Abstract
Pre-emptive DLI (pDLI) is an effective strategy in lowering the risk of relapse without significantly increasing the risk of graft-versus-host disease (GVHD) in the case of T cell lineage mixed chimerism (MC) post allogeneic transplant in hematological malignancies. Many patients, however, fail to receive timely pDLI and have dismal outcomes, which are not taken into consideration. We compared long-term outcomes of 106 patients having T cell MC after day 60 and undergoing allogeneic stem cell allograft for acute leukemia from an unrelated donor (UD), with 111 patients having complete chimerism (CC). Fifty-three (56%) patients received prophylactic pDLI. Thirty-six patients (67%) had a response (RR), 17 (33%) had no response (NR), and fifty-two (54%) did not receive any pDLI (ND). OS was better in MC group as compared to CC (54% vs 43%, p = 0.04), mainly due to reduction in NRM (14% vs 25%, p = 0.05), and all grade acute and chronic GVHD. Within the MC group, response to pDLI was the only significant factor predicting OS, DFS, and relapses with NR and ND having unfavorable outcomes as compared to RR (p = 0.001). T cell MC in patients undergoing UD allografts with alemtuzumab is no longer an adverse prognostic factor, as compared to patients having CC, after timely implementation of pDLI.
Highlights
Allogeneic hematopoietic stem cell transplantation from unrelated donors (UD) using peripheral stem cell grafts (PBSC) is effective in hematological malignancies but has been associated with relatively high rates of both acute and chronic graft-versus-host disease (GVHD) resulting in inferior survival as compared to matched donors (MSD) [1, 2].T-cell depletion, especially alemtuzumab, reduces the risk of GVHD following allogeneic hematopoietic stem cell transplantation (HSCT) [3], but has been associated with an increased frequency of mixed T cell chimerism (MC) [4, 5]
T-cell depletion in UD grafts, especially alemtuzumab is associated with an increased frequency of mixed chimerism (MC) and relapses [4, 7, 11]
[15] studies have focused on comparing pDLI with patients having complete chimerism, not taking into account patients who fail to receive timely pDLI [15, 17] We retrospectively analyzed a large single-center dataset, of patients having mixed T cell chimerism post allogeneic stem cell transplant in alemtuzumabbased setting, and compared their outcomes to patients having CC
Summary
Allogeneic hematopoietic stem cell transplantation from unrelated donors (UD) using peripheral stem cell grafts (PBSC) is effective in hematological malignancies but has been associated with relatively high rates of both acute and chronic graft-versus-host disease (GVHD) resulting in inferior survival as compared to matched donors (MSD) [1, 2].T-cell depletion, especially alemtuzumab, reduces the risk of GVHD following allogeneic hematopoietic stem cell transplantation (HSCT) [3], but has been associated with an increased frequency of mixed T cell chimerism (MC) [4, 5]. Allogeneic hematopoietic stem cell transplantation from unrelated donors (UD) using peripheral stem cell grafts (PBSC) is effective in hematological malignancies but has been associated with relatively high rates of both acute and chronic graft-versus-host disease (GVHD) resulting in inferior survival as compared to matched donors (MSD) [1, 2]. Majority of the studies demonstrating patients receiving pDLI and achieving outcomes similar to patients having complete chimerism (CC-mainly responders) were in pediatric settings, while using antithymocyte globulin [18, 19] and chimerism in CD34/33 fraction. In adults and alemtuzumab-based settings [20], the effectiveness of this strategy was demonstrated in achieving complete donor chimerism, optimal tolerance and outcomes [21, 22] and better efficacy as compared to therapeutic DLI [23], in patients receiving reduced-intensity conditioning regimens. Realistically many patients with MC fail to receive immunotherapy, and they continue to have poor prognosis [22], which was not taken into consideration
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