Donor lymphocyte infusions: the long and winding road: how should it be traveled?

Abstract

Donor lymphocyte infusions (DLI) often are used after allo-SCT to augment the graft-versus-tumor effect. Timing of infusion varies according to indication, for example to treat tumor recurrence, as a planned strategy to prevent disease relapse in the setting of T-cell-depleted grafts or non-myeloablative conditioning regimens, or as a method to convert mixed to full donor chimerism. The optimal strategy of timing, use of cytotoxic conditioning, cell dose and cell product composition, and so on, for DLI administration remains unclear. Despite varied techniques, DLI may lead to 3-year disease-free survivals (DFS) in excess of 60% for all CML patients and approach 90% in patients with only molecular or cytogenetic relapse. Other hematologic malignancies appear much less responsive, as less than 50% of patients respond and provide, at best, 3-year DFS rates of 20-50%. Multiple myeloma patients have overall response rates of 40-45% after DLI, suggesting benefit in relapsed disease, but limited experiences for diseases such as Hodgkin's lymphoma, myelodysplasia and ALL preclude recommendations for use of DLI at this time. Regardless of the indication, treatment-related mortality after DLI is 5-20% and more than one-third of patients will develop acute and/or chronic GVHD after DLI. The risks of these complications appear related, in part, to donor source, cell dose and therapy prior to DLI. Although there are no definitive answers, the information gleaned from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with bulky or aggressive disease may benefit from disease reduction prior to DLI.

Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft

“…10 Depending on the indication, DLI should be termed therapeutic or prophylactic, as response and outcome are markedly different (reviewed in ref. 11). Induction of GvL is associated with induction of GvHD after DLI.…”

“…A total cell dose of 10 Â 10 6 CD3 þ cells/kg for related donors seems to be safe and effective, 13,14 but no consensus on the optimal dosage of DLI has yet been reached. 11,15 G-CSF is routinely used to mobilize CD34-positive hematopoietic stem cells from healthy volunteer donors before leukapheresis. Although cryopreserved DLI has been reported, analyses of efficacy and safety remain anecdotal.…”

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

“…Donor lymphocyte infusions from the original donor of the allograft are given for three main reasons: for relapse (which may be at various levels), pre-emptively in patients at high risk of relapse, and for correction of mixed chimerism in order to preserve a GvM effect and reduce the chance of relapse (reviewed by Tomblyn and Lazarus 45 ). There has been little work aimed at defining the main effector cells (T-cells or natural killer cells), and these may in fact vary from disease to disease.…”

Activated MHC-mismatched T helper-1 lymphocyte infusion enhances GvL with limited GvHD

“…12, 13 Moreover, a significant proportion of patients who receive DLI develop GvHD, which in many cases can be life-threatening. 14 The purpose of the current study was to test, in an allogeneic MHC-mismatched murine BMT setting, the potential of activated allogeneic T helper-1 (aTh-1) lymphocytes to induce GvL while evaluating GvHD. Fully MHC-mismatched HCTs are not performed clinically.…”