scholarly journals A Randomized Study Comparing the Effects of G-CSF and G-CSF/GM-CSF for the Mobilization of Peripheral Blood Stem Cells by Mitoxantrone and High-Dose Cytarabine Chemotherapy

2021 ◽  
pp. 1-6
Author(s):  
Yihong Huang ◽  
Wenlu Dai ◽  
Chunyu Li ◽  
Depeng Li ◽  
Zhenyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Combination Group ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Gm Csf ◽  
Cd34 Cells ◽  
High Dose Cytarabine ◽  
Blood Stem Cells

We investigated the efficiency of mitoxantrone (MIT) and high-dose cytarabine (Ara-C) chemotherapy followed by G-CSF and G-CSF/GM-CSF treatments for the mobilization of peripheral blood stem cells (PBSCs) in patients with leukemia and lymphoma. MIT was intravenously injected at 10 mg/(m2·d) for 2 to 3 days, followed by Ara-C injected intravenously at 2 g/m2 every 12 hours for 1 to 2 days. When white blood cell count recovered from the lowest value, 5 to 7.5 μg/ (kg·d) G-CSF was administered in 23 patients for 5 to 7 successive days. Another 27 patients received 3-5 μg/ (kg·d) G-CSF and 3-5μg/ (kg·d) GM-CSF. Autologous peripheral blood mononuclear cells were collected. Levels of CFU-GM and CD34+ cells were determined after unfreezing. The CD34+ cells and CFU-GM yields of 27 patients in G-CSF plus GM-CSF combination group [(8.79±3.11)×106/kg, (3.52±1.34)×105/kg, respectively] were significantly higher than those of patients receiving G-CSF alone (n=23) [(6.14±2.06)×106/kg, (2.03±1.06)×105/kg, respectively (P < 0.05)]. No obvious changes of T lymphocyte subsets in patients were observed when using G-CSF/GM-CSF, but levels of CD34+ cells increased gradually (P>0.05). The end-point separation blood volume was all above trebling TBV. No severe complications were observed during the mobilization and collection. Autologous PBSCT obtained quick hematopoietic reconstitution. In conclusion, MA chemotherapy combined with G-CSF alone and G-CSF/GM-CSF can safely and effectively mobilize autologous PBSCs, while G-CSF plus GM-CSF is superior to G-CSF alone. Large volume leukapheresis is an important method to enhance the production rate of stem cells and decrease harvesting time.

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.

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.

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

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

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

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.

Peripheral Blood Stem Cell (PBSC) Mobilization and Transplantation (PSCT) in Patients with Malignant Lymphomas and Solid Tumors

1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 71-75 ◽  
Author(s):  
D.J. Richel ◽  
E. Van Der Wall ◽  
J. Slaper ◽  
E. Van Der Schoot ◽  
S. Rodenhuis
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
High Dose ◽  
Malignant Lymphomas ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Peripheral blood stem cells can reconstitute bone marrow function after high-dose chemo-Zradiotherapy. We describe 44 patients related with a three-day course of chemotherapy, for hematopoietic stem cell mobilization, consisting of cyclophosphamide or ifosfamide and etoposide (malignant lymphoma and germ cell tumor) or a one-day course of 5-fluorouracil, epirubi-cin and cyclophosphamide (breast cancer), followed by the administration of recombinant human granulocyte colony-stimulating factor (G-CSF). Maximum numbers peripheral blood stem cells (PBSC) were recruited on day 9-10 of the G-CSF administration. The total number of PBSC cells harvested with median 3.6 leukaphereses was 46 x 104/kg (7.5-136) CFU-GM or 8 x 106/kg (0.7-25.0)CD34+ cells for patients with solid tumors and 26 (4.5-258) CFU-GM's or 6.1 (1-0-39.2) CD34+ cells for patients with malignant lymphomas. Thirty-five patients with malignant lymphomas or solid tumours received high-dose chemotherapy followed by bone marrow and PBSC infusion (n=8) or PBSC cell infusion alone (n=27). The recovery of granulocytes, platelets and reticulocytes after peripheral stem cell transplantation (-PSCT) in addition to or instead of bone marrow, was markedly accelerated compared with the infusion of BM alone. The accelerated haemopoietic recovery was associated with a reduction in platelet and red blood cell transfusion, reduction in fever periods and earlier discharge from hospital. PSCT is an important alternative to autologous bone marrow transplantation (ABMT). This transplantation technique may also allows application of multiple-cycle intensive chemotherapy.

scholarly journals Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.

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