Temporally discordant graft versus leukemia (GVL) and graft versus host (GVH) responses after donor lymphocyte infusion therapy for relapsed chronic myelogenous leukemia
Year: 2004
Type: article
Abstract: Separation of GVL and GVH reactivity after allogeneic hematopoietic stem cell transplantation remains an elusive clinical goal. We have previously observed in murine models that GVL and GVH reactivity can be dissociated based on temporal kinetics whereby the GVL effect antedates GVHD allowing mice mice to eliminate leukemia before they develop lethal GVHD (J Immunol 170:2003). To determine if this observation was relevant to man, we examined the tempo of GVL and GVH reactivity in a cohort of patients receiving DLI for relapsed CML where the kinetics of these responses could be examined in the absence of the confounding effects of the conditioning regimen and immunosuppressive therapy. Between 1992–2002, 38 patients with relapsed CML after allogeneic BMT from either HLA-identical sibling or unrelated donors were treated with DLI. Patients were excluded if they did not have both an antileukemic response and GVHD after DLI (n = 16) or were administered prolonged (>2 weeks) IFN therapy after DLI to control blood counts (n = 4). The remaining 18 patients were in either accelerated phase 4/18 (22%), chronic phase 9/18 (50%), cytogenetic relapse 4/18 (22%), or molecular relapse 1/18 (5%) at time of DLI. All had sustained cytogenetic (CGR) and/or molecular responses (MR)(Houston criteria) attributable to DLI along with documented clinical GVHD. The median time to earliest cytogenetic or molecular response was 53 days (20 -97) while time to complete cytogenetic or molecular remission was 82 days (32 -230). The inital onset of GVHD occurred at a median of 59 days (32 -157) in the entire patient cohort. Eleven of 18 patients had evidence of a CGR or MR that occurred a median of 22 days (range 5–121)before onset of GVHD. In 4 patients a CGR or MR was documented concurrently with GVHD, indicating that a GVL response had already occurred before GVHD became clinically evident, while in 3 patients GVHD developed before an antileukemic response was observed. In 7 patients, the CGR or MR was already complete before GVHD began and antedated the onset of GVHD by a median of 14 days (range 0–84). These data indicate that GVH and GVL responses are not synchronous events but can occur with temporally discordant kinetics. These data also provide rationale for therapeutic strategies designed to dissociate these two events after allogeneic SCT by the targeted elimination of alloreactive donor T cells after the GVL effect has occurred but before clinical GVHD has developed.
Authors: P.N. Hari, W.R. Drobyski
Institution: Medical College of Wisconsin
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W2073292160