Contributions
Abstract: EP1282
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Hematopoietic Stem Cells (HSCs) transplantation is a therapeutic alternative for several malignant blood diseases and hemoglobinopathies. HSCs can be harvested from peripheral blood (PB), bone marrow (BM) or cord blood. The number of transplanted HSCs (CD34+ cells) represents the principal indicator of graft quality [1]. Usually, 2x106 CD34+/kg is the minimal required dose, 4x106 CD34+/kg is the target dose and over 8x106 CD34+/kg the benefice is highly speculative [1]. While autologous HSCs are systematically frozen and cryopreserved for later use, allogeneic HSCs are usually freshly transplanted after a possible manipulation including volume reduction, plasma removal or erythrocyte depletion. These processes may impact HSCs quantity and/or quality.
[1] Carreras et al., The EBMT Handbook.
Aims
The aims of our work were to evaluate (i) the correlation between hematopietic recovery and HSCs quantity and/or quality and (ii) the impact of HSCs manipulations on the hematopoietic recovery objectified by the delay of polynuclear neutrophils (PN) and platelet (PLT) engrafment.
Methods
We realized a retrospective multicentric study including 367 autologous HSCs from PB and 450 allogeneic HSCs (312 from PB and 138 from BM), over the period 2018-2019. The PN and PLT recovery were defined as the first day (d) of PN ≥ 0.5x109/L and PLT ≥ 20 x109/L over 3 consecutive values and at least 7d after the last transfusion [1]. Statistical analyses were performed on GraphPad Prism® V8.4 and results expressed as mean ± standard deviation. Mann-Whitney, Kruskal-Wallis and Spearman's tests were used.
Results
CD34+ cell dose as well as total nucleated cell (TNC) dose were not correlated to PN
(r=-0.066; r=-0.016, p>0.05) nor to PLT recovery (r=0.06054; r=0.027, p>0.05) for allogeneic HSCs from PB neither from BM (r=0.073; r=0.080 for PN and r=-0.049; -0.066 for PLT, p>0.05). In addition, hematopoietic recovery was independent of the CD34+ range doses (x106/kg): < 4, 4 - 8 and > 8 (p>0.05). However, BM volume reduction delayed the PN recovery comparing to the unmanipulated BM (21.9 ± 6.1 d versus 18.6 ± 4.0 d, p<0.05). This may be explained by the reduction of HSCs clonogenicity after this process (6.7% versus 25.3%, p<0.001).
Analysis of autologous graft showed a significant correlation between CD34+ cell dose and PN (r= -0.3086, p<0.0001) and PLT recovery (r= -0.1617, p<0.01). CD34+ cell dose > 4x106/kg reduced time to PN recovery (13.6 ± 3.5 d versus 12.1 ± 2.5 d, p<0.001), whereas dose > 8x106/kg reduced PLT recovery (12.9 ± 5.4 d versus 9.2 ± 4.0 d, p<0.001). Interestingly, the TNC dose was correlated to the PLT recovery (r=0.246, p<0.0001).
Conclusion
Our results showed a significant impact of CD34+ cell dose on the PN and PLT recovery for autografts. CD34+ cell dose > 4x106/kg reduced time to PN recovery whereas dose > 8x106/kg decreased delay to PLT recovery. For allograft, no correlation was found. This difference could be explained by a better quality of HSCs harvested from healthy donors. Indeed, we showed that the decrease of HSCs functionality might delay the hematopoietic recovery. To better understand these mechanisms, we will analyze biological and clinical risk factors of engrafment failure after autologous and allogeneic HSCs transplantation. Finally, it is important to notice that our study was indepedent of pathology and clinical factors. A more specific analysis will be performed.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Autologous hematopoietic stem cell transplantation, CD34+ cells, Engraftment
Abstract: EP1282
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Hematopoietic Stem Cells (HSCs) transplantation is a therapeutic alternative for several malignant blood diseases and hemoglobinopathies. HSCs can be harvested from peripheral blood (PB), bone marrow (BM) or cord blood. The number of transplanted HSCs (CD34+ cells) represents the principal indicator of graft quality [1]. Usually, 2x106 CD34+/kg is the minimal required dose, 4x106 CD34+/kg is the target dose and over 8x106 CD34+/kg the benefice is highly speculative [1]. While autologous HSCs are systematically frozen and cryopreserved for later use, allogeneic HSCs are usually freshly transplanted after a possible manipulation including volume reduction, plasma removal or erythrocyte depletion. These processes may impact HSCs quantity and/or quality.
[1] Carreras et al., The EBMT Handbook.
Aims
The aims of our work were to evaluate (i) the correlation between hematopietic recovery and HSCs quantity and/or quality and (ii) the impact of HSCs manipulations on the hematopoietic recovery objectified by the delay of polynuclear neutrophils (PN) and platelet (PLT) engrafment.
Methods
We realized a retrospective multicentric study including 367 autologous HSCs from PB and 450 allogeneic HSCs (312 from PB and 138 from BM), over the period 2018-2019. The PN and PLT recovery were defined as the first day (d) of PN ≥ 0.5x109/L and PLT ≥ 20 x109/L over 3 consecutive values and at least 7d after the last transfusion [1]. Statistical analyses were performed on GraphPad Prism® V8.4 and results expressed as mean ± standard deviation. Mann-Whitney, Kruskal-Wallis and Spearman's tests were used.
Results
CD34+ cell dose as well as total nucleated cell (TNC) dose were not correlated to PN
(r=-0.066; r=-0.016, p>0.05) nor to PLT recovery (r=0.06054; r=0.027, p>0.05) for allogeneic HSCs from PB neither from BM (r=0.073; r=0.080 for PN and r=-0.049; -0.066 for PLT, p>0.05). In addition, hematopoietic recovery was independent of the CD34+ range doses (x106/kg): < 4, 4 - 8 and > 8 (p>0.05). However, BM volume reduction delayed the PN recovery comparing to the unmanipulated BM (21.9 ± 6.1 d versus 18.6 ± 4.0 d, p<0.05). This may be explained by the reduction of HSCs clonogenicity after this process (6.7% versus 25.3%, p<0.001).
Analysis of autologous graft showed a significant correlation between CD34+ cell dose and PN (r= -0.3086, p<0.0001) and PLT recovery (r= -0.1617, p<0.01). CD34+ cell dose > 4x106/kg reduced time to PN recovery (13.6 ± 3.5 d versus 12.1 ± 2.5 d, p<0.001), whereas dose > 8x106/kg reduced PLT recovery (12.9 ± 5.4 d versus 9.2 ± 4.0 d, p<0.001). Interestingly, the TNC dose was correlated to the PLT recovery (r=0.246, p<0.0001).
Conclusion
Our results showed a significant impact of CD34+ cell dose on the PN and PLT recovery for autografts. CD34+ cell dose > 4x106/kg reduced time to PN recovery whereas dose > 8x106/kg decreased delay to PLT recovery. For allograft, no correlation was found. This difference could be explained by a better quality of HSCs harvested from healthy donors. Indeed, we showed that the decrease of HSCs functionality might delay the hematopoietic recovery. To better understand these mechanisms, we will analyze biological and clinical risk factors of engrafment failure after autologous and allogeneic HSCs transplantation. Finally, it is important to notice that our study was indepedent of pathology and clinical factors. A more specific analysis will be performed.
Keyword(s): Allogeneic hematopoietic stem cell transplant, Autologous hematopoietic stem cell transplantation, CD34+ cells, Engraftment