Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose

Cao, Thai M.; Shizuru, Judith A.; Wong, Ruby M.; Sheehan, Kevin; Laport, Ginna G.; Stockerl-Goldstein, Keith; Johnston, Laura; Stuart, Monic J.; Grumet, F. Carl; Negrin, Robert S.; Lowsky, Robert

doi:10.1182/blood-2004-04-1473

Cited by 55 publications

(41 citation statements)

References 48 publications

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“…As previously reported, 45 we also observed a significant advantage of high graft CD3 + cell dose with respect to OS, PFS and NRM, even after adjustment for pre-transplant ATG use. Interestingly, patients transplanted with high graft CD34…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 89%

“…44 We did not observe such a negative impact of very high dose (data not shown). As previously reported, 45 we also observed a significant advantage of high graft CD3 + cell dose with respect to OS, PFS and NRM, even after adjustment for pre-transplant ATG use. Interestingly, patients transplanted with high graft CD34 + or CD3 + cell doses did not experience higher risks for chronic GVHD.…”

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confidence: 89%

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Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

et al. 2013

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Mobilized peripheral blood has become the predominant stem cell source for allogeneic hematopoietic cell transplantation. In this retrospective single center study of 442 patients with hematologic malignancies, we analyzed prognostic factors for long-term survival after peripheral blood stem cell transplantation from HLA-matched related or unrelated donors. To account for disease/status heterogeneity, patients were risk-stratified according to the Disease Risk Index. Five-year overall survival was similar after transplants with matched related and unrelated donors (45% and 46%, respectively; P=0.49). Because donor age ≥60 years impacted outcome during model building, we further considered 3 groups of donors: matched unrelated (aged <60 years by definition), matched related aged <60 years and matched related aged ≥60 years. In multivariate analysis, the donor type/age group and the graft CD34+ and CD3 + cell doses impacted long-term survival. Compared with matched unrelated donor transplant, transplant from matched related donor <60 years resulted in similar long-term survival (P=0.67) while transplant from matched related donor ≥60 years was associated with higher risks for late mortality (hazard ratio (HR) 4.41; P=0.006) and treatment failure (HR: 6.33; P=0.009). Lower mortality risks were observed after transplant with CD34 + cell dose more than 4.5x10 6 /kg (HR: 0.56; P=0.002) and CD3 + cell dose more than 3x10 8 /kg (HR: 0.61; P=0.01). The Disease Risk Index failed to predict survival. We built an "adapted Disease Risk Index" by modifying risks for myeloproliferative neoplasms and multiple myeloma that improved stratification ability for progressionfree survival (P=0.04) but not for overall survival (P=0.82). Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nHere, we report a large single center retrospective study of PB-HSCT with MRD or 10/10 MUD in patients with hematologic malignancies. To account for disease/status heterogeneity, patients were stratified for disease risk according to the DRI. The aims of this study were: 1) to evaluate how donor type (MRD vs. MUD) and other pretransplant factors may predict for long-term OS and PFS after PB-HSCT; and 2) to evaluate DRI as a predictor for OS and PFS. Methods PatientsWe performed a retrospective analysis of all consecutive patients with hematologic malignancies who underwent a first PB-HSCT from either MRD or MUD at Saint-Louis Hospital (Paris, France) between January 2000 and December 2010. According to institutional guidelines, MRD was considered as the first donor choice and search for MUD was only undertaken if no suitable MRD was identified. For MUD PB-HSCT, only donor/recipient pairs matched at the allelic level at HLA-A, -B, -C, -DRB1 and -DQB1 loci (10/10 HLA-matched) were included. Data concerning pre-transplant characteristics and transplant outcomes were extracted from our transplantatio...

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Section: © F E R R a T A S T O R T I F O U N D A T I O Nsupporting

confidence: 89%

supporting

confidence: 89%

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

et al. 2013

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“…Among T-cell subsets, both CD4 þ and CD8 þ T cells might promote T-cell engraftment, confirming previous observations in a canine model 15 and in patients given HCT after myeloablative 16,17 or nonmyeloablative conditioning. 18,19 Furthermore, since CD14 þ cells contained in G-PBMC grafts secrete large amounts of IL-10 (an immunosuppressive cytokine) and have reduced expression of costimulatory molecules needed for T-cell activation, those cells might provide immunosuppressive effects that reduce host-versus-graft (rejection) reactions. 20 The role of CD3 þ cells for the development of acute and chronic GVHD after allogeneic HCT has been established.…”

Section: Discussionmentioning

confidence: 99%

High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation

et al. 2005

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This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factormobilized peripheral blood mononuclear cells (G-PBMC) (n ¼ 116) or marrow (n ¼ 14) transplantation after nonmyeloablative conditioning with 90 mg/m 2 fludarabine and 2 Gy TBI. The median number of CD34 þ cells transplanted was 6.5 Â 10 6 / kg. Higher numbers of grafted, and CD34 þ (P ¼ 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14 þ (P ¼ 0.01) and CD34 þ (P ¼ 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8 þ (P ¼ 0.005) and CD34 þ (P ¼ 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34 þ cells were associated with higher levels of day 28 donor T-cell chimerism (P ¼ 0.01), rapid achievement of complete donor T-cell chimerism (P ¼ 0.02), and a trend for lower risk for graft rejection (P ¼ 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34 þ cells in unrelated grafts administered after nonmyeloablative conditioning.

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“…Cao et al, using the same preparative regimen combining 2 Gy TBI with or without fludarabine, showed that higher numbers of transplanted CD8 þ T-cells correlated with increased donor T-cell chimerism levels on day 28 after HCT (P ¼ 0.009), and greater likelihood for achievement of full donor T-cell chimerism (P ¼ 0.03) in a study analyzing combined observations in 63 patients given PBSC from either related (n ¼ 38) or unrelated (n ¼ 25) donors. 59 Finally, we analyzed the impact of graft composition on HCT outcomes among 116 patients receiving PBSC from HLA-matched unrelated donors after conditioning with fludarabine and 2 Gy TBI. 60 High numbers of donor T-cells (P ¼ 0.03), CD4 þ T-cells (P ¼ 0.007), CD8 þ T-cells (P ¼ 0.29), NK cells (P ¼ 0.04) and CD34 þ progenitor cells (P ¼ 0.01) in the graft were each associated with high levels of day-28 donor T-cell chimerism.…”

Section: Factors Affecting Chimerism Levels After Reduced-intensity Omentioning

confidence: 99%

Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

2006

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Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose

Cited by 55 publications

References 48 publications

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

High doses of transplanted CD34+ cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation

Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning

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