The Role of SDF-1/CXCR4 in the Procession of Auto-Stem Cell Transplantation of Multiply Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5150-5150
Author(s):  
Caixia Li ◽  
De Pei Wu ◽  
Xue Guang Zhang

Abstract CXCR4, receptor of the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34+ cells, and has been implicated in the process of CD34+ cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and sgp130 in 22 patients, 11 acute Leukemia, 5 non-Hodgkin’s lymphoma, and 6 multiply myloma respectably, receiving cyclophosphamide (Cy) and plus G-CSF, or Mitoxantrone(Mit) and Cytarabine plus G-CSF for peripheral blood stem cell (PBSC) mobilization and autotransplantation. We observed lower plasma levels of SDF-1 in PBSCs compared with premobilized PB and bone marrow samples. The average levels of SDF-1 and sgp130 were 24.67±5.58ng/ml and 106.2±16.4ng/ml respectively while the level of SDF-1 as well as sgp130 decreased to 14659±2.11ng/ml(p<0.05)and 58.8±29.1ng/ml(p<0.05) respectively on day when PBSC was collected after mobilization. SDF-1 levels in the apheresis collections of the “good mobilizers” (patients who collected a minimum of 2 × 106 CD34+ cells/kg in one to three PBSC collections) were significantly lower than the apheresis collections of the “poor mobilizers” (<2 × 106 CD34+ cells/kg in the three cycles of PBSC collections; 14.82 ± 7.08 ng/ml versus 27.2 ± 8.13 ng/ml; p<0.01). The mean percentage of CD34+ cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values ranging from 32.09±5.39% to 22.4±5.92%. But the mean CXCR4 expression on CD34+ cells of the good mobilizers was not different from the expression on CD34+ cells of poor mobilizers. Furthermore, the levels of sgp130 closely correlated with SDF-1 levels (r = 0.87; p < 0.001); the plasma level of SDF-1 and expression of CXCR4 on the CD34+ cells were gradually decreased in the PB of patients during the procession of mobilization; low plasma levels of SDF-1 turned out with good mobilization outcome, and the levels of SDF-1 correlated with sgp130, suggesting an association of these cytokines in mobilization of CD34+ cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7039-7039
Author(s):  
Jeffrey Michael Sivik ◽  
Sesilya Whaley ◽  
Joseph Mierski ◽  
William J. Castellani ◽  
Mitzi Lowe ◽  
...  

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.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3098-3098 ◽  
Author(s):  
Armin Ghobadi ◽  
Mark A Fiala ◽  
Giridharan Ramsingh ◽  
Feng Gao ◽  
Camille N. Abboud ◽  
...  

Abstract Introduction: CD34+-selected peripheral blood stem cell infusions without conditioning have recently been utilized for poor graft function (PGF) with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this pilot trial utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+-selected peripheral blood stem cell infusions for the treatment of PGF. Additionally, to explore relationship of CD34+ dose and response we included a cohort of donors mobilized with plerixafor in addition to the standard G-CSF. Methods: Poor graft function (PGF) was defined as ANC < 0.5k/μL, platelets < 30k/μL, or platelet or RBC transfusion dependence despite full donor chimerism and in the absence of GVHD more than 60 days following allogeneic stem cell transplant (allo-SCT). Three different donor products were used for CD34+ selection: (1) fresh mobilized product using G-CSF only (SC at a dose of 10 μg/kg daily for 5 days), (2) fresh mobilized products using G-CSF (SC at a dose of 10 μg/kg daily for 5 days, days-4 through day 0) and plerixafor (IV at a dose of 320 μg/kg on day 0), and (3) cryopreserved cells mobilized with G-CSF (SC at a dose of 10 μg/kg daily for 5 days). Seventeen donor-recipient pairs were enrolled onto this prospective study. The original allo-SCT donor either underwent an additional peripheral blood stem cell (PBSC) mobilization and collection with G-CSF only (n=5) or G-CSF plus plerixafor (n=9) or a cryopreserved product (n=3) from a previous collection (using G-CSF only) was used to create the CD34+ cells for infusion. CD34+ cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. Neutrophil improvement was defined as neutrophil count > 500/μl without growth factor support for >7 days; platelet improvement was defined as platelet count ≥ 50,000/µl without platelet transfusion support for > 7 days; and RBC improvement was defined as hemoglobin > 9 g/dL and transfusion independence. Complete response was defined as improvement of all involved cells lines; partial response was defined as improvement of platelets and/or neutrophils with continuing RBC transfusion dependence. Results: The mean post-selection CD34+ count per kg of recipient weight was 3.7x106, 12x106, and 1.7x106 for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. Mean CD34+ yields (defined as the number of CD34+ cells after selection/CD34+ cells prior to CD34 selection) was 58%, 67%, and 31% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively (Table 1 and Figure 1). The mean number of CD3+ T cells/kg infused in each product was 0.004 x 106, 0.032 x 106, and 0.015 x 106 for G-CSF only, G-CSF plus plerixafore and cryopreserved groups respectively (Table 1). Following the CD34+-selected stem cell infusion, 12 of the 17 recipients (71%) had a complete response including all 3 who received cryopreserved products; 3 had a partial response (17%) and 2 patients (12%) did not respond. One year relapse-free and overall survival was 71% and 65%. There was no treatment related toxicity reported other than graft-versus-host-disease (GVHD); three (18%) developed acute GVHD (1 grade I localized to the skin, 2 grade II with gut involvement), 6 chronic GVHD (2 limited and 4 extensive) (Table 1). Conclusion: Cryopreserved products seem to be a viable alternative to create CD34+ -selected peripheral blood stem cell infusions for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+ yield over G-CSF alone. Disclosures Abboud: Teva Phamaceutical: Research Funding. Uy:Novartis: Research Funding.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Takahiro Shima ◽  
Teppei Sakoda ◽  
Tomoko Henzan ◽  
Yuya Kunisaki ◽  
Takahiro Maeda ◽  
...  

Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and widely performed in clinical practice. Platelet loss is the major complication of PBSC apheresis, and platelet-rich plasma (PRP) return is recommended in case of severe platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss nor the efficacy of PRP return post-apheresis. To address these questions, we assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated efficacy of PRP transfusion on platelet recovery post-apheresis. Platelet counts reduced up to 70% post-apheresis in both allo- and auto-PBSC settings, while severe platelet count decrease (&lt; 50 x 109/L) was only observed in auto-PBSC patients (Figure 1). We next analyzed the relationship between severe platelet (&lt; 50 x 109/L) after apheresis and several clinical factors by using univariate and multivariate analysis for auto-PBSC patients. As shown in Table 1, in univariate analysis, severe platelet counts following auto-PBSC apheresis was found more frequently in patients with lower platelet count, lower percentage of CD34+ cells in PB at pre-apheresis, repeated round of apheresis, and smaller number of collected CD34+ cells. On the other hand, in multivariate analysis, the white blood cell (WBC) counts pre-apheresis was the only significant risk factor of severe platelet count following apheresis (p = 0.038). We finally analyzed the transitions of platelet counts in the setting of apheresis. The median platelet counts at pre-apheresis, post-apheresis, and post-PRP return were 187.0 x 109/L, 132.0 x 109/L, and 154.0 x 109/L for allo-PBSC apheresis, and 147.0 x 109/L, 111.0 x 109/L, and 127.0 x 109/L for auto-PBSC apheresis (p &lt; 0.0001 for all, allo-PBSC donors and auto-PBSC patients, respectively) (Figure 2), indicating that PRP return post-apheresis facilitated a rapid platelet recovery in both allo- and auto-settings. Collectively, our data suggest that WBC counts pre-apheresis is a useful predictor for severe platelet decrease following auto-PBSC apheresis and that PRP return is an effective mean to facilitate platelet recovery post-apheresis. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Sadik Husian ◽  
Preethi Jeyaraman ◽  
S. K. Gupta ◽  
Reeta Rai ◽  
Sangeeta Pathak ◽  
...  

Abstract Methods This is a retrospective study. G-CSF was administered in the dose of 10 μg/kg subcutaneous as a single dose for 4 days. On day 5, peripheral blood stem cell (PBSC) apheresis was performed using Haemonetics MCS plus or COBE Spectra apheresis machine through a double-lumen central venous catheter. Primary outcome parameters were the total number of CD34+ HSCs/kg of recipient weight mobilized in peripheral blood and the number of days required for neutrophil and platelets engraftment, respectively. Objective We compared the effectiveness and safety of innovator filgrastim versus generic filgrastim in patients who underwent hematopoietic stem cell transplantation (HSCT). Results A total of 91 stem cell mobilizations was analyzed. There were 58 normal healthy donors for allogeneic HSCT and 33 patients for autologous HSCT. There was no statistically significant difference among groups in terms of total collected CD34+ cells value (p = 0.609). The mean time to neutrophil engraftment was 13.7 days in the innovator group and 13.2 days in the Grafeel group (p = 0.518). The mean time to platelet engraftment was 16.2 days in the innovator group and 14.8 days in the generic group (p = 0.435). The patient who received generic filgrastim had more febrile episodes during the course of transplantation (p = 0.020). Conclusion Generic filgrastim was found to be comparable to original filgrastim for peripheral blood stem cell mobilization in normal healthy donors for allogeneic HSCT and patients for autologous HSCT.


1997 ◽  
Vol 15 (2) ◽  
pp. 684-690 ◽  
Author(s):  
T Demirer ◽  
C D Buckner ◽  
B Storer ◽  
K Lilleby ◽  
S Rowley ◽  
...  

PURPOSE To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. RESULTS The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. CONCLUSION Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.


2009 ◽  
Vol 37 (6) ◽  
pp. 673-678 ◽  
Author(s):  
Laura Labonté ◽  
Yuhua Li ◽  
Lin Yang ◽  
Akira Gillingham ◽  
Michael Halpenny ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2922-2922
Author(s):  
Anne-Marie Stoppa ◽  
Norbert Vey ◽  
Reda Bouabdallah ◽  
Catherine Faucher ◽  
Diane Coso ◽  
...  

Abstract The optimal post remission treatment of AML patients(pts) &gt; 60 y is controversial and disappointing with less than 20 % of pts cured. High dose of alkylating agents (BuMel-CyTBI)with peripheral blood stem cell support (PBSC) is recognized as a standard consolidation therapy for pts in AML CR1 younger than 60 y. Moreover, high dose Melphalan (HDMel)is reported as safe and efficient in patients with myeloma up to 75 y.The objective of the IPC-AML2000 study is to assess the feasability of HdMEL and PBSC support for AML CR1 patients &gt; 60 y. From 01/2000 to 06/2004, 74/142 pts obtained CR1 after DNR/ARAC induction. They were offered a 1st consolidation with reduced DNR/ARAC dose and a 2nd consolidation (priming course) with Cyclophosphamide 3000mg/m2, VP16 300mg/m2 followed by lenograstim 263mcg/d and PBSC collection then a final intensification with HDMel 140 mg/m2. Median age of the 74 pts was 67 y(61–79).There were 37m/37f; 17 pts (23%) had secondary leukemia following antecedent of hematologic disorder(n=12) or exposure to radiochemotherapy for cancer(n=5),30% had leucocytosis&gt;30.10*9/ at diagnosis. Cytogenetic analysis revealed favorable risk karyotype in 10% of the pts, intermediate risk in 73% and unfavorable risk in 16%.Thirty four pts(46%)underwent a med of 2 (2–5) apheresis in a med of 15(10–36) days after the priming course, for a med of 8(2,5–23) 10*6/kg CD34+ cells collected. All the 34 patients collected underwent HDMel in a med of 2,5(2–5) months after CR1. Reasons for not receiving HDMel in 40 pts were equally divided in: refusal(27%,n=11)early relapse(25%,n=10)contra indication because of organ dysfonction or poor performance status(27%,n=11) or low CD34 counts (17%,n=7) The med age of the transplanted pts was 67 years(61–71);78% of de novo leukemia pts underwent HDMel compared to 22% of secondary leukemia pts (p=0,02) Following reinfusion of cryopreserved PBSC at Day0 and lenograstim 263mcg/day begining at Day 4,neutrophil reconstitution&gt;0,5 and 1 .10*9/l was observed at Day 11(9–15) and Day12(9–18) respectively.Platelet reconstitution &gt; 25,50,100.10*9/l was observed at Day 13(8–20),Day 14(11–35)and Day 19(13–100) respectively; med platelet and red blood cell transfusion were 0 unit(0–2) and 2 units (0–6) respectively;67% and 32% of the patients did not received any platelet or red blood cell transfusion respectively;20% of patients did not received antibiotherapy. Extra hematological toxicity was limited to mucositis (grade 0/1=57%,gr 2=12%,gr 3=26%,gr 4=5%) Median Day of hospital discharge was Day 14(0–24).No toxic death was observed. With a med follow up of 30(14–68) mths for pts alive, 2 year disease free survival of the 74CR patients and the 34 who received HDMel is 20%[12–31] and 25%[14–42] respectively with a med CR duration of 8 mths(2–68). DFS risk factor analysis for the transplanted pts did not show impact of age, secondary leukemia,hyperleucocytosis,caryotype,but a trend(p=0,003)for shorter DFS in pts receiving high doses of CD34 + cells (&lt;=9.10*6/kg:14 mths,&gt;9:6 mths)These data suggest that consolidation with HDMel and PBSC support is feasible in half of the AML pts &gt; 60 y and can be incorporated safely in the treatment stategy of such pts. Giving the high relapse rate observed, alternative treatment should be considered.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4136-4136
Author(s):  
Ana Marco ◽  
Anna Sureda ◽  
Pedro Madoz ◽  
Gregorio Martin-Henao ◽  
Salut Brunet ◽  
...  

Abstract Peripheral blood (PB) has become the major source of hematopoietic stem cells for autologous stem cell transplantation (ASCT) in the last 15–20 years. Nevertheless, there is a subset of patients who do not mobilize adequate numbers of CD34+ cells. There are no clearly established guidelines with respect to second-line mobilization protocols. The aim of this study has been to analyze our experience as a single center with this population of poor mobilizers trying to identify clinical or biological adverse prognostic factors associated to a poor mobilization of progenitor cells into PB, results of second- and third-line mobilization procedures and outcome after the ASCT of those patients who could be autografted in terms of hematological recovery. Poor mobilizing patients were defined as those in whom the apheresis procedure could not be started because of &lt; 10 CD34+ cells/ul or those in which a less than 2 × 106 CD34+ cells/kg could be collected in the first mobilization attempt. From January/2000 to January/2008, 126 patients [70 males/56 females, median age of 53 years (range, 20–70)] out of a total number of 450 patients mobilized for an ASCT in our institution (28%) were identified as poor mobilizers. Clinical diagnosis were: 29 multiple myeloma, 16 Hodgkin’s lymphoma, 48 non-Hodgkin’s lymphoma, 28 acute leukemias and 5 other diagnosis. Median time from diagnosis to mobilization therapy was 19 (range, 3–120) months and median number of chemotherapy lines received before the procedure was 2 (range, 0–5). The first mobilizing protocol was G-CSF alone (5–10 ug/kg/day sc) in 72% of the patients or the combination of chemotherapy plus G-CSF in 28% of the patients. A second mobilization procedure was attempted in 34 patients (28%) with high-doses of G-CSF alone (16–20 ug/kg/day sc) in 24 patients, the combination of G-CSF plus chemotherapy in 8 patients and the combination of G-CSG with stem cell factor (SCF) in 2 patients. A third mobilization attempt was performed in 6 patients (high-doses of G-CSF alone in 4 patients, G-CSF plus chemotherapy in 1 patient and G-CSF plus SCF in 1 patient). Sixty-nine patients (54%) were finally autografted. Median number of CD34+ cells/kg infused were 2.15 × 106/kg (range, 1.01–4.00). Median time to neutrophil recovery after transplantation was 11 days (range, 4–20). Patients with an inadequate mobilization constitute a significant clinical problem (25% of the whole population of patients with an indication of ASCT in our centre). Nevertheless, half of these patients can be rescued for an ASCT procedure with one or two more attempts. Neutrophil recovery after the autologous transplant in those patients undergoing the procedure seems to be similar to that of the group of patients with an adequate first mobilization attempt. New mobilizing agents should be investigated in order to increase the efficacy of the mobilization processes.


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