Median Number Of Apheresis Procedures Research Articles

The Efficacy of Same Day Plerixafor Dosing on CD34+ Haematopoietic Stem Cell Collection: A Single Centre Australian Experience

Introduction: Haematopoietic stem cell (HSC) transplantation is an important therapeutic option for many haematological conditions, as well as, some solid organ cancers. Plerixafor (a selective inhibitor of CXCR4) can be used in patients for primary stem cell mobilisation; those who have previously failed stem cell mobilisation ("rescue" or "Planned"); or in patients with a poor peripheral CD34+ response to GCSF and/or chemotherapy mobilisation ("on demand", "just in time" or "pre-emptive"). In Australia, Plerixafor is funded for patients with CD34+ count <10 cells/µl on day of collection or if first apheresis has yielded CD34+ <1 x 106cells/kg. In these patients, Plerixafor is administered the evening prior to the planned morning collection but this presents logistical issues as it has to be given after hours. Therefore, it was proposed to administer Plerixafor followed by same day HSC collection to improve the logistics of these "just in time" collections. Methods: A retrospective case note audit identified 96 patients who received Plerixafor for HSC collection between 03/2017 and 06/2021. Patients were categorised into PM (late afternoon/evening dosing) and AM (morning dosing). Transplant HSC dose target was >2 x 106/kg. Results: Of the 96 patients, 17 received 2 doses of plerixafor with 4 of these patients receiving both an AM and PM dose. These 4 patients were excluded from the final analysis. Of the 92 patients remaining, 57% (n=52) of patients received PM and 43% (n=40) AM dosing. Median age was 64 years (range 23 to 78). 58% were male (n=53) and 42% female (n=39). Underlying malignancy included Myeloma (n=51), Lymphoma (n=37) and Solid malignancy (n=4). Median pre plerixafor blood CD34+ count was 8.7x10^6/kg (range 0.3-35.5) in the PM group and 9.2 (range 1.6-38.2) in AM group prior to collection. Median number of HSCs collected post-plerixafor administration was 4.97 x106/kg (range 0.91-34.97) for PM group vs 4.16 x106/kg (range 0.71-9.52) AM group. Total median HSC number collected for patients in the PM group was 6.6x106cells/kg (range 3.14-8.18) vs 5.16x106/kg (range = 2.46-6.45) in the AM group. The AM group had an increased median HSC collected post plerixafor of 83% vs PM median of 75%. A transplantable HSC dose was collected in 97% of those in the AM group and 96% in the PM group. Median number of apheresis procedures with PM dosing was 2 (range 1-5) vs 2.4 with AM dosing (range 1-4). Conclusion: While post plerixafor HSC collection doses were higher with PM dosing this is countered by the total median HSC collection being higher in the AM group. These findings show that same day plerixafor dosing is a feasible option with similar numbers of patients achieving their target HSC collection.

Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study

目的评估65岁以上老年多发性骨髓瘤（MM）患者接受自体造血干细胞移植的疗效和安全性。方法回顾性分析自2006年6月1日至2020年7月31日在中山大学附属第一医院诊断并接受含新药诱导方案序贯自体造血干细胞移植的22例65岁以上MM患者的疗效和安全性。接受移植的老年患者均在移植前对重要脏器功能进行评估，自2016年起同时采用国际骨髓瘤工作组虚弱评分评估移植适应证。结果22例患者接受移植时的中位年龄为66.75（IQR 4.50）岁。共20例患者接受了造血干细胞动员，中位采集造血干细胞单个核细胞数为4.53×108/kg，CD34+细胞数为3.37×106/kg，中位采集次数2次。造血干细胞回输后中性粒细胞植入中位时间11 d，血小板植入中位时间13 d，移植后100 d治疗相关死亡率为0。中位随访48.7个月，中位无进展生存时间未达到，中位总生存时间为111.8个月。结论对于经过筛选的≥65岁老年MM患者，自体造血干细胞移植是安全有效的治疗方案。

Pharmacokinetic and pharmacodynamic study of lenograstim for hematopoietic stem cell mobilization: a prospective randomized study for optimal apheresis

This study evaluated the correlation between the pharmacokinetics and pharmacodynamics of granulocyte colony-stimulating factor (lenograstim) and the impact of initiation time of apheresis on stem cell mobilization in patients with multiple myeloma. Twenty-four patients with multiple myeloma were randomized into one of the two groups (early vs. late). Lenograstim at 10 μg/kg/day once daily was injected for at least 4 consecutive days. Apheresis was initiated 2 hours after the fourth dose of lenograstim in the early collection group and 16 hours after the fourth dose of lenograstim in the late collection group. Blood sampling for pharmacokinetics was performed within 30 minutes before, and 1, 2, 6, and 24 hours after the fourth dose of lenograstim. Overall, the two groups (early vs. late, n = 10 vs. 14) exhibited similar baseline characteristics including age, sex, subtype of myeloma, stage distribution, and myeloma-associated symptoms. No correlation was found between plasma lenograstim concentration and peripheral blood (PB) CD34+ cell counts or hematopoietic progenitor cells. In the late collection group, the median number of apheresis procedures for minimal collection was significantly lower (early vs. late: 2 vs. 1; p = 0.04) and there was a higher number of total collected PB CD34+ cells in a single session of apheresis (1.4 vs. 3.1; p = 0.06). There were no differences in median overall PB stem cell collection efficiency. Late collection positively impacted the number of apheresis procedures for minimal collection, with numerically improved PB stem cell collection efficiency at first apheresis in patients with multiple myeloma.

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma.

BackgroundThe regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin’s lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored.MethodsOur retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP.ResultsThe median CD34+ cell yield was 7.01 × 106 cells/kg body weight (range 1.49–28.39 × 106 cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ≥2.0 × 106 cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1–3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P = 0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P = 0.01). No significant differences in toxicity or engraftment were observed between the two groups.ConclusionThe present study demonstrated that dose-adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.

Impact of rituximab on stem cell mobilization following ACVBP regimen in poor‐risk patients with diffuse large B‐cell lymphoma: results from a large cohort of patients

The ACVBP regimen is an efficient induction regimen for poor-risk patients with diffuse large B-cell lymphoma (DLBCL) before consolidative autologous stem cell transplantation. Adjunction of the monoclonal anti-CD20 antibody rituximab (R-ACVBP) was recently found to be superior to ACVBP alone. This study assessed the impact of rituximab on stem cell mobilization in two similar consecutive groups of patients treated with ACVBP in two prospective, controlled trials. The first trial (LNH-98B-3) involved 137 patients treated with ACVBP alone. In the second trial (LNH-03-3B), 91 patients received an R-ACVBP regimen. Stem cell mobilization was performed after a course of (R)-ACVBP. The median peak numbers of blood CD34+ cell counts recorded before the first apheresis procedure in the ACVBP and R-ACVBP groups were 69×10(6) and 63×10(6) /L, respectively (p=0.55). The median numbers of CD34+ cells collected were 7.1×10(6) and 6.0×10(6) CD34+ cells/kg for the ACVBP and R-ACVBP groups, respectively (p=0.13). The median number of apheresis procedures required for gathering the minimum amount of CD34+ cells (2×10(6) /kg) was the same in the two groups. When compared with ACVBP alone, adjunction of rituximab does not impair stem cell mobilization.

Autologous Stem Cell Transplant in Patients with Multiple Myeloma Previously Treated with Lenalidomide: A Single-Institution Experience Using An Intermediate-Dose Cyclophosphamide-Based Regimen

Abstract 4391 Background:High dose chemotherapy followed by autologous transplantation of peripheral blood stem cells plays an important role in the management of intermediate- and advanced-stage multiple myeloma. In order for successful engraftment to occur, adequate numbers of high quality peripheral stem cells must be harvested prior to transplantation. Mobilization of PBSC in patients treated with lenalidomide has been associated with poor apheresis collections after G-CSF mobilization. The purpose of this study is to present our institution's experience utilizing an intermediate-dose cyclophosphamide-based mobilization regimen. Methods:We retrospectively analyzed data for patients with multiple myeloma who underwent autologous stem cell transplant at UCLA between 2006 and 2010. Data were obtained from the database of the UCLA Heme Malignancy/Stem Cell Transplant Unit, the electronic health record system and stem cell processing laboratory. All patients underwent mobilization with a regimen of cyclophosphamide 2.5g/m2 IVPB, G-CSF 10 mcg/kg/day for 4 days SQ, and prednisone 2mg/kg/day for 4 days po. The number of CD 34+ cells was used as a marker for the number of peripheral stem cells collected. Minimum dose collected to ensure adequate engraftment was 2×106/kg CD34+ cells. Patients were conditioned with melphalan 100mg/m2/d x2 (unless there was evidence of renal failure, in which case the dose was reduced to 100mg/m2) with subsequent infusion of stem cells. Neutrophil engraftment was defined as the first day of absolute neutrophil count greater than 500×106/L ≥ 7 days after transplant. Results:Autologous stem cell transplant was performed in 103 patients with multiple myeloma at UCLA between 2006 and 2010. Median number of apheresis procedures was 1 (1–12) with a median of 4.4×106/kg (1.4–33.5) CD34+ cells collected. Median time to engraftment was 10 (8–18) days. Thirty-five patients received lenalidomide at some point in their pretransplant treatment. Median number of apheresis procedures was 1 in both lenalidomide and non lenalidomide treated groups. In the lenalidomide treated group 54% required only one collection versus 75% in the non lenalidomide treated group (p=0.033). In the lenalidomide treated group 31% required 3 more or more collections versus 10% in non lenalidomide treated group (p=0.0075). Three patients in the lenalidomide group had subsequent mobilization with plerixafor with one of these requiring bone marrow harvesting. Median CD34+ cells collected was 3.5×106/kg and 4.9×106/kg (p=0.246) in the lenalidomide and non-lenalidomide groups respectively. Both groups had a median time to neutrophil engraftment of 10 days with a similar range. Conclusion:Pre-transplant use of lenalidomide adversely affected the number of stem cell apheresis procedures required to procure adequate stem cell dose as evidenced by a greater percentage requiring 3 or more collections. However, despite prior lenalidomide exposure, the use of our mobilization regimen permitted adequate collection, with the majority of patients requiring only one apheresis procedure, and led to an equivalent time to neutrophil recovery. Disclosures:Off Label Use: Cyclophosphamide and G-CSF for mobilization of stem cells.

An Analysis of the Costs Associated with Peripheral Blood Hematopoietic Progenitor Cell Mobilization, Collection and Cryopreservation in Patients with Lymphomas Undergoing Autologous Stem Cell Transplantation

Peripheral blood hematopoietic progenitor cells (HPC) may be mobilized with cytokines alone or with chemotherapy followed by cytokines. The HPC yield is higher and the failure rate is lower with chemo mobilization. Although cell dose of 2 million CD34+ cells/kg is considered adequate, some authors have shown that patients who receive < 5 million CD 34+ cells/kg have higher resource utilization after transplant. The purpose of this study was to analyze the costs associated with HPC chemo mobilization in patients with lymphomas.PATIENTS AND METHODS: We analyzed 149 patients with non-Hodgkin's (N=101) and Hodgkin's (N=48) lymphomas who underwent HPC chemo mobilization at our institution between 1/03 and 12/04. The retrospective chart review was approved by the IRB. Patients who collected < 2million CD34+ cells/kg in 4 leukapheresis procedures were called failures. The estimated costs were divided into pre apheresis, apheresis, and post apheresis costs. (Source: Cleverly and Associates; www.drugstore.com; Redbook™; Thompson PDR)RESULTS: A total of 133 patients underwent chemo mobilization. Chemotherapy regimen was ifosfamide, etoposide, G-CSF, +/− rituximab in 98 (74%) patients. The average inpatient stay for chemotherapy administration was 6 days (range, 3–28). Twenty-four patients required readmission for complications of chemotherapy (22/24 for fever/infections) for a median of 5 days (range, 1–12). Patients received G-CSF for a median of 14 days (range, 6–34). All patients received IV hydration while in the hospital and were discharged on prophylactic oral antibiotics. Average number of days on oral antibiotics was 9 (range, 0–16). For successful mobilizers, the median number of apheresis procedures required to reach target HPC dose of 5 million CD34+ cells/kg was 2 (range, 1–7). Thirty patients (out of 149) failed to collect adequate HPC on the first attempt. Of those 12 patients underwent a BM harvest ($2389/harvest), 4 were remobilized with chemotherapy (1 mobilized successfully), 4 patients underwent an allogeneic transplant ($250,000–500,000/transplant) and 3 patients underwent an autologous transplant with suboptimal cell dose (all had prolonged time to engraftment and 1 patient needed an allogeneic transplant for graft failure). Average pre apheresis costs per patient were $1800 (clinic visit, laboratory evaluation, central venous catheter insertion, and chest x-ray to check placement). The average costs of chemotherapy administration, hospitalization, prophylactic antibiotics and G-CSF were $ 29181 (not including rituximab). This is an underestimation as it does not include the costs associated with supportive care, intravenous fluids, readmission etc. The post apheresis costs were $ 2493. These costs do not account for professional fees.CONCLUSIONS: Although in this present analysis we may have underestimated the actual costs associated with HPC mobilization, the costs are still considerable. Accordingly, the financial implication for transplant centers where reimbursement is DRG (diagnosis related group) or case rate based is significant. Interventions or newer agents that can reduce the failure rate or reduce the number of apheresis procedures required to reach a target HPC dose without increasing the toxicity may reduce the costs associated with transplant especially in patients who do not require chemotherapy for treatment of their primary disease.National Hospital Average Cost in $ $N Median (range)Estimated Total Costs per in $APHERSISChemotherapy AdministrationDaily Room Charge863.006 (3–28)5178* Ifosfamide 3.33 g/m2/d × 3 d372.87/gram19.38 g7227Etoposide 150mg/m2 × 6 d17.61/10mg1746 mg3074Rituximab 375mg/m2 × 2 d1315.43/100mg1455 mg19140Daily CBC,diff935 (3–28)465Readmission (N=24)863.004315Daily Room charge5 (1–12)Daily CBC, diff93465Blood Transfusions (N=64)4941.4 (0–6)692Platelet transfusions (N=64)4941.5 (0–7)741G-CSF52814 (6–34)7392Oral antibiotics Valacyclovir104Fluconazole9 (0–16)89Levofloxacin114Apheresis procedure1917.732 (1–7)3835PB CD34+ analysis1352 (estimated)270POST APHERESISCryopreservation (supplies, labor, storage, sterility)1246.42/apheresis2 (1–7)2493TOTAL (without rituximab)36454*Based on median body surface area (BSA) of 1.94 (range, 1.35–2.45). N=98Study was sponsored by Genzyme Inc.

Effective CD34+ Stem Cell Mobilization with Low-Dose Pegfilgrastim.

Introduction: Numerous strategies utilizing chemotherapy followed by filgrastim allow for the successful mobilization of peripheral hematopoietic progenitor cells. To eliminate the need for self-administration of multiple growth factor injections and to minimize cost, we piloted a mobilization strategy consisting of low-dose Pegfilgrastim and chemotherapy.Methods: Seven consecutive patients scheduled to undergo hematopoietic progenitor cell transplant for hematologic malignancy received a single 6mg injection of Pegfilgrastim 24–48 hours after chemotherapy. The targeted CD34+ collection was 5x106cells/ kg. The number of apheresis, CD34+ cell yield, time to engraftment and toxicities were recorded. These patients were compared to the 15 previous patients who received Filgrastim and chemotherapy for mobilization.Results: In the pilot population, the median age was 60 (range: 39–67) years. Chemotherapy priming before Pegfilgrastin for three patients with multiple myeloma and two with stage IV mantle cell lymphoma was 4.5grams/m2 of cyclophosphamide; one patient with relapsed, stage IV Hodgkin's disease received ICE and one multiple myeloma patient with a serum creatinine of 3.1mg/dL, received 2.5grams/m2 of cyclophosphamide. Five patients required a single apheresis, two patients required two apheresis collections. The median CD34+ yield was 6.7 x106/kg (range: 3.2–13.7). The median time to neutrophil engraftment was 10 days (range: 9–12). The median time from Pegfilgrastim to apheresis was 9 days (range: 7–10). The Pegfilgrastim cost per patient was $3,250.00. Toxicity was limited to grade II bone pain.The comparison group consisted of seven multiple myeloma, four leukemia and four lymphoma patients. Their median age was 51.5 years (range: 24–67). The median number of apheresis procedures was 2 (range: 1–3). The median CD34+ yield was 5.6 x106/kg (range: 2.9–17.6). The median time to neutrophil engraftment was 11 days (range: 9–11). The median time from cytokine to apheresis was 8.5 days (range: 3–16). The median cost of Filgrastim per patient was $3,650.00 (range: $2,290–$8,760). The median number of Filgrastim injections was 10 (range: 10–14). Toxicity was limited to grade II bone pain.Discussion: In a two cohorts of patients with hematologic malignancies Pegfilgrastim as compared to Filgrastim resulted in a decreased cytokine cost, a fewer number of apheresis collection procedures, a more predictable time to first apheresis and no self-administration of medication. There was no significant difference in the time to engraftment.Conclusion: Low-dose Pegfilgrastim in conjunction with chemotherapy results in as effective CD34+ progenitor cell mobilization with less drug cost and apheresis time as compared to Filgrastim with chemotherapy.

Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients.

We compared retrospectively the efficacy of granulocyte colony stimulating factor (G-CSF) alone with chemotherapy plus G-CSF in mobilizing CD34-positive cells in patients with malignant lymphoma. 35 patients underwent peripheral blood stem cell (PBSC) collection following mobilization either with 24 microg/kg G-CSF for 4 consecutive days (n = 18) or Dexa-BEAM chemotherapy plus 5 microg/kg G-CSF (n = 17). High-dose G-CSF was well tolerated with only slight bone pain and/or myalgia. The Dexa-BEAM therapy required hospitalization with a median duration of 21 d. The median number of apheresis procedures in both groups was two (range two to four), resulting in a median of 5.3 and 5.1 x 10(6) CD34+ cells/kg. No patients in the G-CSF group, but one in the Dexa-BEAM group, failed to reach the target of collecting >2.0 x 10(6) CD34+ cells/kg. The number of CFU-GM (10.4 v 6.0 x 10(5)/kg) and of BFU-E (10.6 v 4.5 x 10(5)/kg; P = 0.04) was higher in the G-CSF group than in the Dexa-BEAM group. A subset analysis of CD34+ cells was performed in 16 patients showing a higher mean of Thy-1 (CD90w) coexpression in the G-CSF than in the Dexa-BEAM group (4.8 v 1.8%, P = 0.12). Additionally the percentage of CD34+/CD38- cells was higher in the G-CSF group (10.66% v 8.8%). However, these differences were not statistically significant. The median time to leucocyte and platelet engraftment after high-dose chemotherapy was slightly shorter in the G-CSF than in the Dexa-BEAM group (9 v 10 and 12 v 13.5 d, respectively). These results demonstrate that high-dose G-CSF is as effective as Dexa-BEAM plus G-CSF in mobilizing peripheral blood stem cells and produces prompt engraftment. The major advantages of G-CSF mobilization were the safe outpatient self-application and the fixed-day apheresis.

Four-step high-dose sequential chemotherapy with hematopoietic progenitor-cell support as induction treatment for patients with solid tumors

Despite recent progress in modern chemotherapy, metastatic solid tumors still have a poor outcome. The delivery of increased dose intensities of cytotoxic agents could improve response rates. We assessed the feasibility and safety of a high-dose sequential chemotherapy program in chemotherapy-naive patients with solid tumors. Thirty patients (14 with carcinoma of unknown primary site, seven with metastatic breast cancer, six with small-cell lung cancer, and three with other diseases) were treated by an induction therapy regimen consisting of four cycles of high-dose chemotherapy with hematopoietic progenitor cell and growth factor support. Peripheral blood progenitor cells were collected by apheresis as the leukocyte counts recovered from the nadir induced by the first cycle of chemotherapy (doxorubicin 75 mg/m2, cyclophosphamide 6000 mg/m2). Patients then received two cycles of etoposide (800 mg/m2) and carboplatin (900 mg/m2) separated by one cycle of doxorubicin (75 mg/m2) and cyclophosphamide (3000 mg/m2). G-CSF (5 microg/kg/d) was given until engraftment. Cycles were scheduled to be delivered every three weeks. A total of 108 cycles of chemotherapy were administered. Six patients went off study before the end of the program (three because of progressive disease, three because of toxicity). After the first cycle, a median number of 10 x 10(6)/kg CD34+ cells (range 8-30) were collected. The median number of apheresis procedures was 1 (range 1-3). From cycle 2 to cycle 4, the median number of days when there was an absolute neutrophil count of less than 500/microl increased from three to five, and the median number of days when the platelet count was less than 25,000/microl increased from three to six. Episodes of febrile neutropenia occurred in 36%, 50% and 46% of cycles during cycles 2, 3 and 4, respectively. The median numbers of days between cycle 1 and cycle 2, cycle 2 and cycle 3, cycle 3 and cycle 4 were 24 (range 20-30), 22 (range 20-36) and 22 (range 18-35), respectively. There were no treatment-related deaths. Non-hematologic toxicity included severe (WHO grades 3 or 4) nausea/vomiting in 19 (18%) cycles, mucositis in 8 (7%) cycles and diarrhea in 7 (6%) cycles. Support with hematopoietic progenitor cells and growth factors allows the timely administration of repetitive cycles of high-dose chemotherapy in chemotherapy-naive patients, resulting in a significant increase in dose intensity. Toxicity is noteworthy but manageable and does not compromise further therapy.

Allogeneic Peripheral Blood Stem Cell Transplantation: Is there an increased risk of graft vs host disease in leukemia patients?

Fifteen patients with hematological malignancies [9 acute nonlymphoblastic leukemia (ANLL), four chronic myelogenous leukemia (CML), two acute lymphoblastic leukemia (ALL)] received allogeneic peripheral blood stem cell transplantation (alloPBSCT) from HLAidentical sibling donors. Donors received 2.5-15 μg/kg/day of recombinant human granulocyte colony stimulating factor (rhG-CSF) for 5-10 days. Administration of rhG-CSF was well tolerated except for mild to moderate bone pain occurring in all the donors which was relieved by oral paracetamol. A total of 40 leukaphereses were performed for the 15 donors using the bilateral antecubital veins. None of the donors needed central venous line insertion. The median number of apheresis procedures for each patient was 3 (2-3). A median of 7.7 (4-38.2) × 108/kg mononuclear cells, 35 (2.4-90.0)x 106/kg CD34+ cells, 1.85 (0.45-4.8) × 108/kg CD3 and 0.3 (0.16-1.01) × 108/kg natural killer cells were given without any manipulation. Cyclosporin A (CsA) plus short-course methotrexate (MTX) (12 patients) and CsA alone (3 patients) were used for graft versus host disease (GVHD) prophylaxis. Median granulocyte and platelet engraftments were done on days 11 (10-31) and 16 (11-54) respectively. Grades II-IV GVHD occurred in 62% of the patients and grades III-IV in 15%. Twelve patients are still alive with full engraftment and disease-free. In conclusion, alloPBSCT is an alternative to allogeneic bone marrow transplantation, because of the ease of collection and rapid hematological recovery. However, there is a trend for increased acute GVHD in our leukemia patients compared to allogeneic bone marrow.