Reduced-intensity conditioning prior to allogeneic transplantation of hematopoietic stem cells: the need for T cells early after transplantation to induce a graft-versus-lymphoma effect

Glaß, Bertram; Nickelsen, Maike; Dreger, Peter; Claviez, Alexander; Hasenkamp, Justin; Wulf, Gerald; Trümper, Lorenz; Schmitz, Norbert

doi:10.1038/sj.bmt.1704600

Cited by 29 publications

(19 citation statements)

References 21 publications

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“…91 T-cell depletion of the graft has been shown to have a negative impact particularly on patients with aggressive lymphoma. 105,106 Both observations support the clinical importance of the GvL effect. Occasional responses (including complete responses) to DLI in patients with aggressive lymphoma have been reported.…”

Section: Graft-versus-lymphoma Effect In Aggressive Histologiessupporting

confidence: 72%

Allogeneic transplantation in lymphoma: current status

Schmitz

Dreger²,

Glaß³

et al. 2007

Haematologica

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Allogeneic transplantation of hematopoietic stem cells (allo-SCT) is being increasingly used to treat patients with lymphoma. We describe current results of allo-SCT in patients with Hodgkin's disease, indolent lymphoma including Waldenström's disease, and aggressive lymphoma including mantle cell lymphoma and mature T-cell lymphomas. A Graft-vs.-Lymphoma (GvL) effect is present in most entities as evidenced by the generally lower relapse rates after allo-SCT and the results of donor lymphocyte infusions. Slowly proliferating diseases like chronic lymphocytic leukemia, indolent lymphomas, and some T-cell lymphomas are particularly sensitive to the effects of allogeneic T-cells while patients with Hodgkin's disease and aggressive lymphoma may need vigorous debulking before allo-SCT to achieve optimal results. Although reduced-intensity conditioning has lowered transplant-related mortality in most and improved survival in some sub-entities, relapse rates in patients with Hodgkin's disease and aggressive B-cell lymphomas, as well as in patients with heavily pre-treated and refractory lymphoma, remain high and further improvement is undoubtedly needed. Large prospective studies in well-defined entities are necessary to further clarify the role of allo-SCT in lymphoma.

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Section: Graft-versus-lymphoma Effect In Aggressive Histologiessupporting

confidence: 72%

Allogeneic transplantation in lymphoma: current status

Schmitz

Dreger²,

Glaß³

et al. 2007

Haematologica

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“…Donor T-cells are the most likely effectors in this process, as suggested by the increased relapse rates reported in transplantation studies using T-cell-depleted grafts 34 and the recent finding that donor T -cells are a relevant factor in the anti-tumor response on solid tumors. 35 The possible involvement of alloreactive donor natural killer (NK) cells, 36 although not specifically administered, can however not be excluded.…”

Section: Discussionmentioning

confidence: 89%

Graft-versus-tumor effects on murine mammary carcinoma in a model of nonmyeloablative haploidentical stem cell transplantation

Vanclée

Gelder

Schouten

et al. 2006

Bone Marrow Transplant

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Despite a slight decrease in mortality over the last decade, breast cancer still remains a leading cause of cancerrelated death in women. Although anti-tumor effects have been observed after allogeneic stem cell transplantation (SCT), this treatment is not standard care owing to graftversus-host disease (GVHD) and scarcity of suitable donors. With the aim of reducing treatment-related mortality and increasing donor availability in clinical situations, we developed a preclinical mouse model that combines nonmyeloablative conditioning with the use of haploidentical donor-recipient pairs. To mimic active disease, CB6F1 mice were inoculated with 5 Â 10 4 4T1 mammary carcinoma cells 10 days before transplantation. Keratinocyte growth factor (KGF) was used as GVHD prophylaxis. Syngeneic (CB6F1) SCT did not cure any of the mice and KGF treatment did not influence tumor development. After transplantation with haploidentical (B6CBAF1) bone marrow and splenocytes, however, tumor outgrowth was reduced and long-term disease-free survival (43 months) was observed in 9/18 (50%) (P ¼ 0.0011) of the animals. We conclude that in a model of murine breast cancer, a graft-versus-tumor effect can be induced by a nonmyeloablative haploidentical SCT procedure.

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“…Reduced-intensity conditioning regimens are successful probably only in patients achieving an early CR with no or minimal residual DLBCL cells at the time of transplant. 61,62 Novel transplantation strategies integrating high-dose chemotherapy in combination with high-dose (myeloablative) anti-CD20 radioimmunoconjugates 63 have reported encouraging results. However, the number of elderly patients included in these studies was too small and the follow-up too short to allow for a solid interpretation of the data.…”

Section: Treatment Of Relapsed and Refractory Diseasementioning

confidence: 99%