ATRA and Anthracycline based treatment in APLATRA and Anthracycline based treatment in APL

Ramzi Jeddi,ESH 28-30 October 2010

TreatmentTreatment

1998-20041998-2004

From 2004…From 2004…

APL diagnosesAPL diagnosesEuropean APL 93European APL 93 Fenaux et alFenaux et al

Spanish PETHEMA LPA99Spanish PETHEMA LPA99 Sanz et alSanz et al

MorphologyMorphologyAuer rods,hypergranular,microgranularAuer rods,hypergranular,microgranular

Cytogenetic analysisCytogenetic analysist(15;17) since 1997t(15;17) since 1997

Molecular analysisMolecular analysisRT-PCR PML/RARA since 2004RT-PCR PML/RARA since 2004

ATRA era since 1998

Fenaux P Blood 1999;14:1192-1200

Sanz MA Blood 2004;103:1237-1243

European APL 93

65yr and i WBC<565yr and i WBC<5 >65yr or i WBC>5>65yr or i WBC>5

ATRA CTATRA CT ATRA + CT3ATRA + CT3 ATRA + CT1ATRA + CT1

AA BB CC

CT=Ara-C+DNRCT=Ara-C+DNR

Patients,n 34

M 15

F 19

Age,median,range 28(6-60)

WBC,median,range 3(0.6-97)

Morphology Hypergranular 33 Variant 1

Add. cytog. abn. 26 ,4%

Sanz’s score Low 32%

Intermediaite High

53%15%

CR 82%

Early death 18%

Results with European APL 93Results with European APL 93 (Tunis,n=24,Sfax,n=10)(Tunis,n=24,Sfax,n=10)

Age,yr 13 25 22 26

Sanz’s score HR RI RI HR

IF CD2-

CD56-

CD2-

CD56-

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

Relapse rate =14.2%

ASCT PML/RARA-

From 2004…From 2004…

Spanish PETHEMA LPA 99Spanish PETHEMA LPA 99

Spanish Contribution to APL treatmentNo AraC!

Complete remission

Mortality rate

Failure in LPA 99=Early Death

Hemorrhage DS

Hemorrhage

Breccia M Haematologica 2010;853-4

In our studyMedian time from first sign and treatment 18 days (range,3-90)

Differentiation syndrome

11 pts with DS

Moderate=4Severe=7

Mortality=3

BMI> 30Baseline WBC > 20

BMI> 30Baseline WBC > 20

Normal Promyelocytes

APL cells

OB_Rs

BMI> 30Baseline WBC > 20

Normal Promyelocytes

APL cells

OB_Rs

Adipose tissue

BMI> 30Baseline WBC > 20

Normal Promyelocytes

APL cells

OB_Rs

Adipose tissue

Leptin

BMI> 30Baseline WBC > 20

Normal Promyelocytes

APL cells

OB_Rs

Adipose tissue

Leptin

Release of cytokines

BMI> 30Baseline WBC > 20

Normal Promyelocytes

APL cells

OB_Rs

Adipose tisuue

Leptin

Release of cytokines DS

confirmed in larger series > 1000 ptsIncluded 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 45 Adults

APL936

LPA9914

LPA9927

APL9318

ATRA dose=25mg/m2

Children vs Adults

GIMEMA

Emerging problem?

Cumulative dose of Anthracycline

- IDA =90mg/m2- MTZ=50mg/m2

APL in childrenAPL in children

APL in childrenAPL in children

Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48

US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

APL in childrenAPL in children

Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48

US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

APL in childrenAPL in children

Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48

US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

APL in childrenAPL in children

Our series (2010) ATRA+CT 20 12(4-19) 95 75 NA 75 48

US intergroup 0129 ATRA vs No ATRA 53 ---- 81 48 -- 69 --

ConclusionsConclusions

- Acceptable results- Acceptable results

- Improvement is required:- Improvement is required:

* reach CR of 90% in adults* reach CR of 90% in adults

* Maintain OS between 75-80%* Maintain OS between 75-80%

- Availability of ATO for relapses- Availability of ATO for relapses

AknowledgmentAknowledgment

Balkis MeddebBalkis MeddebHèla Ben AbidHèla Ben AbidZaher BelhadjaliZaher BelhadjaliRaihane Ben LakhalRaihane Ben LakhalHdiji SondesHdiji SondesRaouf Hafsia Raouf Hafsia Emna GouiderEmna GouiderSamia MénifSamia MénifLamia AissaouiLamia AissaouiRamzi Ben AmorRamzi Ben AmorKarima KacemKarima KacemWalid BoutéraaWalid BoutéraaYosr Ben AbdennebiYosr Ben AbdennebiHéla GhédiraHéla Ghédira

Pierre FenauxPierre FenauxMiguel SanzMiguel Sanz