Bone marrow transplantation: how important is CD34 cell dose in HLA-identical stem cell transplantation?

Abstract

data has been undertaken to investigate the association of infused CD34 cell dose with various clinical outcomes after HLA-identical transplantation. Separate assessments for unrelated vs related donors and the use of bone marrow or mobilized G-CSF stimulated peripheral blood mononuclear cells (G-PBMC) have been incorporated. The three primary findings are: (1) Higher CD34 dose results in better neutrophil and platelet recovery in all settings. (2) Higher CD34 doses (>8 Â 10 6 /kg) are associated with the development of more chronic graft-versus-host disease when using related G-PBMC. (3) Higher CD34 dose is correlated with improved survival after unrelated donor bone marrow transplantation. These data suggest that the CD34 content of a graft can have a significant impact on clinical outcome after allogeneic transplantation, but defining an optimal dose is dependent on both the type of donor and the stem cell source.

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

“…4 Similar results were observed with other studies on haematological cancers, including a review of the long-term transplant data from Seattle. 25 The reasons behind the favourable influence of PBSC source rather than actual CD34 þ cell count on neutrophil recovery are not clear from our study. However, it may be because of the fact that our lower CD34 þ cell dose subgroup had only 13 patients, which compromises statistical power.…”

“…For haematological disorders in general, investigators have found a greater risk of chronic GVHD with PBSC transplant in the setting of a large CD34 þ cell dose. [25][26][27] This may be due to increased type-2 cytokines and IL-10-producing monocytes, which together result in late immune dysregulation. 28 The notable reduction in the incidence of severe forms of GVHD could partly be attributed to the extensive use of alemtuzumab for conditioning in the majority of our patients.…”

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

“…These results should highlight the need for further investigation into the range of characteristics that constitute an 'optimal' PBPC allograft. [26][27][28] There appeared to be a modest dose-response effect with GM-CSF since donors mobilized greater total numbers of CD34 þ cells following an increase in the dose of GM-CSF to 15 mg/kg/day. However, we noted that the kinetics of CD34 þ mobilization in the GM10 group were more gradual in comparison to G-CSF, with peak CD34 þ cell levels achieved on days 6-7 rather than the typical days 4-5 peak observed following G-CSF.…”

Quantification of biological variation in blood‐based therapy – a summary of a meta‐analysis to inform manufacturing in the clinic

“…Measurement variation is a factor of the equipment and its limitations, the skill of the operator, the sampling methods and the detection system. An example of this is the difference between CD34 + staining and flow cytometry‐gating methods such as ISHAGE, Milan and Norway techniques that can lead to different values being reported 29.Error and Defects – This is a common challenge within manufacturing and in this instance contributes to a number of the previous sources of variation. These are usually as a result of human error that leads to defects in the product.…”

“…Measurement variation is a factor of the equipment and its limitations, the skill of the operator, the sampling methods and the detection system. An example of this is the difference between CD34 + staining and flow cytometry‐gating methods such as ISHAGE, Milan and Norway techniques that can lead to different values being reported 29.…”