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.

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 Pilot Study of Peripheral Blood Hematopoietic Stem Cells Mobilization with the Combination of Bortezomib and G-CSF in Multiple Myeloma and Non-Hodgkin's Lymphoma Patients.

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1902-1902
Author(s):  
Divaya Bhutani ◽  
Vidya sri Kondadasula ◽  
Joseph P. Uberti ◽  
Voravit Ratanatharathorn ◽  
Lawrence G. Lum ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Median Number ◽  
Peripheral Blood Cd34 ◽  
Cd34 Cells ◽  
Group A ◽  
Cell Mobilization ◽  
Group B ◽  
Stem Cell Collection

Abstract Background: Bortezomib has become an integral part of front-line therapy of multiple myeloma in a large majority of patients. There are preliminary reports which show that addition of bortezomib can augment the peripheral blood CD34 count during stem cell mobilization. In this single center prospective trial we added bortezomib to G-CSF to evaluate the effects of bortezomib on peripheral CD34 counts and collection. Methods: Patients aged 18-70 years with diagnosis of multiple myeloma (MM) or non-hodgkin's lymphoma (NHL) who were eligible for autologous stem cell transplantation (ASCT) and had received no more than three prior chemotherapeutic regimens were eligible for the study. Patients were enrolled in two groups. Group A (N=3) received G-CSF 16mcg/kg for 5 days and proceeded to stem cell collection on D5 and then received bortezomib 1.3mg/m2 on D5 after stem cell collection and G-CSF 16mcg/kg on D6, 7, 8 and repeat stem cell collection on D6, 7, 8 till the goal was achieved. Group B (N=17) received G-CSF 16mg/kg on D1-5 and received bortezomib 1.3mg/m2 on D4 and proceeded to stem cell collection on D5. If the patient was not able to collect the predefined goal CD34, G-CSF was continued on D 6, 7, 8 and a second dose of bortezomib 1.3mg/m2 was given on D7. Mobilization procedure was stopped once the predefined goal CD34 collection (4 x 106/kg for MM and 2 x 106/kg for NHL) had been collected. Primary objectives of the study was to determine if addition of bortezomib to G-CSF will result in an increase in PBSCs by > 2-fold and to achieve median neutrophil engraftment 12 days post ASCT. Secondary objectiveswere to evaluate the collected product for co-mobilization of lymphoma or myeloma cells and to determine if the use of bortezomib increases the mobilization of immune-stimulatory Dendritic cell (DC) -1 subsets. Results: A total of 23 patients were enrolled and 20 were evaluable for the results. Only one patient with NHL was enrolled and rest had MM. Median age of pts was 57 years, M/F 8/12, median number of previous chemotherapy regimens was 1 (range 1-3). The median peripheral blood CD34 count pre and post bortezomib in all patients were 28.8 x 106/kg and 37 x 106/kg respectively. All three patients in group A had drop in peripheral blood CD34 counts on D6 post bortezomib as they had undergone stem cell collection on day 5. In part B (N=17), 15 patients had increase in peripheral blood CD 34+ve cell counts with 4 patients achieved doubling while 11 pts had less than doubling of peripheral blood CD34 count after receiving bortezomib. Two patients had minimal drop in the peripheral blood CD34 counts post bortezomib. Median number of CD34 cells collected in15 patients (part B) were 5.06 x 106 CD34 cells/kg (range 4-15.1). 18 patients proceeded to ASCT and median time to neutrophil engraftment (ANC ≥500/cumm) post transplant was 12 days (range 11-16) and platelet engraftment (Plt count ≥ 20,000/cumm) was 18 days (range 15-27). There was no significant change in DC1/DC2 ratio in both groups following treatment with bortezomib and G-CSF (Figure 1). In group A all three patients collected goal CD34 count on day 5 and 2/3 patients collected >4 x106 CD34 cells/kg on D6 post bortezomib and1/3 patients collected 2.6 x 106 on D6 post bortezomib. In group B (n=17), 2 patients were unable to collect because of low CD34 counts on D4 and D5, 11 pts collected the goal in one day (D 5) and 4 pts required two days of apheresis (D 5 and 6). None of the patients received D7 bortezomib. Conclusion: Use of bortezomib during autologous stem cell collection was safe and well tolerated. Majority of patients had increase in peripheral blood CD34 counts post bortezomib administration on D4. Future trials should explore bortezomib as an alternate strategy to chemo-mobilization in combination with growth factors. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 1. DC1/DC2 ratio in group A and group B at various time points. Figure 2. Figure 2. Disclosures Off Label Use: Bortezomib for stem cell mobilization. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding. Abidi:celgene: Speakers Bureau; Millenium: Research Funding.

Effect of mobilization chemotherapy with cyclophosphamide and etoposide on stem cell collection by lenalidomide

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7096-7096
Author(s):  
G. Talamo ◽  
D. F. Claxton ◽  
W. C. Ehmann ◽  
J. Mierski ◽  
W. Rybka ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Median Number ◽  
Inhibitory Effect ◽  
Standards Of Care ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells ◽  
Group A ◽  
Group B ◽  
Stimulating Factor

7096 Background: The combination of dexamethasone and lenalidomide is currently considered one of the standards of care for induction therapy of patients with multiple myeloma (MM) before autologous stem cell transplantation (ASCT). Increasing evidence suggests that lenalidomide impairs the ability to collect peripheral blood stem cells (PBSC). Methods: We retrospectively analyzed the outcomes of PBSC collections of MM patients who received induction therapy with dexamethasone and lenalidomide, and who were collected with either granulocyte-colony stimulating factor (G-CSF) alone, 10–16 mcg/Kg/day (group A, n= 12), or G-CSF 5 mcg/kg/day + mobilization chemotherapy, consisting of cyclophosphamide 5,000 mg/m2 and etoposide 1,000 mg/m2 (group B, n=27). In all patients, lenalidomide was stopped 2 weeks before the predicted day of PBSC collection. Results: The median number of PBSC collected was 3.2 million CD34+ cells/Kg in group A (range, 0.3–6.3) and 28.1 million CD34+ cells/Kg in group B (range, 4.8–134) (p<0.01). The median number of days to collect PBSC was 1 in group A (range, 1–4) and 2 in group B (range, 1–5) (p=0.015). Three patients in group A failed to collect an adequate number of PBSC, either for a single ASCT (n=1) or tandem ASCT (n=2). No PBSC collection failures were observed in group B. No difference in the rapidity of PBSC engraftment was seen between the two groups. Conclusions: Chemotherapy with cyclophophamide and etoposide can overcome the inhibitory effect of lenalidomide in the collection of PBSC for ASCT in MM patients. No significant financial relationships to disclose.

Comparison of four different strategies of stem cell mobilization in patients with multiple myeloma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7039-7039
Author(s):  
Jeffrey Michael Sivik ◽  
Sesilya Whaley ◽  
Joseph Mierski ◽  
William J. Castellani ◽  
Mitzi Lowe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Median Number ◽  
Cd34 Cells ◽  
Group A ◽  
The Mean ◽  
Cell Mobilization ◽  
Group B ◽  
Group D

7039 Background: There is no consensus among institutions for the optimal strategy of peripheral blood stem cell (PBSC) collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). Methods: We retrospectively analysed the outcomes of PSBC collection in MM patients using the following mobilization regimens: cyclophosphamide 5,000 mg/m2 + etoposide 1,000 mg/m2 + G-CSF 5 mcg/Kg/day (Group A, n = 49); cyclophosphamide 2,000-3,000 mg/m2+ G-CSF 5 mcg/Kg/day (Group B, n = 25); G-CSF 16 mcg/Kg/day (Group C, n = 21); G-CSF 16 mcg/kg/day + plerixafor 0.24 mg/Kg (Group D, n = 128). Results: The median number of PBSC collected was 28.1 (range, 2.1-134), 4.5 (0.1-39.7), 4.0 (0-7.3) and 8.4 (0.2-41.2) million CD34+/kg in groups A, B, C and D, respectively (p <0.001). The mean number of collection days was 1.3, 2.2, 2.4, and 1.3 in groups A, B, C, and D, respectively (p <0.001). Febrile neutropenia occurred in 16 (32.7%), 1 (4%), 0, and 0 patients in groups A, B, C, and D, respectively. One patient who received CTX 3 g/m2 died of septic shock during the neutropenic phase. Failure to collect PBSC, defined as <2x106 CD34+ cells/Kg for a planned single ASCT or <4x106 for planned tandem ASCTs, was observed in 2/49 (4%), 5/25 (20%), 4/21 (19%), and 9/128 (7%) patients in groups A, B, C, and D respectively (p=0.037). Conclusions: Plerixafor + G-CSF provided the greatest benefit to risk ratio for PSBC collection in MM patients.

The Effect Of Prior Chemotherapy Courses With MD-AraC On The Hematopoietic Stem Cell Mobilization

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5446-5446
Author(s):  
Ru Feng ◽  
Muchen Xie ◽  
Yu Zhang ◽  
Yongqiang Wei ◽  
Fen Huang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem ◽  
Prior Chemotherapy ◽  
Failure Group ◽  
Cd34 Cells ◽  
Success Group ◽  
Group A ◽  
Cell Mobilization ◽  
Group B

Abstract Objective To explore the number of courses of prior medium-dose cytarabine(MD-AraC) chemotherapy correlates with mobilization and transplantion efficiency. Methods 90 consecutive patients with acute nonlymphocytic leukemia (ANLL) who underwent PBSC mobilization and apheresis in Haematology department of Nanfang hospital from August 1999 through November 2012 were analyzed. All patients with complete remission (CR) stages underwent leukapheresis after received granulocyte colony-stimulating factor (G-CSF) plus EA chemotherapy regimen for the mobilization, counted CD34 +cells by FACS. 85 patients finally has performed autologous hematopoietic stem cell transplantation (auto-HSCT), 1 performed allogeneic hematopoietic stem cell transplantation (allo-HSCT), 4 give up transplantation after mobilization. Patients were divided into two groups, MD-AraC 0-1 course in group A, MD-AraC 2 courses in group B, MD-AraC 3-5 courses in group C, then comparative analysis mobilization outcome, hematopoietic engraftment, relapse and survival of two groups. According to the acquisition of CD34 + cells number ≥ 2.0 x 10 6 / kg, < 2.0 x 10 6 / kg at most 3 leukapheresis by one mobilization, divided patients into success mobilizer group, the failure mobilizer group, then compared two groups of prechemotherapy and mobilization loads. Results The mobilization outcome of 87 patients who could be evaluated, members in group A,B,C collected CD34 + cells (×106 /Kg) was 4.67,2.65,2.33, A>B>C, comparative difference was statistically significant (P = 0.003). Overall 26 (29.9%) mobilizer cellected CD34 + cells < 2.0 x 10 6 / kg and there are 7 (15.2%) patients ,10 (47.6%) patients, 9 (45.0%) patients respectively in A ,B, C, the group B and C failure mobilizer rates is significantly higher than group A (χ = 10.05, P = 0.007).while ,There patients were lowest blood volume, apheresis times, G-CSF doses in A group collected suffucuent CD34+ cell-dose, A<B<C. The success group patients’ MD-AraC courses(one course) with median was lower than the failure group patients’(two courses), the difference was statistically significant (P=0.012).While, the blood volume, apheresis times, G-CSF doses and days were lower in the success group (P<0.05). Engraftment after transplantation in A,B,C 3 groups were no difference. While, Megakaryocyte engraftment in success group were better than the failure group (P< 0.001).Of the 85 auto-HSCT patients, 23(27.6%) patients relapse, the incidence of relapse was not significantly different between the A, B and C groups or non-PM and PM groups( P>0.05). There was no difference in disease-free survival (DFS) and overall survival (OS) of A, B and C groups. Conclusion Patients who received more course chemotherapy with MD-AraC, acquired more difficulty of mobilization and lower incidence rate of good mobilization, and didn’t enhanced the post-transplantation DFS and OS. We conclude that prior chemotherapy is the most important potentially controllable variable for stem cell mobilization. In preparationfor Auto-HSCT, take into account the stem cell collection, patients should be minimize exposure to MD-AraC chemotherapy courses before mobilization. Disclosures: No relevant conflicts of interest to declare.

Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer.

1998 ◽  
Vol 16 (8) ◽  
pp. 2601-2612 ◽  
Author(s):  
A Weaver ◽  
J Chang ◽  
E Wrigley ◽  
E de Wynter ◽  
P J Woll ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Randomized Study ◽  
Cd34 Cells ◽  
Cell Mobilization ◽  
High Yields ◽  
Higher Doses

PURPOSE This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.

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.

Plerixafor and G-CSF For Autologous Stem Cell Mobilization In AL Amyloidosis: A Single Center Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4516-4516
Author(s):  
Esha Kaul ◽  
Gunjan L Shah ◽  
Chakra P Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Stem Cell ◽  
Research Funding ◽  
Median Number ◽  
Initial Therapy ◽  
Stem Cell Mobilization ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Cd34 Cells ◽  
Cell Mobilization

Background Risk-adapted melphalan and stem cell transplant (SCT) is standard initial therapy for a minority of patients with systemic AL amyloidosis (Blood 2013;121: 5124; Blood 2011;118: 4298). Stem cell mobilization is often accomplished with high dose G-CSF (16μg/kg/d) (Blood 2011;118:4346). In the current era with effective new agents such as bortezomib, many AL patients are receiving initial therapy and achieving profound rapid cytoreduction with organ improvement (Blood 2012;119:4391; Blood 2011;118:86). But not all patients respond and in some cases the duration of response is limited. In addition, the use of SCT for consolidation after an initial response, although reasonable, has not been systematically evaluated. Whether SCT is employed as consolidation or as a second- or third-line option, the efficacy and tolerance of mobilization become important issues. Because AL patients have organ involvement limiting chemotherapy-based mobilization options, we decided to explore the option of Plerixafor and G-CSF for stem cell mobilization, based on the phase III experience in MM (Blood 2009;113:5720). We now report the first experience with this mobilization approach in AL. Patients and Methods Patients were evaluated and diagnosed by standard criteria including, in all cases, tissue biopsies showing amyloidosis. They were mobilized and collected between 4/16/12 and 6/19/13 with G-CSF 10μg/kg/d subcutaneously (SC) for 5 days (continued through collection process) and Plerixafor adjusted for renal function starting on day 4 and continuing until collection was completed. Results We report on 10 patients whose median age at mobilization was 58 years (range 46-72), 60% of whom were men. Median number of organs involved was 2 (range 1-3). Heart and kidneys were the most frequently involved organs (7 patients in each group). Median time from diagnosis to mobilization was 9 months (range 2-123). Eight patients had received prior bortezomib-based therapy. The median number of cycles was 3 (range 0-6). One had received a prior MEL 140 transplant 10 years prior and had relapsed, and 2 were treatment naïve, one of whom was 1 year status post orthotopic heart transplant. At the time of mobilization, 3 patients had non-responsive hematologic disease, 3 had achieved PR, 1 VGPR and 1 had achieved CR. Five patients had a creatinine ≥ 1.5 mg/dL including 2 patients on hemodialysis. The target cell dose was 10x106CD34/kg for all but one patient (with previous history of transplantation). The median number of collections was 2 (range 2-3). On day one, the median number of CD34+ cells collected per kg was 3.6 x106 (0.4-6x106) and on day two 6.4 x106 (2.7-19x106). The median total CD34+ cells collected per kg was 12.5x106 (5-18x106). Two patients had grade 1 bleeding from the catheter site during apheresis and one patient had dyspnea with suspected fluid overload which responded to a single dose of intravenous furosemide. There were no significant toxicities observed with Plerixafor in mobilization. All patients went on to receive high dose chemotherapy with melphalan followed by autologous stem cell transplant. The median length of hospital stay was 25 days (18-32). The median stem cell dose infused was 7.6x106CD34/kg and median days to ANC > 500 was 11 (10-22), to platelets > 20K untransfused 22 (15-44) and to lymphocytes > 500/μl 14.5 (11-25). One patient who had VOD and persistent thrombocytopenia was given the remainder of his stem cells on day +31 with full recovery and normalization of the blood counts by day +65. Conclusions In the era of more effective initial therapies, an era in which AL patients are living longer, many with moderate organ damage, mobilization with Plerixafor and G-CSF was well tolerated and made it possible to collect ample numbers of CD34+ cells with limited leukaphereses in previously treated patients and in those with advanced renal failure. This approach not only allowed the collection of sufficient CD34+ cells for optimal immediate stem cell dosing but also permitted the cryopreservation of aliquots for post-SCT boost and potentially for future cell-based therapies. Disclosures: Comenzo: Millenium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Prothena: Research Funding; Teva: Research Funding.

Non Interventional Prospective Clinical Study on Peripheral Blood Stem Cell Mobilization in Patients with Relapsed Lymphomas

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3852-3852
Author(s):  
Gwendolyn van Gorkom ◽  
Herve Finel ◽  
Sebastian Giebel ◽  
David Pohlreich ◽  
Avichai Shimoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Clinical Study ◽  
Research Funding ◽  
Median Number ◽  
Stem Cell Mobilization ◽  
Prospective Clinical Study ◽  
Cd34 Cells ◽  
Relapsed Lymphoma ◽  
Cell Mobilization

Abstract Introduction: Autologous stem cell transplantation (ASCT) is the standard of care for many patients with relapsed chemosensitive lymphoma. Peripheral blood stem cells have become the main source for the ASCT worldwide, because of its advantages over bone marrow. Several risk factors have been identified for poor stem cell mobilization, and diagnosis of lymphoma is one of the most important ones, with an inadequate stem cell harvest reported in 4 to 25% of the cases. Even though stem cell mobilization in relapsed lymphoma patients can be relatively difficult, mobilization strategies have not been standardized and there is a significant variation amongst centers. The aim of this non-interventional prospective clinical study was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate the failure rates. Methods: All EBMT centers were invited to participate in this non-interventional prospective clinical study that was started in 2010 and ended in 2014. Centers were requested to collect data on all consecutive patients with relapsed lymphoma considered to be candidates for an ASCT and were 18 years of age or older. Data collected included age, sex, diagnosis, number of prior chemotherapy regimens, mobilization regimen, collected CD34+ cells and marrow harvests. Results: In total, 275 patients with relapsed lymphoma from 30 EBMT centers were registered for this study. There were 158 males and 117 females with a median age of 51 (range 18 – 77) years; 181 patients (66%) with non-Hodgkin’s lymphoma (NHL) (DLBCL 28%, FL 17%, MCL 6%, PTL, 3%, other 12%) and 94 patients (34%) with Hodgkin’s lymphoma (HL). The median number of chemotherapy lines received before this relapse was one (range 1 – 8). 263 patients (96%) were mobilized with chemotherapy + G-CSF being DHAP (43%) and ESHAP (11%) the most frequent protocols, and 12 patients (4%) were mobilized with G-CSF alone. Thirteen patients (5%) who were mobilized with chemotherapy + G-CSF, received additional PLX in the first mobilization. These were all patients that were mobilized with chemotherapy as part of the mobilization regimen. Thirty patients (11%) failed to mobilize adequate stem cells (<2 x 10⁶ CD34+ cells/kg) during first mobilization despite the use of PLX in four patients. The median number of stem cells collected at first mobilization was 5.6 x 10⁶ CD34+ cells/kg (range: 0 – 82). In 255 patients (92.7%) only one mobilization course was given, 18 patients (6.5%) had two mobilization courses, 2 patients (0.7%) underwent three mobilization courses. Three patients had a mobilization failure after only G-CSF; they all were successfully harvested in a second attempt after chemotherapy + G-CSF. Five of the patients failing the first mobilization with chemotherapy + G-CSF received PLX at second mobilization, but only three succeeded. One patient failed both first and second mobilization and received PLX at third mobilization without success. 22 patients (8%) still had an inadequate amount of stem cells in the end. Of those, only 4 patients (1.5%) underwent bone marrow harvest. Conclusion: In the EBMT centers participating in this study, a primary mobilization strategy based on the combination of salvage chemotherapy plus G-CSF was used for virtually all patients with relapsed lymphoma. PLX was used in only 5% of the mobilization procedures during the time period analyzed. With 11% after the first mobilization attempt and 8% after several attempts, the failure rate was relatively low. Disclosures van Gorkom: Sanofi: Research Funding. Sureda:Takeda Pharmaceuticals International Co.: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics, Inc.: Research Funding.

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