Peripheral Blood Stem Cell Collection Research Articles

Safe peripheral blood stem cell collection in patients less than 10 kg: A single-center review.

Peripheral blood stem cell collection (PBSCC) is well-documented in adults and pediatric patients with larger total blood volume (TBV). However, very little data are available for the successful PBSCC of pediatric patients weighing less than 10kg. Here, we highlight our institutional approach to PBSCC in this smaller-sized patient population. Our protocol, including blood prime, was reviewed for PBSCC for bone marrow transplantation (BMT) in 18 children weighing 4.5-9.9kg who safely underwent 37 PBSCC procedures at a single institution, Children's Hospital Colorado, between September 2016 and February 2022. We attained the individualized collection goals in all 18 patients with an average yield of 17.03 million CD34+ cells/kg of patient body weight (range: 0.84-67.45 million/kg). The average collection efficiency of the procedures was 41.5% (range: 23.0%-71.5%). We performed all 37 procedures safely and without complication. The estimated average TBV was 587 mL (range: 351-765 mL), the average blood volume processed was 596 mL (range: 351-756 mL), and the average TBVs processed was 2.5 (range: 1-4). PBSCC in patients ranging from 4.5 to 9.9kg is safe and effective for collecting peripheral blood stem cells for BMT.

A survey on preoperative autologous blood donation policy in bone marrow stem cell donors in Italy.

The high safety of homologous blood components, together with the introduction of the Patient Blood Management strategy, has led to the progressive abandonment of preoperative autologous blood donation (PAD) in surgery. Furthermore, recent scientific publications provide evidence about the non-usefulness of PAD in the collection of hematopoietic stem cells (HSC) from bone marrow (BM), also in consideration of harvest procedure safety. Nevertheless, no conclusive studies have been published yet. Blood Establishments (BE) and Bone Marrow Collection Centers (BMCC) participated in a specific qualitative survey proposed by Italian National Blood and Transplant centers with the support of the relevant Italian Scientific Societies. The survey aimed at evaluating the policy adopted for PAD in related and unrelated adult HSC donors in Italy during the period 2018-2020. Forty-one BE corresponding to 37 BMCC filled in the questionnaire. Of 830 BM donors, 661 (80%) underwent 1063 PAD (mean 1.6 PAD/donor). The remaining 169 donors (20%) underwent BM harvest without PAD. No serious adverse events were reported for either donor group. In the case of ineligibility of donors for the PAD program, due to low hemoglobin values, 7/10 centers shifted donors to peripheral blood stem cell collection and three centers chose a different donor. Remarkably, only 51% of the PAD units requested were eventually transfused during the BM harvest process. Finally, the iron support policy among centers was heterogeneous. The results of this survey show that PAD is heterogeneously applied in Italian BMCC, as in other countries. However, all BMCC except two are willing to adopt a Patient Blood Management strategy as an alternative approach to adult related and unrelated BM donor harvests.

Strategies to Optimize the Utilization of Stored Autologous Peripheral Blood Stem Cells for Second Transplantation in Multiple Myeloma

Introduction: Autologous stem cell transplantation (ASCT) is the standard of care and a mainstay in the management of eligible patients with multiple myeloma (MM) and remains relevant in the era of novel therapeutics. ASCT requires stem cell mobilization to collect ample stem cells to provide hematological recovery after myeloablative conditioning. Second ASCT (ASCT2) as salvage therapy in relapsed/refractory MM (RRMM) is a treatment option for patients who achieved disease control for 2 to 3 years after first ASCT (ASCT1). The reported difficulties in mobilizing and collecting additional stem cells following myeloablative ASCT1 have led to the currently adopted practice to collect and store adequate peripheral blood stem cells (PBSCs) for two transplants before ASCT. The preferred PBSC cell dose is 2 to 5 × 106 CD34+ cells per kilogram of recipient weight (CD34+ cells/kg) per transplant; however, with the influx of effective novel agents available for RRMM, the use of ASCT2 is declining. A retrospective cost utilization study showed that at a median follow-up of 3.5 years, only 3% of the cohort received ASCT2. The additional cost of collecting and storing these products is an average of 16,590 USD/patient. Given the limited use of salvage ASCT2, current practice of collecting PBSCs for two transplants should be re-evaluated and carefully selected case-by-case. We investigated potential strategies to reduce the financial burden of PBSC collection, processing, and storage by identifying a subgroup of patients who are less likely to receive an ASCT2, herein avoiding storing extra cells. Materials and Methods: With Institutional Review Board approval, we performed a retrospective descriptive analysis of all MM patients who underwent frontline ASCT from 1/1/2012 to 6/23/2022. We excluded patients who had planned tandem transplants and those who underwent a single ASCT and had all cells infused with no remaining stored cells. We classified all patients who collected a sufficient cell dose for ASCT1 and ASCT2 into two cohorts according to the number of ASCT received; those who received ASCT1 and those who received ASCT1 and ASCT2. Results: We report the descriptive statistics of eligible MM patients from a single stem cell transplant center. Over a median follow-up of 2.0 years, we report findings of 240 patients who collected sufficient PBSCs for ASCT1 and ASCT2. Patients’ median age at PBSC collection was 61 (range 32-77). We classified our cohort by gender, age, race, and average number of days for PBSC collection. We aim to collect a cell dose of 10 x 106 CD34+ cells/kg. Our cohort included more males than females (132/108) and a higher prevalence of African Americans (59%) than Caucasians. Our study showed that only 7% of patients underwent ASCT2 (17/240) with average time between ASCT1 and ASCT2 of 2.9 years. We noticed that 88% (15/17) of patients who received ASCT1 and ASCT2 were ≤ 61 years old at the time of ASCT1 and two patients (12%) were ≥ 70 years. Additionally, a higher proportion of patients utilizing ASCT2 in the youngest age groups is noticeable. Six of 30 patients under 50 years and three of seven patients under 40 years of age (20% and 43%, respectively) underwent ASCT2. The data highlights that utilization of ASCT2 is less common in the elderly population; hence considering PBSC collection for one transplant among the elderly would be a cost-effective strategy. Most stem cell transplant centers inherited a strategy to collect PBSC 10 x 106 CD34+ cells/kg. We noticed that 102 patients required >1 day of PBSC collection to meet the collection goal. Of these patients, 35% were age 65 or older. If we were to change practice and consider PBSC collection for one transplant among the elderly, we could have reduced the number of collection days by 25 and reduced the associated costs of collection, processing, storage, and staffing, as well as space requirements for storage. Conclusion: The utilization of ASCT2 in MM patients is decreasing with the influx of novel therapeutics. Potential strategies are needed to change the practice and reduce the additional financial burden of excess stem cell collection and storage. We suggest that elderly MM patients be considered for PBSC collections for a single transplant. 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

Altered Cellular Sedimentation during Apheresis Impacts Outcomes of Peripheral Blood Stem Cell Collection Efficiency in Patients with Sickle Cell Disease

Recent reports have demonstrated the potential for gene therapy as a therapeutic option to achieve a durable cure in patients with sickle cell disease (SCD). However, for these emerging cell therapies, relatively large numbers of peripheral blood hematopoietic stem cells (PB HSCs) are required to generate a therapeutic dose. Outcomes of stem cell collections in patients with SCD are highly variable, at times yielding far fewer numbers of HSCs in the product than predicted by the number of PB CD34+ cells. While the CXCR4 antagonist plerixafor has emerged as a safe and reliable drug to mobilize CD34+ cells in patients with SCD, collection failures continue to occur requiring additional cycles or failure to generate a gene therapy product. We sought to understand the mechanics affecting stem cell sedimentation in real time and posited that SCD disease associated changes to red cells results in altered HSC sedimentation during apheresis, negatively impacting collection. Methods Autologous PB stem cell collections were performed in patients with SCD following mobilization with 240ug/kg plerixafor. To uncover the mechanisms impacting apheresis efficiency for collecting PB HSCs, we devised a method to interrogate the sedimentation of cells in peripheral blood in real time, by interrupting the return collection circuit line. Cellular composition analyses of the collecting interfaces were performed including CD34+ enumeration by flow cytometry, CBC and differential, reticulocyte counts, and surface CD47 expression of red blood cells (RBCs). Results Patients were mobilized with 240ug/kg of plerixafor up to 6 hours before apheresis collection. We collected fewer cells than predicted (3.78 million cells/kg) in these patients with an overall average apheresis collection efficiency of 38%, and a strikingly wide range of 2%-107%. We determined that the lower collection efficiency outcomes were primarily derived when using standard apheresis interface settings. The pre-apheresis PB CD34+ counts were less predictive of total CD34+ cells collected (p=0.012) in patients with SCD (r2=0.2557, p=0.0023) when compared to historical control patients without SCD (r2=0.7638, p<0.0001). Real time measurement of cell counts at standard (Hematocrit 3%, S) and deep (Hematocrit 5%, D) collecting interfaces of the apheresis machine showed a significant decrease in lymphocytes (p=0.0146), increase in monocytes (p=0.0496), and increase enrichment in CD34+ cells at the D interface (Panel A). Enrichment of CD34+ cells correlated with monocyte enrichment and (n=21, r2=0.6706, p<0.0001) and an increased fold change in CD34+ cells between the S and D interfaces correlated with higher PB reticulocyte percentage (r2=0.5295, p=0.0111). Further analysis of the individual collection interfaces revealed that most RBCs were HbS containing despite a PB HbS concentration <30%, consistent with an enrichment for shorter lived sickle red cells. CD47 expression has been previously reported in higher concentrations on the surface of younger RBCs during erythropoiesis. Surface expression of CD47 was found to be significantly higher at both the S and D interfaces compared to the PB of patients, indicating that the accumulation of a younger population of RBCs at the collecting interfaces. As microcytic RBCs have been associated with poor collection efficiencies, the SCD red cell hemoglobin concentration in the PB was used as a marker for size and a significant correlation was determined (r2=0.6086, p=0.0001). Patients with SCD can mobilize PB HSC in response to plerixafor but demonstrate specific characteristics that impede the collection of stem cells. During apheresis, CD34+ stem cells sediment at a deeper hematocrit interface in the buffy coat as a result of displacement by the younger patient-derived population of RBCs. The relative shift in erythrocyte sedimentation requires a corresponding alteration in collection strategies to improve the collection efficiency. In addition to red cell age, other factors that affect red cell buoyancy including iron status or additional globin gene mutations negatively impact apheresis stem cell collections. Full assessment of red cell parameters can identify patients that are at risk for poor stem cell collection outcomes. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Same Players, Better Results: How Experience and Growth Factors Better Usage Improve Peripheral Blood Stem Cells Collection Outcome

The Same Players, Better Results: How Experience and Growth Factors Better Usage Improve Peripheral Blood Stem Cells Collection Outcome

Genetic Landscape of BPDCN Arising in CML Remission

Background BPDCN (blastic plasmacytoid dendritic cell neoplasm) is a rare and highly aggressive hematologic malignancy which often affects skin lesion. BPDCN initially responds to traditional chemotherapy, but has a high relapse rate and a poor prognosis even after autologous or allogeneic stem cell transplantation (SCT). Almost all patients have CD123 positive tumor, and CD123 targeting therapies are being developed. BPDCN mainly develops de novo, however, up to 20% of BPDCN patients have prior history of other hematologic malignancies (CMML, AML, MDS). Some groups propose to classify BPDCN with PCHM (preexisting or concurrent hematologic malignancies) into a unique subtype based on the clinical course (Blood (2019) 134 (Supp.1): 2723). On the other hand, there are attempts to classify BPDCN according to molecular profile, and they defined two subclasses based on somatic mutations (Blood Cancer Journal (2022) 12:101). Thus substantial efforts are being made to classify BPDCN from various aspects, the classification is still under development due to insufficient number of cases. Herein we experienced a rare case of BPDCN arising in the course of CML as a history of PCHM. Unexpectedly, there have been no reports of BPDCN with preexisting CML, therefore, we report the clinical course and genetic background in our case. Case: 70 year old male Clinical course of CML: He was referred to our hospital at age 60 with elevated white blood cell count (93,550/ul, blast 1.0%). Diagnosis of CML (chronic phase) was made; Sokal score was 0.31 (low risk). With initial therapy of dasatinib 100 mg, his disease status achieved complete molecular response (CMR) at 24 months of treatment; achieved CMR (MR 4.5) at 43 months. Due to side effects (pleural effusion and cytopenia), dasatinib was discontinued at month 74 of treatment, and however, CMR has been maintained. Clinical course of BPDCN: At 48 months after completion of dasatinib treatment, multiple bruise-like skin lesions appeared on the head and abdomen. Skin biopsy revealed diffuse proliferation of blastic cells. Immunohistochemistry and flow cytometry were positive for CD4, CD56, and CD123, and a diagnosis of BPDCN was made. Bone marrow involvement (13%) was also observed. HyperCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and arabinocytocine) was selected as induction therapy. The skin and bone marrow lesions rapidly improved and the patient achieved hematological remission, but a few CD123-positive tumor cells remained in the bone marrow. Considering autologous SCT, peripheral blood stem cell collection was performed. Unfortunately, the graft was contaminated with CD123-positive cells, and it was determined that autologous SCT was not expected. Allogeneic SCT was not planned due to age and regimen related toxicity. We are currently preparing to conduct a clinical trial of CD123-targeting agent. Molecular Analysis WES of peripheral blood and bone marrow samples was performed. At the hematological remission after 2 cycles of HyperCVAD/MA, high VAF mutations in the splicing factor ZRSR2 gene (p.Y292X (84.6-85.2% VAF)) as well as the histone modifiers ASXL1 (p.L743fs (40.6-43.1% VAF)) and TET2 (c.3955-2A>G (36.2-38.3% VAF), p.T1959fs (42.1-47.0% VAF)) were observed. ZRSR2 nonsense mutation site in our case was located 3 residues upstream of the previously reported site, which has not been reported in previous BPDCN cases (Cancer Discovery (2022) 12: 522-541). Although the tumor cell rate in each sample was less than 10%, the VAF of ZRSR2 mutation was high (84.6-85.2%), indicating that clonal hematopoiesis with ZRSR2 mutations underlies the development of BPDCN. Conclusion This is the first report of BPDCN with a history of CML as a preceding hematologic malignancy. Based on WES data at the remission of BPDCN, we confirmed that the patient had clonal hematopoiesis with not only ASXL1 and TET2 mutations, but also ZRSR2 mutation, a driver mutation characteristic of BPDCN. Despite the fact that clonal hematopoiesis with ASXL1 and TET2 mutations is occasionally observed after CML treatment with TKIs (Blood (2017) 129: 38-47), there were no case reports of BPDCN in patients with preexisting CML. These facts suggest that the presence of mechanism is essential for the development of BPDCN other than driver mutation in ZRSR2. Further investigation of BPDCN with PCHM would provide useful information on the pathogenesis of BPDCN. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Peripheral blood stem cells collection by apheresis in very low-weight children with malignant diseases-A single center experience.

Hematopoietic stem cell transplantation is used in the treatment of children with malignant and non-malignant diseases. However, apheresis of peripheral blood stem cells (PBSC) represents a challenge in children below 10kg. A retrospective trial was conducted in the Cellular Therapy Department of Portuguese Oncology Institute of Porto. children with body weight inferior to 10kg who underwent autologous PBSC apheresis until 2021. Demographic and clinical data were collected and our institutional protocol was described. COBE Spectra apheresis system (TerumoBCT, Lakewood, Colorado) until 2012 and then Spectra Optia (TerumoBCT) were used. Sixteen leukocytaphereses were performed in 13 patients-nine females (69%). Mean age and weight were 13.31 months (±5.26) and 8.31 kg (±1.17), respectively. The initial CD34+ cells/μL in peripheral blood was 70.8 (±61.9). A central venous catheter (CVC) was exclusively used in all but one patient, in whom a peripheral vein was also required. In 10 procedures, both heparin and anticoagulant citrate dextrose solution-formula A (ACD-A) were used; in the remaining ones, only ACD-A was employed. The median duration of each procedure was 168 minutes (±45) and 2.96 blood volumes (±0.31) were processed. Median CD34+ cells yield per leukocytapheresis was 6.52 × 106 /kg (±9.87 × 106 ). CD34+ cell extraction rates were not significantly different between the two apheresis systems. Platelet and magnesium levels were significantly lower after collection (P < .001 and P=.009, respectively). Although recommendations are lacking, we have successfully and safely performed leukocytaphereses in children with body weight below 10kg. The authors believe that a permanent and dynamic comprehensive evaluation of each child is paramount for attaining good results.

VALIDATION OF LONGER FRESH STORAGE TIME FOR PERIPHERAL BLOOD STEM CELLS INTENDED FOR CLINICAL USE

Peripheral blood stem cells (PBSC) storage conditions may influence cell quality and/or functionality, which may directly impact recipients'clinical outcomes. Thus, the Brazilian Health Regulatory Agency (ANVISA) demands validation of fresh storage times greater than 48 (forty-eight) hours, with technical-scientific evidence about the quality and safety of the product. The aim of this study was to verify the effects of longer fresh storage times in the viability and functionality of PBSC intended for Hematopoietic Progenitor Cells (HPC) transplantation. Ten aliquots of PBSC units were analyzed. The samples were storage fresh at 2°C to 8°C. Measurements were performed immediately (I) and 72 h after PBSC collection storage (AS), by flow cytometry analysis and clonogenic assays. CD45+ and CD34+ cells viability, white blood cells (WBC) counts and CD34+ cell concentrations and colony forming units (CFU) were evaluated. All clonogenic assays were performed in duplicate with 1 × 10 4 cells/mL. The results of these assays were expressed as the arithmetical mean of the duplicates. A descriptive analysis and T-dependent test were performed (SPSS 15 software). : According to the in-process controls, the median interval between the end of collection and temporary storage was 72 hours, with the maximum time being 91 hours and 48 minutes and the minimum storage time being 69 hours and 25 minutes. This variation in storage time is due to the end time of some collections that were longer than the laboratory's operating hours, so the samples had to be analyzed within the possibilities of the routine. Median viability of CD34+ cells immediately after collection was 100%, minimum viability was 98.8%, so all cases were in compliance with the laboratory quality indicator target. The median viability of CD34+ cells after fresh storage was 99.75%. There were two cases with viability below 98%, and the minimum viability was 97.1%. The average loss of viability of CD34+ cells in relation to the mean obtained in fresh samples was 0.66%. One case had a 2.99% loss of viability. Despite the significantly decreased CD45+ cells viability after storage (I: 98,3%; AS: 90,4%; p =< 0,0001), no significative changes were noted in CD34+ cell viability (I: 100%; AS: 99,75%), as well as in WBC (I: 248350/μl; AS: 242705/μl) and CD34+ cells (I: 5,24 × 10 6 /kg; AS: 4,67 × 10 6 /kg) concentrations. Moreover, no significant decrease in colony-forming unit numbers was observed in units stored for 72 hours (I: 34,5; AS: 21,5). Despite the significant decrease in CD45+ cell viability after 72 hours storage, no significant changes were observed in CD34+ cell viability, as well as in WBC and CD34+ cell concentrations in the same period. These results are reinforced by the functional assays, in which no significant decrease in colony-forming unit numbers was observed and it also demonstrated that the cells maintain their proliferation and differentiation potential. These results lead to the assumption that the fresh storage time of 72 hours had no significative impact in variables of concern (CD34+ cells and clonogenic assays) and thus does not impact the quality and safety of the product. Nonetheless, despite the strong recommendation of infusing fresh graft as soon as possible, our data suggest that, when necessary, it is safe to use PBSC until 72h after collection.

HL-041 The Efficacy and Safety of BV-ICE Salvage Therapy for Relapsed/Refractory Hodgkin Lymphoma: A Single-Center

ASCT is the standard of care in R/R HL. Brentuximab-vedotin (BV) has been studied as maintenance post-ASCT, as single-agent after failure chemotherapy or in combination with different protocols. This study is to evaluate the CMR post salvage BV-ICE in patients with R/R HL prior to ASCT. The secondary endpoints: PFS, OS, RR, safety profile, and the delay to platelets and neutrophils engraftment post ASCT. Retrospective study of patients with R/R HL treated and followed at AUBMC between 2018 and 2021 Results: We identified 14 R/R HL patients, median age 30 yrs. 13 were nodular sclerosis (NS) subtype. 1 patient had mixed cellularity. All received ABVD initially. Median duration from diagnosis to relapse was 9.6 months. Patients were divided into 3 categories, 43% primary refractory, 21% relapsed within 3 to 12 months, 36% relapsed after 12 months from initial therapy. 57% were stage II on relapse and 36% stage IV. 14% received E-BEACOPP and 7% received DHAP as 1st salvage therapy. 21% received BV-ICE as 2nd salvage and 79% received BV-ICE as 1st salvage. Median duration from 1st relapse to BV-ICE was 1 month. BV was given on day 1 at 1.8mg/kg IV, etoposide 100 mg/m2 IV on days 1-3 and ifosfamide 5mg/m2 plus mesna 5g/m2 IV over 24 h on day 2, carboplatin IV AUC5 on day 2 for 2 cycles every 21-day cycle. All received GCSF 24hrs after treatment. Disease evaluation after 2nd cycle of BV-ICE using PET-FDG showed 93% CR and 7% PR. All did one attempt for SCC after cycle 2 without plerixafor. 93% were in CR and 7% in PR prior to transplant. The median PBSC collection was 14.7×106 CD34+cells/Kg, median of 10.96×106 CD34+ cells/Kg were infused. All received 3rd BV-ICE cycle and went into ASCT using BEAM conditioning. Median days to ANC engraftment was 9 and to platelet engraftment was 16.5. At day 100, 79% had CR, 14% PR, 7% had progression. After a median follow-up [E2] of 12.3 months the OS was 100% and PFS of 77%. Most common adverse event was hematological toxicity: 50% grade 3 anemia, 72% grade 3 thrombocytopenia, 72% FN. 7% developed grade 4 PN with reversible symptoms. BV-ICE as 1st salvage in R/R HL showed high ORR of 100% to be translated into improvement in DFS with acceptable toxicity profile.

Administration of G-CSF for PBSC collection may unmask pre-existing IgA-nephropathy: A case report

It is utterly important to ensure the safety of stem cell donors and limit the incidence of long-term adverse events. Additionally, the willingness to donate the potentially life-saving stem cells, depends among other reasons, on the donor’s trust in the safety of the procedure as our case highlights. Here we present the case of a 35-year-old patient who developed macrohematuria and proteinuria following peripheral blood stem cell (PBSC) donation. 4 years later he was diagnosed with IgA-nephropathy (IgAN) and the disorder was causally attributed to the PBSC donation. He discouraged his family and friends from registering as donors because of this. In the current case report, we review the literature on the relationship between IgAN and PBSC donation and suggest under which conditions stem cell donation can still be performed even with a prior diagnosis of IgAN.

Successful Mobilization of Autologous Hematopoietic Peripheral Blood Stem Cells after Salvage Chemotherapy in Patients with Low CD34 Blood Cell Counts

A major barrier for proceeding to autologous stem cell transplantation (ASCT) is an inability to mobilize and collect an adequate number of peripheral blood (PB) stem cells (PBSC) for the transplant graft. Plerixafor added to granulocyte colony stimulating factor (G-CSF) alone, without prior chemotherapy, significantly improves the mobilization of autologous PBSC in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM). However, the efficacy of plerixafor and the best timing to give the drug to poorly mobilizing patients with very low PB CD34+ cell counts after salvage chemotherapy and G-CSF are not well defined. We hypothesized that PBSC mobilization and collection might be improved in heavily treated patients who mobilized very poorly after salvage chemotherapy and G-CSF by alternating the days of plerixafor administration and leukapheresis. A day of rest between plerixafor doses, while continuing G-CSF, could allow time for some replenishment of the marrow stem/progenitor cell pool before the next mobilization. A retrospective review of collection results in poorly mobilizing patients at our center was undertaken. Three cohorts were identified: those who got every-other-day plerixafor and leukapheresis, those who got sequential plerixafor and leukapheresis and those who got risk adapted plerixafor. Overall, 69% of patients with NHL and MM with PB CD34+ cell counts <5/µL after salvage chemotherapy and G-CSF were ultimately able to collect adequate CD34+ cells to support ASCT using daily plerixafor and leukapheresis. On the alternating plerixafor and leukapheresis schedule, all 17 patients achieved the cumulative CD34+ cell product goals required for ASCT. This positive observation after salvage chemotherapy and G-CSF led to the incorporation at our center of an alternate-day schedule of plerixafor and leukapheresis into our real-time risk adapted strategy for poor mobilizers.© 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients

BackgroundSecond line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. Patients and MethodsForty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. ResultsThirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. ConclusionOur results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Patient-Reported Outcome Data from the RDSafe and BMT CTN 0201 Clinical Trials

There is a lack of evidence about how health-related quality of life (HRQoL), including psychosocial factors, might affect donation-related experiences and clinical markers in the context of hematopoietic stem cell donation. The broader literature suggests that psychological factors, including anxiety and depression, are associated with higher levels of inflammatory burden leading to poorer postprocedural outcomes including longer hospital stays and increased pain perception. In this study, we aimed to evaluate whether predonation HRQoL markers predict toxicity profile and stem cell yield after peripheral blood stem cell (PBSC) donation in healthy donors. The study population comprised adult granulocyte colony-stimulating factor mobilized PBSC-related donors (RD) (n=157) and unrelated donors (URD) (n=179) enrolled in the related donor safety study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HRQoL was assessed using the Short-Form-12 (SF-12) in RDSafe and SF-8 questionnaire in BMT CTN 0201 (higher score is better). The aims of this study were to (a) determine the impact of pre-donation HRQoL on peri-collection pain and acute toxicities experienced and (b) to investigate the pre-procedural HRQoL indicators on stem cells yield. URDs were younger than RDs (median age 35 versus 63). A higher proportion of RDs were female (50% versus 40%) and obese (41% versus 35%). A higher proportion of RD PBSC donations required 2 days or more of apheresis (44% versus 21%). More RD collections were lower volume procedures (<18L, 16% versus 28%), and required a central line (28% versus 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% versus 8%) and other toxicities (16% versus 6%). Among RDs, a lower pre-donation physical component summary (PCS) score was associated with significantly more grade 2-4 pain at 1 month (P=.004) and at 1-year after donation (P=.0099) in univariable analyses. In multivariable analysis, pre-donation PCS remained significantly associated with grade 2-4 pain 1 month after donation (P=.0098). More specifically, RDs with predonation PCS scores in the highest quartile were less likely to report pain compared with donors with PCS scores in the lowest quartile (odds ratio 0.1; 95% confidence interval 0.01-0.83; P=.005). There was also a trend toward higher grade 2-4 pain at 1-year post-donation among RDs with lower predonation PCS score (P=.018). Among URDs, neither PCS nor mental component summary (MCS) scores were associated with pain or toxicities at any time point after donation based on the univariable analysis. Because of low rates of postdonation grade 2-4 pain and toxicities, multivariable analysis was not performed in the URD setting. Moreover, there was no correlation between preapheresis HRQoL score (PCS or MCS) and PBSC collection yield in either the RD or URD setting. Our study demonstrates that pre-donation HRQoL scores are significantly associated with the toxicity profile after PBSC donation in the RD setting, with adult RDs with lower predonation physical HRQoL experiencing higher levels of pain at 1 month and persisting up to 12 months after a PBSC collection procedure. There were no such associations found in URD. Our findings can help clinicians identify donors at higher risk of pain with donation, and lead to personalized information and interventions for specific donors. Lack of correlation between predonation HRQoL and stem cell yield may be due to a small sample size and warrants further evaluation.

MEDB-86. A re-induction regimen for children with recurrent medulloblastoma

Medulloblastoma is the most common malignant brain tumor of childhood. Despite multi-modal therapies, ~30% of patients experience disease recurrence, which portends a poor prognosis. At initial recurrence, intensive chemotherapy may be effective prior to various consolidation therapies including high dose chemotherapy with autologous stem cell rescue or irradiation. We report outcomes for nine children treated at two institutions with the following regimen: cyclophosphamide 1500mg/m2/dose days 1,2; irinotecan 125mg/m2/dose days 1,8; temozolomide 150mg/m2/dose days 1-5, and oral etoposide 50mg/m2/dose days 1-7. Patients received 2-4 cycles based upon disease response and physician preference. The mean time from initial diagnosis to first recurrence was 19 months. After receiving two cycles of therapy, two patients had complete response (CR) and proceeded to consolidation. Of the remaining seven patients, five had partial response (PR) and two had stable disease (SD). Overall response rate was 78% after 2 cycles. Two patients with PR proceeded directly to consolidation with irradiation. Five patients (3 PR, 2 SD) received 2 additional cycles. After four cycles there was one CR, two with minimal residual disease, one SD and one progressive disease (PD). Four patients (44%) are alive with no evidence of disease (NED). One patient died of consolidation-related toxicity but had NED at time of death 28 months from initial recurrence. Five patients developed PD. Two patients died of disease, two are alive with disease, and one is alive with NED after PD and additional therapy. There were no treatment-related deaths. Infection was the most common complication. Five patients had febrile neutropenia and two developed sepsis. One patient required dose reduction for prolonged thrombocytopenia. Peripheral blood stem cell collection was achieved in all patients for whom it was attempted. This re-induction regimen is generally well-tolerated and effective in inducing responses for children with recurrent medulloblastoma.

Autologous peripheral blood stem cell mobilization and collection in patients with lymphoma and multiple myeloma: A single-center experience using the plerixa for pre-emptive approach.

Objectives:To review and assess the efficiency of pre-emptive plerixafor administration for poor mobilization (PM) and to review and assess mobilization efficiency (≥2×106 CD34+ cells/kg) in patients who received autologous stem cell transplantation for lymphoma and multiple myeloma (MM) at the Department of Adult Hematology/Blood Marrow Transplant, Princess Noorah Oncology Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia, over the past 7 years.Methods:This retrospective study evaluated all patients with MM and lymphoma undergoing peripheral blood stem cell mobilization and collection at our institution between February 2014 and August 2021. Plerixafor was administered pre-emptively by a plateau of <10 peripheral blood CD34+/µl after chemotherapy-based mobilization or CD34+ of <8/µL on day 4 after mobilization with G-CSF alone. Between peak CD34+ levels of 10-15/µl, plerixafor will be used at the discretion of the treating physician.Results:In total, 215 patients were enrolled. Among them, 80% had peak CD34+ level ≥20/µL, 11% had clear poor mobilization (peak CD34+ levels <10/µL), and 9% had borderline PM (CD34+ between 10-19/µL). Plerixafor was administered pre-emptively in 13% of the patients and 75% of patients with borderline PM were collected without plerixafor, suggesting that plerixafor is not needed if CD34+ >15/µL on the anticipated collection day. Mobilization failed in only one patient (<1%).Conclusion:Our data showed that with plerixafor pre-emptive administration, the primary endpoint was achieved for most patients identified with PM, preventing the need for a second mobilization attempt.

Addition of plerixafor in poorly mobilized allogeneic stem cell donors.

BackgroundPeripheral blood stem cells (PBSCs) are the predominant graft source for adult allogeneic hematopoietic stem cell transplantation (HSCT). In poorly mobilized autologous donors, plerixafor improves collection outcomes. We examine plerixafor use in allogeneic donors who mobilize poorly with granulocyte colony‐stimulating factor (G‐CSF) in those who are healthy and those with pre‐existing medical conditions, and determine the optimal threshold to add plerixafor.Study Design/MethodsWe retrospectively examined all allogeneic PBSC collections from January 2013 to October 2020 at our center. Donors received G‐CSF 10 mcg/kg daily for 4 days before undergoing apheresis collection on day 5. Plerixafor was added based on poor CD34+ cell collection yield after the first or second collection day.ResultsOf the 1008 allogeneic donors, 41 (4.1%) received one dose of plerixafor in addition to G‐CSF due to poor collection yield. After starting plerixafor there was a 0.75‐ to 7.74‐fold (median 2.94) increase in CD34+ yield from the previous day. No donors with G‐CSF‐only mobilization who collected <2.0 × 106 CD34+ cells/kg recipient weight on day one achieved the goal of ≥4.0 × 106 CD34+ cells/kg recipient weight total over 2 days but 59.2% of donors who used rescue plerixafor did.ConclusionDonors both healthy and those with pre‐existing disease responded well to plerixafor with minimal side effects. If the first‐day collection yield is less than ~63% of the collection goal, addition of plerixafor may be necessary to reach the collection goal and limit the number of collection days in allogeneic donors.

Influence of Pretransplant Anemia on Red Blood Cell Transfusions in Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation

Background and Objectives: Anemia during peripheral blood stem cells (PBSCs) transplant is considered a bad prognostic marker. The study aimed to determine whether pretransplant anemia influence peritransplant transfusion requirements in myeloma patients. Methods: Myeloma patients planned for PBSC transplant were stratified based on hemoglobin levels at time of mobilization, PBSC collection, and PBSC infusion. Univariate and multivariate analysis was performed to study the predictors for good mobilization, adequate CD34 yield by apheresis, and red blood cell (RBC) transfusion in the peritransplant period. Results: Of 67 patients, the prevalence of anemia at mobilization, PBSC collection, and PBSC infusion was 37%, 58%, and 70%, respectively. Eighty-five percent had good mobilization with peripheral blood CD34 count of 50 cells/μl (8–123) and 81% had adequate CD34 yield with first apheresis. Thirty-two percent patients received peritransplant RBC transfusion with the median of one unit (range: 0–5). Anemia on the day of infusion did influence the RBC transfusions in the peritransplant period (P = 0.03). Conclusion: One third of myeloma patients require RBC transfusion support in the peritransplant period. We identified pretransplant anemia neither influenced mobilization nor PBSC collection but increased the risk for RBC transfusion in the peritransplant period.

The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)

The Effect of Daratumumab, Lenalidomide, Dexamethasone (DRd) on Peripheral Blood Stem Cell Mobilisation (PBSC)

The Impact of Pre-Apheresis Health Related Quality of Life on Peripheral Blood Progenitor Cell Yield and Donor's Health and Outcome: Secondary Analysis of Rdsafe and BMT CTN 0201

Introduction: The adverse events associated with hematopoietic stem cell donation have been extensively studied. There is an increasing literature linking psychological factors including stress, anxiety and depression to higher levels of inflammatory burden leading to poorer post-procedural outcomes including longer hospital stays and increased pain perception. Here, we aimed to evaluate whether pre-donation health related quality of life (HRQoL) markers predict toxicity profile and stem cell yield following stem cell donation in healthy donors.Methods: The study population included adult granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cell (PBSC) related donors (RD) (n= 157) and unrelated donors (URD) (n=179) who were enrolled in Related Donor Safety Study (RDSafe) and Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0201 clinical trials. Pre-donation HR QoL was assessed using the Short-Form (SF-8) in RDSafe and SF-12 questionnaire in BMT CTN 0201 (higher score is better). Pain and toxicity were collected on study specific forms. The primary outcome was the incidence of skeletal pain on day 5 of G-CSF administration. The secondary outcomes were the incidence of skeletal pain and highest toxicity level across selected body symptoms at 1 month, 6 months and 1-year post-donation. Another secondary outcome included CD34+ per liter of blood processed (x10 6/L) on day 5 of G-CSF as a measure of collection yield. The association between pre-apheresis HRQOL measures and pain and acute toxicities was characterized using means and SDs and compared using the t-test. Association between HRQoL and cell yield was assessed using the Pearson correlation coefficient. RD and URD were analyzed separately.Results: URDs were younger than RDs (median age 35 vs. 63). A higher proportion of RDs were female (50% vs. 40%) and obese (41% vs. 35%). A higher proportion of RD PBSC donations required 2 days or more (44% vs 21%). More RDs were collected with lower volume procedures (<18L, 28% vs. 16%), and required a central line (28% vs. 11%). RDs were more likely to report pre-donation grade 1-2 pain (27% vs. 8%) and other toxicities (16% vs. 6%).The mean pre-donation physical component summary (PCS) and mental component summary (MCS) score of RDs were 54.5 (SD 7.0) and 55.1 (SD 5.8), respectively . In the univariate analysis (table 1), pre-donation lower PCS score of RDs was associated with significantly more grade 2-4 pain at 1 month (p=0.0038) and 1-year post-donation (p=0.0099) (Table 1). In multivariable analysis (table 2), pre-donation PCS remained significantly associated with grade 2-4 pain 1-month post-donation (p=0.0098). More specifically, RDs with pre-donation PCS scores in the higher quartile were less likely to experience pain compared with donors with PCS scores in the lower quartile (OR 0.1; 95% CI 0.01-0.83; p=0.005). There was also a trend toward increased grade 2-4 pain at 1-year post-donation among RDs with lower PCS score (p=0.0176). Other outcomes such as pain at day 5 of G-CSF, other toxicities at day 5 of G-CSF, 1 month, 6 months and 1-year post-donation were not associated with pre-donation PCS score. Similarly, there was no significant association between RD pre-donation MCS score and collection-related symptoms at any time point.The mean pre-donation PCS and MCS scores of URDs were 56.2 (SD 4.7) and 54.5 (SD 5.5), respectively . In a univariate analysis, there was no association between PCS score or MCS score and donation associated pain and toxicities at any time point post-donation. Due to low event rates, multivariable analysis was not performed in the URD setting. Based on the multivariable regression analysis, there was no correlation between pre-apheresis HRQoL score (PCS or MSC) and PBSC collection yield in either the RD or URD setting.Conclusion: Our study demonstrates that pre-donation QoL markers are significantly associated with the toxicity profile after PBSC donation in the RD setting as adult RD with lower pre-donation physical QOL experience increased levels of pain after a PBSC collection procedure. There were no such associations found in URD in this small sample. Our findings may help clinicians to identify donors at higher risk of pain with donation, and lead to personalized information and interventions (e.g. increased analgesia) for specific donors. Future study with a larger sample is required to validate the results. [Display omitted] DisclosuresFarhadfar: Incyte: Consultancy. Stefanski: Novartis: Honoraria. Pulsipher: Equillium: Membership on an entity's Board of Directors or advisory committees; Adaptive: Research Funding; Jasper Therapeutics: Honoraria. Shaw: mallinkrodt: Other: payments; Orca bio: Consultancy.