Evidence that donor intrinsic response to G-CSF is the best predictor of acute graft-vs-host disease following allogeneic peripheral blood stem cell transplantation

Dhédin, Nathalie; Chamakhi, Ines; Perreault, Claude; Roy, Denis‐Claude; Sauvageau, Guy; Ducruet, Thiérry; Busque, Lambert; Fish, Douglas; Bélanger, R; Roy, Jean

doi:10.1016/j.exphem.2005.09.013

Cited by 11 publications

(11 citation statements)

References 37 publications

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“…Because the , however, did not find any correlation between host gyTCR + T cells and GVHD in mice. In our study, the overall CD3 + cell dose did not show any significant association with GVHD, TRM, relapse, or survival being consistent with previous studies (4,8,31,32). Interestingly, we detected a significant association between an increased donor gyTCR + T-cell dose and the cumulative incidence estimates of aGVHD grade II-IV, concurring with Maeda and Blazar (15,29), which was proven even in a multivariate analysis.…”

Section: Discussionsupporting

confidence: 81%

“…Nevertheless, we cannot rule out a distinct influence of the type of conditioning on the results of our study. We could not see a significant association between CD34 + cell dose and cGVHD, relapse, TRM, or survival, being consistent with most of the studies (7,8,31).…”

Section: Discussionsupporting

confidence: 76%

“…In fact, our study is the first to show the impact of CD34 + cell dose in the setting of unrelated PBSCT after intensive conditioning. Interestingly, the results do not agree with the data published for related transplants (4,5,7,31,32), i.e., higher CD34 + cell dose correlated with a reduced risk of aGVHD. However, there was a significant correlation between CD34 + and Treg cells possibly explaining the fact that the CD34 + cell dose only remained significant in the multivariate analysis when excluding Treg cells from the analysis.…”

Section: Discussioncontrasting

confidence: 56%

“…Nevertheless, most of these data were obtained in the setting of bone marrow transplantation and not PBSCT. Although Zaucha et al showed patient age and CMV status to have an impact on aGVHD as well as age, sex, and stage of disease on cGVHD (3), Przepiorka and Dhedin were not able to see such an association after PBSCT (31,32). In our study, only CMV status showed significant association with aGVHD, whereas HLA, age, and sex mismatch remained insignificant.…”

Section: Discussioncontrasting

confidence: 48%

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The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors

Pabst

Schirutschke

Ehninger

et al. 2007

Clinical Cancer Research

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Purpose: Recently, high numbers of regulatory T cells within the stem cell graft were described to be associated with less graft-versus-host disease (GVHD) after related peripheral blood stem cell transplantation (PBSCT). Studies in mice also suggest a distinct role of gyTCR + T cells in mediating GVHD. Therefore, the aim of this study was to define the yet-unknown role of regulatory and gyTCR + Tcells in human PBSCT from unrelated donors. Experimental Design: The frequency of bothT-cell subsets within the graft was analyzed in 63 patients receiving unrelated allogeneic PBSCT. The respective amounts were quantified by flow cytometry and PCR and further correlated with clinical outcome. + cells had a lower cumulative incidence of acute GVHD II-IV (44% versus 65%, P = 0.03). Interestingly, in patients who received higher concentrations of donor gyTCR + Tcells, acute GVHD II-IV was more frequent (66% versus 40%, P = 0.02). In multivariate analysis, only the graft concentration of gyTCR + Tcells (P = 0.002) and a positive cytomegalovirus status of the recipient (P = 0.03) were significantly associated with the occurrence of acute GVHD II-IV. Conclusion: Graft composition of T-cell subsets seems to affect the outcome of patients receiving allogeneic PBSCT from unrelated donors. Therefore, selective manipulation or add-back of particular subsets might be a promising strategy to reduce the incidence of GVHD.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 76%

Section: Discussioncontrasting

confidence: 56%

Section: Discussioncontrasting

confidence: 48%

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The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors

Pabst

Schirutschke

Ehninger

et al. 2007

Clinical Cancer Research

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“…Currently, there is no evidence that the factors commonly associated with GVHD after BM transplants have a role in the setting of PBSC transplant. [6][7][8][9][10][11] Furthermore, in contrast to results obtained after BM transplants, several studies, mainly in myeloablative PBSC transplantation from HLA identical sibling donors, demonstrated that the number of infused CD34 þ cells strongly impacts the incidence of acute or chronic GVHD in PBSC transplant; 6,7,[12][13][14] however, in the case of PBSC transplantation after RIC, the data remain controversial. [15][16][17][18][19][20] In this setting, the heterogeneity of conditioning regimens and donor sources, including HLA identical sibling donor but also unrelated donors, could explain why opposite conclusions have been reported in previous studies.…”

Section: Introductionmentioning

confidence: 99%

Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation

Dhédin¹,

Prébet

Latour

et al. 2012

Bone Marrow Transplant

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The correlation between the incidence of GVHD and the number of infused CD34 þ cells remains controversial for PBSC transplantation after a reduced-intensity-conditioning (RIC) regimen. We evaluated 99 patients transplanted with an HLA-identical sibling after the same RIC (2-Gy-TBI/fludarabine). Donor and recipient characteristics, donor's blood G-CSF-mobilized CD34 þ cell count, and number of infused CD34 þ and CD3 þ cells were analyzed as risk factors for acute and chronic GVHD There was a trend for an increased incidence of extensive chronic GVHD in the quartile of patients receiving more than 10 Â 10 6 CD34 þ cells/kg (P ¼ 0.05). Interestingly, the number of donor's blood CD34 þ cells at day 5 of G-CSF mobilization was closely associated with the incidence of extensive chronic GVHD, that is, 48% (95% CI: 28-68) at 24-months in the quartile of patients whose donors had the highest CD34 þ cell counts versus 24.3% (95% CI: 14-34) in the other patients (P ¼ 0.007). In multivariate analysis, the only factor correlating with extensive chronic GVHD (cGVHD) was the donor's blood CD34 þ cell count after G-CSF (HR 2.49; 95% CI: 1.16-5.35, P ¼ 0.019). This study shows that the incidence of cGVHD is more strongly associated with the donor's ability to mobilize CD34 þ cells than with the number of infused CD34 þ cells.

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High CD4/CD8 ratio in allografts predicts adverse outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation for chronic myeloid leukemia

Luo

Chang

et al. 2009

Ann Hematol

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HLA-mismatched/haploidentical hematopoietic stem cell transplantation (haplo-mismatched HSCT) has improved the outcome of chronic myeloid leukemia (CML) in patients without an HLA-matched donor. To further improve the treatment outcome of haplo-mismatched HSCT in CML, a modifiable prognostic factor needs to be found. The cellular composition of grafts obtained from 75 HLA-mismatched/haploidentical related donors was prospectively correlated with the outcome of patients with CML undergoing haplo-mismatched HSCT following a modified regimen of BU/CY 2 plus antithymocyte globulin. The concentration of T-cell subsets, CD14+, and CD34+ cells and their relative proportions were analyzed. In univariate analyses, disease-free survival (DFS) and overall survival (OS) conversely correlated with the CD4/CD8 ratio in primed bone marrow graft (G-BM) (p = 0.012 and p = 0.040); similarly, CD4/CD8 ratio in total grafts was also negatively associated with DFS and OS (p = 0.018 and p = 0.020). In multivariate analyses, a CD4/CD8 ratio in G-BM higher than the median value remained the only factor negatively affecting DFS (p = 0.030; 95% confidence interval [CI], 1.166-19.341). Expectedly, high CD34+ cell dose was associated with accelerated platelet engraftment (p = 0.009; 95% CI = 1.181-3.271) after controlling for a high risk of disease. No other clinical parameter was influenced by graft composition. Our results suggest that a high CD4/CD8 ratio in allografts may predict adverse survival in patients with CML undergoing haplo-mismatched HSCT.

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Evidence that donor intrinsic response to G-CSF is the best predictor of acute graft-vs-host disease following allogeneic peripheral blood stem cell transplantation

Cited by 11 publications

References 37 publications

The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors

The Graft Content of Donor T Cells Expressing γδTCR+ and CD4+foxp3+ Predicts the Risk of Acute Graft versus Host Disease after Transplantation of Allogeneic Peripheral Blood Stem Cells from Unrelated Donors

Extensive chronic GVHD is associated with donor blood CD34+ cell count after G-CSF mobilization in non-myeloablative allogeneic PBSC transplantation

High CD4/CD8 ratio in allografts predicts adverse outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation for chronic myeloid leukemia

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