peripheral blood stem cell transplant
TRANSCRIPT
PBSC revisited in present practice
Didier Blaise, MDBangkok
August, 28th, 2015
Members of Stem Cell Trialists’ Collaborative Group9 trials included (N=1,111 patients)
Ben DjulbegovicBill BensingerCorey CutlerIztok HozoClaudio AnnasettiHeloisa SoaresAmbuj Kumar
Nobert Schmitz
Alois Gratwohl
Jane Apperley
Roy Baynes
James Matcham
Didier Blaise
Mohamad Mothy
Mathieu Kuentz
Ray PowlesBhawna SirohiMike ClarkeSue RichardsRobert HillsKeith Wheatley
Dag Heldal
Jan Cornelissen
B Van der Holt
Stephen Couban
Tony Panzarella
David Simpson
Jeff Lipton
Carmino A de Souza
Afonso Vigorito
Eliana CM Miranda
James Morton
Entezam Sahovic Ed ColcolMahmoud Al-Jurf
Stem Cell Trialists , JCO, 2006
Stem Cell Trialists , JCO, 2006
PREVALENCE OF CGVHD
Months post-transplantation
Prev
alen
ce o
f cG
VHD
(%)
0 18 36 540
25
50
75
100BMTBCT
D Blaise et al , Blood, 2002
M Mohty et al , Leukemia 2003
BM versus PBSC
• Myeloablative CDT
• Mainly Familial HLA-Identical Donor
• GVHD prophylaxis: CSA/FK506 and MTX
M Mohty et al , Blood 2003
The increase from 2.5 to 5 mg/kg of r-ATG dose in RIC is beneficial
R Devillier et al , BMT 2012 9
CD34 dose after RIC: High dose or not?
11
Outcomes in RIC regimen
Mohty, Leukemia 2003
Extensive chronic GVHD
MACNo ATG
MRDCsA/MTX
RIC ATG
MRD/MUDCsA
12
Heterogeneity of the studies
Blood (2009) BBMT (2014) BBMT (2015)Pulsipher Törlén Remberger
Patients number 932 1054 544High doses CD34 OS OS OSDiseases Myeloid AML or DMS All Donor MUD MRD or MUD MRD or MUDConditionning R MAC/RIC/NMA RIC or NMA MAC or RICGVHD prophylaxis Heterogeneous Heterogeneous Heterogeneouscut off cd34 4.5x10.6/kg MRD 4x10.6/kg /MUD 6x10.6/kg 8.1x10.6/kg
Heterogenous population
13
Impact of CD34/CD3 cell dose
Homogenous population
CsA
RICPBSC
14
1) Peripheral blood stem cells
2) HLA identical : - Matched related - Matched unrelated donor;
3) Reduced intensity conditioning (RIC) regimen;
4) Ciclosporine A alone;
Selection criteria
FLU 30 mg/m²
FLU 30 mg/m²
FLU 30 mg/m²
FLU 30 mg/m²
FLU 30 mg/m²
BU 130mg/m2
BU 130mg/m2
ATG 2.5mg/kg
ATG 2.5mg/kg
Day-2 Day 0Day-1
HSCT
Day-5 Day-4 Day-3Day-6
15
Patient characteristics
N = 246 %
Age, years, median (range)
CD3 (106/kg), median (range)
Matched related donor
Lymphoid malignancies
Disease Risk Index Low
HCT-Comorbidity Index ≥ 3
All patients
CD34 (106/kg), median (range) 6.5 (2-14.2)
46%
59 (19-71)
279 (61-1919)
142 58%
132 54%
44 18%
110
16
Variables adjusted by Age, donor, HCT-CI, DRI, CD3
CD34≤6.5x106/kg CD34>6.5106/kgN=124 (%) N=122 (%)
3-4 AGVHD 10 8 0.674 1.2 0.581Ext CGVHD 24 21 0.539 0.7 0.243NRM 19 23 0.638 0.9 0.841RI 30 22 0.179 0.8 0.244PFS 62 68 0.179 0.8 0.322OS 52 55 0.405 0.8 0.200
pp HR
Univariate model Multivariate model
CD34 median
CD34 : median cut off
Extensive chronic GVHD
Initial Study, Leukemia 2003 Present Study, 2015
MAC RIC
18
CD3 : multivariate model
Variables adjusted by Age, donor, HCT-CI, DRI, CD34
HR 95CI p
PFS 0.8 [0.56-1.17] 0.272
OS 0.8 [0.54-1.24] 0.346
NRM 0.8 [0.46-1.47] 0.512
0.8CIR [0.50-1.30] 0.352
AGVHD III-IV 0.8 [0.36-1.68] 0.526
CGVHD Extensive 1.1 [0.65-1.93] 0.668
CD3 ≥ median
19
CONCLUSION
Impact of in vivo T cell depletion?
Myeloablative conditionning Reduced intensity conditionning No rational for limiting the maximal amount of CD3 or CD34 cell dose in the setting of RIC with ATG.
CD34 : No impact
CD3 : No impact
BM or PBSC for haplo HSCT
PBSC for HaploMarseille Experience on 102 patients
Characteristics
• Age: 59 (22 – 73)• Follow-up: 15 months (1 – 31)• CD 34+ (mediane) 5.1 x 106/Kg • CD3+ (mediane) 262 x 106/Kg • DRI: Intermediate 59%; High 30%; V.High 7%• HCT-CI ≥ 3: 63%• CDT: 68% Baltimore; 32% RTC
Hematologic RecoveryANC > 0,5x109/Lmediane 21 (14 – 47) jours
PLT > 20x109/Lmediane 35 (10- 134) jours
Chimerism J+90(séquençage CD3+) 98%
Graft Failure 2%
GVHD
2-y RI and 2-y NRM
0.0 0.5 1.0 1.5 2.0
0.0
0.2
0.4
0.6
0.8
1.0
2-y RI = 24%
Years from transplant
Cum
ulati
ve in
cide
nce
Time to Relapse (median, range): 3.3 months (0.5 – 14)
0.0 0.5 1.0 1.5 2.0
0.0
0.2
0.4
0.6
0.8
1.0
2-y NRM = 23 %
Cum
ulati
ve in
cide
nce
Years from transplant
100-day NRM 12%
2-y OS and PFS
BM PBSC P value
N° pts 46 23Age 44 (19-68) 54 (25-65) .06Follow-up (jours) 721 (365-728) 332 (135-498) <.0001PNN > 0,5 x 109/L (jours) 20 21 .18PLT >20 x 109/L (jours) 29 29 .13GVH aigue 2-4 25% 33% .43GVH chronique 13% 13% .21NRM 22% 12% .96
Probabilité de OS et PFS à 2 ans = 68 et 62%non statistiquement différente
L. Castagna et al. BBMT 2015
BMT CTN(BM)
IPC/UK/AUS/FHCRC(PBSC)
p value
Patients (N°) 43 43Follow-up (mos) 36 16
100 d aGVHD grade 3-4 0% 5% 0.410
2 y cGVHD 28% 18% 0.2142 y OS 58% 56% 0.735
Conclusions
• No increase for acute or chronic GVHD
• NRM, OS or PFS similar
• No benefit for hematologic recovery
• Ease for large program