Peripheral Stem Cell Collection Research Articles

Prior Daratumumab Exposure and It's Correlation to Parameters Related to Apheresis Prior to Hematopoietic Stem Cell Transplantation in Multiple Myeloma

A number of recent studies have brought to light the potential detrimental effect the biologic monoclonal antibody daratumumab, directed towards CD38, may have on the collection of stem cell collection for hematopoietic stem cell transplantation (HSCT). In our evaluation of this claim, we retrospectively reviewed multiple myeloma patients who underwent autologous HSCT at a major tertiary transplant center between 2017 and 2022. A total of 240 patients were identified which included 62 patients who received daratumumab prior to stem cell collection and 178 patients who had no prior daratumumab exposure. Basic demographic data was collected as well as radiation, chemotherapy, and smoking history. No significant differences were identified between the groups based on demographics, smoking, or radiation exposure. Parameters related to peripheral stem cell collection were identified and recorded. We found that in patients exposed to daratumumab prior to apheresis, the mean number of days of apheresis required to reach the target collection goal was statistically increased compared to control (1.42 days ± 0.07 vs 1.26 ± 0.03; p<0.05). Furthermore, medications used to increase peripheral stem cell collection yield were also increased. It was demonstrated that the mean number of doses of plerixafor and G-CSF analogs were increased in the daratumumab group vs the control (1.08 ± 0.12 vs 0.6 ± 0.05; p<0.001 and 5.98 ± 0.31 vs 5.17 ± 0.06; p <0.001 respectively). Total number of stem cells collected both as an absolute number and controlled for the number of days of apheresis were lower in the daratumumab group compared to the control (5.31x10^6 ± 0.31 vs 6.68x10^6 ± 0.20; p<0.05 and 4.16x10^6 ± 0.32 vs 5.84x10^6 ± 0.21; p < 0.001 respectively). These results suggest that pre-apheresis exposure to daratumumab has a detrimental effect on peripheral stem cell collection. These results have a significant implications for both long term patient care and healthcare system resource utilization. The clinical outcome implications of daratumumab are currently not well known and further study is needed to determine if alterations in stem cell collection protocols would result in improved stem cell collection yields for patients with pre-collection daratumumab exposure. All data is expressed as mean ± SEM

Orthotopic Heart Transplantation Followed By Autologous Stem Cell Transplantation in Patients with Cardiac AL Amyloidosis: Results from a Single Centre Prospective Study

Background: Patients with advanced cardiac AL amyloidosis have a dismal prognosis, with an overall survival (OS) of only 5 months for Stage IIIb patients (Palladini et al, 2023). Induction chemotherapy followed by high dose chemotherapy and autologous stem cell transplantation (HDT and ASCT) has been widely used as treatment for AL amyloidosis. However, patients with advanced cardiac AL amyloidosis are often not suitable for HDT and ASCT due to high transplant related mortality (TRM). Orthotopic cardiac transplantation (OHT) following induction treatment may improve patient fitness and thus allow HDT and ASCT to deepen and prolong responses. We present our single centre, prospective study of patients with Stage IIIa and Stage IIIb cardiac AL amyloidosis who received OHT followed by sequential HDT and ASCT. Aims: The primary outcomes were 3 year OS and progression-free survival (PFS). Efficacy and safety were assessed as secondary outcomes. Efficacy was evaluated by light chain and cardiac response after ASCT. Safety was assessed by rate of TRM, cardiac rejection, opportunistic infections, and cytopenia related complications. Methods: During 2015 to 2021, patients with Stage IIIa or Stage IIIb AL amyloidosis aged under 65 years underwent OHT followed by HDT and ASCT. Patients with multiple myeloma were excluded. At approximately 6 months following OHT, patients underwent stem cell mobilization with granulocyte colony-stimulating factor alone followed by peripheral blood apheresis stem cell collection. Mycophenolate immunosuppression was temporarily withheld during stem cell mobilization and collection. Patients then received a high dose melphalan ASCT followed by 3-6 monthly assessments. Results: Nine patients (median age of 53 years, range 47-60 years) completed both OHT and ASCT. Seven other patients were screened but did not proceed with OHT. The cohort included both stage IIIa (55%) and stage IIIb (44%) patients. Most patients received cyclophosphamide-bortezomib-dexamethasone induction therapy (89%) and one patient received lenalidomide-bortezomib-dexamethasone. The median time from diagnosis of AL amyloidosis to OHT was 11 months (range 5-57 months) and median time from OHT to ASCT was 7 months (range 5-8 months). 3 year OS was 83% and PFS was 56% (Figure 1). At a median follow up of 37 months (range 17-69 months), 89% of patients remain alive. One patient with Stage IIIa disease who underwent HDT and ASCT with progressive disease (PD) died 28 months following ASCT due to PD. Subgroup analysis demonstrated 3 year OS in Stage IIIa patients of 75% compared to 100% in Stage IIIb (p=0.48). 3 year PFS was 53% in Stage IIIa patients and 66% in Stage IIIb (p=0.8). Patients in complete remission (CR) prior to ASCT had an improved 3 year OS of 100% compared to 66% for those in partial remission (PR) or with PD (p=0.32). 3 year PFS was significantly improved at 100% when ASCT occurred in CR compared to 0% in those in PR or with PD (p=0.01) (Figure 2). All patients either maintained a CR or achieved an improved haematological response following HDT and ASCT, with 89% of patients in CR at 6 months post ASCT. At the median follow up of 37 months, 78% were in CR and 22% had PD. At last follow up, there has been no documented amyloid recurrence in a cardiac allograft. There was no TRM noted in this study. All patients had cardiac rejection with 66% developing Grade 3A/2R rejection requiring methylprednisone. The most common infective complication was CMV reactivation (44%). Other infective complications included cryptococcal infection (11%), aspergillus and MAC infection (11%) and HSV reactivation requiring hospitalization (11%). During admission for HDT and ASCT, 89% had febrile neutropenia and there were no bleeding complications. Conclusions: We have demonstrated, in a prospective design, that sequential OHT/ASCT following induction therapy is safe in patients with Stage IIIa/b cardiac AL amyloidosis without an increase in TRM. This approach was associated with excellent survival outcomes compared with historical cohorts. Given the deep and prolonged responses seen with daratumumab based induction, a risk adapted strategy may be more appropriate moving forward, with only those not achieving a haematological CR undergoing consolidation ASCT following OHT.

Comparison of different plerixafor-based strategies for adequate hematopoietic stem cell collection in poor mobilizers

Objectives: The main objective of the present study was to evaluate whether the use of plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) or subsequent use of isolated G-CSF and then plerixafor following disease-specific chemotherapy, and whether it would allow for adequate peripheral stem cell collection in patients. Methods: The retrospective study evaluated 54 patients with previous mobilization failure who were administered plerixafor in 2 centers. In patients without any side effects, CD 34+ cell counts, the percentage of patients who were found eligible for autologous transplantation, the engraftment kinetics of the patients who underwent transplantation, and their overall survival results were compared between the two groups where G-CSF was used with plerixafor, or where plerixafor was used after isolated G-CSF following chemotherapy. Results: The median age of the patients was 49 years (range: 17-70), and 64.8% (n = 35) were males. It was identified that 31 (57.4%) patients underwent mobilization treatment with isolated G-CSF and plerixafor, and 23 (42.6%) patients underwent mobilization treatment with chemotherapy plus G-CSF and plerixafor. In all patients, mean hemoglobin level (11.3 ± 1.5 g/dL vs. 9.3 ± 1.3 g/dL; p < 0.001) and median platelet level (129.2 ×103/µL vs. 58.4 ×103/µL) were found to be higher, while febrile neutropenia rate (3.3% vs. 60.9%), the percentage of replacement patients (6.7% vs. 65.2%), and median days of G-CSF (6 vs. 9) were found to be lower on the day of plerixafor administration in the isolated G-CSF and plerixafor group compared to the chemotherapy and G-CSF and plerixafor group. Conclusions: In conclusion, our study demonstrated that administration of plerixafor is generally safe and well-tolerated. Regardless of the underlying disease, it offers an effective alternative for patients with previous failed mobilization attempts using conventional regimens, and allows stem cell collection with fewer apheresis sessions.

Primed for change: The effect of a blood prime on peripheral blood stem cell collection and accuracy of a prediction tool in pediatric patients.

Pediatric apheresis collection of peripheral blood stem cells for autologous transplantation often requires use of a blood prime. We evaluated the relationship between pre-apheresis blood CD34+ counts and final CD34+ yield with use of a blood prime. Forty patients underwent apheresis stem cell collection in a 5 year period in our hospital, of which 27 required blood priming of the apheresis machine. Despite the blood prime group having significantly higher pre-apheresis CD34+ cell counts, this group processed a relatively higher volume of blood due to a higher dilutional effect and collected significantly less than predicted CD34+ cell yield. Use of weight-specific collection efficiencies and dilution-adjusted pre-apheresis CD34+ counts will help in accurately estimating the whole blood volume to process for PBSC collection and therefore increase efficiency and decrease the overall cost of collection.

A comparison of peripheral blood stem cell collection outcomes for multiple myeloma; mobilization matters in the era of IMiD induction.

Collection of peripheral blood stem cells (PBSCs) for autologous stem cell transplant (ASCT) requires mobilization from the bone marrow. There is variation in mobilization choice; during the COVID-19 pandemic BSBMT&CT guidelines recommended using granulocyte-colony stimulating factor (G-CSF) alone to minimize the use of chemotherapy. We report on the impact of mobilization regimen on stem cell collection, and whether IMiD-containing induction therapy impacts on mobilization and consequently transplant engraftment times for 83 patients undergoing ASCT at Leeds Teaching Hospitals. Cyclophosphamide plus G-CSF (cyclo-G) mobilization yielded more CD34+ cells (8.94vs. 4.88 ×106/kg, p=<0.0001) over fewer days (1.6vs. 2.4 days, p=0.007), and required fewer doses of salvage Plerixafor than G-CSF only (13.6%vs. 35%, p=0.0407). IMiD-containing induction impaired all of these factors. CD34+ doses>8×106/kg were more frequent with Cyclo-G (62%vs. 11%, p=0.0001), including for those receiving IMiD 1st line induction (50%vs. 13.3%, p=0.0381). Note that 92.6% of those receiving IMiD-free inductions were mobilized with Cyclo-G. The novel agents used in modern induction regimens (e.g Daratumumab) have been shown to impair yields, increasing the importance of optimizing mobilization regimens in the first instance. Furthermore, as cellular therapies become established in the management of multiple myeloma emerging data highlights the potential benefits of stem cell top up in the management of the haematological toxicities of these therapies. Our findings support re-adoption of Cyclo-G as the gold standard for mobilization to optimize PBSC harvesting and ensure sufficient cells for subsequent ASCTs.

Prediction of success of CD34+ collection for autotransplantation in children

Intensive chemotherapy with autologous stem cell transplantation is a therapeutic tool used in paediatric oncology. In adult patients, a peripheral blood CD34+ cell count superior to 20/μL enables an adequate collection of peripheral blood stem cells. There are no recommendations for children. This study aimed to determine whether the count of circulating CD34+ cells on the day before cytapheresis predicts successful collection in paediatric patients. We retrospectively studied all paediatric patients who underwent apheresis for stem cell autotransplantation in the CHU of Rennes between 2010 and 2019. Successful apheresis was defined as a collection superior to 3×106 CD34+/kg. "Success" and "failure" groups were compared. In total, 122 apheresis procedures were performed in 105 patients. It was a successful procedure in 81% of patients and a failure in 19% of patients. A minimal cut-off of circulating CD34+ count superior to 13/μL on D-1 allowed us to predict a collection of at least 3×106 CD34+/kg (PPV 94,8%, NPV 51,4%). For children aged<6 years, the association with leucocyte increase during the 5 days before the procedure improved the prediction of success. The peripheral blood CD34+ cell count is a predictive factor for successful collection in paediatric patients. The minimal cut-off that allows an adequate collection of peripheral blood stem cells is inferior to the minimal cut-off in adult patients. Nevertheless, this minimal number of circulating CD34+ cells is insufficient to predict the success or failure of apheresis in patients younger than 6 years of age.

The Optimal Time of Peripheral Blood Hematopoietic Stem Cell Collection for Autologous Transplantation May Be Predicted By Immature Granulocytes and Nucleated Red Blood Cells

The time of initiating stem cell collection is very important for successful transplantation and is determined according to peripheral blood CD34+ cell count analysed by flow cytometry. In this study, we aimed to find the role of new complete blood count parameters to determine the optimal time of stem cell collection. Eighty-six patients who underwent stem cell mobilization were included in the study. Peripheral blood CD34+ cells and complete blood count were analysed on the same day. Patients with peripheral blood CD 34+ cell counts ≤ 20/μL and &amp;gt; 20/μL were determined as Group 1 and Group 2, respectively. The difference of CBC parameters between 2 groups and the relationship of these parameters with peripheral blood CD34+ cell counts were evaluated. It was found that immature granulocytes ratio, nucleated red blood cells ratio and count were positively correlated with peripheral blood CD34+ cell count and these parameters were significantly different between two groups (P&amp;lt; 0.001, P= 0.011 and P= 0.012, respectively). The new index formulated by using immature granulocytes and nucleated red blood cells ratios was significantly different between two groups (P&amp;lt;0.001), and had the highest diagnostic accuracy to determine the time of stem cell collection (AUC= 0.766). Immature granulocytes and nucleated red blood cells can be used to determine the time of peripheral blood stem cell collection faster and cheaper compared to flow cytometry.

Plerixafor and granulocyte colony stimulating factor for poor mobilizers in patients undergoing autologous peripheral hematopoietic stem cell transplantation: Single institution study

BackgroundAutologous hematopoietic stem cell transplantation (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%–30% of patients. To improve mobilization, plerixafor is used along with granulocyte colony-stimulating factor (G-CSF).Patients and methodsWe conducted a retrospective single center study involving patients who received plerixafor pre-ASCTs between January 2013 and December 2020 at a tertiary care center in Lebanon. We identified a total of 84 consecutive adult patients. All patients identified were poor mobilizers and have eventually received plerixafor either as pre-emptive use before first apheresis in those with peripheral CD34 + of less than 20 cells/ul, or after failure of first apheresis in those with peripheral stem cells (PSC) &amp;gt;2.0 × 106 cells/Kg.ResultsThe median age at ASCT was 52.7 years (22–74) with 61% male predominance. Multiple myeloma was the most prevalent disease 64% followed by Lymphoma 32%. The majority of patients were in complete remission 64% at the time of ASCT. Most patients received proteasome inhibitor-based induction therapy 67% and Melphalan-based conditioning therapy 68%. The median follow-up from ASCT was 9 months (1–59). It was noted that greater body mass index (BMI) is a significant factor for better PSC collection whether premobilization (P = 0.003), or post plerixafor mobilization (P = 0.024). Moreover, Multiple Myeloma patients showed better mobilization using Plerixafor (P = 0.049). Using Plerixafor along with G-CSF in poor mobilizers post G-CSF alone showed a statistically significant increase in the collected PSC mean from 0.67 × 106 cells/Kg to 4.90 × 106 cells/Kg (P &amp;lt; 0.001) with a failure rate only for 12 patients (15%). The infusion of PSC &amp;gt; 2.5 × 106 cells/Kg has shown 3 days decrease in time to platelet engraftment (P = 0.021) and a 36% decrease in progression/relapse rate (P = 0.025).ConclusionPlerixafor is effective in increasing the PSC yield in poor mobilizers. Low BMI and hematologic malignancies other than Multiple Myeloma are risk factors for poor mobilization. More studies should be performed to establish more risk factors, helping us to identify poor mobilizers more accurately and initiate plerixafor mobilization early on.

Mobilization and Hematopoietic Stem Cell Collection in Poor Mobilizing Patients with Lymphoma: Final Results of the German OPTIMOB Study

Introduction: Successful mobilization and collection of peripheral hematopoietic stem cells (HSCs) are necessary for lymphoma patients eligible for myeloablative chemotherapy with subsequent autologous stem cell transplantation (ASCT). Albeit G-CSF alone or combined with chemotherapy is well-established methods for HSC mobilization, up to 40% of the patients fail to mobilize (poor mobilizer, PM). Plerixafor (PLX) is commonly used in PM patients resulting in increased migration of HSCs into peripheral blood and thus improves the collection outcome. Methods: The prospective, multicenter, open-label, non-interventional OPTIMOB study assessed mobilization and collection parameter of patients with lymphoma or multiple myeloma to get deep insights in the treatment of those patients in clinical routine focusing on PM patients. PM was defined as follows: (1) no achievement of ≥20 CD34+ progenitor cells/µL before first apheresis, (2) PLX administration at any time point during the observational period, (3) reduction of the initially planned CD34+ progenitor cell yield as necessity due to failed mobilization or HSC collection, and (4) no performance of apheresis due to low CD34+ progenitor level. Primary objective of the study was to assess mobilization success by the proportion of PM patients achieving >2 × 106 CD34+ progenitor cells/kg body weight on the first day of apheresis. Here, the data of the lymphoma cohort are presented. Results: Out of 238 patients with lymphoma documented in the study, 32% were classified as PM. 87% of them received PLX. Demographic data revealed no obvious differences between PM and good mobilizing (GM) patients. All patients were treated highly individualized prior to mobilization. Majority of all PM patients were able to undergo apheresis (95%) and reached their individual requested CD34+ progenitor cell target (72%). 57% of the PM patients achieved >2.0 × 106 CD34+ progenitor cells/kg body weight on day 1 of apheresis and nearby 70% of them underwent ASCT. Median time to engraftment was similar in PM and GM patients of the lymphoma cohort. Conclusions: Majority of PM patients with lymphoma were successfully mobilized and underwent ASCT. Most of them received PLX during the study.

Predicting Successful Hematopoietic Stem Cell Collection in Healthy Allogeneic Donors

Introduction: Collection of peripheral blood stem cells (PBSCs) from healthy donors is a well-established process. We aimed to identify factors predictive of successful CD34+ PBSC collection and established a formula capable of predicting CD34+ cell yield. Methods: We retrospectively evaluated 588 healthy adult donors (median age 29 years, range 18–69 years) at our institution from 2017 to 2022. The predicted minimal number of CD34+ cells was calculated as follows: (peripheral CD34+ cells/µL × adjusted collection efficiency of 30%) × total liters processed. This formula was further modified according to donor and recipient body weight (BW). Results: Median total collection was 8.0 × 106 CD34+ cells/kg BW (range 1.0–47.1 × 106 cells/kg BW) with 522 donors (89%) collecting ≥5.0 × 106 cells/kg of recipient BW. A second leukapheresis (LP) was performed in 49 donors. Need for two LPs was more common in female donors (OR 6.68, 95% CI, 2.62–17.05; p p = 0.003), donors with WBC count 9/L after 5 days of granulocyte-colony stimulating factor (G-CSF) stimulation (OR, 4.33; 95% CI, 1.59–11.83; p = 0.004), and a donor/recipient weight ratio p 6 CD34+ cells/kg of recipient BW) were peripheral blood (PB) CD34+ cell count >50/µL (OR 12.82, range 6.34–25.92, p p = 0.04), and a donor/recipient weight ratio >1 (OR 3.12, range 1.57–6.24, p = 0.001). WBC, platelets, hemoglobin, and age had no significant predictive value. Predicted versus observed number of CD34+ cells/kg BW collected demonstrated a very strong linear correlation (r = 0.925, 95% CI, 0.912–0.936, p Conclusions: Of the routinely monitored indicators in PBSC donors, CD34+ cell count in PB is the most important factor in predicting G-CSF-induced PBSC yields. Higher age, female sex, WBC 9/L, and a donor/recipient weight ratio

A tale of two peripheral blood CD34+ cell counts: Evaluation of unexpectedly high values prior to peripheral stem cell collection

Hematopoietic stem cells (HSCs) form the foundation of treatment for many hematologic and neoplastic diseases. The ability to collect HSCs that have been released into peripheral blood (PB) rather than harvesting from bone marrow (BM) directly has dramatically improved the likelihood of successful collection while minimizing donor discomfort [1]. To facilitate the release of HSCs into PB, cytokines that stimulate cell proliferation and agents that directly antagonize stromal adherence factors are administered for several days pre-collection.

Selinexor in Combination with R-GDP for Patients with Relapsed/Refractory B-Cell Lymphoma: Final Results of 18 Patients Treated at RP2D of Selinexor in the Selinda Phase Ib Lysa Study

Background: Salvage chemotherapy followed by high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) is an option to treat young patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). A complete remission before ASCT is the most important prognosis factor for a better outcome. Selinexor is a first-in-class, oral selective inhibitor of nuclear export which, through XPO1 blockade, causes nuclear accumulation and activation of tumor suppressor proteins, reduction in oncoproteins and cancer cell apoptosis. Selinexor has been approved by the US Food and Drug Administration for the treatment of R/R DLBCL, including de novo or transformed from follicular lymphoma (FL) pts after ≥2 therapies. The phase Ib SELINDA (EUDRACT 2015-005612-15) study assessed safety and efficacy of selinexor, in combination with R-GDP for pts with R/R B-cell lymphoma. Patients & methods: Eligible pts <70 years with R/R B-cell lymphoma after first or second treatment failure received every 21 days (d) 3 cycles of rituximab 375 mg/m² on D1, dexamethasone 40 mg on D1 to 4, cisplatin 75 mg/m² D1 and gemcitabine 1000 mg/m² on D1 and 8 (R-GDP) in combination with escalating doses of selinexor. Two dose levels of selinexor, 40mg and 60mg, were evaluated via 3+3 design. Initial dosing of selinexor for dose level 1 (DL1) was 40 mg on D1, 3, 8, 10. The dosing was modified to 40mg and 60mg on D1, 8, 15 for DL1 and DL2, respectively. The primary endpoint of SELINDA was the determination of the recommended phase 2 dose (RP2D) of selinexor in combination with R-GDP. Secondary and exploratory endpoints were safety, efficacy, and feasibility of ASCT after selinexor-R-GDP. Results: The R2PD for selinexor in combination with R-GDP was established as 40mg on days 1, 8, and 15 (Maerevoet, IMCL 2021#176). Between January 2017 and January 2021, 32 pts received selinexor-R-GDP. We focused on the 18 pts who received the R2PD: 15 had DLBCL, 2 FL, 1 marginal zone lymphoma. In this cohort, median age was 61 years (range 44-69); 14 pts (78%) had stage III/IV, 6 had disease refractory to last treatment, 12 had relapsed. Thirteen pts received 1 previous line of treatment before inclusion, 5 pts received 2 previous lines. Four pts prematurely discontinued treatment: 2 for thrombocytopenia, 1 for COVID, 1 for disease progression. Major adverse events (AEs) in >10% of pts were reversible neutropenia (55 %), thrombocytopenia (44 %), and nausea (22%). No fatal AEs were observed. One patient is not evaluated, 7 pts (39%) achieved a complete metabolic response (CMR), 5 pts (28%) partial metabolic response (PMR) and 5 pts (28%) stable disease or progressive disease. According to Lugano criteria's, overall response rate (ORR) assessed at the end of treatment was 67%. Nine of the 15 pts (60 %) with DLBCL had metabolic response (CMR: 4, PMR: 5). Per protocol, peripheral stem cell collection and ASCT were optional, 4 pts of this RP2D cohort proceeded to high dose therapy with BEAM conditioning and ASCT. For this RP2D cohort, the 1-year overall survival is 72.2% and the 1 Year-PFS is 45%. The median duration of response was not reached (95%CI: 0.4-NA) (figure 1) Conclusion: This study established the safety profile of weekly 40mg of selinexor in combination with R-GDP for R/R B cell lymphoma with an ORR of 67%, the median DOR is not reached. Reversible AEs were as expected for a platinum combination regimen. An ongoing randomized phase 2 study comparing R-GDP with or without selinexor in pts with R/R DLBCL will further evaluate the safety and efficacy of the combination. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Does Choice of Salvage Regimen Impact Stem Cell Mobilization in Hodgkin's Lymphoma?

INTRODUCTION: Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care in the management of relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Historically, salvage chemotherapy regimens such as ICE (Ifosfamide, carboplatin, and etoposide) and GDP (gemcitabine, dexamethasone, cisplatin) have been used. However, newer regimens such as bendamustine with brentuximab-vedotin (BBV), and BV with nivolumab are being increasingly used owing to their improved efficacy. The impact of the newer regimens on subsequent mobilization and collection of peripheral blood stem cells (PBSCs) for ASCT is not studied in detail. Furthermore, despite its well reported use, the mobilizing agent "plerixafor", which is approved for multiple myeloma and non-Hodgkin lymphoma, is not FDA approved for HL. This creates a logistic barrier in using it in HL patients. METHODS: We conducted a retrospective chart review of patients with R/R HL referred to Karmanos Cancer Institute and considered for ASCT between January 1, 2015, and December 31, 2021. Patients were grouped in two groups based on the pre-ASCT salvage chemotherapy regimen used: ICE/GDP and BBV. We analyzed multiple parameters to study the impact of ICE/GDP versus BBV on mobilization/collection of PBSCs for ASCT in R/R HL. We also describe our institutional experience with the usage of plerixafor in addition to G-CSF for PBSC mobilization. RESULTS: A total of 53 patients with R/R HL who underwent mobilization for ASCT. The salvage regimen was ICE/GDP in 33 (62%) and BBV in 20 (38%) patients. There was no difference in the median age at diagnosis (32 vs 37 years, p=0.59), and distribution of sex (p>0.99), race (p>0.99) and ECOG performance status (p=0.60) (See Table 1). Majority of the patients received ABVD/AVD (Adriamycin, bleomycin, vinblastine, dacarbazine) as their initial treatment (ICE/GDP 91% vs BBV 85%, p=0.06), with a median of 6 cycles (p=0.16), and no difference in the use of radiation therapy (p=0.14). Thereafter, around two-third of the patients underwent salvage chemotherapy for relapsed, and one-third for refractory disease in both arms. The median number of cycles was 2 (1-4) versus 3 (2,4) (p=0.267), and the CR rate was 67% versus 80% in ICE/GDP and BBV respectively (p=0.36). Stem cell mobilization was performed using G-CSF and median peripheral CD34 count (×106) on day 1 of collection was higher at 22.5 (range, 4.12-314) in the ICE/GDP group versus 13.1 (0-97.15) in the BBV group (p=0.049). Twenty (61%) patients in the ICE/GDP had a successful stem cell harvest following G-CSF (>2 million cells/kg) compared to 5 (25%) in the BBV group on first planned day of collection (p=0.02). Among the patients who failed successful stem cell collection with G-CSF on the first day of collection, 6 (46%) received plerixafor in the ICE/GDP and 7 (46%) in the BBV group (See Table 2). Notably, 3 (23%) patients in the ICE/GDP whereas 7 (46%) patients in the BBV group failed the first attempt of mobilization and had to undergo a separate second attempt with GM-CSF, cyclophosphamide and/or plerixafor. The cumulative number of mobilizing agents other than filgrastim used in any attempt was 11 (0.3 per patient) and 15 (0.75 per patient) in ICE/GDP and BBV groups respectively. Furthermore, 2 patients in the BBV group had a failure of adequate mobilization/collection of PBSCs despite more than one attempt, and were unable to proceed with ASCT. One of these patients died of progressive HL. In contrast, all the patients were able to undergo ASCT in ICE/GDP group. There was no difference in the day of neutrophil or platelet engraftment between the two groups. CONCLUSIONS: We conclude that BBV regimen led to poor mobilization and collection of stem cells on the first day, consequently requiring additional mobilization agents/attempts. Although, PBSC collection and subsequent ASCT was eventually successful in a majority of the patients in the BBV group, two patients in our population failed to undergo ASCT given inadequate mobilization/collection. With the increasing utilization of brentuximab-vedotin in salvage as well as in the first line setting, larger studies are needed to study its impact on PBSC collection and ASCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High-Dose Idarubicin Plus Busulfan As Conditioning Regimen to Autologous Stem Cell Transplantation Improves Prognosis in Patients with Favorable and Intermediate-Risk AML

Introduction: The optimal post-remission therapy (PRT) for patients with favorable and intermediate-risk acute myeloid leukemia (AML) remains uncertain. We retrospectively analyzed and compared the efficacy of high-dose idarubicin plus busulfan conditioning regimen combined with autologous stem cell transplantation (ASCT) and intermediate- to high-dose cytarabine consolidation chemotherapy for post-remission treatment (PRT) in patients with favorable- and intermediate-risk AML. Methods: A total of 116 patients with favorable- and intermediate-risk AML according to 2022 ELN risk stratification who were treated with ASCT (n=58) or intermediate- to high-dose cytarabine regimen (n=58) were enrolled in this study. All the patients received IA regimen (idarubicin 10-12 mg/m2 on days 1 to 3 and cytarabine 100 mg/m2/d on days 1 to 7) as induction and complete remission (CR) was obtained in all the patients after one course of induction. Fifty-eight patients were subjected to 2-4 courses of intermediate- to high-dose cytarabine (cytarabine 2-3 g/m2 twice daily on days 1-3). High-dose idarubicin plus busulfan conditioning regimen (I-Bu; idarubicin 20 mg/m2 continuous i.v. from days -13 to -11, busulfan in intravenous formulation: 3.2 mg/m2 or oral formulation: 4.0 mg/m2 from day -5 to -2) combined with ASCT was given to the other 58 patients 2-3 courses of intermediate- to high-dose cytarabine and mobilization and collection of peripheral blood stem cells. Clinical outcomes were retrospectively analyzed for patients belonging to the two treatment arms. Results: The median age was 38 (14-60 years) and 32 years (14-59 years) in ASCT and chemotherapy cohort, respectively. After a median follow-up of 68 months (1-200 months), and the median overall survival (OS) has not been reached in both groups. The 5-year and 10-year OS in the ASCT group was 77.5% and 71.5%, and 5-year and 10-year disease-free survival (DFS) was 73.9% and 71.1%, respectively. The 5-year OS and DFS in the chemotherapy group were 53.5% and 52.4%, respectively. The median OS and DFS of the patients in ASCT group were significantly better than those in chemotherapy group (OS: p=0.009, HR=0.444, CI 0.237 to 0.831; DFS：p=0.018, HR=0.494,CI 0.268 to 0.911). No treatment-related early death (death within 8 weeks after treatment) was observed in the ASCT group. All the patients experienced severe bone marrow suppression and severe (grade 3 or 4) hematological toxicity, and we did not observe severe (grade 3 or 4) cardiotoxic complications during or after ASCT in all the patients. Conclusions: ASCT with I-Bu regimen is possibly a promising PRT for patients with favorable- and intermediate-risk AML in the first CR, improving prognosis of these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of CD34+ Cell Count at Different Time Points Following Plerixafor Administration in Autologous Hematopoietic Stem Cell Transplantation

Background: In apheresis, collecting an adequate number of CD34+ cells is required for successful autologous hematopoietic stem cell transplantation (auto-HSCT) procedure. It is difficult to harvest a sufficient number of stem cells in certain patients due to their old age and history of intensive chemotherapy. Plerixafor could mobilize stem cells and facilitate peripheral blood hematopoietic stem cell collection. However, not enough information is available on the appropriate time intervals from plerixafor administration to apheresis. Objectives: In this study, we aimed at evaluating the level of peripheral blood CD34+ cells at plerixafor administration time and every three hours to identify the peak time of circulating CD34+ cells. Methods: Circulating CD34+ cells were enumerated by flow cytometry on day 4 post mobilization. Plerixafor was administered to patients with poor mobilization based on the count of peripheral blood hematopoietic stem cells. The number of circulating CD34+ cells was evaluated before and 3, 6, 9, and 12 hours after plerixafor administration to assess the time it takes for stem cells to reach their peak level. Results: The highest level of stem cell concentration was found in 9 hours after plerixafor administration with an increasing trend. A statistically significant relationship was also observed between factors including platelet count on the first day of GCSF injection and the day of stem cell infusion, leukocyte count on admission, and basal levels of CD34+ cells in peripheral blood and the amount of harvested stem cells. Conclusions: We demonstrated that plerixafor causes an incremental trend in CD34+ cells mobilization, reaching its peak after 9 hours. Further research should be performed to provide insights into graft cells’ population and hematologic and immunological recovery.

326 - Central Venous Access for Peripheral Stem Cell Collection in Autologous Donors: Safety-Related Outcomes of an Outpatient Transplantation Program

326 - Central Venous Access for Peripheral Stem Cell Collection in Autologous Donors: Safety-Related Outcomes of an Outpatient Transplantation Program

Successful "on-demand" plerixafor for autologous peripheral blood stem-cells transplantation for relapsed/refractory germ cell tumors.

BackgroundGerm cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first‐line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high‐dose chemotherapy and autologous stem‐cells transplantation as second‐line treatment even though stem‐cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label.Materials and methodsIn our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/μL) and CD34+ cell count (<15/μL) the day before apheresis procedure.ResultsOn the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/μL vs 35/μL, respectively, P > .05).ConclusionTherefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem‐cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis.

Selinexor in Combination with R-GDP for Patients with Relapsed/Refractory B-Cell Lymphoma: Results of the Selinda Phase Ib Lysa Study

Selinexor in Combination with R-GDP for Patients with Relapsed/Refractory B-Cell Lymphoma: Results of the Selinda Phase Ib Lysa Study

Central Venous Access for Peripheral Stem Cell Collection in Autologous Donors: Safety within an Outpatient Transplantation Program

IntroductionOne important aspect of quality assurance in transplantation relates to the maintenance of central venous access (CVA), especially in outpatient conditions in which patients have a higher degree of activity and manipulation of CVA tends to be more frequent. A comprehensive program oriented to prevent and control complications related to CVA insertion, maintenance and removal is thought to be a highly effective strategy to improve safety outcomes.MethodsA retrospective study evaluating complications related to central venous access (CVA) in patients undergoing hematopoietic stem cell transplantation (HSCT) was conducted using electronic medical records (EMR) at our center. Laboratory and radiology reports were collected in order to identify complications related to CVA. Patients from May 2015 to July 2021 were included in the study. As per local protocol, insertion of Mahurkar catheter for cell collection is conducted by an experienced surgeon under general anesthesia on day -3 and after a short-stay (6 hours) in hospital patients are discharged. On day -2, cell collection is accomplished following all cautionary measures and removal of catheter is done on day -1. Maintenance and care of CVA is guided by standardized protocols related to cleaning, manipulation, blood sample collection and removal. All patients signed a consent to participate in the study and the study protocol was approved by Clínica Ruiz IRB. To be considered as statistically significant, results had to display a two-sided p value <0.05.ResultsA total of 1088 patients recruited since May 2015 were included in the study. Main indication for auto-HSCT was multiple sclerosis with 1066 (98%), followed by chronic inflammatory demyelinating polyneuropathy with 16 (1.5%) and 5 (0.5%) patients with other autoimmune disorders. Median age of donors was 46 (40 - 54) years. Median dose of CD34 + cells x10 6/kg infused per patient was 7.0 (3.7 - 11.3) and the median of collection events per patient was 1 (1 - 2). Cell collection was accomplished via apheresis in (99.5%) of patients, of those CVA was used as collection site in 998 (92%) patients, while a change for peripheral venous access occurred in 85 (8%) patients, due to different reasons, most frequent being any type of CVA obstruction in 62 (83%) of donors. Pneumothorax occurred in 11 (1.1%) patients in whom CVA was used for collection. All cases were successful managed with pleural drainage and hospital admission longer than 24 hours was required for 3 (27%). Furthermore, catheter-related bloodstream infections were identified in 3 (0.3%) patients whom were admitted and treated with broad-spectrum antibiotics and discharged with no further events. There were no misplacement, thrombotic- nor hemorrhagic-related events in patients with CVA. A multifactorial analysis revealed that relevant factors such as, age, sex and type of disease were not correlated with any type of CVA-related complications.ConclusionsWe have shown that prevention and control of complications related to CVA at our campuses are highly effective. The proportion of patients experiencing a CVA-related complication was minimal in comparison with other experiences. DisclosuresGomez-Almaguer: Roche: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau.

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells

Factors affecting the mobilization and collection of autologous peripheral blood hematopoietic stem cells