When to harvest peripheral-blood stem cells after mobilization therapy: prediction of CD34-positive cell yield by preceding day CD34-positive concentration in peripheral blood.

1996 ◽  
Vol 14 (3) ◽  
pp. 970-973 ◽  
Author(s):  
C Elliott ◽  
D M Samson ◽  
S Armitage ◽  
M P Lyttelton ◽  
D McGuigan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Number ◽  
Cell Yield ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Mobilization ◽  
Wbc Count ◽  
Therapy Prediction

PURPOSE To evaluate whether the CD34+ yield from a single peripheral-blood stem-cell (PBSC) harvest could be predicted by measurement of the patient's circulating WBC and CD34+ cell concentrations on the day before harvest. PATIENTS AND METHODS Thirty-nine patients with hematologic or nonhematologic malignancy underwent 41 stem-cell mobilization episodes with cytotoxic chemotherapy and/or granulocyte colony-stimulating factor (G-CSF), and a total of 63 leukapheresis procedures were performed. Peripheral-blood samples were analyzed for WBC and CD34+ cell concentration both on the day before and the day of leukapheresis. RESULTS The median WBC and CD34+ concentrations on the day preceding leukapheresis were 10.0 x 10(9)/L (range, 0.4 to 44.4) and 24.9 x 10(6)/L (range, 0.1 to 349.4), respectively. On the day of harvest, the corresponding figures were 15.1 x 10(9)/L (range, 1.5 to 52.6) and 29.3 x 10(6)/L (range, 0.1 to 543.1), respectively. The median CD34+ cell number collected in a single leukapheresis was 2.6 x 10(6)/kg body weight (range, 0.1 to 26.1). Both the preceding day (r = .84, P < .001) and harvest day (r = .95, P < .001) CD34+ circulating concentrations correlated significantly with the number of CD34+ cells per kilogram collected at leukapheresis. The correlation between CD34+ cells per kilogram collected and harvest day WBC count was also significant (r = .43, P <.001), but with the preceding day WBC count was nonsignificant. CONCLUSION The number of CD34+ cells harvested in a single leukapheresis can be predicted by measurement of the preceding day peripheral-blood circulating CD34+ concentration, and on the basis of these data a table of probable CD34+ cell yield has been constructed. This correlation may facilitate the efficient organization of leukapheresis procedures.

A Randomized Clinical Trial Comparing Cytokine Administration Sites for Mobilization of Peripheral Hematopoietic Progenitor Cells for Patients with Hematological Malignancies Undergoing Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4230-4230
Author(s):  
Heather Renfroe ◽  
Edmund K. Waller ◽  
Mike Arnold ◽  
Louette Vaughn ◽  
R. Donald Harvey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Injection Site ◽  
Research Funding ◽  
Randomized Study ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Group A ◽  
Cell Mobilization ◽  
Group B

Abstract Abstract 4230 Background The optimal injection site for cytokine administration when used to mobilize peripheral blood stem cells for collection is unclear. There are known differences in the pharmacokinetics of subcutaneously injected drugs based upon site adiposity. We hypothesized that injection in lower adipose-tissue-containing sites in the extremities would result in a reduced reservoir effect leading to lower exposures of granulocyte colony stimulating factor (G-CSF) and therefore reduced stem cell collection following cytokine mobilization. Methods We completed a prospective single institution IRB-approved randomized study to determine the efficiency and tolerability of different injection sites among patients with multiple myeloma or lymphoma undergoing stem cell mobilization and apheresis. The primary end-points were the total number of CD34+ cells collected and the number of days of apheresis required to collect target numbers (5 × 10E6 CD34+ cells/kg for patients with lymphoma; 10 × 10E6 CD34+ cells/kg for patients with myeloma). Forty patients were randomized to receive cytokine injections in their abdomen (group A) or extremities (group B). Randomization was stratified based upon diagnosis (myeloma; N=29 vs. lymphoma; N=11), age (≤50; N=13 vs. >50; N=27), and mobilization strategy (cytokines alone; N=27 vs. chemomobilization; N=13). Both group A and B were balanced with respect to the stratification criteria. Filgrastim was planned at a dose of 10 ug/kg/day for patients undergoing chemomobilization or 15 ug/kg/day for patients undergoing cytokine-only mobilization. Actual mean cytokine doses were 11.78 ug/kg/day using chemomobilization and 12.96 ug/kg/day using cytokines alone due to rounding to nearest vial size. Patients recorded the injection site for G-CSF and symptoms daily. Results Of those enrolled, 90% were evaluable with 18 patients in each group. Four were deemed non-evaluable due to failure to proceed to the planned mobilization procedure (1 in group A and 2 in group B) or lack of consistent injection site (1 patient). In addition, one patient in group B received a non-protocol specified injection of plerixafor due to poor mobilization and collected a total of 13.62 × 10E6 CD34+ cells/kg in 2 days of apheresis. Among the 36 evaluable subjects, 1 subject in each group failed collection with a total of < 2.0 × 10E6 CD34+ cells/kg collected. Mean BMI at the time of mobilization was not different between groups A and B (27.25 ± 4.7 versus 29.39 ± 5.7, respectively; p=NS). Mean numbers of CD34+ cells (±SD) collected were not different between groups A and B (9.15 ± 4.7 versus 9.85 ± 5 × 106/kg, respectively; p=NS). The mode and median duration of apheresis was 2 days for both groups. Subjects from both groups reported similar toxicities of pain and discomfort at the injection site. Conclusions Based upon the analysis, G-CSF administration site (extremities versus abdomen), does not affect the number of CD34+ cells collected by apheresis or the duration of apheresis needed to reach the target cell dose. Disclosures: Lonial: Celgene: Consultancy; Millennium: Consultancy, Research Funding; BMS: Consultancy; Novartis: Consultancy; Gloucester: Research Funding.

Ex-Vivo Expanded Peripheral Blood Stem Cells (EVEC) Compared with Un Manipulated Peripheral Blood Stem Cells (PBSC) Autologous Transplantation for Multiple Myeloma: A Pair Match Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 502-502 ◽  
Author(s):  
Noel-Jean Milpied ◽  
Gerald Marit ◽  
Bernard Dazey ◽  
Jean-Michel Boiron ◽  
Zoran Ivanovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Seizures During Infusion of Autologous Peripheral Blood Stem Cells Are Related to High White Blood Cell Concentration in the Peripheral Blood Stem Cell Product and Can Be Prevented by Dilution of Product with Autologous Plasma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4386-4386
Author(s):  
Carlos Bachier ◽  
Grant Potter ◽  
Joshua Potter ◽  
Charles F. LeMaistre ◽  
Paul Shaughnessy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Blood Cell ◽  
White Blood Cell ◽  
Peripheral Blood ◽  
Cell Transplant ◽  
Autologous Plasma ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Abstract 4386 Seizures are rare during infusion of autologous peripheral blood stem cells (PBSC). We retrospectively analyzed 159 adult patients (pts.) collected consecutively between January 2006 and July 2009. Pts. were collected on either COBE Spectra (COBE) (n=85) or Fresenius AS 104 (Fresenius) (n=74) cell separators and mobilized with granulocyte colony stimulating factor (G-CSF) alone (n=47), G-CSF and Plerixafor (n=26), or G-CSF and chemotherapy (n=66). Pts. characteristics did not differ between the COBE and Fresenius cohorts, but there were differences in PBSC product (Table). Pts. collected with COBE had higher white blood cell (WBC) and total nucleated count (TNC) but lower mononuclear cell (MNC) percentage and cell viability than pts. collected with the Fresenius. Absolute CD34+ cells in the PBSC product, CD34+ cells / kg and total CD34+ cells / kg infused at transplant were not significantly different. CD34+ yields (calculated as the ratio of CD34+ cells /μl of the PBSC product to the patient's peripheral blood CD34+ cells / μl taken on the day of collection) were significantly higher on the COBE than Fresenius. No serious adverse events occurred during PBSC infusion except 3 of 159 pts. developed seizures during infusion of PBSC; all collected on the COBE and all three had product WBC > 590 × 103/μl (compared to a median of 163.3 × 103/ μl for all other products)(Figure). Evaluation of pts. did not identify abnormalities in imaging studies, cerebrospinal fluid analysis, electrolytes, or past history which might explain etiology of seizures. No significant difference in WBC or platelet engraftment was observed in pts. collected with COBE or Fresenius. We then prospectively correlated WBC counts midway and at the end of PBSC collections. Fourteen pts. had 15 apheresis using the Fresenius. Mid- and post-WBC concentrations were 64 +/− 23 × 103/μl and 69 +/− 20 × 103/μl, respectively. Fifty-one pts. had 66 apheresis using COBE, with WBC counts obtained midway and at the end of collection of 287 +/− 150 × 103/μl and 273 +/− 144 × 103/μl, respectively. Mid-WBC accurately correlated with WBC at the end of the collection in both the COBE and Fresenius cohorts (r2 = 0.940 and r2 = 0.904, respectively). Using this information, we prospectively evaluated 65 pts. who underwent 80 PBSC collections in anticipation of an autologous (n=44) or allogeneic (n=7) stem cell transplant between June 2009 and January 2010. Collections for these pts. were performed using the COBE (n=66) or the Fresenius (n=15). Mid-WBC were obtained and products with mid-collection WBC concentration > 450 × 103/uL (n=29) had additional autologous plasma collected at the time of collection for final product dilution to < 450 × 103/uL prior to cryopreservation. Pts weight, volume of PBSC product and CD34+ cells/kg infused did not differ between the pts who received diluted PBSC product and those who did not. There were also no differences in either ANC (12 ± 1.3 days vs. 11.5 ± 1.3 days, dilution vs. non-dilution, p = 0.760) or in platelet engraftment (18 ± 3.7 days vs. 16 ± 2.7 days, dilution vs. non-dilution, p = 0.561). No serious adverse infusion effects were observed in either group. In conclusion, high number of WBC in COBE collections is a possible cause of PBSC infusion related seizures. No seizures were observed after dilution of PBSC with high WBC concentration.TIENT AND PRODUCT CHARACTERISTICSCOBE (±SD)Fresenius (±SD)Number of Products165180Number of Patients8574Age at collection56 ± 1456 ± 15Weight at Collection (kg)82.7 ± 17.979.5 ± 15.9Collections / Patient2 ± 12 ± 1Blood Volume Processed at end of Collection (L)18.0 ± 2.418.1 ± 2.7(*)Product Volume (ml)241 ± 56.8402 ± 72.0Peripheral WBC (103/ μl)36.6 ± 18.933.3 ± 24.5(*)Product WBC(103/ μl)163.3 ± 136.055.8 ± 29.3(*)TNC (1010)3.51 ± 1.861.95 ± 1.19(*)MNC (1010)2.36 ± 1.191.60 ± 0.09(*)MNC (%)75.0 ± 23.385.0 ± 10.8Volume prior to freezing(ml)100 ± 54100 ± 32(*)Post Freeze Viability (%)70 ± 1475 ± 10Peripheral CD34+/ μl24.0 ± 43.825.3 ± 79.1(*)Product CD34+/μl726.7 ± 1325.9264.63 ± 781.0(*)Product / Peripheral CD34+24.87 ± 10.9010.91 ± 6.64Absolute Product CD34+ cells (108)1.77 ± 3.521.14 ± 3.35Product CD34+/kg (106)2.02 ± 4.671.39 ± 4.15Total CD34+ cells infused (106 / kg)3.85 ± 3.203.85 ± 2.24(*) = p values < 0.05 Disclosures: No relevant conflicts of interest to declare.

scholarly journals G-CSF Plus Preemptive Plerixafor Versus Cyclophosphamide Plus G-CSF for Autologous Stem Cell Mobilization in Multiple Myeloma: Effectiveness, Safety and Cost Analysis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5823-5823
Author(s):  
Ahmad Antar ◽  
Zaher Otrock ◽  
Mohamed Kharfan-Dabaja ◽  
Hussein Abou Ghaddara ◽  
Nabila Kreidieh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Mobilization ◽  
Cell Yield ◽  
Fixed Dose ◽  
High Dose ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization

Abstract Introduction: The optimal stem cell mobilization regimen for patients with multiple myeloma (MM) remains undefined. Most transplant centers use either a chemo-mobilization strategy using cyclophosphamide (CY) and granulocyte-colony stimulating factor (G-CSF) or a steady state strategy using G-CSF alone or with plerixafor in case of mobilization failure. However, very few studies compared efficacy, toxicity and cost-effectiveness of stem cell mobilization with cyclophosphamide (CY) and G-CSF versus G-CSF with preemptive plerixafor. In this study, we retrospectively compared our single center experience at the American University of Beirut in 89 MM patients using fractionated high-dose CY and G-CSF as our past preferred chemo-mobilization strategy in MM patients with our new mobilization strategy using G-CSF plus preemptive plerixafor. The change in practice was implemented when plerixafor became available, in order to avoid CY associated toxicity. Patients and methods: Patients in the CY group (n=62) (Table 1) received either fractionated high-dose CY (n=56) (5g/m2 divided in 5 doses of 1g/m2 every 3 hours) or CY at 50mg/kg/day for 2 doses (n=6). G-CSF was started on day +6 of chemotherapy at a fixed dose of 300 µg subcutaneously every 12 hours. All patients in the plerixafor group (n=27) (Table 1) received G-CSF at a fixed dose of 300 µg subcutaneously every 12 hours daily for 4 days. On day 5, if peripheral blood CD34+ was ≥ 20/µl, apheresis was started immediately. Plerixafor (240 µg/kg) was given 7-11 hours before the first apheresis if CD34+ cell count on peripheral blood on day 5 was <20/µl and before the second apheresis if CD34+ cells on the first collect were <3х106/kg. The median number of prior therapies was 1 (range: 1-3) in both groups. Results: Compared with plerixafor, CY use was associated with higher median peak peripheral blood CD34+ counts (35 vs 111 cells/µl, P= 0.000003), and total CD34+ cell yield (7.5 х 106 vs 15.9 х 106 cells/kg, P= 0.003). All patients in both groups collected ≥4x106 CD34+ cells/Kg. Moreover, 60 (96.7%) and 46 (74.2%) patients in the CY group vs 24 (88.8%) and 6 (22%) patients in the plerixafor group collected >6х106 and >10x106 CD34+ cells/kg, respectively (P=0.16; P<0.00001). Only 4 (6.4%) patients required two apheresis sessions in the CY group compared to 11 (40%) in the plerixafor group (P=0.0001). Conversely, CY use was associated with higher frequency of febrile neutropenia (60% vs 0%; P<0.00001), blood transfusions (27% vs 0%; P<0.00001), platelets transfusion (25% vs 0%; P<0.00001) and hospitalizations (64% vs 0%; P<0.00001). No one required intensive level of care and all recovered. Autografting was successfully performed in all patients using high-dose melphalan with a median time from mobilization to the first transplant of 31 days (range: 16-156) in the CY group compared to 13 days (range: 8-40) in the plerixafor group (P=0.027); and median infused CD34+ cells were 7х106/kg (range: 3.1-15.3) versus 5.27 (2.6-7.45), respectively (P=0.002). The average total cost of mobilization using the adjusted costs based on National Social Security Fund (NSSF) prices in Lebanon in the plerixafor group was slightly higher compared with the CY group ($7964 vs $7536; P=0.16). Conclusions: Our data indicate robust stem cell mobilization in MM patients with either fractionated high-dose CY and G-CSF or G-CSF alone with preemptive plerixafor. The chemo-mobilization approach was associated with two-fold stem cell yield, slightly lower cost (including cost of hospitalization) but significantly increased toxicity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bortezomib in Combination with Cyclophosphamide and G-CSF for Hematopoietic Stem Cell Mobilization in Patients with Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2067-2067 ◽  
Author(s):  
Bhausaheb Bagal ◽  
Anant Gokarn ◽  
Avinash Bonda ◽  
Swapnil Chavan ◽  
Sachin Punatar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Yield ◽  
Hematopoietic Stem ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
Cell Harvest

Abstract Background: Proteasome inhibitors (PI) have become integral part of front-line treatment of multiple myeloma. Murine model experiments have shown mobilization of hematopoietic stem cells from bone marrow to peripheral blood after PI administration via down regulation of very late antigen 4 (VLA-4) which mediate adherence of hematopoietic stem cells to the bone marrow microenvironment via interaction with vascular cell adhesion molecule (VCAM-1). Human studies with bortezomib in combination with G-CSF for mobilization have yielded encouraging results with no additional toxicity and no malignant plasma cell mobilization was observed. Cyclophosphamide based chemo-mobilization offers advantage in term of higher stem cell yield and is able to overcome adverse impact of prior lenalidomide therapy on stem cell harvest. In the current study we added bortezomib to cyclophosphamide-GCSF (B-Cy-GCSF) chemo-mobilization regimen to study the effect of bortezomib on stem cell harvest and compared this with our earlier protocol of only cyclophosphamide-GCSF (Cy-GCSF) mobilization. Methods: Patients of multiple myeloma aged between 18 to 70 years were eligible for the study in the period between March 2016- June 2018. Patients after induction therapy achieving at least partial response and having no more than grade 1 peripheral neuropathy were enrolled. Patients received bortezomib at a dose of 1.3 mg/m2 on day 1, 4, 8 and 11 and cyclophosphamide (Cy) was administered at a dose of 1 g/m2 on day 8 and 9 followed by G-CSF 10µg/kg in two divided doses from day 11 onwards till target stem cell collection of at least 5 X 106/Kg. The peripheral blood CD34 (PB CD34) counts were monitored from day 14 and harvest was initiated when it reached above 20 cells/µL. The peak PB CD34 count achieved, the number of days of harvest required, the CD34 dose yield and the engraftment kinetics were recorded and compared with earlier patients who had undergone Cy-GCSF chemo-mobilization. These patients had received Cy 1 g/m2 on d1 and d2, G-CSF 10 mcg/kg from d4 onwards and PBCD34 monitored from d7 onwards. Result: A total of 37 patients were enrolled between March 2016 and June 2018. Median age of study cohort was 46 years (range 27-63) and 27 (73 %) were males. Median lines of therapy received were 1 (range 1 to 2) and 8 (21.6 %) had received lenalidomide prior to stem cell harvest. The median peak peripheral blood CD34 cell counts 71.3 cells /µL (range 27.5 -306). Median CD34 cells collected were 9.21 X 106 /Kg (range 4.95-17.1). Target CD34 cell collection was achieved after a median of one day harvest (range 1-2). Median time to neutrophil and platelet engraftment was 11.5 and 13.5 days respectively. These results were compared with 88 patients who had undergone Cy-GCSF chemo-mobilization earlier at our center from May 2008 till February 2016 as seen in Table1 . In Cy- G-CSF cohort, median number of harvest required for target CD34 was 2 (range 1-4) and median CD34 cell yield was 8.2 X 106/Kg (0.4-24.2). Target CD34 cells yield of 5 X 106/Kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-G-CSF group, although this was not statistically significant (p=0.1). While 3(3.4 %) had failed chemo-mobilization after Cy-GCSF, none of patients in bortezomib group had mobilization failure. Conclusion: Patients undergoing B-Cy-GCSF mobilization have higher stem cell yield and required less days of harvest. This strategy should be explored in a larger cohort of patients. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation with Peripheral Blood Stem Cells Mobilized by Pegylated-G-CSF.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1970-1970
Author(s):  
Geoff Hill ◽  
Edward S. Morris ◽  
Maddona Fuery ◽  
Cheryl Hutchins ◽  
Jason Butler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Cell Function ◽  
Ideal Body Weight ◽  
Stem Cell Mobilization ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
12Mg Dose

Abstract The mobilization of stem cells with pegylated-G-CSF (peg-G-CSF) modulates regulatory T cell and NKT cell function, separating graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects in animal models. We have initiated a phase I/II study to analyse the feasibility of mobilizing stem cells from sibling donors with peg-G-CSF and their ability to restore hematopoiesis in HLA matched transplant recipients who have received myeloablative conditioning. Results were compared to a cohort of donors mobilized with standard G-CSF at 10ug/kg/day (n=19). The administration of 6mg of peg-G-CSF (n=6) resulted in suboptimal stem cell mobilization with a peak peripheral blood CD34+ count of 29 ± 4/uL. Apheresis 4 days after peg-G-CSF administration yielded 2.7 ± 0.3 x106 CD34+ cells/kg recipient ideal body weight and all patients required a second collection on day 5 to yield a total of 4.0 ± 0.5 x106 CD34+ cells/kg recipient weight. Following escalation of the dose to 12mg (n=9), the peak CD34+ count was 109 ± 13/uL and all donors collected sufficient stem cells for transplantation in a single apheresis (9.8 ± 1.7 x106 CD34+ cells/kg recipient weight). The 6mg dose of peg-G-CSF was significantly inferior to standard G-CSF for stem cell mobilization (P<0.01) while the 12mg dose was at least equivalent (P=0.07). Bone pain was similar between the 6mg and 12mg cohorts and to that seen with standard G-CSF. However, in addition to the expected rises in serum ALP and LDH, transient rises in hepatic transaminases were noted 5 to 12 days after peg-G-CSF administration in 7 of 9 donors receiving the 12mg dose. One donor developed NCI grade 3 hepatic toxicity and splenomegaly. After allogeneic transplantation of peg-G-CSF mobilized grafts (Cy/TBI conditioning in 13 of 14 recipients), median neutrophil and platelet engraftment occurred on days 18 and 14 respectively and was identical to that seen with grafts mobilized by standard G-CSF. With a median follow up of 165 days (range 55–532), the incidence of grade II-IV and grade III/IV acute GVHD is 50% and 21% respectively. No patients have relapsed to date and overall survival is 86%. The mobilization of stem cells with peg-G-CSF in normal donors is feasible and 12mg appears the optimal dose. Further data are required to more closely analyse the effect of peg-G-CSF on donor liver function and the ability of stem cell grafts to separate GVHD and GVL effects. Figure Figure

Peripheral Blood Stem-Cell Mobilisation and Autologous Stem Cell Transplantation In HIV-Related Malignancies.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4592-4592
Author(s):  
Marcus Hentrich ◽  
Xaver Schiel ◽  
Fuat Oduncu ◽  
Arthur Gerl ◽  
Clemens Scheidegger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Hiv Rna ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Neutrophil Engraftment

Abstract Abstract 4592 Introduction: Patients (pts) with HIV-infection are generally excluded from clinical trials that evaluate the role of high dose chemotherapy (HDCT) in malignant lymphoma or relapsed germ cell tumor (GCT). However, recent data indicate that HDCT followed by autologous peripheral blood stem cell transplantation (ASCT) may be effective in relapsed HIV-related lymphoma. Methods: This is an observational cohort study including patients with HIV-related lymphoma or HIV-related GCT who have peripheral blood stem cells mobilized by a combination of chemotherapy (CT) and G-CSF. Pts did or did not undergo consecutive ASCT. The primary outcome measure is feasibility. High-dose BEAM was used as a conditioning regimen in pts with HIV-related lymphoma while high-dose carboplatin/etoposide (CE) was chosen for pts with GCT. Results: From 07/05 to 03/10 peripheral blood stem cells (PBSC) were successfully harvested in 10 of 11 HIV-infected pts with diffuse large B-cell lymphoma (DLBCL) [n=4], Burkitt's lymphoma (BL) [n=3], plasmablastic lymphoma (PL) [n=2], Hodgkin lymphoma (HL) [n=1] and testicular GCT [n=1]. The mean number of collected stem cells was 15.7×106/kg CD34+ cells (range, 6.3 – 33). PBSC-mobilisation failed in one pt with relapsed BL. 7 of 11 pts were mobilized following salvage CT for DLBCL [n=4], BL [n=1], HL [n=1] or GCT [n=1] while 4 pts were under primary CT for BL or PL. So far, 5 of 10 pts received HDCT + ASCT. Pt 1 (44 yrs, CDC C3; HIV-RNA< 50 cop/ml at time of SCT) received HDCT as 3rd salvage therapy for DLBCL. A total of 9.2 × 106/kg CD34+ cells were transplanted. Neutrophil engraftment occurred on day +14. The pt achieved a partial remission but died of progressive lymphoma 6 months after ASCT. Pt 2 (60 yrs, CDC B3; HIV-RNA< 50/ml) underwent HDCT + ASCT (13.8 × 106/kg CD34+ cells) for a 1st relapse of HL. Neutrophil engraftment was observed on day +10. The pt is well and disease free 25 months after ASCT. Pt 3 (26 yrs, CDC C3, HIV-RNA< 50/ml), a hepatitis C co-infected haemophiliac, received HDCT + ASCT for refractory DLBCL but died of liver cirrhosis and neutropenic sepsis with multi-organ failure on day +16. Pt 4 (25 yrs, CDC A3, HIV-RNA< 50/ml) received 3 sequential courses of HD-CE followed by ASCT in 3-week intervals for a 3rd relapse of a nonseminomatous GCT. Neutrophil engraftment occurred on day +10, + 12 and +14, respectively. A complete remission (CR) was achieved. However, the pt suffered another relapse involving the central nervous system and died of progressive GCT 15 month after the 3rd transplant. Pt 5 (41 yrs, CDC C3, HIV-RNA 220/ml) underwent HDCT in 2nd complete remission after successful salvage-CT for a first sensitive relapse of DLBCL. A total of 12.9 × 106/kg CD34+ cells were transplanted. The pt is currently alive and neutropenic (day +3). ASCT was not performed in the other 6 pts because of refractory BL [n=1], ongoing first remission following induction CT for BL [n=2] and PL [n=2] and concomitant histoplasmosis necessitating antifungal therapy [n=1]. Conclusions: Successful mobilisation of PBSC is feasible in the majority of pts with HIV-related malignancies. ASCT seems effective in selected pts with chemo-sensitive relapse of malignant lymphoma or GCT. HIV-infected pts should no longer be excluded from HDCT-programs. Disclosures: No relevant conflicts of interest to declare.

High Dose Sargramostim (GM-CSF) Combined with IV Plerixafor for the Mobilization of Peripheral Blood Stem Cells (PBSC) From Normal HLA-Matched Allogeneic Sibling Donors Results in Hypercoagulability

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4095-4095
Author(s):  
Mark A. Schroeder ◽  
Sandra Lopez ◽  
Michael P. Rettig ◽  
Kathryn Trinkaus ◽  
Peter Westervelt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Phase Ii Trial ◽  
Peripheral Blood Stem Cells ◽  
Gm Csf ◽  
Blood Stem Cells ◽  
Cell Mobilization ◽  
Higher Doses

Abstract Abstract 4095 We report an interim safety analysis of a phase II trial evaluating GM-CSF and plerixafor for the mobilization of peripheral blood stem cells in normal HLA-matched allogeneic sibling donors, performed due to unexpected toxicity observed with this combination. We have previously reported a lower than expected incidence of acute GVHD in recipients of sibling donor allogeneic HSC transplants mobilized with GM-CSF alone (Devine et al. Blood), as well as similar results using a mouse model of GVHD, in which increased Tregs as well as putative myeloid derived suppressor cells (MDSCs) were observed. However, the use of GM-CSF as a single agent for stem cell mobilization has been limited by an unacceptably high (∼30%) incidence of failure to mobilize and collect adequate stem cell numbers in a single 20 L apheresis procedure. Based upon observed synergy between GM-CSF and plerixafor for HSC mobilization in mice, we hypothesized that this combination in humans might overcome the low stem cell yields observed with either agent alone and result in a PBSC product enriched in Tregs and MDSCs that could reduce GvHD after transplant. A phase II trial was designed, which is ongoing, to evaluate the efficacy of GM-CSF, initially at a dose of 10 mcg/kg SC daily × 5 – 6 days, and plerixafor 320 mcg/kg IV daily starting on day 5, with the primary objective of reduction in the day 1 mobilization failure rate from 33% to <10%, and a planned enrollment of 17 patients. To date 14 donors have been mobilized and 13 recipients transplanted. Initial mobilization with GM-CSF 10mcg/kg was complicated by a high incidence (4/4 donors) of unexpected catheter and IV tubing-associated thrombosis at the time of apheresis, requiring line revision, and in some cases placement of central venous access. The trial was halted for an interim safety analysis, resulting in reduction in the dose of GM-CSF to 5 mcg/kg SC daily × 5–6 days. Since this dose reduction, no significant problems with thrombosis precluding a full 20 L apheresis have been observed among 13 subsequent donors. No evidence of systemic thrombosis has been observed in any donors with this combination. The most common adverse effects have included first dose reaction of severe acute onset bone pain (only in 10mcg/kg dose of GM-CSF), diarrhea, nausea, fatigue, bone pain, injection site reaction, and cardiovascular disorders including bradycardia and transient hypotension. There have been no grade 3–4 adverse events related to mobilization. A preliminary analysis of mobilization in 10 donors with a 20 L minimum apheresis volume demonstrated a failure to collect ≥2×106 CD34/kg recipient weight in 1/10 donors. The mean CD34/Kg recipient weight collected from these donors was 5.25 × 106 CD34/Kg. Among donors who failed to undergo a minimum 20 L apheresis collection, only 2/4 required a second day of aphereis to achieve a collection goal of 2 × 106 CD34/kg, and no donor failed to reach this goal after two days of apheresis. CD34 cell mobilization peaked at 4–9 hours after plerixafor infusion with mean CD34/uL = 38 at 6 hours (SD = 10.35). No recipients had primary graft failure. The median time to neutrophil engraftment was 13 days (range 11 – 15), and median time to platelet engraftment was 24 days (range 19 – 28). All evaluable recipients had 100% peripheral blood donor chimerism at day 30 post transplant. One recipient developed secondary graft failure at day +51, and required reinfusion of G-CSF-mobilized stem cells from his initial donor. The incidence of grades II–IV and III-IV acute GvHD, respectively, among recipients of a GM+P mobilized product was 45% and 18%. The incidence of cGvHD was not evaluable due to the short duration of follow-up. CMV viremia incidence was 38%. Peripheral blood from donors was collected for correlative studies including phenotyping and functional studies, but has not yet been analysed. Further studies evaluating the hypercoagulability associated with higher doses of GM-CSF are ongoing. GM-CSF combined with IV plerixafor is a feasible combination. Higher doses of GM-CSF (10mcg/kg) are associated with first dose reactions, hypercoaguability and catheter thrombosis. Disclosures: Schroeder: Sanofi Oncology/Genzyme: Research Funding. DiPersio:genzyme: Honoraria.

scholarly journals To Predict Success of Postapheresis Yield and Post–Autologous Transplant Engraftment Based on Preapheresis Peripheral Blood CD34+ Cell Counts: An Indian Scenario–Based Study

2021 ◽  
Author(s):  
Pinki Devi ◽  
Ganapathi Bhat ◽  
Harish S. Ahuja
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Peripheral Blood Cd34 ◽  
Cell Counts ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Introduction The use of hematopoietic stem cells for autologous and allogeneic transplantation has increased in the recent past significantly, due to introduction of newer chemotherapeutic drugs, immunological techniques, and better stem cell technology. Among the bone marrow and peripheral blood stem cells, collection of the latter being more convenient to the patient and associated with faster granulocyte and platelet engraftment has been known as preferred method for mobilization. Peripheral blood stem cells can be extracted from the autologous or allogeneic donor. Mobilization of the stem cells for autologous stem cell transplant is traditionally done using growth factors alone or in combination with chemotherapy, with or without an additional mobilizing agent. A significant number of hematological malignancy patients are poor mobilizers, (i.e., they are unable to achieve the minimal target cell dose during their first round of mobilization).Therefore, a prediction for a successful stem cell mobilization ideally should be made before initiating any apheresis procedure to spare those with a low rate of success from the risks associated with apheresis procedure. Preapheresis CD34 cell count can predict postapheresis yield and hence, can help to reduce the collection sessions. Reduction of apheresis sessions decreases the discomfort, inconvenience, time, and monetary expenses. Objectives This study was aimed to analyze preapheresis and postapheresis CD34+ cell counts. Materials and Methods Patients of any age and gender with diagnosis of hematological malignancies admitted for autologous stem cell transplantation for hematological malignancies (including Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma) and germ cell tumors in our institute from July 2008 to July 2016 were included in the study. The post-GCSF CBC, preapheresis CBC, CD34+ cell counts, and postapheresis CBC, CD34+ cell counts, mononuclear cell counts to predict the outcome of amount of yield. The effect on engraftment will be measured according to the defining criteria of achieving a sustained peripheral blood neutrophil count of >500 × 106/L (Wolff 2002) and a platelet count of more than >20 × 109/L (Teltschik et al. 2016) independent of platelet transfusion for at least 7 days. Collection of stem cells was done using apheresis machine (COBE SPECTRA). Complete peripheral blood counts using automated analyzers. Peripheral blood CD34 + cell counts and postapheresis CD34+ cell count using BD FACS CANTO II flow cytometer. To calculate postapheresis yield, the related CD34 count measured by flow cytometer was multiplied by the apheresis product volume and divided by the recipient’s body weight (kg). Number of CD34+ cells collected = (CD34 cell concentration in final product) × (final product volume). Results A total of 100 patients who underwent a total of 320 apheresis sessions were included in the study. There were 78 males and 22 females. We also found a significant correlation between preapheresis CD34 + cell count and postapheresis CD34 percentage on days 1, 2, and 3 of the apheresis sessions. In our study, to obtain more than 1.31 × 106 cells (median = 1.04, range: 0.15–4.70), an absolute count of pre apheresis CD34 + cells ≥14 cells would be necessary. A target of CD34 + cells ≥ 2 × 106/kg was obtained in majority of patients if a concentration of ≥25 CD34 + cells was present in postapheresis collection. Conclusion Compiling our results with the previous published data, we conclude that there is a strong correlation between preapheresis absolute CD34 + cell counts and postapheresis CD34 + cell count. Our study also suggests that the minimum absolute cell count of >10 cells/μL is required, to achieve a target of >2–5 × 106 cells for postapheresis yield.

scholarly journals Intrabone Injection of T-Cell Depleted Peripheral Blood Stem Cells from HLA-Haploidentical Donors to Reduce the Risk of Graft Rejection in Children

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1146-1146
Author(s):  
Luisa Strocchio ◽  
Marco Zecca ◽  
Patrizia Comoli ◽  
Perotti Cesare ◽  
Claudia Del Fante ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Stem Cell ◽  
T Cell ◽  
Graft Rejection ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells ◽  
Cell Inoculum

Abstract Background. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective treatment option for patients with malignant and non-malignant hematologic disorders lacking an HLA-compatible donor. Strategies for T-cell depletion (TCD) of the graft, such as positive selection of CD34+ cells, offer the potential to prevent acute and chronic graft-versus-host disease (GVHD). The risk of graft rejection associated with the extensive depletion of both T lymphocytes and accessory cells can be overcome by infusing a very high number (megadose) of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) (exceeding 10x106/kg recipient body weight) to overcome the HLA barrier (Aversa F. et al. Blood 1994). Moreover, the infusion of a megadose of CD34+ cells (higher than 20x106/kg and 12.4x106/kg, respectively) has been shown to result in faster immunological recovery and improved leukemia-free survival probability in children (Handgretinger R. et al. Bone Marrow Transplant 2001; Klingebiel T. et al. Blood 2010). Nevertheless, in the case of donors considered “poor mobilizers” (10-30% of cases), the threshold dose of CD34+ cells needed to ensure the inoculum of a megadose of stem cells might not be achieved. In the setting of cord blood (CB) transplantation, one of the strategies aimed at overcoming the problem of low cellularity is represented by the intrabone injection of CB stem cells, with good engraftment rates even in adult patients. We explored the same strategy in the context of T-cell depleted haplo-HSCT and low graft cellularity due to poor donor mobilization, ensuing in inadequate dose of CD34+cells available after positive selection TCD. Patients and methods. From September 2009 to April 2013, 11 pediatric patients affected by malignant or non-malignant hematological disorders (5 acute lymphoblastic leukemias, 1 acute myeloid leukemia, 1 myelodysplastic syndrome, 2 dyskeratosis congenita, 1 Fanconi anemia) received a T-cell depleted CD34+positively selected PBSC allograft from an HLA-haploidentical related donor. Due to the failure to achieve a target cell dose higher than 12x106 purified CD34+ cells/kg, part of the stem cell inoculum was infused as intrabone injection. The procedure was carried out at the patient bedside by multiple intrabone injections in the superior-posterior iliac crests under sedoanalgesia, as previously described (Frassoni F. et al. Lancet Oncol 2008). The median dose of CD34+ cells infused was 9x106/kg (range, 5-12) while the median number of CD3+ lymphocytes was 0.7x104/kg recipient body weight (range, 0.3-11). About one third of the stem cell inoculum, corresponding to a total volume of 20-40 ml, was given intrabone, while the remaining stem cell portion was infused intravenously. Results.No complication occurred during, or immediately after, the intrabone injection. Nine out of the 11 patients achieved a complete donor engraftment, while graft rejection occurred in 2 patients. The median time for neutrophil engraftment was 13.5 days (range, 12-20), while the median time for platelet recovery was 14 days (range, 13-24). One patient developed grade II acute GVHD and only 1 case of limited chronic GVHD was observed. No transplant-related deaths were observed. Conclusions. Our data suggest that, in the haplo-HSCT setting, the intrabone injection of positively selected CD34+ cells, can be safely used in cases of low graft cellularity due to poor donor mobilization, with the aim of minimizing the risk of graft rejection or poor engraftment. Our preliminary data need to be confirmed in larger series of patients and compared with those obtained with conventional intravenous administration of comparable dose of CD34+ cells. Disclosures No relevant conflicts of interest to declare.

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