Factors for graft‐<i>versus</i>‐host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose

Fozza, Claudio; Szydlo, Richard; Abdel-Rehim, Marwa M.; Nadal, E.; Goldman, John M.; Apperley, Jane F.; Dazzi, Francesco

doi:10.1111/j.1365-2141.2007.06501.x

Cited by 26 publications

(9 citation statements)

References 13 publications

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“…Immunosuppression is frequently maintained until 3 mo after transplantation in humans, long after the replacement of DC and LC, but not macrophages, by donor cells. In addition, there are clear threshold effects to GVHD induction by DLI in humans (34–38), and persistent recipient macrophages could promote post-DLI GVHD by raising the frequency of alloreactive T cells above a critical level. Recipient macrophages in a number of sites might also contribute to chronic GVHD, and provide a source of recipient hematopoietic minor histocompatibility antigen, to stimulate graft versus leukemia responses.…”

Section: Discussionmentioning

confidence: 99%

“…The search for persistent recipient APC in humans has been further promoted by a wealth of clinical data indicating that the risk of acute GVHD after immunosuppression withdrawal or donor lymphocyte infusion (DLI) remains significant for up to 12 mo after transplantation (33–38). It is known that recipient LC persist after donor hematopoietic stem cell engraftment, especially after reduced intensity conditioning, and that donor LC engraftment is stimulated by GVHD (39, 40).…”

mentioning

confidence: 99%

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Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation

Haniffa

Ginhoux

Wang

et al. 2009

Journal of Experimental Medicine

223

215

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Animal models of hematopoietic stem cell transplantation have been used to analyze the turnover of bone marrow–derived cells and to demonstrate the critical role of recipient antigen-presenting cells (APC) in graft versus host disease (GVHD). In humans, the phenotype and lineage relationships of myeloid-derived tissue APC remain incompletely understood. It has also been proposed that the risk of acute GVHD, which extends over many months, is related to the protracted survival of certain recipient APC. Human dermis contains three principal subsets of CD45+HLA-DR+ cells: CD1a+CD14− DC, CD1a−CD14+ DC, and CD1a−CD14+FXIIIa+ macrophages. In vitro, each subset has characteristic properties. After transplantation, both CD1a+ and CD14+ DC are rapidly depleted and replaced by donor cells, but recipient macrophages can be found in GVHD lesions and may persist for many months. Macrophages isolated from normal dermis secrete proinflammatory cytokines. Although they stimulate little proliferation of naive or memory CD4+ T cells, macrophages induce cytokine expression in memory CD4+ T cells and activation and proliferation of CD8+ T cells. These observations suggest that dermal macrophages and DC are from distinct lineages and that persistent recipient macrophages, although unlikely to initiate alloreactivity, may contribute to GVHD by sustaining the responses of previously activated T cells.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation

Haniffa

Ginhoux

Wang

et al. 2009

Journal of Experimental Medicine

223

215

View full text Add to dashboard Cite

show abstract

“…[29][30][31][32][33][34][35][36][37][38] Although many of the reports include only small numbers of patients, four large series have been reported and are summarized in Table 3. 29,33,36,37 These analyses comprise over 500 patients in whom nearly half had only molecular or cytogenetic relapse at the time of DLI. None of these patients received salvage therapy prior to DLI with the exception of hydroxyurea for the control of hematologic relapse.…”

Section: CMLmentioning

confidence: 99%

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

Tomblyn

Lazarus

2008

Bone Marrow Transplant

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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.

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“…Lymphocyte dose did not influence the incidence of GVHD. 23 The role of the pre-DLI donor chimerism in predicting outcomes after DLI is more controversial. In patients who relapsed after T-cell-depleted HCT, inferior remission rates (15 vs 77%) were seen for those with o40% as compared with 440% donor T lymphocytes at the time of DLI.…”

Section: Discussionmentioning

confidence: 99%

G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or incomplete engraftment after allogeneic hematopoietic transplantation

Abbi

Zhu

Ehmann

et al. 2012

Bone Marrow Transplant

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There is little data comparing the activity and toxicity of donor lymphocyte therapy with granulocyte (G)-CSF-mobilized cells (G-donor lymphocyte infusion (DLI)) with the conventionally collected DLI (C-DLI) after allogeneic blood or marrow transplantation. We retrospectively evaluated 67 patients to compare the efficacy and toxicity of GCSF-mobilized DLI with C-DLI in the treatment of relapse of malignant disease or poor donor engraftment post transplant. We assessed clinical outcomes that may represent the immunological outcome of DLI. The median OS was 210 days (range 3-2436 days), 291 days (range 17-1491 days) in the G-DLI group (15 patients) and 207.5 days (range 3-2436 days) in the C-DLI group (52 patients). The median PFS time was 72 days (range 8-1491 days) in the G-DLI group vs 82 days (range 1-2436 days) in the C-DLI group. Rates of post DLI GVHD and improvement in donor engraftment were similar in the G-DLI and C-DLI groups. We conclude that G-DLI appears to have similar therapeutic activity to that seen with C-DLI, and where such cells are available they may be substituted for conventional donor lymphocytes.

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Factors for graft‐versus‐host disease after donor lymphocyte infusions with an escalating dose regimen: lack of association with cell dose

Cited by 26 publications

References 13 publications

Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation

Differential rates of replacement of human dermal dendritic cells and macrophages during hematopoietic stem cell transplantation

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

G-CSF mobilized vs conventional donor lymphocytes for therapy of relapse or incomplete engraftment after allogeneic hematopoietic transplantation

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