ATRA and Anthracycline based treatment in APL
Ramzi Jeddi,
ESH 28-30 October 2010
ATRA era since 1998
Treatment
European APL 93
Fenaux et al
APL diagnoses
Morphology
Auer rods,hypergranular,microgranular
1998-2004
Spanish PETHEMA LPA99
Sanz et al
From 2004…
Cytogenetic analysis
t(15;17) since 1997
Molecular analysis
RT-PCR PML/RARA since 2004
Fenaux P Blood 1999;14:1192-1200
Sanz MA Blood 2004;103:1237-1243
European APL 93
65yr and i WBC<5
A
ATRA
>65yr or i WBC>5
C
B
CT
ATRA + CT3
CT=Ara-C+DNR
ATRA + CT1
Results with European APL 93
(Tunis,n=24,Sfax,n=10)
Patients,n
34
M
15
F
19
Age,median,range
28(6-60)
WBC,median,range
3(0.6-97)
Morphology
Hypergranular
Variant
Add. cytog. abn.
Sanz’s score
33
1
26 ,4%
Low
32%
Intermediaite
High
53%
15%
CR
82%
Early death
18%
Relapse rate =14.2%
Age,yr
13
25
22
26
Sanz’s score
HR
RI
RI
HR
IF
CD2CD56-
CD2CD56-
NA
NA
Median,month
24
46
36
4
site
M
M
M+CNS
M
Salvage therapy
APL93
LPA99
APL93
APL93
Outcome
Death
Alive
Death
Death
ASCT
PML/RARA-
From 2004…
Spanish PETHEMA LPA 99
Spanish Contribution to APL treatment
No AraC!
Complete remission
Mortality rate
Failure in LPA 99=Early Death
Hemorrhage
DS
Hemorrhage
Breccia M Haematologica 2010;853-4
In our study
Median time from first sign and treatment 18 days (range,3-90)
Differentiation syndrome
11 pts with DS
Moderate=4
Severe=7
Mortality=3
BMI> 30
Baseline WBC > 20
BMI> 30
Baseline WBC > 20
Normal Promyelocytes
OB_Rs
APL cells
BMI> 30
Baseline WBC > 20
Normal Promyelocytes
OB_Rs
APL cells
Adipose tissue
BMI> 30
Baseline WBC > 20
Normal Promyelocytes
OB_Rs
APL cells
Adipose tissue
Leptin
BMI> 30
Baseline WBC > 20
Normal Promyelocytes
OB_Rs
APL cells
Release of cytokines
Adipose tissue
Leptin
BMI> 30
Baseline WBC > 20
Normal Promyelocytes
OB_Rs
Adipose tisuue
Leptin
APL cells
Release of cytokines
DS
confirmed in larger series > 1000 pts
Included in APL93 & APL2000
and will be presented as poster in ASH
Annual meeting 2010
Relapse rate
Relapse rate
Relapse rate
Childhood APL
Jeddi R .Med Oncol Aug 10
65 APL pts
20 Children
APL93
6
LPA99
14
ATRA dose=25mg/m2
45 Adults
APL93
18
LPA99
27
Children vs Adults
GIMEMA
Emerging problem?
Cumulative dose of
Anthracycline
- IDA =90mg/m2
- MTZ=50mg/m2
APL in children
APL in children
Our series (2010)
US intergroup 0129
ATRA+CT
ATRA vs No ATRA
20
12(4-19)
95
75
NA
75
48
53
----
81
48
--
69
--
APL in children
Our series (2010)
US intergroup 0129
ATRA+CT
ATRA vs No ATRA
20
12(4-19)
95
75
NA
75
48
53
----
81
48
--
69
--
APL in children
Our series (2010)
US intergroup 0129
ATRA+CT
ATRA vs No ATRA
20
12(4-19)
95
75
NA
75
48
53
----
81
48
--
69
--
APL in children
Our series (2010)
US intergroup 0129
ATRA+CT
ATRA vs No ATRA
20
12(4-19)
95
75
NA
75
48
53
----
81
48
--
69
--
Conclusions
- Acceptable results
- Improvement is required:
* reach CR of 90% in adults
* Maintain OS between 75-80%
- Availability of ATO for relapses
Aknowledgment
Balkis Meddeb
Hèla Ben Abid
Zaher Belhadjali
Raihane Ben Lakhal
Hdiji Sondes
Raouf Hafsia
Emna Gouider
Samia Ménif
Lamia Aissaoui
Ramzi Ben Amor
Karima Kacem
Walid Boutéraa
Yosr Ben Abdennebi
Héla Ghédira
Pierre Fenaux
Miguel Sanz