Hematopoietic Transplantation for Aplastic Anemia

Richard Champlin, MD

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

Champlin et al Blood 2007

days from BMT

% O

vera

ll S

urvi

val

0,000

0,250

0,500

0,750

1,000

0,0 1500,0 3000,0 4500,0 6000,0

Survival Plot

GG_BMT_F

Su

rviv

al

C54

0123

A

BC

D

A= <20yy n=681 83%B= 21-30yy n=339 73%C= 31-40yy n=146 68%D=>40yy n=111 51%

p<0.0001

HLA id siblings 1991-2002 : CY 200 mg/kg

Preparative regimen (current version)

Days -1 -6 -5 -4 -3 -2 0

F F F F

C C BMT

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

Rest

T TTT

C C A

Patient characteristics (2)

Cell sourceBMPBSCUCB

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%)

21 (all PD)

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%)

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%)

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)

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%).

Marsh et al BMT 2014

Alemtuzumab vs ATG for HSCT for Aplastic Anemia

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