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.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1157-1157
Author(s):  
Jens Klaus ◽  
Doris Herrmann ◽  
Ute Hegenbart ◽  
Gerlinde Egerer ◽  
Friedrich W. Cremer ◽  
...  

Abstract 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 (>1.0x10e9/L), and platelet recovery (>20x10e9/L and >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<0.001). In view of previously reported cut-offs, three groups were defined (low: <=2.5x10e6; high: >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 >20x10e9 (low/intermediate/high CD34+: 11/11/9 days), and platelet recovery >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 >20x10e9 (low/intermediate/high CD34+: 12/11/9 days), and platelet recovery >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.

Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  

Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.


Blood ◽  
1998 ◽  
Vol 91 (9) ◽  
pp. 3148-3155 ◽  
Author(s):  
Nicolas Ketterer ◽  
Gilles Salles ◽  
Michel Raba ◽  
Daniel Espinouse ◽  
Anne Sonet ◽  
...  

Abstract Optimal numbers of CD34+ cells to be reinfused in patients undergoing peripheral blood progenitor cell (PBPC) transplantation after high-dose chemotherapy are still unknown. Hematologic reconstitution of 168 transplantations performed in patients with lymphoproliferative diseases was analyzed according to the number of CD34+ cells reinfused. The number of days from PBPC reinfusion until neutrophil recovery (>1.0 × 109/L) and unsustained platelet recovery (>50 × 109/L) were analyzed in three groups defined by the number of CD34+ cells reinfused: a low group with less than or equal to 2.5 × 106 CD34+ cells/kg, a high group with greater than 15 × 106 CD34+cells/kg, and an intermediate group to which the former two groups were compared. The 22 low-group patients had a significantly delayed neutrophil (P < .0001) and platelet recovery (P < .0001). The 41 high-group patients experienced significantly shorter engraftment compared with the intermediate group with a median of 11 (range, 8 to 16) versus 12 (range, 7 to 17) days for neutrophil recovery (P = .003), and a median of 11 (range, 7 to 24) versus 14 (range, 8 to 180+) days for platelet recovery (P< .0001). These patients required significantly less platelet transfusions (P = .002). In a multivariate analysis, the amount of CD34+ cells reinfused was the only variable showing significance for neutrophil and platelet recovery. High-group patients had a shorter hospital stay (P = .01) and tended to need fewer days of antibotic administration (P = .12). In conclusion, these results suggest that reinfusion of greater than 15 × 106 CD34+ cells/kg after high-dose chemotherapy for lymphoproliferative diseases further shortens hematopoietic reconstitution, reduces platelet requirements, and may improve patients' quality of life.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5235-5235
Author(s):  
James L. Gajewski ◽  
Rima Saliba ◽  
Gabriela Rondon ◽  
Naoto T. Ueno ◽  
Michele L. Donato ◽  
...  

Abstract We evaluated intensive chemotherapy prior to PBSC mobilization vs. G-CSF alone for PBPC mobilization in a randomized controlled trial of 143 patients who received high dose chemotherapy with cyclophosphamide 6 g/m2, thiotepa 750 mg/m2 and BCNU 450 mg/m2 over 3 days with PBSC support for treatment of breast cancer. 74 patients were randomized to chemomobilization with cisplatin 135 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide 4.5 g/m2 over 3 days plus G-CSF (6mcg/kg q12h)(CVP-G), while 69 patients received G-CSF alone with the collection goal &gt;4 x 106 CD34(+) cells/kg. 77 patients were stage II–III, 66 were stage IV. The CVP-G group had improved mobilization with a collection of 18 (range 3–141) x 106 CD34(+) cells/kg compared with 4(2–13) x 106/kg for the G-CSF group (p&lt;0.001). Granulocyte and platelet recovery post-transplant was 9/9 days for the CVP-G mobilized group, 10/11 days for the G-CSF group (p&lt;0.001). Actuarial risk of progression at 6 years in patients mobilized with CVP-G was 59±7% vs. 66±6% for G-CSF alone (p=0.2). Rate of progression post-transplant was evaluated according to quantities of collected CD34(+) cell dose [for CVP-G, first quartile ≤ 9.0, second ≤17, third ≤40, and fourth &gt;40]. Only one patient in the G-CSF alone group collected &gt;9 x 106 CD34(+) cells. In the CVP-G group progression trended toward being reduced in patients with CD34(+) cell doses collected of &gt;9 x 106/kg (57±9% vs. 65±11%, p=0.06) This effect was consistent for all stages. Overall survival was improved in the CVP-G patients collecting ≥9 x 106 CD34(+)/kg 62±7% vs. 27±11% those collecting less. For patients receiving CD34(+) doses ≤9 x 106/kg, the progression rate was 65±11% in the CVP-G group and 68±6% in the G-CSF group (p=NS). Higher doses of CD34(+) cells collected by chemomobilization than G-CSF alone and those patients with the higher doses of CD34(+) collected trended toward lower disease progression after high dose chemotherapy.


2019 ◽  
Vol 3 (8) ◽  
pp. 1267-1271 ◽  
Author(s):  
Juliet N. Barker ◽  
Jane Kempenich ◽  
Joanne Kurtzberg ◽  
Claudio G. Brunstein ◽  
Colleen Delaney ◽  
...  

Abstract CD34+ cell dose is critical for cord blood (CB) engraftment. However, the CD34+ content of the CB inventory in the United States is unknown. We examined the CD34+ cell content of 126 341 red blood cell–depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 107 and a cryovolume of 24-55 mL. Median pre-cryopreservation TNC content was 127 × 107 (interquartile range [IQR], 108-156 × 107); CD34+ cell content was 44 × 105 (IQR, 29 to 67 × 105). The median CD34+:TNC ratio was 0.34%. TNC and CD34+ cell content correlation was weak (r = 0.24). Of 7125 units with TNCs of ≥210 × 107, only 47% had CD34+ content of ≥100 × 105. However, some units had high CD34+ content for a given TNC count. Only 4% of CB units were acceptable as single-unit grafts (TNCs, ≥2.5 × 107/kg; CD34+ cells, ≥1.5 × 105/kg) for 70-kg patients; 22% of units were adequate for 70-kg patients using lower dose criteria (TNCs, ≥1.5 × 107/kg; CD34+ cells, ≥1.0 × 105/kg) suitable for a double-unit graft. These findings highlight that units with the highest TNC dose may not have the highest CD34+ dose, units with unexpectedly high CD34+ content (a ratio of &gt;1.0%) should be verified, and the US CB inventory of adequately sized single units for larger patients is small. They also support the ongoing use of double-unit grafts, a focus on banking high-dose units, and development of expansion technologies.


2016 ◽  
Vol 5 (4) ◽  
pp. 365
Author(s):  
Antoni D’Souza ◽  
Anushree Algotar ◽  
Ling Pan ◽  
Steven M Schwarz ◽  
William R Treem ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5219-5219
Author(s):  
Gerhard Ehninger ◽  
Stefan Fruehauf ◽  
Kai Hubel ◽  
Uwe Platzbecker ◽  
Karin Badel ◽  
...  

Abstract Background: High dose chemotherapy with autologous stem cell transplantation (ASCT) improves disease free and overall survival in pts with MM; tandem ASCT may further enhance clinical benefits. Mobilization with G-CSF alone fails to yield sufficient CD34+ cells for a tandem ASCT in the majority of MM pts. A mobilization regimen including G-CSF and cyclophosphamide is more effective, but associated with significant toxicity. This phase II study evaluated the efficacy and safety of a non-cytotoxic mobilization regimen of AMD3100 plus G-CSF for ASC mobilization in pts with MM. Methods: Mobilization treatment consisted of subcutaneous G-CSF (Filgrastim 10 μg/kg) given in the morning on 5 consecutive days and a single dose of AMD3100 (240 μg/kg) in the evening of day 4, 10–11 hours prior to leukapheresis. These procedures could be repeated for up to 5 additional days in order to collect an adequate number of cells for transplantation. Monitoring of CD34+ cells in peripheral blood (PB) was performed immediately prior to each AMD3100 administration and prior to the aphereses. Patients were treated with high dose chemotherapy in preparation for transplantation according to local standard of care guidelines. Pts did not receive hematopoietic growth factors following ASCT. The primary endpoint of the study was safety; secondary endpoints included 1) % of pts with >2-fold increase of CD34+ cells following AMD3100, and 2) % of pts in with hematopoietic recovery between day 14 and day 21. Results: 31 pts were evaluable, including 19 males (median age: 57 yrs, range: 40–73) and 12 females (median age: 61 yrs, range: 53–67). Pts had received a maximum of 4 prior chemotherapy cycles. The cumulative proportion of pts reaching a target of 5×10^6/kg CD34+ cells was 60% on day 1, 87% on day 2, and 93% on day 3. For the initial mobilization, AMD3100 increased absolute CD34+ counts ≥ 2-fold in 78% of pts (median fold increase: 2.8; range: 1.1–15.2). Additional aphereses showed a ≥ 2-fold increase in 21% of cases (median fold increase: 1.4; range: 0.7–6.5). Overall, the median number of CD34+ cells yielded was 7.1×10^6/kg (range: 3–28×10^6/kg). The majority of pts (n=19) underwent only a single apheresis, whereas additional procedures were needed in 12 cases. Nineteen pts received a single transplant, 11 pts a tandem transplant. Autografts contained a median of 3.1×10^6/kg CD34+ cells (range 2.4–9.2×10^6/kg). After first transplant, median time to neutrophil and platelet engraftment was 14 and 13 days, respectively. All patients had complete engraftment within 20 days except 1 pt who had neutrophil recovery at day 34 (single transplant) and 1 had platelet recovery at day 27 after the 2nd transplant. AMD3100 was well tolerated, drug-related adverse events (AEs) were limited to 2 cases of mild nausea/vomiting. Conclusions: The addition of AMD3100 to G-CSF doubled the number of mobilized CD34+ cells in the majority of pts, allowing the collection of sufficient CD34+ cells for tandem ASCT in 1–2 aphereses. Unlike chemotherapeutics commonly used to enhance stem cell mobilization, AMD3100 was not associated with any significant toxicity.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5197-5197
Author(s):  
Hiroyoshi Watanabe ◽  
Tsutomu Watanabe ◽  
Hiroko Suzuya ◽  
Yoshifumi Wakata ◽  
Toshihiro Onishi ◽  
...  

Abstract The purpose of this study was to examine the yield of PBSC, mobilized with G-CSF alone, and engraftment kinetics after autologous transplantation in pediatric cancer patients. In 55 patients (median age; 7 years, range 0–21) with various pediatric and adolescent solid tumors, PBSC were mobilized with G-CSF alone, and the yields of PBSC and engraftment following autologous PBSCT were evaluated retrospectively. Patients were categorized according to prior treatment; patients who had received less than 4 or 4 cycles of chemotherapy with/without local irradiation (Group 1: N= 21), patients who received more than 4 cycles of chemotherapy or 3 or more cycles of chemotherapy with extended irradiation (Group 2: N= 23), and patients who received high-dose chemotherapy with stem cell support (Group 3: N= 11). Ten microgram per kg of G-CSF was injected subcutaneously for mobilization when patients showed no influence of previous chemotherapy, and administration was continued for five days. The peaks of CD34+ cells and CFU-GM were observed on day 5 of G-CSF administration essentially in all patients. Aphereses were performed on days 5 and 6 of G-CSF treatment. Mobilization failure was observed in four patients in all groups. Compared with the results in patients mobilized by chemotherapy plus G-CSF (N=18), the progenitor cell yields were lower in those mobilized with G-CSF alone. However, there were no significant differences in WBC engraftment speed compared to the chemotherapy plus G-CSF mobilization group, although platelet recovery was delayed in patients with G-CSF alone, especially in patients in Group 3. The median time taken for ANC and platelet counts to reach 500 and 20K was 12 days (range 8–28) and 15 days (8–55), respectively, in all patients who were mobilized by G-CSF alone except for patients with progressive disease. In summary, mobilization with G-CSF alone can mobilize a sufficient number of CD34+ cells for successful autografting and sustained hematological reconstitution in pediatric patients with cancer, even in heavily pre-treated patients. Mobilization with G-CSF alone might offer some advantages, such as ease of determining a collection schedule without a daily determination of CD34+ cells in the blood, and the avoidance of neutropenic fever and additional transfusion.


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