Risk factors and organ involvement of chronic GVHD in Japan

Abstract

on behalf of the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.

Allogeneic HY antibodies detected 3 months after female-to-male HCT predict chronic GVHD and nonrelapse mortality in humans

“…F→M HCT usually accounts for only 25% of patients undergoing allo-HCT, but in general, F→M HCT is an established independent risk factor for cGVHD. [5][6][7] Furthermore, HY-Abs would play a role not only as a biomarker but also as a direct assessment of alloimmunity. Investigating HY-Abs in F→M HCT is an important model of humoral alloimmunity.…”

“…A 2-tailed P value ,.05 was considered significant. Receiver operating characteristic (ROC) curves were estimated, and areas under the curve (AUCs) were compared for cGVHD predictive potential based on HY score alone, clinical factors alone, 5,6 and the combination of both. All analyses and data management were performed using Stata v.12.0 (StataCorp, College Station, TX); R v.3.0.1 (R Foundation, Austria); and EZR 18 (Saitama Medical Center, Jichi Medical University, available at www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmedEN.html).…”

“…3,4 Established risk factors for development of cGVHD include acute GVHD (aGVHD), peripheral blood stem cell transplant, donor and recipient age, and sex mismatch. [3][4][5][6] Sex-mismatched transplantation remains a model system for human cGVHD studies involving both biological and clinical analyses. Specifically, hematopoietic cell transplant (HCT) of male recipients with female donors (F→M) has been long-recognized as a significant risk factor for the development of cGVHD.…”

“…Specifically, hematopoietic cell transplant (HCT) of male recipients with female donors (F→M) has been long-recognized as a significant risk factor for the development of cGVHD. [5][6][7] The biological explanation is that naïve female-donor lymphocytes recognize several proteins encoded by the Y chromosome of a male recipient, which are called H-Y minor histocompatibility antigens. Our group has previously shown that alloantibodies against H-Y antigens (HY-Abs) were detected in 39 F→M recipients using enzyme-linked immunosorbent assay and that H-Y antigen-specific B cells developed in F→M HCT patients.…”

Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy

“…Several factors have so far been identified as risk factors for GVHD or inferior survival: age, disease, disease status, HLA-mismatch, unrelated donors, and cytomegalovirus (CMV) serostatus. [1][2][3][4][5][6] Among these risk factors, sex-mismatched HCT, especially HCT of male recipients with female donors (Female→Male), is well known to be associated with a higher incidence of GVHD and inferior survival. [1][2][3][4][7][8][9][10] This adverse effects of Female→Male HCT are thought to result from allogeneic immune responses against minor histocompatibility antigens encoded on the Y-chromosome of a male recipient (H-Y antigens).…”