Novel therapies for aplastic anemia Richard Champlin, MD

1. Hematopoietic Transplantation for
Aplastic Anemia
Richard Champlin, MD

2. Questions for HSCT for Aplastic
Anemia
• Preparative regimen and GVHD prevention
– Cyclophosphamide +/- ATG
– Cyclophosphamide, fludarabine + ATG or alemtuzumab
– ? Role of TBI for MUD
• Effect of Race
• Cell Source
– Bone marrow
– PBPC
• Alternative Donors
– Cord blood
– Haploidentical transplants

3. Champlin et al Blood 2007

4. HLA id siblings 1991-2002 : CY 200 mg/kg
Survival Plot
p<0.0001
days from BMT
% Overall Survival
1,000
0,750
0,500
0,250
0,000
0,0 1500,0 3000,0 4500,0 6000,0
GG_BMT_F
Survival
C54
0
1
2
3
A
B
C
D
A= <20yy n=681 83%
B= 21-30yy n=339 73%
C= 31-40yy n=146 68%
D=>40yy n=111 51%

5. Preparative regimen (current version)
Days -6 -5 -4 -3 -2 -1 0
F F F F
C C Rest
BMT
A C C
T T T T
From Bacigalupo et al, BMT 2005. Used in 13 patients. A: Admission.
F= Fludarabine 30 mg/m2; C = Cyclophosphamide 300 mg/m2; T=
Thymoglobulin 3.75 mg/kg (MRD: three doses only). GVHD
prophylaxis: tacrolimus - miniMTX

6. Patient characteristics (2)
Cell source
BM
PBSC
UCB
17 (MRD n=6; MUD n=11)
3 (MRD n=1; MUD n=2)
1
Donor
Matched related
Matched unrelated
7 (33%)
14 (67%)
Prior ATG therapy 17 (80%)

7. Engraftment and chimerism
• ANC 500: day 15 (8-30)
• PLT 20K : day 15 (9-73)
• Graft failure: 2/20 evaluable (10%).
• No late graft failures.
• Chimerism (best): --- ≥ 90% Donor 13 (65%)
--- Mixed 6 (30%)
--- NE 1 (5%)

8. Graft-vs-host-disease (GVHD)
• GVHD prophylaxis: CSA or tacrolimus + MTX
• Acute GVHD (day 100): Y / N 4/20 ev pts
(20%).
• Chronic GVHD (at any time): Y / N 6/16 ev pts
(37%)

9. Patient outcome
• Eight deaths (38%). Thirteen a/w.
• Causes of death: ---- graft rejection n=1
---- EBV PTLD n=2
---- GVHD n=2
---- infection n=2
---- organ failure n=1
• Median f/up: 11 mo (0.5-112).
• EBV reactivation: 9/20 pts (45%), including EBV-PTLD
(n=2)

10. Overall survival
Overall survival (actuarial estimate) for the whole group (n=20: 61%) (curve A) and for the
thirteen patients treated according to Bacigalupo et al (BMT 2005; 36, 947) (curve B; 82%).

11. Alemtuzumab vs ATG for HSCT for
Aplastic Anemia
Marsh et al BMT 2014

15. Alternative Donors
• Considered in patients who fail immunosuppressive
therapy with ATG and have no HLA matched donor
– Prep regimen not well standardized
• Cord Blood- Only small reports, initially high rate of TRM,
graft failure; improved recent results
– Chan 7 of 9 children alive
– Yamamoto M-Flu TBI 4 cGy 10 of 12 adult patients alive with
engraftment Blood 2011
• Haploidentical- improved results in general with haplos
using post transplant cyclophosphamide, where results are
similar to matched MUD, little data in AA
– Xu et al BMT 2012 N=19 Bu Cy ATG 64% survival
– Gao et al BMT 2014 N=26 Cy Flu ATG 84% survival