Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis

Abstract

After allogeneic stem cell transplantation, graft-versus-host disease (GvHD) occurs through recognition of histocompatibility mismatches by donor T lymphocytes. The same mechanism operates in eliminating malignant cells (the graft-versus-tumor or GvT effect). We hypothesized that comparing the correlation between GvHD and relapse might provide a surrogate marker for the susceptibility of diseases to allo-immune effects. We studied 48 111 first allogeneic transplants performed between 1998 and 2007. In chronic myeloid leukemia (CML), the relapse risk declined clearly and proportionally to severity of acute and chronic GvHD. Acute lymphoblastic leukemia and BCR-ABL-negative myeloproliferative neoplasias were comparably sensitive to GvHD as CML, whereas myelodysplastic syndromes and lymphoproliferative disorders showed intermediate sensitivity. GvHD was only associated with modest reductions in relapse risk in acute myeloid leukemia (AML) and plasma cell disorders (PCDs). Except for PCD, hazard rates for relapse decreased to almost 0 at 48 months of follow-up in all diseases. These data confirm observations of potent GvT effects associated with GvHD. The strength of the GvHD/GvT correlation differs significantly between hematological malignancies. The parallel drop of relapse rates in different diseases despite differences in GvHD/GvT ratios suggests that GvT effects might operate in the absence of GvHD, particularly in AML.

Allogeneic stem cell transplantation for multiple myeloma: is there a future?

“…49,50 However, in a large series of patients with hematological disorders including MM undergoing allo-SCT, the presence of GVHD is associated with only modest reduction in relapse risk in MM and AML, suggesting the presence of graft-vs-tumor effect in the absence of GVHD. 51 Similarly, in another study of high-risk relapsed MM patients undergoing allo-SCT, OS and PFS were comparable to other studies in the absence of GVHD. 52 There is a report of complete remission in a patient after immunosuppression withdrawal in patient progressing after allo-SCT.…”

Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis

“…9 Specifically, subset analysis was performed on 446 adult patients with AML receiving PBSC grafts following a MA conditioning regimen without serotherapy and who received cyclosporine (CSA) and methotrexate (MTX)-based GVHD prophylaxis. In this subset analysis, CMV reactivation as a time-dependent covariate did not associate with decreased risk for relapse by 1 year (CMV reactivation: n 5 113, relapse 26% [95% CI, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] vs no CMV reactivation: n 5 333, relapse 27% [95% CI, 22-32%]; P 5 .80). Likewise, D/R CMV serology itself did not associate with reduced risk for relapse (data not shown).…”

“…21 In this regard, mechanisms for how CMV reactivation might actually protect against AML relapse remain unknown. CMV reactivation may induce expansion in mature natural killer cells (CD56 dim NKG2C 1 CD57 1 ), which have enhanced interferon g production 22 and can mediate a graft-versus-leukemia response against AML.…”

Is peripheral blood or bone marrow a better source of stem cells for transplantation in cases of HLA-matched unrelated donors? A meta-analysis

“…One study analyzed the sensitivity of different hematological malignancies to graft-versus-host effects, and the results revealed that CML was highly sensitive to GVHD, while ALL and BCR-ABL-negative myeloproliferative ONCH-1972 neoplasias were comparable to CML; MDS and lymphoproliferative disorders showed intermediate sensitivity. GVHD was associated with only modest reductions in the risk of relapse in acute myeloid leukemia (AML) and plasma cell disorders (PCDs) [35]. This could explain the inconsistent outcome between incidences GVHD and relapse.…”