic myeloid leukemia.
PG  - 2206-2214
LID - 10.3324/haematol.2018.214809 [doi]
AB  - The majority of patients with newly diagnosed chronic myeloid leukemia (CML) will 
      enjoy a life expectancy equivalent to that of unaffected individuals, but will 
      remain on life-long treatment with a concomitant requirement for on-going 
      hospital interactions for molecular monitoring and drug dispensing. In order to 
      determine more accurately the frequency of monitoring required, we performed a 
      'real-life' retrospective single-center cohort study of 450 patients with CML in 
      at least major molecular remission (MR3) to analyze the risk of loss of MR3 
      [defined as at least 2 consecutive real-time quantitative polymerase chain 
      reaction (RT-qPCR) results >0.1% International Scale (IS)]. Patients who achieved 
      sustained MR4 (sMR4, BCR-ABL1 RT-qPCR <0.01% IS for 12 months) had a probability 
      of loss of MR3 at 1 and 5 years of 0 and 2.6% (95%CI: 1.2-5.4) respectively, 
      compared to 4.4% (95%CI: 1.9-9.8) and 25.4% (95%CI: 16.7-36.7) respectively, in 
      those who achieved sustained MR3 (sMR3) but not sMR4 (P<0.001). No patient who 
      improved their response to a deep molecular level (at least MR4) lost MR3 if they 
      were considered compliant, had no history of resistance and remained on standard 
      dose tyrosine kinase inhibitor (TKI). MR4 maintained for at least one year 
      represents a secure response threshold for patients with CML, after which no MR3 
      loss occurs if certain conditions are satisfied (standard TKI dose, full 
      compliance, and lack of previous TKI resistance). This finding may justify 
      reduction of the frequency of hospital interaction, with an associated positive 
      impact on quality of life, survivorship, and economic burden to both patients and 
      healthcare providers.
CI  - Copyright(c) 2019 Ferrata Storti Foundation.
FAU - Claudiani, Simone
AU  - Claudiani S
AD  - Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS 
      Trust, London, UK simone.claudiani@nhs.net.
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Gatenby, Aoife
AU  - Gatenby A
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Szydlo, Richard
AU  - Szydlo R
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Nesr, George
AU  - Nesr G
AD  - Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS 
      Trust, London, UK.
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Abulafia, Adi Shacham
AU  - Abulafia AS
AD  - Institute of Hematology, Davidoff Cancer Centre, Beilinson Hospital, Rabin 
      Medical Centre, Petah-Tiqva, Israel.
FAU - Palanicawandar, Renuka
AU  - Palanicawandar R
AD  - Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS 
      Trust, London, UK.
FAU - Nteliopoulos, Georgios
AU  - Nteliopoulos G
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Khorashad, Jamshid
AU  - Khorashad J
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Foroni, Letizia
AU  - Foroni L
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Apperley, Jane F
AU  - Apperley JF
AD  - Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS 
      Trust, London, UK.
AD  - Centre for Haematology, Imperial College London, London, UK.
FAU - Milojkovic, Dragana
AU  - Milojkovic D
AD  - Department of Haematology, Hammersmith Hospital, Imperial College Healthcare NHS 
      Trust, London, UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190328
PL  - Italy
TA  - Haematologica
JT  - Haematologica
JID - 0417435
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use
MH  - Biomarkers, Tumor
MH  - Female
MH  - Fusion Proteins, bcr-abl/*genetics
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*diagnosis/drug 
      therapy/*genetics/mortality
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use
MH  - *Real-Time Polymerase Chain Reaction/methods
MH  - Transcription, Genetic
MH  - Young Adult
PMC - PMC6821602
EDAT- 2019/03/30 06:00
MHDA- 2020/07/14 06:00
PMCR- 2019/11/01
CRDT- 2019/03/30 06:00
PHST- 2018/12/16 00:00 [received]
PHST- 2019/03/21 00:00 [accepted]
PHST- 2019/03/30 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2019/03/30 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - haematol.2018.214809 [pii]
AID - 1042206 [pii]
AID - 10.3324/haematol.2018.214809 [doi]
PST - ppublish
SO  - Haematologica. 2019 Nov;104(11):2206-2214. doi: 10.3324/haematol.2018.214809. 
      Epub 2019 Mar 28.