Factors Predicting Gvhd Free, Relapse Free Survival (GRFS) after Allogeneic Hematopoietic Cell Transplantation; A Multivariable Analysis of 531 Allografts from a Single Center

The ideal outcome of allogeneic hematopoietic cell transplantation (allo-HCT) is based on survival that is free of morbidity. The most common causes of treatment failure and morbidity after HCT are relapse, GVHD and non-relapse death.  A composite endpoint that measures survival free of clinically significant negative events may be a useful way to determine the success of allo-HCT (1). We assessed GVHD and relapse-free survival (GRFS) where the events were acute GVHD grade 3-4, moderate to severe chronic GVHD, relapse or death in 531 consecutive adult patients who received an allo- HCT between 2006 and 2014 at our center. Median follow up of living patients was 46 months (12-123). Patients were treated using standardized supportive care algorithms at our center. Although this was a retrospective analysis, patient characteristics and outcomes including GVHD grading were obtained from our institutional database where they had been prospectively documented. The median age was 52 (18-77) years. 266 (50%) received myeloablative conditioning, and 428 (81%) received PBSC as stem cell source. Donor type was HLA matched related (MRD, n=198, 37%), matched unrelated (MUD, n=205, 39%) and haploidentical using T-replete grafts and post-transplant cyclophosphamide (HIDT, n=128, 24%). 36% of patients had a high/very high Dana farber disease risk index (DRI). The most common indications for transplant were AML (n=197, 37%), MDS/MPS (n=114, 21%), NHL (n=132, 25%) and ALL (n=68, 13%).1 year OS, disease free survival DFS and GRFS were 78%, 64% and 33% respectively. GRFS after MRD, MUD and HIDT was 39%, 27% and 35% respectively, with MRD recipients having a better GRFS than MUD (p=0.004). Regression analysis showed that GRFS at the one year was lower for, patients transplanted before 2011 than those transplanted between 2011 and 2014(27% vs 39%, p=0.0031), high CIBMTR disease risk than low CIBMTR risk (24% vs 39%, p=0.009) and high/very high DRI than low DRI (23% vs 48%, p<0.001). On multivariable analysis, year of transplant before 2011 (HR =1.2, p=0.03), age >= 50 years (HR 1.22, p=0.05), MUD donor (HR 1.3, p=0.004) and high/very high DRI risk (HR 2.05, p<0.001) were all associated with a worse GFRS at one year post HCT.

GFRS is an endpoint that is worth investigating in further trials as a marker of successful HCT. These data suggest that GRFS can be predicted by patient age and DRI but not by HCT-CMI. Importantly the GRFS appears to have improved in more recently transplanted patients and MUD donors produce inferior GRFS to MRD whereas haploidentical donors do not.

 Table 1: Predictors of GRFS at one year

 

	N=531	1 year GRFS	HR	95% CI	P value
Year of BMT 2005-2010 2011-2014	270 (51%) 261 (49%)	30% 37%	1.00 0.80	25%-35% 32%-43%	- 0.03
Age Age <50 years Age >= 50 years	228 (43%) 303(57%)	37% 31%	1.00 1.22	31%-43% 26%-36%	- 0.05
Donor Type MRD MUD Haplo Haplo vs MUD	198(37%) 205 (39%) 128 (24%)	39% 27% 35%	1.00 1.30 1.13 0.81	33%-45% 22%-33% 27%-42%	- 0.004 0.379 0.112
DRI Low Intermediate High/very high	78(15%) 258 (49%) 189 (36%)	48% 36% 23%	1.00 1.42 2.05	38%-58% 31%-42% 18%-29%	- 0.025 <0.001

 

1.            Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125(8):1333-8.