CD34 cell dose in granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen–identical sibling transplantation

Zaucha, Jan Maciej; Gooley, Theodore A.; Bensinger, William I.; Heimfeld, Shelly; Chauncey, Thomas R.; Zaucha, Renata; Martin, Paul J.; Flowers, Mary E.D.; Storek, Jan; Georges, George E.; Storb, Rainer; Torok‐Storb, Beverly

doi:10.1182/blood.v98.12.3221

Cited by 220 publications

(184 citation statements)

References 30 publications

(26 reference statements)

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“…42 However, the observation that higher CD34 þ cell doses are associated with a greater risk of acute GVHD has not been supported by other studies and a mechanistic basis for the observation remains elusive. 39,43 On multivariate analysis, we were unable to find any association between CD34 þ cell dose and the risk of acute GVHD. We therefore consider our observations as hypothesis generating rather than definitive.…”

Section: Discussionmentioning

confidence: 71%

“…While some studies have suggested that high doses of CD34 þ cells are associated with a greater likelihood of chronic GVHD, our data suggest that other factors may be more important since the risk of chronic GVHD was high within GM-CSF group despite the fact that they received a relatively modest median CD34 þ cell dose (3.1 Â 10 6 /kg). 10,38,39 Despite the fact that the cohort of donors receiving combination G/GM-CSF mobilized the greatest numbers of CD34 þ cells without significant additive toxicity, this did not translate into any clear clinical advantages to the recipients as the rate of hematopoietic engraftment, incidence of chronic GVHD, risk of relapse, and overall likelihood of survival did not differ significantly from the G-CSF alone group. In fact, the risk of acute GVHD was greatest in this combination group.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

Devine

Brown

Trinkaus

et al. 2005

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

Devine

Brown

Trinkaus

et al. 2005

Bone Marrow Transplant

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“…In previous studies it was shown that the threshold of CD34 þ cell numbers above which a deleterious increase in the incidence of cGVHD may occur, can be estimated at around 8 Â 10 6 /kg. 18,19 The significance of the above observations is obvious, since these results, if proved, may lead to the improvement of transplant outcome simply by tailoring the composition of the graft in accordance with the patient status pre-transplant, for example, patients with high-risk disease should receive higher doses of CD34 þ cells than patients with low-risk disease and low probability of relapse.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Although no significant association between the number of infused CD3 þ cells and incidence of GVHD was found; paradoxically they showed that the more CD34 þ cells infused, the higher the incidence of cGVHD. 18,19 An explanation for this interesting finding remains a mystery. In elegant experiments, Reisner et al 20 showed that donor CD34 þ cells can act as 'veto' cells and may inactivate host T-cells, with donor alloreactivity.…”

Section: Discussionmentioning

confidence: 99%

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

Tsirigotis

Shapira

et al. 2009

Bone Marrow Transplant

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The influence of graft composition on the outcome of reduced-intensity (RIC) allogeneic PBSC transplantation (allo-PBSC) remains controversial. In this study, we analyzed the impact of CD34 þ cell dose on the incidence of GVHD, and on the outcome after allo-PBSC, in 103 patients with hematological malignancies, using a uniform RIC regimen. The following variables were included in statistical analysis: (1) number of C34 þ cells, (2) highrisk vs low-risk disease status, (3) matched related vs matched unrelated donor, (4) female donor to male recipient vs any other combination, (5) age of recipient (above vs below the median). Univariate and multivariate analysis did not reveal any association between CD34 þ cell dose and acute grade-2 to grade-4, cGVHD, nonrelapse mortality (NRM), relapse rate (RR) and OS. High-risk disease status was the only variable independently associated with increased NRM (P ¼ 0.001), increased RR (P ¼ 0.012) and decreased OS (Po0.001). The same results were obtained when analysis was restricted to a subgroup of 55 patients with myeloid neoplasms. The influence of graft composition on the outcome of RIC allo-PBSC should be further investigated via well-controlled randomized prospective studies.

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“…Previous studies found a greater incidence of extensive chronic GVHD in recipients of a higher CD34 + dose after PBSCT. 17,18 However, in our pediatric cohort a higher CD34 + dose resulted only in the salutary effect of decreasing relapse and improving survival without increasing the risk for either acute or chronic GVHD. One factor that we believe is key to the lack of association between cell dose and GVHD was the use of rabbit ATG (2.5 mg/kg per day for 3 days) during conditioning before transplant.…”

Section: Discussionmentioning

confidence: 65%

Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies

et al. 2014

Bone Marrow Transplant

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PBSCs are increasingly being chosen as the mode of donation among unrelated donors. Pediatric patients, in particular, may receive very high CD34 + and CD3 + doses during unrelated PBSCT. In this work, we analyzed survival and GVHD outcomes in a cohort of 81 children who received unrelated PBSCT with uniform antithymocyte globulin (ATG)-based in vivo T-cell depletion for treatment of hematologic malignancy, with emphasis on the impact of cell dose on transplant outcomes. EFS was 61.5 ± 5.6%, with higher CD34 + dose (410.0 × 10 6 /kg) and lower patient risk status predicting improved survival in multivariate study. Cumulative incidence of relapse was 30.2 ± 5.2%; a low CD34 + dose was the only significant factor for relapse. Neither CD34 + nor CD3 + dose was a significant determinant of acute or chronic GVHD. Importance of CD34 + dose was reaffirmed in a subcohort of younger patients who received greater median cell doses than the overall cohort. In summary, for children who received unrelated PBSCT with ATG-based T-cell depletion for treatment of hematologic malignancy, the CD34 + dose was the most important factor for relapse and EFS, and neither the CD34 + nor the CD3 + dose influenced incidence of acute or chronic GVHD. INTRODUCTIONIn many countries, G-CSF-mobilized PBSCs have become an important cell source in unrelated hematopoietic cell transplantation (UHCT). The relative ease of PBSC collection has resulted in unrelated donors favoring PBSC rather than BM as their mode of donation. Consistent with this predilection for PBSC among unrelated donors, several studies have reported on unrelated PBSCT, mainly in the context of comparing important transplantrelated outcomes to BMT. 1-6 Studies deriving from a mostly adult HCT population, including a recent randomized trial, conclude that unrelated PBSCT results in similar survival when compared with unrelated BMT, but with a greater incidence of chronic GVHD. 1,2 However, several pediatric studies report that with antibody-based T-cell depletion, such as the use of antithymocyte globulin (ATG) or alemtuzumab (Campath), unrelated PBSCT may result in outcomes that are similar to BMT without an increased risk of GVHD, underscoring the notion that PBSC donation may be as valid an option as BM donation for children in the unrelated transplant setting. [3][4][5][6] Despite the significant number of reports indicating comparable outcomes for unrelated PBSCT and BMT among pediatric patients, the literature on PBSCT in children outside the framework of comparisons with BMT is limited. For example, risk factors for both acute and chronic GVHD after PBSCT are not clear. A factor that may have a major impact on pediatric transplant outcomes is the infused cell dose, especially since collection of PBSC results in cell numbers that are far greater than those found in BM, and children, particularly infants, may receive very high cell doses per patient weight. Previous studies on unrelated HCT showed that

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CD34 cell dose in granulocyte colony-stimulating factor–mobilized peripheral blood mononuclear cell grafts affects engraftment kinetics and development of extensive chronic graft-versus-host disease after human leukocyte antigen–identical sibling transplantation

Cited by 220 publications

References 30 publications

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

Reduced risk of acute GVHD following mobilization of HLA-identical sibling donors with GM-CSF alone

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies

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