mds the role of haploidentical allogeneic sct: results and for … · 2019. 3. 26. · mds –the...
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MDS – The role of haploidentical allogeneic
SCT: results and for whom do I consider?
Fábio Kerbauy
July/2018•No major health issues, anemia and pulmonary infeccion in july/2018•L: 800 (400n); Hb: 9.0; PLQ: 30.000
Bone marrow: 18% blast, dysplastic features 3 series
IFT: 16,2% progenitor cels: CD34+ and CD13, CD33, CD38, CD71, CD105, CD117, HLA DR e MPO
Kt: 44,XX,+der(6)t(3;6)(p21;q25),-7,der(7)t(1;7)(p22;p22),der(10)t(5;10)(q22;q11.2),-
17, -18,add(19) (p13)[6]/46,XX[14]
FISH: deleção do gene TP53
MDS – AREB-II Very High Risk
Case study– SMDS, 55a
Revised-IPSS
Greenberg PL et al. Blood, 2012; 120(12): 2454-2465
Targeted therapy for MDS - 2019
Alesheen A and Greenberg PL Blood, 2019; 2(20): 2787-2797
NCCN- 2017 – Low Risk
NCCN- 2017 – High/Int Risk
Current treatment algorithm - 2018
Steensma DP Blood Cancer Journal, 2018; 8(47): 2-7
High Risk MDS – Phase III 5-Aza
Fenaux P. et al. Leukemia 2009
OS benefit: + 9.5 mos
Time to AML: 17.8 vs. 11.5 mos
Donor x No Donor – High risk MDS
Robin M et al, Leukemia, 2015
HCT for SMD – CIBMTR
Allo HCT in 70+ yo patients – USAMedian age: 72 (70-84)
EBMT activity survey. Passweg et al. BMT, 2017; 52: 191-196
Impact of drug development on SCT
Possible donors (by august/2018 – 2 months from diagnosis)
•1 Brother: HLA incompatible
•4 sons – haploidentical
•Brazilian donor registry – REDOME (1 international donor available)
While wainting
•5-AZA as a bridge to HCT
QUESTION: MUD x haplo?
Case study– SMDS, 55a
MA (BuTCy) in MDS – Median 46yo
Deeg et al, Blood 2002; 100:1201-1207
TRM 100d e 1 y
MRD=12% / 28%
MUD = 13% / 30%
MRD x MUD in MDS patients - CIBMTR
Saber W et al. Blood, 2013; 122(11): 1974-1982 Robin M et al. BMT, 2013; 1-6
Post HCT Cy for haplo – Johs Hopkins
Brodsky RA et al.BMT;42: 523-527,2008
Post HCT Cy for haplo – Johs Hopkins
Brodsky RA et al.BMT;42: 523-527,2008
Post HCT Cy for haplo – OS (n=210)
MRD = MUD
X
Haploidentical (Post transplant Cyclophosphamide)
ASH - 2016
Type of donor for MDS patients
Only a handful of HCTs from haploidentical donors for patients with MDS have been performed to date, and very few were performed using the novel platform of posttransplant cyclophosphamide.
HLA- identical siblings and 8/8 matched unrelated donors be consideredstandard therapy for MDS
AML/MDS - Haplo x MRD x MUD Haplo (n=32)
Di Stasi et al. BBMT, 2014; 20(12): 1975-1981
AML/MDS - Haplo x MRD x MUD Haplo (n=32)
Di Stasi et al. BBMT, 2014; 20(12): 1975-1981
Haplo HCT for MDS – EBMT 2017(n=228)
Robin M et al. Blood, 2017; 1(22): 1876-1883
Chang YJ et al.J Hematol Oncol, 2016; 9(35): 8-12
Selecting the best haplo donor
• PRA (anti-HLA)• ABO/Rh• CMV status
Case study– SMDS, 55ªPRA+ (DSA+)
Disensitizatin for DSA+
Ciurea SO et al. BMT, 2018
By December/2018 – 5 months from diagnosis)
•4 cycles of 5-Aza: Less transfusion dependence
•BM: 20% blasts
•1 son– haploidentical ABO/CMV matched (DSA+)
•1 MUD 10/10
Case study– SMDS, 55a
TODAY: D+60 post HCT
•Low HCT-CI
•MUD (PBSC 6 x 10e6 CD34+/kg)
•Bu (6000 AUC) + Fludarabine / FK/MTX/ATG
•Complications: Mucositis grade IV/neutropenic fever
•Engraftment: D+12
•GVHD skin grade 2 resolved
•100% chimerism/ MRD-
Case study– SMDS, 55a
MDS and mutations
Bejar R et al. NEJM, 2011
HCT in TP53 mutations AML/MDSImpact of HCT-CR
Ciurea SO et al. Blood, 2018
•Standard of care: MRD or MUD
•Haplo as alternative
-High-risk/very high-risk patients
-Fit patients (HCT-CI score)
-Choose the best donor (ABO/CMV/PRA)
-MA x NMA
Haplo for MDSFor whom I consider
Haplo for MDSFor whom I consider
ALWAYS DISCUSS CASE BY CASE
-Specific risk scores
-Pre HCT therapy
-Conditioning regimen intensity
-Post HCT maintenance
