1. Haploidentical BMT with Post Transplant Cyclophosphamide
“The Great Equalizer”
Heather Symons, MD, MHS
Clinical Director, Pediatric Blood and Marrow Transplantation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, USA

2. Conflict of interest statement
Jazz – Speaker’s Bureau
Novartis – Clinical trial participation
BMS – Clinical trial participation

3. HaploBMT with PTCy has what it takes!✓
Safe
Efficacious
Simple/Transportable
Inexpensive
Track record of success
National/International Reputation
Used for a wide variety of diseases ✓ ✓ ✓ ✓ ✓ ✓

4. Single Institution Success

5. National Success in Hematologic Malignancies
National, multi-center trials with successful outcomes
Outcomes of Haplo= HLA-matched graft sources

6. Haplos with PTCy have caught up to HLA-matched 3 year progression free survival, stratified by disease risk index
Matched
Haplo
Disease Stage/
Risk
1997*
(matched sib)
2015†
(sib + MUD)
2015‡
Early/Low Risk 66 25 63
Intermediate 44 31 20 39
Advanced/High Risk 12 15 22
*R Szydlo et al. J Clin Oncol 15: , 1997
†Personal communication with P. Armand (n=614)
‡S McCurdy et al. Blood 125: , 2015

7. Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide Compared With 10/10 Allele-Matched Unrelated and HLA-Identical Sibling Donors Transplantation Bashey A, et al. BBMT 2016: 22:

8. RIC Haplo-BMT vs Matched URD HCT for lymphoma Kanate AS, et al
RIC Haplo-BMT vs Matched URD HCT for lymphoma Kanate AS, et al. Blood 2016; 127:

9. Parallel Phase 2 Trials Using Partially HLA-MM Related Bone Marrow or Unrelated dUCB Grafts Brunstein CG, Fuchs EJ, Carther SL, et al. Blood 2011; 118:
CTN Study: 2 Parallel Multicenter Phase 2 Studies
56% AML (cord), 44% AML (haplo)
RIC Regimen of FLU/CY/ Low dose TBI for both groups
Early TRM higher with UCBT (24% vs 7%) but relapse rate lower (31% vs 45%)
UCBT 1 year OS 54%, PFS 46%
Haplo-BMT 1 year OS 62%, PFS 48%
Haplo aGVHD Gr 3-4 = 0%

10. Pediatric Specific DataN
Engraftment
aGVHD II-IV
aGVHD III-IV
Mod-severe cGVHD
TRM
Relapse (3y)
EFS
(3y) OS
Hopkins
(NMA)1 40
91%
33% 5% 7%
13%
52%
46%
32%
(MA)2 29
96%
18% 4%
12%
10%
25%
55%
72%
AIEOP-GITMO3 33
97%
22% 3% 9%
24%
61% (1y)
72% (1y)
PBMTC 0%
1 Klein et al, BBMT, 2017
2 Symons et al, BBMT, 2016
3 Berger et al, BBMT , 2016

11. HaploBMT success in nonmalignant disorders

12. Haplo-BMT with PTCY for non-malignant disorders
Disease N
Engraftment
GVHD
Death
Sickle Cell and thal (ATG, Flu, Cy, 400cGy TBI, sirolimus)1 17
94%
2 (Gr 2)
1 (Gr 3)
1 mod CGVHD
Thalassemia2 31 1
Aplastic Anemia3 16
100%
2 (Gr 1-2 skin) 0%
Immunodeficiencies/
BMF4 11
90%
2 (Gr 1)
1 (Gr 2)
1 cGVHD
1 Jones, et al, ASH abstract 2017
2 Anurathapan et al, Bone Marrow Transplant (2016)
3 DeZern et al, BBMT, 2017
4 Klein et al, BBMT, 2016

13. Bonus Points No PTLD with antibody-therapy free platforms1
No increase in donor derived malignancies2
# of HLA mismatches does not matter3
Can use second degree haplo relatives4
Can d/c CNI at Day 60 safely5
DLI feasible and potentially beneficial6
Low rate of infections and rapid immune reconstitution as c/w T cell depleted haplos7,8,9
1 Kanakry et al, BBMT, 2013
2 Majzner et al, BBMT, 2017
3 McCurdy et al, Blood Adv, 2018
4 Elmariah et al, BBMT, Ciurea et al, BBMT, 2012
5 Kasamon et al, BBMT , Luznik et al, Blood, 2001
6 Zeiden et al, BBMT, Crochiollo et al, Trnsp Infec Dis, 2015

14. HaploBMT with PTCY is the platform for new national haplo initiatives

15. BMT CTN 1502: Aplastic Anemia Haploidentical Cohort
Flu
Flu
Flu
Flu
Flu
GVHD Prophylaxis:
Tacrolimus, MMF, & Post-HSCT Cy Cy Cy
ATG
ATG
ATG
TBI Cy Cy
Flu
= Fludarabine 30 mg/m2 IV daily Cy
= Cyclophosphamide 14.5 mg/kg IV daily
TBI
= 200 cGy Cy
= Cyclophosphamide 50 mg/kg IV daily
ATG
= Thymoglobulin 0.5 mg/kg (day-9) & 2 mg/kg (day -8,-7)

16. Reduced Intensity Conditioning before HLA-Haploidentical Bone Marrow Transplantation in Patients with Symptomatic Sickle Cell Disease
BMT CTN protocol development
Michael R. DeBaun MD MPH
Adetola Kassim, MD
Mark Walters, MD Robert Brodsky, MD

17. HaploBMT with PTCy Summary
PTCY is the dominant method of GVHD prophylaxis in the haplo setting
15 years of experience
Safe and efficacious for malignant and non-malignant disorders
All conditioning intensities possible- myeloablative, RIC or non-myelo
Low rates of acute and chronic GVHD and non-relapse mortality
Relapse on par with other graft sources when DRI is factored in
Efficacious for malignant and non-malignant disorders
Haplo plus PTCy outcomes are = cord blood or HLA-matched BMT
Low cost, easily transportable, simple, no extra training required
New national initiatives to treat sickle cell disease and aplastic anemia using haploBMT with PTCy

18. “In character, in manner, in style, in all things, the supreme excellence is simplicity” Henry Wadsworth Longfellow
PTCy
Day + 3, hours from the start of graft infusion
Ideally avoid other immunosupressive agents before this time
a/b depletion
CliniMACS® TCRαβ-Biotin system,
Three IDE exemption cross references: BB MF 12011, SN 073 (Clinimacs® CD19 reagent system), BB MF 12251, NS 054 (Clinimacs® depletion tubing set), and BB MF 15678, SN 012, Clinimacs® TCR α/β reagent system)
Long instruction booklets that requires a cell processing lab with skilled personnel and equipment

19. Haplo with PTCy: may not be the most sophisticated or attractive approach but it’s a clear winner