High CD34+ Cell Dose Is a Significant Factor for Hematologic Reconstitution of Patients with Multiple Myeloma (MM) or AL-Amyloidosis Undergoing Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Klaus Jens , Herrmann Doris , Hegenbart Ute , Egerer Gerlinde , Cremer Friedrich W. , Breitkreutz Iris , Benner Axel , Fruehauf Stefan , Moehler Thomas , Ho Anthony D. , Goldschmidt Hartmut 
Published: April 2020

Background: The optimum number of CD34+ cells to be reinfused in patients undergoing peripheral blood stem cell (PBSC) transplantation (PBSCT) after high-dose chemotherapy is still unknown.

Patients and Methods: Hematologic reconstitution was analyzed with respect to the number of CD34+ cells reinfused in 768 patients with advanced MM or AL-amyloidosis treated by PBSCT between 06/1992 and 06/2004. 539 transplantations were performed upfront and 229 transplantations after relapse. Endpoints of the study were the number of days from PBSCT until neutrophil recovery (&gt;1.0x10e9/L), and platelet recovery (&gt;20x10e9/L and &gt;50x10e9/L). A multivariable analysis was performed using Cox proportional hazards regression to model the dependence of neutrophil and platelet recovery on CD34+ cell dose reinfusion (included as continuous variable), age at PBSCT, number of previous regimens, number of cycles with alkylating agents, response status prior to PBSCT (CR or not), CD34+ enrichment, total body irradiation and previous partial irradiation.

Results: The number of CD34+ cells reinfused was the only factor being statistically significant for neutrophil as well as platelet recovery (p&lt;0.001). In view of previously reported cut-offs, three groups were defined (low: &lt;=2.5x10e6; high: &gt;8x10e6 CD34+ cells/kg; and intermediate). In the patients treated by PBSCT up-front, the 100 patients of the high-group experienced a shorter median time until neutrophil recovery (low/intermediate/high CD34+:14/14/12 days), platelet recovery &gt;20x10e9 (low/intermediate/high CD34+: 11/11/9 days), and platelet recovery &gt;50x10e9/L (low/intermediate/high CD34+: 13/13/11 days) compared to patients of the intermediate and low groups. These 100 patients required less platelet and red blood cell transfusions, experienced a shorter hospitalization, had fewer days with antibiotic and antimycotic treatment, and required less partial and total parenteral nutrition. In the patients treated by PBSCT at relapse, the 29 patients of the high-group also experienced a shorter median time until neutrophil (low/intermediate/high CD34+: 13/14/12 days), platelet recovery &gt;20x10e9 (low/intermediate/high CD34+: 12/11/9 days), and platelet recovery &gt;50x10e9/L (low/intermediate/high CD34+: 15/14/11 days) compared to patients of the intermediate and low groups. The advantages for the 29 high group relapse-patients regarding the supportive care after PBSC transplantation were similar to those observed in the 100 upfront-patients: shorter duration of hospitalization, fewer days of antibiotic and antimycotic treatment, fewer days of partial parenteral nutrition and total parenteral nutrition, less platelet and red blood cell transfusions.

Conclusion: The number of CD34+ cells reinfused significantly influences time until neutrophil as well as platelet recovery. Comparison of groups suggests that reinfusion of more than 8x10e6 CD34+ cells/kg after high-dose chemotherapy for advanced MM or AL-amlyoidosis shortens hematopoietic reconstitution, reduces platelet and red blood cell transfusions, and reduces days of hospitalization.