Transplantation For Scleroderma: Data from the Phase I/II Pilot Multicenter Study (FHCRC protocol 1019)

Transplantation For Scleroderma: Data from the Phase I/II Pilot

Multicenter Study

(FHCRC protocol 1019)

Transplantation For Scleroderma: Data from the Phase I/II Pilot

Multicenter Study

(FHCRC protocol 1019)

TRANSPLANT REGIMEN*TRANSPLANT REGIMEN*

TBI 2Gy x 4‡ = 8 Gy

CTX60mg/kgx2

- 5 - 4 - 3 -2 -1 0 1 3 5

CD34+AUTOPBSC

DAY

G-CSF

Equine ATG 15 mg/kg/dose§

* PBSC mobilized with G-CSF at 16 ug/kg/d

‡ TBI administered with lung shielding (lung dose= 200 cGy) for last 26 pts

§ Prednisone with Equine ATG then 0.5 mg/kg/day; day 6-30, taper to day 60

McSweeney, Blood, 2002

Patient Characteristics

N=33 Median Range

Female (N =26)

Age (yrs) 41 23-61

Primary Organ involvement

lung=33; kidney=1; heart=8; GI=22

Skin score (mRSS): 30 3-48

DLCO adjusted for Hgb (mm/Hg) 62 40-95

FVC % 72 27-103

Serum Creatinine (mg/dL) 0.7 0.4-1.4

Disease Duration (months) 20 4-51

Decrease in Rodnan Skin Score after SCTDecrease in Rodnan Skin Score after SCT

GEE; p<0.0001

Skin

Mean, Baseline (n=34)

Mean Change,

Final (n=25)

mRSS (0-51)

30.12 -22.08, p<.0001

Mean Value

Nash, Blood 2007

Resolution of Dermal Fibrosis Patient 11 Skin Biopsy

A+B : Pre-HCT: grade 5; low + high power

C+D : 1 year post-HCT: grade 3; low + high power

E+F: 5 years post-HCT: grade 0; low + high power

Nash, Blood 2007

HEALTH ASSESSMENT (mHAQ)HEALTH ASSESSMENT (mHAQ)

Pulmonary Function after SCT for SScPulmonary Function after SCT for SSc

Forced Vital Capacity DLCO (corrected for Hgb)

GEE, p=0.002Mean Change +2.11, p= .50

GEE, p=0.40Mean Change -7.07, p=.02

Autologous Hematopoietic Cell Transplantation: Survival (n=34)

Autologous Hematopoietic Cell Transplantation: Survival (n=34)

Progression (from SCOT):1. Respiratory failure-decrease of DLCO >30% or FVC >20%.2. Renal failure- dialysis or kidney transplantation.3. Clinical heart failure or LVEF <30%.

Progression (from SCOT):1. Respiratory failure-decrease of DLCO >30% or FVC >20%.2. Renal failure- dialysis or kidney transplantation.3. Clinical heart failure or LVEF <30%.

5 yr overall survival= 64%5 yr PFS= 64%

Overall Survival: SCOT-Comparable Patients and Treatment (n=22)

Overall Survival: SCOT-Comparable Patients and Treatment (n=22)

n=23 Excluded:No lung shielding -8Rabbit ATG -1Eject F. (47%) -1FVC (27%) -1Renal failure/PHT -1

3 year OS= 87%

3 year OS= 91%5 year OS= 78%