A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 × 106 CD34+ cells/kg be considered the minimum threshold?

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.

Section: Discussionmentioning

confidence: 88%

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

et al. 2008

“…5,6 As observed in both animal and human studies, G-CSF induces IL-4 and IL-10 production in peripheral T cells (that is, the TH2 lymphokine profile) instead of TH1-polarized proinflammatory cytokines; in addition, G-CSF induces a reduction in the total number of BM T cells and reverses the CD4 þ /CD8 þ ratio. [18][19][20][21] Although some conflicting data have been reported, the majority of studies agree that pBM or sBM SCT reduces the incidence of chronic GVHD compared to PBSCT. 6,7,9 Thus, considering both in vitro and clinical findings regarding acute and chronic GVHD, pBM appears to be an appropriate stem cell source for use in patients with critical comorbidities because it is less likely to result in chronic GVHD.…”

Section: Cause Of Deathmentioning

confidence: 99%

“…According to the literature, several G-CSF regimens have been used to stimulate BM, ranging from 2-to 5-day priming periods at doses of 3À10 mg/kg per day. [3][4][5][6]18 Our modified G-CSF regimen was chosen based on previous data indicating that two doses (that is, DÀ2 and DÀ1) produce sufficient CD34 þ and CD3 þ cells to allow rapid engraftment with modest transfusion requirements and a decrease in hospitalization by a mean of 10 days. 3 The CD34 þ and CD3 þ cell contents per kilogram recipient body weight were comparable with values observed in previous studies.…”

Section: Cause Of Deathmentioning

confidence: 99%

Overcoming various comorbidities by G-CSF-primed unmanipulated BM SCT in adult patients with AML

Kim

et al. 2009

We examined whether the use of G-CSF-primed unmanipulated bone marrow (pBM) permits successful transplantation in patients with adverse comorbid pretransplantation conditions. A total of 33 patients at variable risk of AML undergoing allogeneic SCT from an HLA-identical sibling participated. The patients suffered from a variety of treatment-related sequelae before SCT and many cases also featured the presence of major organ dysfunction. The median follow-up duration of patients who were among the overall survivors was 58 months (range, 11À125 months). The median number of CD34 þ cells infused was 3.5 Â 10 6 per kg (range, 0.8À15.6 Â 10 6 per kg). The median number of days for recovery of ANC and platelet count without transfusion was 13 (range, 6À22) and 18 (range, 11À29) days, respectively. Four patients (12%) died due to nonrelapse causes and only one patient developed the same course of infectious complication as before SCT. No particular finding in the context of CMV infection or other post transplant complication was observed. The estimated 10-year overall survival rate was 68%. Our results suggest that the use of pBM allows successful engraftment without increasing complications in patients with various comorbidities before transplantation.

“…In the same year, Singhal et al recommended a CD34 þ dose of 2 Â 10 6 /kg as the minimum threshold for allogeneic sibling blood or marrow SCT. 3 Two years later, Bittencourt et al concluded that a CD34 þ dose of 3 Â 10 6 /kg was optimal for allogeneic BMT in terms of faster engraftment, decreased treatment-related mortality and increased OS. 4 Allo-SCT is a potentially curative therapeutic option for aplastic anaemia (AA).…”

Section: Introductionmentioning

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.