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

Hasskarl, Jens; Zerweck, Alf; Wäsch, Ralph; Ihorst, Gabriele; Bertz, Hartmut; Finke, Jürgen

doi:10.1038/bmt.2011.45

Cited by 25 publications

(26 citation statements)

References 29 publications

(33 reference statements)

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“…[12][13][14] Administration of DLI has been shown to promote full-donor chimerism 15 and this may result in lower relapse rates. 14,[29][30][31][32] We postulated that early mixed T-cell chimerism may be effectively converted to full-donor T-cell chimerism by using preemptive low-dose DLI, even in the absence of relapse or persistence of malignancy. We also postulated that continuation, rather than withdrawal of post transplant immunosuppressive therapy, following DLI may minimize the risk of acute GVHD.…”

Section: Discussionmentioning

confidence: 99%

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial

Solomon

Sizemore

Zhang

et al. 2014

Bone Marrow Transplant

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Although pretransplant alemtuzumab can reduce GVHD following allogeneic transplantation, it may also increase the risk of mixed donor T-cell chimerism and infections. We hypothesized that the early use of DLI without withdrawal of immunosuppressive drugs in patients with mixed T-cell chimerism would lower the risk of relapse without significantly increasing the risk of GVHD post DLI. Thirty-six patients (median age 59 years) were treated in this phase II trial using reduced-intensity conditioning including s.c. alemtuzumab (total dose 43 mg) and a PBSC graft from a matched unrelated donor (UD). DLI without withdrawal of immunosuppressive drugs was administered to all 25 patients with o50% donor T-cell chimerism on day þ 60. The cumulative risks of acute and chronic GVHD were 42% and 59%, respectively. Estimated probabilities of non-relapse mortality (NRM) at day 100 and 1 year were 3% and 14%, respectively. With a median follow up 2.4 years, estimated survivals at day 100, 1 and 2 years were 97%, 71% and 57%, respectively. In multivariate analysis, the occurrence of acute GVHD was associated with an increased risk of mortality, whereas the occurrence of chronic GVHD had a protective effect, associated with decreased relapse and improved disease-free survival. Low-dose alemtuzumab and preemptive DLI provides favorable transplant outcomes including low NRM in an older patient population with high-risk malignancies undergoing UD transplantation.

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Section: Discussionmentioning

confidence: 99%

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial

Solomon

Sizemore

Zhang

et al. 2014

Bone Marrow Transplant

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“…A matched pair analysis of patients receiving or not receiving DLI showed a significant advantage of patients given DLI; matching criteria were CR1 at day 120 from transplantation, absence of GvHD, and infection (54). Prophylactic DLI produced 80% long-term survival in several studies (55–58), involving around 340 AML and ALL patients. GvHD was seen in 28% of patients given DLI, but it was fatal only in 9% of all patients treated (58).…”

Section: Prophylactic and Preemptive DLImentioning

confidence: 99%

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

et al. 2017

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The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

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“…Thus, G-CSF-primed DLI may behave differently depending upon the clinical conditions, and the evidence has shown that it may have a better role in the case of mixed chimerism, molecular or cytogenetic relapse and prophylactic therapy. [39][40][41] The rapid pace of the relapsed disease sometimes largely impedes the effect of DLI against acute leukemia. In addition, insufficient antigen presentation by the leukemic blasts with reduced or missing expression of co-stimulatory molecules to fail to induce significant T-cell proliferation could be another reason for the inferior DLI results.…”

mentioning

confidence: 99%

“…[39][40][41] Levine et al employed a salvage strategy with chemotherapy, followed by G-CSF-primed DLI for relapsed patients after BMT. Twenty-seven of fifty-seven assessable patients experienced a CR.…”

mentioning

confidence: 99%

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

Chang

Zang

Xia

2015

Bone Marrow Transplant

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DLI is an effective strategy for patients with recurrent hematological malignancies after allogeneic hematopoietic SCT (allo-HSCT). DLI has been widely applied to boost the graft vs tumor (GVT) or GVL effects. However, given the potentially severe complications associated with conventional DLI and transient GVL effect, new strategies for DLI are emerging. In this review, we have discussed the recent important studies on DLI as a prophylactic or therapeutic modality for relapsed hematological disorders after allo-HSCT. The strategies to separate GVL from GVHD have also been discussed. Leukemia-targeting therapy and lymphodepletion combined with DLI, and prophylactic DLI after allo-HSCT are often employed for patients with high risk of relapse, which has been reviewed as well. In addition, we have also discussed the issues on DLI to be further addressed, such as the doses, timing and frequency of DLI in different clinical settings, leukemic antigen-specific DLI as well as how to augment GVL effect while attenuating GVHD.

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

Cited by 25 publications

References 29 publications

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

New strategies of DLI in the management of relapse of hematological malignancies after allogeneic hematopoietic SCT

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