Association Of Graft Vs. Host Disease (GVHD) With a Lower Relapse/Progression Rate After Allogeneic Hemopoietic Stem Cell Transplantation (HSCT) With Reduced Intentsity Conditioning In Patients With Follicular and Mantle Cell Lymphoma: A Cibmtr Analysis

Abstract

IntroductionReduced intensity conditioning (RIC) transplantation is an established platform of immunotherapy for lymphoma due to the graft-vs.-lymphoma (GVLy) effect. The objective of this study was to determine if GVLy was associated with acute (aGVHD) or chronic GVHD (cGVHD) in B cell and T cell lymphomas, and to analyze whether this effect differs in myeloablative and RIC transplants. MethodsInclusion criteria were patients older than 18 years undergoing HLA-identical sibling or unrelated donor HSCT between 1997 and 2009, with diagnosis of Hodgkin lymphoma (HL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), peripheral T cell lymphoma (T-NHL), and mantle cell lymphoma (MCL). Twin transplants, cord blood, and ex vivo T-cell depletion cases were excluded. The effect of aGVHD and cGVHD on relapse/progression in each subtype of lymphoma, and by conditioning regimen (myeloablative vs RIC) was analyzed in a multivariate analysis. Results2611 cases were included (HL, n=466; DLBCL, n=579; FL, n=871; T-NHL, n=195; MCL, n=500). 56% of transplants were from unrelated donors (37% matched and 18% partially matched/mismatched). RIC conditioning regimen was used in 63% (n=1641), and the graft source was peripheral blood stem cells (PB) in 77% (n=2002). Some characteristics of the patients and results of the univariate analysis of clinical outcomes are shown in Table 1. In multivariate analysis, aGVHD II-IV was associated with a lower risk of relapse/progression in FL (RR 0.51; 95% CI 0.27-0.94; p=0.031), and cGVHD was associated with a lower risk of relapse/progression in MCL (RR 0.33; 95% CI 0.18-0.61; p<0.001). There was no significant association of either aGVHD or cGVHD with risk of relapse/progression in HL, T-NHL and DLBCL. aGVHD was associated with a higher non-relapse mortality (NRM) in all disease subtypes and with a worse progression free survival (PFS) in MCL, FL, and DLBCL. cGVHD was associated with a higher NRM and inferior PFS in FL and DLBCL. When all myeloablative cases (n=954) were analyzed per lymphoma subtype in the multivariate analysis, neither aGVHD nor cGVHD were associated with a lower incidence of relapse/progression. In contrast, when RIC cases (n=1641) were analyzed together in the multivariate analysis, both aGVHD and cGVHD were associated with a lower incidence of relapse/progression in FL (RR 0.33; 95% CI 0.14-0.75; p=0.01, and RR 0.47; 95% CI 0.15-0.90, respectively), and cGVHD was associated with a lower incidence of relapse/progression in MCL (RR 0.31; 95% CI 0.16-0.62; p<0.001).Table 1Characteristics of patients and univariate analysis of outcomesVariableHodgkin DiseaseDLBCLFollicularT cellMantle cellKarnofsky score<90%138 (30)221 (38)245 (28)76 (39)145 (29)≥90%288 (62)325 (56)592 (68)111 (57)322 (64)Chemoresistant166 (36)202 (35)243 (28)61 (31)108 (22)Prior autologous transplant311 (67)148 (26)96 (11)25 (13)95 (19)Myeloablative123 (26)268 (46)331 (38)99 (51)149 (30)RIC261 (56)224 (39)307 (35)64 (33)177 (35)Non-myeloablative transplant (NST)82 (18)87 (15)233 (27)32 (16)174 (35)OutcomeHodgkin DiseaseDLBCLFollicularT cellMantle cellaGVHD II-IV @100 days40 (36-44)35 (31-39)34 (31-37)39 (32-46)36 (32-40)cGVHD @5 years52 (48-57)37 (33-41)53 (50-56)54 (47-61)49 (44-53)NRM @5 years41 (36-46)47 (43-51)36 (33-39)38 (31-46)43 (39-48)Relapse/Progression @5 years38 (34-43)31 (27-34)14 (12-17)32 (25-39)25 (21-29)PFS @5 years21 (17-25)22 (19-26)50 (47-54)30 (23-37)32 (27-36)Survival @ 5 years29 (25-33)24 (21-28)56 (53-59)37 (29-45)41 (36-45) ConclusionThere is a significant association of GVHD with a lower relapse/progression rate after allo-HCST in patients with FL and MCL. However, development of GVHD did not translate into an improvement of survival or PFS in these subtypes of lymphoma due to excess NRM. The relation of GVHD with a lower relapse/progression rate seems to be more prominent in RIC transplants than in myeloablative transplants. Disclosures:No relevant conflicts of interest to declare.