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CHRONIC MYELOID LEUKEMIA, THE TUNISIAN EXPERIENCE IN IMATINIB ERA

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... (La Tunisie m dicale 2007) 77 patients : - Median of IM initiation: 9 Months (1-180 M) - CHR ... – PowerPoint PPT presentation

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Title: CHRONIC MYELOID LEUKEMIA, THE TUNISIAN EXPERIENCE IN IMATINIB ERA


1
CHRONIC MYELOID LEUKEMIA, THE TUNISIAN
EXPERIENCE IN IMATINIB ERA
  • Ben Amor R, Ben Lakhal R, Ghedira H, Belaaj H,
    Laatiri MA, Ben Youssef Y, Ben Romdhane N,
    Msadek F, Menif S, Elloumi M, Khelif A, Meddeb
    B.

2
IN TUNISIA
  • - IMATINIB June 2002
  • - 1st referential October 2005 monitoring
    of response
  • - 1st retrospective study April 2007 (La
    Tunisie médicale 2007)
  • ? 77 patients
  • -
    Median of IM initiation 9 Months (1-180 M)
  • - CHR
    95, Partial CyR (12M) 63
  • - 2nd referential October 2008
  • - Definition of responses (ELN)
  • - Dose-Adaptation
  • - Management of resistances (2nd gen TK-i, IM
    dosing)

3
OBJECTIVE
  • Retrospective Tunisian multicenter study
  • - Evaluate the response to IM according to the
    ELN criteria CCyR - MMR
  • - Analyze the predictives response factors, the
    event free survival (EFS) and the overall
    survival (OS)

4
PATIENTS
  • 160 CML Selected
  • ? ? 116 CML Included
  • - July 2002 - Dec 2008
  • - 6 Hematologic centers
  • - Aziza Othmana Hospital
    51 patients
  • - Sfax 25
    patients
  • - Monastir
    16 patients
  • - Sousse 12
    patients
  • - La Rabta
    8 patients
  • - Military Hospital (Tunis)
    4 patients

5
PATIENTS
  • - The median age 44 years (13 76 years).
  • - Sex ratio 1,6 (72M/44F)
  • Chronic phase (CP) 104 patients
  • Accelerated phase (AP) 12 patients

6
PATIENTS
  • Cytogenetic
  • t(9,22) 113 patients
  • Additional 10 pts
  • - Trisomy 18 2
    patients
  • - Del 11 1
    patient
  • - Del 7 Del 13 1 patient
  • - Complex Translocation 6 patients

7
PATIENTS, SOKAL Score
8
PATIENTS
  • - IM 400mg/day was initiated at least one year
    after diagnosis
  • - Median of 3 months (1 - 12months)
  • - Response evaluation  ELN criteria

9
MONITORING
Blood count Caryotype Q-PCR
Diagnostic weekly Before TTT Before TTT
CHR monthly - -
CCyR Every 3 months 6 - 12 -18 months Every 6 months
MMR Every 3 months Every 12 months Every 6 months
10
METHODS
  • STATISTIC STUDY
  • 1- Predictives response factors (Sokal, Time to
    CCR, TTT Dicontinuation )
  • ( Chi-square test, p lt 0.05 )
  • 2 - The event free survival and the overall
    survival
  • (Kaplan-Meier method and Log-Rank test)
  • - Univariate study
  • - Multivariate study

11
RESULTS
12
RESPONSE TO IM ACCORDING TO  ELN Criteria 
N
Optimal Response 38 33
Suboptimal Response 53 46
Primary Resistance 25 21
Secondary Resistance 13 11,2
13
RESULTS CCyR
- Complete cytogenetic response (CCyR) 76
- Median 12 months (3 - 36 months)
N
CCyR ? 6 months 43 37
6-12 months 31 27
12-18 months 9 8
gt 18 months 5 4
Fail of CCyR 28 24
14
Predictive factors of CCyR
N P
Sokal - Low - High or Intermediate 34/36 25/74 94,4 66,2 0,001
Discontinuation of IM Yes NO 9/20 77/96 45 80,2 0,001
Independent Factors multivariate study
15
RESULTS MOLECULAR RESPONSE
  • - Molecular Monitoring Performed in 80 of
    cases
  • 20
  • - Pb of monitoring
  • - No CCyR
  • ? 62 MMR
  • Mediane 18 months ( 6 48 months)

16
Predictive factors of MMR
P
Sokal - Low - Intermediate - High 47 47 19 0,034
17
PRIMARY RESISTANCE 25pts
  • - No CHR at 3 months 5 patients
  • - No CyR at 6 months 20 patients
  • - IM Dose escalation 18 pts ? 5 CCyR (24-36
    mo)
  • - Same dose of IM 7 pts ? 2 CCyR (24 mo)
  • - Mutation 5 cases ( 1 )

18
  • SECONDARY RESISTANCE ( 4 44 months)
  • 13 patients
  • Loss of CCyR 7 Loss of CHR
    6
  • ? IM 7
  • Death 2 ? IM 4

- 4 suboptimal Response - 2 resistances ? 1
Allo, 1 Death - 1 progression ? Allo SCT
- 2 Death - 2 Resistances
19
DOSE ESCALATION 37 pts
  • - Suboptimal Response 10 pts / 53
    19
  • - Primary Resistance 18 pts
    / 25 72
  • - Secondary Resistance 9 pts / 13
    70

20
TREATMENT DICONTINUATION
  • 2O Patients ( 7 days 2 months )
  • 15 pts Cytopenia
  • 4 pts No adherence to treatment
  • - 1 pt Missed in follow up

21
MUTATION
  • 7 patients
  • - 5 Negative
  • - 1 mutation T 315i F 359c
  • - 1 mutation M 244v

22
RESULTS EFS
  • EFS at 5 years follow-up 79

23
EFS
  • 2007
    2010

24
EVENT FREE SURVIVAL, univariate study
EFS P
Initial Response Yes No 87 68 0,008
Phase Chronic Accelerated 87 58 0,002
CCyR - Yes - No 92 58 0,0000
Time to CCR lt 12M gt 12M 100 85 0,02
25
RESULTS EFS

  • p 0,0001
  • EFS CCyR

26
RESULTS EFS
P 0,002
EFS INITIAL DISEASE STATUE
27
RESULTS EFS
P 0,008
EFS INITIAL RESPONSE
28
RESULTS EFS


  • p
    0,2
  • EFS MMR
  •  

29
OVERALL SURVIVAL
  • OS at 5 years 88

30
RESULTS OS


  • p
    0,00001


  • OS CCyR
  •  

31
COMMENTS 1
  • - Hopeful results
  • EFS
  • OS

32
COMMENTS 2
  • Monitoring difficulty
  • - 160 patients selected
  • 116 included
  • 44 pts Not included
  • ? ? Synchronize the follow up
  • - To All the patients
  • - In All the centers
  • according the Tunisian referential updated in
    2009

33
COMMENTS 3
  • - Management of resistances and suboptimal
    responses
  • ? Dose escalation benefit to only 42 of
    patients eligible for IM escalation (38/91)
  • Primary resistance maintain and escalation of
    IM
  • CCyR in some cases
  • No increase of survival in most of cases

34
CONCLUSION
  • - The management of our patients can be improved
    by better monitoring of response and dose
    escalation
  • The newly introduced
  • BCR-ABL mutational analysis
  • Plasma dosing of IM
  • Use of 2nd generation tyrosine-kinase
    inhibitors
  • ? improve the outcome of resistance

35
(No Transcript)
36
ACKNOWLEGMENT
  • Ben Lakhal R, Menif S
  • Ghedira H, Achour M
  • Belaaj H
  • Laatiri MA
  • Ben Youssef Y
  • Ben Romdhane N
  • MSadek F
  • Saad A
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