Program: Oral and Poster Abstracts
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Method: We retrospectively reviewed 668 consecutive patients who underwent allo-HCT between 2004 and 2012 at the Princess Margaret Cancer Centre, Toronto, Canada, among whom 277 patients diagnosed as cGVHD and received systemic corticosteroids as a frontline cGVHD therapy. Chronic GVHD was classified and graded using the NIH consensus criteria. We evaluated non-relapse mortality (NRM), relapse and failure-free survival (FFS). FFS was defined as time to a switch in systemic therapy, NRM or relapse. The Kaplan-Meier method was used for FFS. The cumulative incidences of NRM, relapse and the treatment switch (TS) were calculated considering competing risks. Multivariate analysis was performed using the Cox proportional hazard regression model for FFS.
Results: With a median follow-up duration of 26 months, the median time from HCT to cGVHD treatment was 183 days (range, 61-828). 102 patients (36.8%) were classified as classical cGVHD and 175 (63.2%) as overlap syndrome. At the start of cGVHD treatment 25 patients (9.0%) had mild cGVHD by the NIH GS, 189 (68.2%) moderate and 63 (22.7%) severe.
Median age at allo-HCT was 51 year-old (range, 19-70). 162 patients (58.5%) were males and 65 (23.5%) patients were gender match of female donor to male recipient. 257 patients (92.8%) received peripheral blood stem cells (PBSC).175 grafts (63.2%) were from matched sibling donors (MSD). 180 patients (65%) received myeloablative conditioning. GVHD prophylaxis was calcineurin inhibitor (CNI) and methotrexate (n=82, 29.6%), CNI and mycophenolate mofetil (n=141, 50.9%), CNI and T-cell depletion (n=37, 13.5%) or others (n=17, 6.1%).
The median FFS was 255 days (95% CI, 218-321). The severity of cGVHD, NIH GS correlated with FFS: median FFS was 164 days in severe vs 238 days in moderate vs 304 days in mild (p=0.001). The overlap syndrome was associated with a shorter FFS than classical cGVHD (223 vs 329 days, p=0.015). Patients receiving MSD graft showed longer FFS (329 days) than unrelated donor (196 days; p=0.004).
The cumulative incidence of TS was 47.7% at 1 year. The NRM was 7.1% and relapse rate was 6.8% at 1 year. The MSD was associated with a lower 1-year NRM than the unrelated donors (4.2% vs 12.3%, p=0.003) while no difference between 2 groups for TS (p=0.731) or relapse at 1 year (p=0.565).
Patients with overlap syndrome had higher NRM at 1 year than with classical cGVHD (10.0% vs 2.2%, p=0.009), but no differences in TS or relapse at 1 year (p=0.167 and p=0.138). Chronic GVHD severity by NIH GS showed a significant correlation with TS (28% in mild, 51.9% in moderate, and 43.8% in severe grade at 1 year, p=0.02) and NRM (4% in mild, 3.6% in moderate, and 19.1% in severe grade at 1 year, p<0.001), but with relapse (p=0.784).
Multivariate analysis for FFS confirmed that the use of unrelated donor showed a worse FFS (hazard ratio (HR) 1.660, p=0.001). FFS was also associated with the severity of cGVHD, NCC GS (mild vs moderate vs severe; HR 1 vs 2.1 vs 2.9, p=0.002) and the cGVHD subtype (classical vs overlap, HR 1 vs 1.39, p=0.028).
We then assigned score 0 for NIH GS mild, 1 for moderate, and 2 for severe; for NIH subtype, score 0 for classical and 1 for overlap; for donor types, score 0 for MSD and 1 for unrelated donors. After summation of the scores, we regrouped them into low (score 0, n=11, 3.9%), intermediate (score 1-2, n=168, 60.6%), and high risk groups (score 3-4, n=98, 35.3%). The risk stratification model correlated nicely with FFS (FFS duration, 1977 days in low vs 341 days in intermediate, and 150 days in high risk group, p<0.001).
Conclusion: the use of unrelated donor, overlap subtype of chronic GVHD and severe grade of chronic GVHD at the time of initiation of chronic GVHD treatment affect adversely on failure-free survival.
Disclosures: Kim: Novartis Pharmaceuticals: Consultancy , Research Funding ; Bristol-Myers Squibb: Consultancy , Research Funding .
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