Influence of CD34+ marrow cell dose on outcome of HLA-identical sibling allogeneic bone marrow transplants in patients with chronic myeloid leukaemia

We evaluated the incidence of GVHD, risk factors and the impact of graft composition on acute GVHD (aGVHD) in 92 children who underwent BMT for thalassemia following busulfan/cyclophosphamide (BUCY)-based conditioning regimens and GVHD prophylaxis with CSA/short-MTX and methylprednisolone. The incidence of grade 2-4 and 3-4 aGVHD was 35% (95% confidence interval (CI) 25-44) and 9% (95% CI 4-16), respectively. We found that CD3 þ and CD34 þ cell doses above the median were associated with high incidence of grade 2-4 aGVHD (49 vs 20%, P ¼ 0.005 and 46 vs 23%, P ¼ 0.021, respectively). In multivariate analysis, high CD3 þ (hazard ratio (HR) 4.6; 95% CI 1.4-14.7; P ¼ 0.010) and CD34 þ (HR 4.3; 95% CI 1.4-12.7; P ¼ 0.011) cell doses were associated with grade 2-4 aGVHD. We further examined the effect of CD3 þ and CD34 þ cell doses on aGVHD using quartile cutoff points and found a minimum threshold for CD3 þ (38 Â 10 6 /kg) and CD34 þ (4 Â 10 6 /kg) cells above which the incidence of grade 2-4 aGVHD is significantly increased. This study shows for the first time a positive correlation between the number of CD3 þ and CD34 þ cells and aGVHD in children receiving sibling BMT, and indicates that using tailored and more intensive post transplant immunosuppression may permit to better control aGVHD.

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Gaziev

Isgrò

Marziali

et al. 2011

“…[24][25][26][27] In our study, almost all patients achieved satisfactory hematopoietic engraftment, although the mean number of infused CD34 þ cells was relatively low (2.14(0.46-9.69) Â 10 6 per kg). This implies that the high number of T cells infused may help to the engraftment of plt, as suggested by Zaucha et al; 28 however, the interaction between T-cell subsets and CD34 cells in engraftment is difficult to verify.…”

Section: Discussionmentioning

confidence: 99%

The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT

et al. 2008

This study examines the absolute numbers and relative proportions of CD4 þ , CD8 þ , CD14 þ and CD34 þ cells contained in allografts and their impact on early engraftment and later clinical outcomes in 141 patients with hematological malignancies who underwent unmanipulated HLA-mismatched/haploidentical hematopoietic SCT without in vitro T-cell depletion. These patients received G-CSF-primed BM grafts (G-BM) and peripheral blood grafts (G-PB) following a modified regimen of BU/CY 2 plus antithymocyte globulin. Multivariate analysis showed that high CD34 þ cell numbers were associated with accelerated plt engraftment (P ¼ 0.001). Meanwhile, patients with a higher CD4/CD8 ratio in G-BM (X1.16) had a survival disadvantage (Po0.01) and a trend towards relapse (P ¼ 0.086) after controlling for disease status. A higher CD4/CD8 was also associated with a significantly increased risk of acute GVHD grades II-IV (P ¼ 0.013), even after adjusting for an ABO major mismatch. No aspect of graft composition affected neutrophil engraftment or chronic GVHD. In conclusion, the differences in CD34 þ cell dose and the CD4/CD8 ratio in grafts seem to affect engraftment and clinical outcomes; in particular, a lower CD4/CD8 ratio in primed BM graft is associated with a survival benefit.

“…CD34 þ cell quantification was performed using the standard technique of immunofluorescence flow cytometry. 14 The immunophenotyping section of our laboratory is validated every 2 months by mandatory participation in the UK National External Quality Assessment Service and the CD34 þ cell count results have shown consistency and comparability to other similar laboratories within the country. CD34 þ cells were infused on the same day or cryopreserved with DMSO, stored in liquid nitrogen and thawed at 37 1C before infusion at a later date.…”

Section: Patients and Eligibilitymentioning

confidence: 99%

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

Islam

Anoop

Datta-Nemdharry

et al. 2009

The precise effects of CD34 þ cell dose on the outcome of allogeneic transplantation for aplastic anaemia (AA) are not known. Previous studies have used the total mononuclear cell count to quantify stem cell dose. We evaluated the effects of CD34 þ cell dose on the clinical and haematological end points of transplantation. The transplant variables and outcome parameters on 46 patients with acquired AA were assessed by comparing low vs high CD34 þ cell doses. Infusion of less than 2 Â 10 6 /kg of CD34 þ cells was associated with an increased incidence of graft failures (P ¼ 0.03), higher incidence of bacterial infections (P ¼ 0.006) and a delay in the engraftment of neutrophils (P ¼ 0.046). The latter was found to be an effect of stem cell source (non-PBSC) rather than the CD34 þ count. Other parameters, such as plt engraftment (P ¼ 0.63), red cell (P ¼ 0.94) and plt (P ¼ 0.31) transfusion independence, chimerism, acute and chronic GVHD (P ¼ 1.0) and OS (P ¼ 0.57), were not significantly influenced by the CD34 þ cell dose. These findings are different to the published studies on the relevance of CD34 þ cell dose in allogeneic transplantation for haematological cancers.