scholarly journals On Demand Plerixafor As a Rescue Strategy in Healthy Donors to Achieve Adequate Stem Cells - a Pilot Study from South India

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5640-5640
Author(s):  
Kishore Kumar ◽  
Kishore Kumar ◽  
Chezhian Subash
Keyword(s):  
Stem Cells ◽  
Pilot Study ◽  
Side Effects ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Control Study

Aims & Objectives: The aim of the study is to check the safety and feasibility of using Plerixafor in healthy donors who have failed to mobilise > 2 x 10 6/kg of CD34 cells on day 1 of aphresis. The indication at present remains off label. Patients/Materials & Methods: Seventeen healthy donors, all more than 18 years of age were enrolled in this study after a proper written informed consent who failed to mobilise adequately on day 1 collection. The dose of Plerixafor used was 0.24mg/kg body weight of donor, 10-11 hours before the aphresis procedure. The GCSF was given from day -5 and the last dose was given 4 hours before the second day aphresis. CD34 was done in pre-aphresis peripheral blood and in product bag and compared with day 1 data. Results: The median donor bw was 54 kg (IQR, 42 kg to 69 kg) and the median recipient bw was 58 kg (IQR, 44 kg to 76 kg).The median CD34+ count in peripheral blood was 11.2/µl on day 4 after G-CSF alone and 24.7.0/µl on day 5 after G-CSF plus Plerixafor. The use of Plerixafor increased the number of circulating CD34 cells in peripheral blood by 2.2 fold.There were no major side effects except for the manageable bone pains which can be attributed to GCSF also. There were no differences in the engraftment statistics and rates of GVHD in comparison to historical cases. Though this is not a randomised control study to compare with second day high dose GCSF cases, the amount of increase in stem cells were statistically significant comparing with historical controls(p< 0.05). After a median followup of six months, no adverse effects were noted in donors. Discussion & Conclusion: Plerixafor is well tolerated in healthy donors and can be used safely in situations of poor mobilisers or when there is a significant difference in weight of donor to receipient. Its a small pilot study. We need a proper randomised control study and a longer follow up to look infor the side effects on healthy donor. Disclosures No relevant conflicts of interest to declare.

Use of Plerixafor to Overcome Stem Cell Mobilization Failure: Long Term Follow up of Patients Proceeding to Transplant Using Plerixafor Mobilized Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4390-4390 ◽  
Author(s):  
Abhinav Deol ◽  
Judith Abrams ◽  
Ashiq Masood ◽  
Zaid Al-Kadhimi ◽  
Muneer H. Abidi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Effects ◽  
Cell Count ◽  
Peripheral Blood ◽  
Cd 34 ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Abstract 4390 Background: Plerixafor is a CXCR 4 antagonist which is now approved for use for stem cell (SC) mobilization with granulocyte colony stimulating factor (GCSF) in patients with non Hodgkin lymphoma (NHL) or multiple myeloma (MM). Prior to the approval of plerixafor, we enrolled 49 patients in a compassionate use protocol at our institution to mobilize SC for patients who previously failed at least one mobilization attempt. Methods: Patients received 0.24 mg/kg of plerixafor subcutaneously 9 –11 hrs prior to apheresis in addition to twice daily GCSF. Results: Median age of the patients was 64 years (range, 23–74 years). NHL was the most common diagnosis in 27 (55%) patients, followed by MM with 17(35%) patients and HD with 5 (10%) patients. Thirty nine patients (80%) had been treated with more than 2 chemotherapeutic regimens prior to the first attempt at stem cell collection. Thirty seven patients (76%) failed one previous mobilization attempt, while 12 (24%) had failed 2 or more previous attempts. Using the combination of Plerixafor and GCSF we collected ≥ 2.5 × 106 CD34+ cells/Kg in 33 patients (67%). The median days for pheresis were 1 day with a range of 1 to 3 days. The median SC dose collected was 4 × 106 CD34+ cells/Kg, with a range 2.5 – 14.3. The median CD-34+ peripheral blood count on the 1st day of their collection with plerixafor was 22.4/uL. In contrast the median peripheral blood CD-34+ cell count in these patients on the day of their first collection which failed was 6.2 /uL. The median increase using G-CSF and plerixafor was 14.9 CD-34+ cells/uL. We collected ≥ 2.5 × 106 CD34+ cells/Kg on 4/5 (80%) patients with HD, 13/17 (76%) patients with MM and 16/27 (59%) patients with NHL. Sixteen patients (33%) collected < 2.5 × 106 CD34+ cells/Kg. The median cell dose collected in these patients was 1.4 × 106 CD34+ cells/Kg with a range, 0.4–2.2. The median number of days of pheresis was 2 days (range, 1–4 days). In these16 patients the median CD-34+ count on the day of their previous failed collection was11.2/uL. Their CD-34+ cell count on their first day of collection after the use of G-CSF and plerixafor was 8.3/ul. Figure 1 shows the change in peripheral CD34 counts with the prior mobilization attempt and after plerixafor mobilization, for 38 patients in whom data was available. The most common side effects attributed to plerixafor were diarrhea, fatigue, thrombocytopenia and bone pain; observed in 12%, 8%, 8% and 6% patients, respectively. Forty three of the 49 patients proceeded to an autologus peripheral blood SC transplant, 34 patients received ≥ 2.5 × 106 CD34+ cells/Kg. Thirty two of these patients used the plerixafor collection as the only source of SC. Two patients had their plerixafor mobilized SC combined with a previous suboptimal SC collection. Nine patients received < 2.5 × 106 CD34 + cells/Kg; 4 patients received plerixafor mobilized SC alone, 5 patients received plerixafor mobilized SC combined with their previously mobilized SC. The preparative regimens used were R- BEAM (20 patients), Melphalan (16 patients), BEAM (6 patients) and Etoposide+TBI (1 patient). All patients received GCSF from day +6 till WBC engraftment. The median days of WBC and platelet engraftment were day +11 (range, 9–13 days) and day +16 (range, 11–77 days), respectively. There was no significant difference in days to engraftment between the patients who collected greater or less than 2.5 × 106 CD34 + cells/Kg. With a median follow up 13.7 months, long term engraftment data is available on 27 patients. The median white cell count, hemoglobin and platelet count 1 year after transplant was 4.7 × 109/L, 12.2 g/dL and 109 ×109/L, respectively. There was no significant difference in counts at the 1 year mark between patients who collected more or less than 2.5 × 106 CD34 + cells/Kg. To date 15 patients have evidence of disease progression. Two patients have developed MDS/AML post transplant. Conclusion: Overall, plerixafor leads to mobilization of sufficient stem cells in a vast majority of patients who have failed previous mobilization attempts and allows more patients to proceed to an autologous SC transplant. Plerixafor is well tolerated with minimal side effects, acceptable time to engraftment and acceptable peripheral blood counts at 1 yr after the transplant. Our analysis suggests that failure to increase peripheral CD34 count after plerixafor when compared to previous attempts may predict unsuccessful mobilization. Disclosures: Lum: Transtarget Inc: Equity Ownership, Founder of Transtarget.

Outpatient Hematopoietic Grafting in Patients with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells: A Feasibility Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5489-5489
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
Andrés León-Peña ◽  
Emilio Medina-Ceballos ◽  
Alejandro Ruiz-Arguelles ◽  
Manuel A Ruiz-Delgado ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
High Dose ◽  
Outpatient Basis ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Background: Multiple sclerosis (MS) is a chronic, inflammatory, debilitating disease that causes destruction of central nervous system (CNS) myelin, with varying degrees of axonal damage. With the goalofd re-setting the immune system, autologous hematopoietic stem cell transplantations (HSCT) have been done in patients with MS since 1996 and more than 700 HSCTs have been performed around the world. The risk of transplant related mortality in HSCT for MS has declined over the past years. Material and methods: Consecutive patients with MS were autografted in a single center using: Hematopoietic stem cells (HSC) were mobilized with cyclophosphamide (Cy), 3 gr/m2 and G-CSF, the procedure was conducted on outpatient basis employing peripheral blood non-frozen HSC and conditioning with high-dose Cy (100 mg/Kg) and post-transplant G-CSF and rituximab. Antibiotics, antimycotics and antivirals were given orally. Results: Thirteen patients with MS were prospectively accrued in the study. There were 7 females and 6 males. Median age was 48 years, range 24 to 65. The expanded disability status scale (EDSS) score of these patients had a median of 5 points (range 1 to 6). All the autografts were started on an outpatient basis and two persons were admitted to the hospital during the procedure (persistent nausea/vomiting and neutropenic fever); they stayed in the hospital for 48 hours. In order to obtain a minimum of 1 x106 viable CD34+ cells/Kg, one to four apheresis were done (median 1). The total number of viable CD34+ cells infused to the patients ranged between 1 and 9.6x106 (median 3.1). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). No individuals needed transfusions of red blood cells nor platelets transfusions. There were no transplant-related deaths and the 23-month overall survival of the autografted patients is 100%. Median cost of the procedure was 30 000 USD. In 8 persons the EDSS was assessed three months after the graft; it diminished from a median of 4.5 to a median of 2.5. In 5 patients, the three months re-assessment of the EDSS has not been possible as a result of the time elapsed after the autograft. Discussion: These data indicate that it is possible to conduct autotrasplants for patients with MS employing a simplification of the conventional procedures by means of non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to asses the efficacy of these procedures in the treatment of patients with MS. Disclosures No relevant conflicts of interest to declare.

Utility of Plerixafor In Addition to Chemotherapy and G-CSF Mobilization Regimens

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4443-4443
Author(s):  
Farrukh Awan ◽  
David Deremer ◽  
Elaine Mebel ◽  
Samith Thomas Kochuparambil ◽  
Anand P. Jillella
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Chemotherapeutic Agents ◽  
Phase Iii ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Significant Difference

Abstract Abstract 4443 Introduction: Various chemotherapeutic agents particularly cyclophosphamide (CY) are utilized in combination with growth factors in an attempt to increase the number of stem cells available for collection in the peripheral blood. Plerixafor (P) is a reversible antagonist of CXCR4 and interrupts its interaction with SDF-1. This results in a rapid release of hematopoietic stem cells from the marrow to the circulation. Recent pivotal phase III trial data has established the efficacy of P in combination with G-CSF (G) in patients who had failed prior attempts at stem cell collection. However, there is limited data about the utility of plerixafor in patients who are being mobilized with chemotherapy and G. Method: In this single institution study of uniformly treated patients we describe our experience with the use of P as a salvage option in patients who fail to optimally mobilize CD34+ cells (>5 × 106 CD34+ cells/kg). Patients received CY (3-4 g/m2) followed by GCSF (10 mcg/kg) from day 1 to day 10. Thirteen patients (6 NHL, 4 MM, 2 Hodgkin lymphoma, 1 Ewings sarcoma) received salvage P from 2008–2010. Their outcomes were compared with 10 matched, historic controls mobilized with (CY n=8; CY + etoposide n=1; CY + topotecan n=1) plus G-CSF (10mcg/kg/d) identified from our institutional database. Data was collected on mobilization and transplant outcomes and analyzed utilizing SPSS version 13.0. Patients receiving P were closely matched to historic controls (CY+G). Result: Both groups were similar with regards to age, gender, disease type, prior therapies and performance status (p>0.05 for all). Patients in the P arm received a median of 2.5 doses (range 1–8). The mean CD34+ count was 21.5cells/ul in the P arm and 32.5 cells/ul in the CY+G arm (p=0.2). Similarly, no significant difference was observed in the average number of apheresis sessions in the P vs. CY+G arms (4.2 vs. 4.4, p=0.8) or the total number of CD34+ stem cells collected (4.0×106/kg vs. 3.9×106/kg, p=0.9). However, 7 out of the 13 patients who received P did have an increase of >10 CD34+ cells/ul in their peripheral blood. Utilizing a cut-off of 5×106 CD34+/kg, 3 (23%) patients in the P arm and 3 (30%) patients in the CY+G arm had a successful harvest. Three NHL patients required >4 doses of P, but all eventually collected >2 × 106 CD34+ cells/kg. Neutrophil and platelet engraftment dynamics were similar in both groups of patients. Median time to neutrophil engraftment was 10 days for both groups, p=0.8, and to platelet engraftment was 22 days vs. 20.5 days, p=0.1, respectively for P vs. CY+G. Conclusion: Our limited single-center retrospective case-controlled outcomes data, suggests that when compared with CY+G, the addition of P as a salvage agent does not significantly improve mobilization outcomes. Further evaluation is needed to combine P with CY+G in terms of optimal timing and potentially dosing of chemotherapy agents utilized. We suggest that the combination P+G would provide better potential outcomes such as improved collection and less hospitalization and reduce the use of chemo-mobilization prior to an Autologous Hematopoietic Stem Cell Transplant. Disclosures: No relevant conflicts of interest to declare.

Pro- and Antiapoptotic Proteins Expression on Bone Marrow and Peripheral Blood CD34+Cells in Acute Leukemia (AL) Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4996-4996
Author(s):  
Elena E. Khodunova ◽  
Elena N Parovichnikova ◽  
Irina V. Galtzeva ◽  
Sergey M. Kulikov ◽  
Valeri G Savchenko
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Expression Level ◽  
Leukemia Cells ◽  
Control Group ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Blast Cells

Abstract Abstract 4996 It was shown that drug resistance, poor-risk cytogenetics and poor prognosis in AL is associated with high level of Bcl-2 expression and low Bax/Bcl-2 ratio (<0,3). Fas-antigen (CD95) as a protein triggering the extrinsic apoptotic pathway is differently expressed on hematopoietic precursors. More immature CD34+/CD38- AML blast cells have lower expression of Fas/Fas-L and lower Fas-induced apoptosis than CD34+/CD38+cells. CD34+/CD38− leukemia precursors also have a reduced sensitivity to daunorubicin in vitro and increased expression of multidrug resistance genes (mrp/lrp). CD34+ leukemia cells have not yet been properly characterized regarding the expression of angiotensin converting enzyme (ACE) which regulatory influence on hematopoiesis is now beeing extensively investigated. ACE expression on blast cells is high, but it's still unknown how CD34+ACE+ leukemia cells behave after chemotherapy. Recent publications indicate that CD34+ACE+ hematopoietic precursors transplanted into NOD/SCID mice contribute 10-fold higher numbers of multilineage blood cells than their CD34+ACE- counterparts. We have studied the dynamics of Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in peripheral blood (PB) and bone marrow (BM) in AL pts during treatment. PB and BM samples were collected before and on +36 day after chemotherapy. The antigens were detected by flow cytometry using monoclonal antibodies. We calculated 10 000 cells in each sample. 19 pts were included in the study: 10 - AML and 9 - ALL. The control group comprised 8 healthy donors. At time of diagnosis there were 40±5,7% of CD34+ cells in BM and 26±4,9% - in PB. There was no significant difference between AML and ALL. CD34+ cells in BM and PB of healthy donors constituted 1,6% and 0,27%, respectively. After induction therapy (+36 day) CD34+ cells decreased in BM to 6,1%±3,3 (p=0,0001), in PB to 3,7%± 2,7 (p=0,0008) in all pts. The data on antigens expression on CD34+ cells of BM and PB are presented in table 1 CD34+/Bcl-2+ CD34+/Bax+ CD34+/CD95+ CD34+/ACE+ BM PB BM PB BM PB BM PB AML pts n=10 0 day 38±11,6* 41±14 24,4±7,9 29,2±7,6* 16,4±8,5 23,2±7,8 21,7±9,5 20,8±8,7* 36 day 13,5±3,4** 23,7±5** 46,2±11,5 50,3±11 19,9±5,5 36,4±10 34±6,6 35±9,2** ALL pts n=9 0 day 36±11 33,7±12 46,2±9,4 37,4±3,7* 3,4±1,1* 7,1±2,5* 41±10,9 33,2±9,7* 36 day 18,4±5,8 26±8,9 38±11,8 40,5±10 26,2±9,1** 40,9±9,2** 34±10 62,8±10** Donors n=8 11,7±1,6 26,1±5,9 22,8±4 67,8±6,7 13,4±3,2 47,7±11,6 28±5,3 68,2±10,2 * − p<0.05 compare with donors ** − p<0.05 compare with day 0 CD34/Bcl-2 expression in BM in AML pts is significantly higher (p=0,04) at the diagnosis comparing with donors. CD34/Bcl-2 expression in PB in AML pts and in BM and PB in ALL pts is higher too, but not significantly. This expression level decreased substantially in BM and PB in AML pts on +36 day comparing with day 0 (p<0,05). We did not found significant changes in ALL pts. CD34/Bax expression in PB is significantly lower (p=0,003) both in AML and ALL pts in comparison with donors. In AML, not in ALL, chemotherapy caused augmentation of Bax expression in CD34+ BM and PB cells on +36 day. BM and PB CD34+ cells in donors had different expression characteristics of Bcl-2 and Bax, demonstrating much higher level of pro- and antiapoptotic markers in PB cells. On the contrast CD34+ leukemia cells in BM and PB had similar characteristics regarding CD34/Bcl-2 and CD34/Bax expression. This fact demonstrates the heterogeneity of donor CD34+cells in BM and PB and points that leukemia CD34+cells in BM and PB are rather similar. CD95 expression on CD34+ BM and PB before treatment is significantly lower (p=0,01, p=0,008) in ALL pts in comparison with donors, and this expression level increased after chemotherapy (p<0,05). CD34/CD95 expression in AML pts is similar with donors, and we didn't find changes after treatment. CD34/ACE coexpression in BM cells of leukemia pts and donors did not differ much at any time of evaluation. But CD34/ACE expression in PB cells of AML and ALL pts was much lower (p<0,05) than in donors and substantially increased on the day 36. So, our data demonstrate that Bcl-2, Bax, CD95 and ACE expression on CD34+ cells in AL pts and donors significantly differs. The chemotherapy provokes critical changes in CD34/CD95 expression in BM and PB in ALL pts, CD34/Bcl-2 expression in AML pts and ÑÂ34/ACE expression in PB in all AL pts. Disclosures: No relevant conflicts of interest to declare.

Influence of Different Dosages of Cyclophosphamide on Stem Cell Mobilization and Engraftment In Newly Diagnosed Multiple Myeloma Patients Treated with a Thalidomide Containing Regimen.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3494-3494
Author(s):  
Joost TM De Wolf ◽  
Gustaaf Van Imhoff ◽  
Gerwin A Huls ◽  
Edo Vellenga
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Target Yield ◽  
Cd34 Cells ◽  
Significant Difference ◽  
Blood Stem Cells

Abstract Abstract 3494 Introduction: Treatment of multiple myeloma (MM) patients (<65 yrs) consists of induction chemotherapy for 3–6 months followed by peripheral blood stem cell collection and transplantation. Both high dose cyclophosphamide (HD-C, 2 gr/m2/day, on days 1–2) and lower dosage of cyclophosphamide (1 gr/m2/i.v.on day 1) combined with doxorubicin (15 mg/m2/day, on days 1–4) and dexamethason 40 mg orally, days 1–4 (LD-C) are used, in combination with G-CSF, to mobilize hematopoietic stem/progenitor cells. A great variability was observed in the engraftment of different hematopoietic lineages post-ASCT. Therefore we questioned whether the dose of cyclofosfamide as mobilizing agent might affect the neutrophil and platelet recovery post-ASCT. The studied MM patients were treated with VAD or TAD (Blood 2010;11:115). Peripheral blood stem cells were collected after LD-C and HD-C with the Cobe Spectra; in each collection, 10 – 12 L of blood was processed in 3 – 4 hours. The target yield was 10 × 106/kg CD34+ cells. Results: 92 patients were treated according to VAD and 41 patients with TAD. In the VAD arm 89% of the patients reached the target yield of CD34+ cells after 1 collection compared to 61% in patients treated with TAD (p = 0.0003). The number of CD34+ cells collected at the first day and the total CD34 yield after HD-C or LD-C was significantly higher in patients treated with VAD compared with TAD: 16.6 ± 11.6 × 106/kg vs. 10.4 ± 9.3 × 106/kg (p=0.003), and 16.9 ± 11.1 × 106/kg vs 12.3 ± 8.6 × 106/kg (p=0.02). No significant difference was observed in the total yield of collected CD34+ cells in the VAD arm or TAD arm between HD-C vs. LD-C. In all patients high dose melphalan (200 mg/m2) was used as conditioning regimen followed by reinfusion of peripheral blood stem cells. In the VAD arm no difference in neutrophil and platelet engraftment (absolute neutrophil count > 0.5 × 109/L and platelet count > 20 × 109/L without platelet transfusions) was noticed between patients mobilized with LD-C (22 ±12 days and 23 ±13 days) or HD-C (18 ± 5 (p=0.1) and 21 ±11 days (p=0.5)); in contrast a significant difference was demonstrated in neutrophil and platelet engraftment between patients treated according the TAD arm and mobilized with LD-C (20 ± 8 days and 20 ±19 days) or HD-C (34 ± 11 days (p<0.0001) and 43 ±22 days (p=0.001)). These differences could not be ascribed to differences in the number of infused CD34+ cells: VAD arm: LD-C: 5.7 ± 2.6 × 106/kg, HD-C: 5.7 ± 2.5 × 106/kg: TAD arm: LD-C: 5.2 ± 2.5 × 106/kg and TAD-HD-C 6.4 ± 2 × 106/kg. It might be assumed that the higher dosage of cyclophosphamide had a positive effect on tumor response. However the impaired engraftment was not associated with differences in relapse free survival between the different arms (p = 0.2). In summary these data demonstrate that thalidomide containing regimen in MM patients impair mobilization of stem/progenitor cells and that a mobilization with high dose cyclophosphamide and not low dose cyclophosphamide after treatment with thalidomide prolong the engraftment post-transplantation. Disclosures: No relevant conflicts of interest to declare.

Use of the G-CSF Biosimilar Ratiograstim® to Mobilize Peripheral Stem Cells in Healthy Donors for Allogeneic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1928-1928
Author(s):  
Michael Schmitt ◽  
Diestel Lena ◽  
Catarina Schneider ◽  
Xun Xu ◽  
Kersten Borchert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Stem Cell ◽  
Side Effects ◽  
Cell Count ◽  
Peripheral Blood ◽  
Cell Counts ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Peripheral Stem Cells

Abstract Abstract 1928 INTRODUCTION: There is limited experience in the application of the biosimilar Ratiograstim® for mobilization of peripheral stem cells and especially in healthy donors (HD). The G-CSF biosimilar Ratiograstim® was approved by the EMA for mobilization of peripheral stem cells. Here, we investigated on two cohorts the efficacy and safety of peripheral stem cell mobilization by either the biosimilar or the reference G-CSF. MATERIAL AND METHODS: 22 patients and their related donors were investigated for: 1. leukocyte-count in the peripheral blood of healthy donors, 2. number of collected CD34+ stem cells, 3. number of apheresis procedures, 4. CD34+ cell count per kg body weight of the patients, 5. time till regeneration, 6. side effects. RESULTS: In HD receiving subcutaneously Ratiograstim®, WBC counts in the peripheral blood ranged from 29.9 G/L to 64.6 G/L (mean 48.9 G/L) and the CD34 cell counts from 19.3/μl to 114.6/μl (mean 67.6/μl). In a mean of 1.45 apheresis procedures 172.5×106 up to 494×106 CD34+ cells (mean 354.7×106) were collected. This resulted in CD34+ cell numbers of 2.28×106 up to 1×107 (mean 5.17×106) per kg body weight of the patients. In HD receiving subcutaneously the reference G-CSF, WBC counts ranged from 27.1 G/L up to 62.5 G/L (mean 43.3 G/L) and the CD34+ cell counts from 13.55/μl up to 122.4/μl (mean 57.3/μl). A mean of 1.27 apheresis procedures were necessary to collect 181.74×106 up to 598.00×106 CD34+ cells (mean 370.49×106) absolutely. This translates into 2.33×106 up to 7.9×106 (mean 4.95×106) CD34+ cells per kg body weight of the patients. Patients regenerated >0.5 G/L neutrophils/μl within 15 days in the Ratiograstim® cohort versus 17 days in the reference group. SUMMARY: In total we analyzed two cohorts, one cohort of 22 patients and donors receiving the biosimilar Ratiograstim® versus another cohort receiving reference G-CSF. No unexpected side effects and no increased frequencies in side effects as flu-like symptoms, allergic reactions and alterations in kidney and liver function were observed. In comparison to the reference group we did not see significant differences in 1. WBC count in the peripheral blood after mobilisation, 2. CD34+ cell count after mobilisation, 3. CD34+ cell count absolute numbers, 4. CD34+ cells per kg body weight of the patients, 5. engraftment, 6. regeneration of WBC, neutrophils and platelets. All patients engrafted. Therefore, the efficacy of the biosimilar Ratiograstim® when compared to the reference G-CSF was comparable in our cohort of patients in the context of allogeneic stem cell transplantation. Disclosures: Schmitt: ratiopharm: Honoraria, Research Funding. Freund:Medac: Honoraria, Research Funding.

scholarly journals Viability of Stem Cells without Cryopreservation: How Good and How Long?

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5637-5637
Author(s):  
Mie Mie Khine ◽  
Hnin Mya Thandar ◽  
Aye Aye Gyi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Storage Period ◽  
Daily Basis ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells

Although cryopreservation of stem cells is a standard practice for autologous haematopoietic progenitor cells transplantation to treat haematologic malignancies, it has many limitations including toxicities of cryo-protectant, requirement for cryopreservation facilities as well as trained personnel which causes barriers for transplant programs in resource limited countries. To overcome these limitations, a newly established first transplant centre at the North Okkalapa General and Teaching Hospital of Myanmar has been using ordinary refrigerator at 4 degree Celsius to store autologous peripheral blood stem cells collected by apheresis during the interval between collection and transplantation for patients with multiple myeloma who underwent high dose melphalan therapy and autologous stem cell rescue. During early days of the centre, in addition to microbiological testing, to ensure the quality of stem cells, serial measurement for stem cell count and viability were made on daily basis till the day of transplant and continued testing if adequate samples of aliquots were available for analysis. Viable CD34+ cells were analyzed by BD FACS Canto II flow cytometer using BD stem cell enumeration kits that incorporate 7-Amino Actinomycin D viability dyes. The results of the viable CD34+counts of 13 myeloma patients, 5 males and 8 females, median age- 57 years, who underwent autologous peripheral blood stem cell transplantation during early periods of the transplant center from May 2014 to January, 2019, were retrospectively reviewed for the quality of stem cells from the non-cryopreserved methods. Mean CD34 + cells enumerated at the time of reinfusion were 3.45 x 106 cells/kg (range 1.45 - 4.87 x 106 cells/kg). The mean viability of stem cells on day of collection (day 0) were 96.13% (range 83.33% -100%) which was almost unchanged one day after collection (day 1) at 95.93% (85.70% -99.24%). On second and third day after collection, mean viability of the collected cells although fallen below 90% were reasonably preserved at 88.7% (81.74-95.61) on day 2 and 88.08% (87.07-89.09) on day 3, and 85.37% on day 4. Median neutrophil engraftment time was 11 days (range 9-12) and that for platelet engraftment was 16 days (range 9-44). There were no graft failure or mortality during first 100 days. It was encouraging to observe that even at the refrigerator temperature at 4degree Celsius, without any additives or manipulation, stem cell viability could be maintained above 85% minimum of four days with good transplant outcome. Further studies are needed to investigate maximum storage period which could allow reasonable viability and function of the stem cells. Disclosures No relevant conflicts of interest to declare.

Very High Efficacy of Stem Cell Mobilization Using Intermadiate-Dose Cytosine Arabinoside + G-CSF in Patients with Lymphoid Malignancies, Including Predicted and Proven Poor Mobilizers

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4131-4131
Author(s):  
Tomasz Kruzel ◽  
Tomasz Czerw ◽  
Maria Sadus-Wojciechowska ◽  
Jacek Najda ◽  
Magdalena Glowala-Kosinska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cytosine Arabinoside ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
High Dose ◽  
Lymphoid Malignancies ◽  
Cd34 Cells ◽  
Poor Mobilizers

Abstract Abstract 4131 Background: High-dose therapy followed by autologous peripheral blood stem cell transplantation (autoPBSCT) is widely applied in the treatment of lymphoid malignancies. However, a significant proportion of patients fail to mobilize sufficient number of stem cells after commonly used protocols. Patients and Methods: In this study we evaluated efficacy of first-line mobilization based on cytosine arabinoside (AraC) 1600 mg/m2 + G-CSF (filgrastim) 5–10 ug/kg. Results of 70 subsequent patients (diagnosis multiple myeloma, MM-39, Hodgkin's lymphoma, HD-9, non-Hodgkin lymphoma, NHL-22) were compared with 45 individuals mobilized with cyclophosphamide (CTX) (4 g/m2) + G-CSF in a preceding period (MM-25; HD-4; NHL-16). In respective groups, 39 (56%) and 30 (67%) patients were classified as “predicted” poor mobilizers, defined as the presence of at least one risk factor: age >60 years, thrombocytopenia, preceding treatment with melphalan, fludarabine, preceding radiotherapy on pelvis, >8 courses of chemotherapy for MM, >3 courses containing cisplatin or carboplatin for lymphomas, preceding high-dose treatment with autoHSCT. In addition, we analyzed efficacy of AraC+G-CSF in 14 patients who had failed previous chemo-mobilization, mostly with CTX+G-CSF. Results: All but three patients (96%) treated with AraC reached >15 CD34+ cells/uL in peripheral blood, compared to 67% in the CTX+G-CSF cohort (p<0.0001). Median peak level was 127 (3–780) CD34+ cells/uL vs. 33 (1–240), respectively (p<0.0001). After AraC, 68 (97%) patients collected >=2×10e6 CD34+ cells/kg and 58 (84%) collected >=5×10e6 CD34+ cells/kg with the median 14.9 (2.3–54.6), which was achieved with a single leukapheresis in 92% patients. Using CTX, 67% patients collected sufficient number of stem cells (p<0.0001) and 76% required 2 or more leukaphareses (p<0.0001). AraC+G-CSF was effective in 37 (97%) predicted poor mobilizers compared with 16 (64%) in the CTX+G-CSF group (p=0.0006). The toxicity related to both regimens was comparable. Among patients who proceeded to autoPBSCT the time to neutrophil recovery after transplantation was the same for AraC and CTX cohorts (median 12 days), while platelet engraftment was faster for patients mobilized with AraC (13 days vs. 14 days, p=0.06). All 14 patients who had failed previous mobilization collected >=2×10e6 CD34+ cells/kg after AraC+G-CSF, with the median 9.3 (2.5–25.9). It was achieved with a single apheresis in 10 (71%) cases. Conclusions: Mobilization based on intermediate doses of AraC+G-CSF is highly effective allowing adequate CD34+ harvest in almost all patients with lymphoproliferative diseases, including predicted and proven poor mobilizers. The level of mobilized CD34+ cells is four times higher compared to protocol based on CTX. Disclosures: No relevant conflicts of interest to declare.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Sign in / Sign up

Export Citation Format

Share Document