Peripheral Blood Stem Cell Research Articles

Case report: CD7-targeted autologous CAR-T therapy for the treatment of T-cell acute lymphoblastic leukemia undergoing allogeneic peripheral blood stem cell transplantation in the long-term follow-up

IntroductionChimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising approach for treating relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL). However, it is mostly used as a bridging therapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, secondary allo-HSCT is costly and associated with significantly high treatment-related mortality rate than the primary transplants. In this report, we present the case of an adult T-ALL patient who underwent CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT.Case presentationThe adult T-ALL patient relapsed for a third time after undergoing allogeneic peripheral blood stem cell transplantation (PBSCI) and achieving the first complete remission (CR1). Therefore, the patient was administered CD7-targeted autologous CAR-T cell therapy that was not bridged with secondary allo-HSCT. Towards this, the endogenous CD7-deleted CAR (CD7-CAR7) T cells were generated using CRISPR/Cas9 gene-editing technology. However, after the first infusion, the CD7 CAR-T cells did not show significant proliferation when analyzed at two weeks and the patient became positive for peripheral measurable residual disease (MRD). Therefore, after a two-week period, an augmented dose of CAR-T cells was administered. MRD was monitored in the peripheral blood and bone marrow samples. The patient achieved complete remission and did not require targeted treatment after the completion of CD7 CAR-T-cell therapy. The current follow-up data has shown that the patient is negative for MRD and has been disease-free for more than 42 months.ConclusionThe results of this case study provide evidence for the long-term efficacy of CD7-targeted autologous CAR-T-cell therapy without requiring secondary allo-HSCT in patients with r/r T-ALL that have relapsed after previous allogeneic PBSCT.

CTNI-38. SINGLE-CENTER COMPARATIVE ANALYSIS ABOUT OUTCOMES OF MULTI-AGENTS CHEMOTHERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA; R-MPV SHOWED A FAVOR RESULT

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a malignant tumor in the brain, spinal cord, and eyes. Radiotherapy may cause delayed leukoencephalopathy so that the first-line treatment is methotrexate (MTX)-based multi-agent chemotherapy. We had used the Bonn protocol based on MTX and cytarabine, but since 2020, we have adopted the R-MPV protocol. This study analyzes the outcomes of patients treated initially at our institution. METHODS AND RESULTS We reviewed 57 out of 88 newly diagnosed PCNSL patients treated with chemotherapy alone between December 2005 and January 2023. Initial treatments included the Bonn protocol in 25 patients (12 with rituximab, forming R-Bonn) and R-MPV in 26 patients. High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) was given as consolidation in 4 Bonn and 9 R-MPV patients. The Bonn protocol was completed by 20 patients (80%) with a complete response (CR) in 19 (76%). The R-MPV protocol was completed by 23 patients (88%) with CR in 22 (85%). Post-treatment outcomes were compared using survival analysis. Median progression-free survival (mPFS) had not been reached in the R-MPV group and was significantly better than 33.1 months in the Bonn protocol and 58.6 months in the R-Bonn protocol (log-rank test; p=0.0296, 0.0036). Overall survival (OS) did not show significant differences. PBSCT’s impact on outcomes suggested improvement in PFS and OS after R-MPV, but this was not statistically significant. DISCUSSION We examined the efficacy of different chemotherapy regimens for PCNSL at our institution. The R-MPV protocol showed superior completion rates, response rates, and treatment efficacy. Consolidation with PBSCT may improve outcomes, though further investigation with more cases and longer observation is necessary.

Bone marrow versus peripheral blood allogeneic haematopoietic stem cell transplantation for haematological malignancies in adults.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is an established treatment option for many malignant and non-malignant haematological disorders. Peripheral blood stem cells represent the main stem cell source in malignant diseases due to faster engraftment and practicability issues compared with bone marrow stem cells. Since the early 2000s, there have been many developments in the clinical field. Allo-HSCT using haploidentical family donors (haplo-HSCT) has emerged as an alternative for people who do not have human leukocyte antigen (HLA)-matched siblings or unrelated donors. In addition, the introduction of new methods and strategies in allo-HSCT, such as the use of post-transplant cyclophosphamide (PT-Cy), better donor selection, the more frequent administration of anti-thymocyte globulins (ATGs), but also improved management of side effects such as graft-versus-host disease (GvHD) and infection, have impacted outcomes after allo-HSCT. In addition, as transplant indications and strategies continue to adapt in line with novel research findings, the effect of the stem cell source on post-transplant outcomes is unclear. For our analysis, we considered peripheral blood stem cells as the standard graft source for adults with haematological malignancies. This is an update of a review first published in 2014. To assess the effect of bone marrow transplantation versus peripheral blood stem cell transplantation in adults with haematological malignancies with regard to overall survival, disease-free survival, incidence of non-relapse or transplant-related mortality, incidence of extensive chronic graft-versus-host disease (GvHD), incidence of acute GvHD grades III to IV, incidence of overall chronic GvHD, and quality of life. For this update we searched CENTRAL, MEDLINE, Embase, and two trials registries on 2 November 2022 with no language restrictions. We included randomised controlled trials (RCTs) comparing bone marrow transplantation (BMT) with peripheral blood stem cell transplantation (PBSCT) in adults (aged ≥ 18 years) with haematological malignancies. Two review authors independently selected studies and extracted data. We evaluated risk of bias using the original Cochrane risk of bias tool (RoB 1), and we evaluated the certainty of the evidence using the GRADE approach. The updated search identified no new studies for inclusion. We found two additional reports relating to a previously included study; they provided new data on quality of life and infection rates after transplantation. As these are clinically relevant outcomes, quality of life was added to the summary of findings table (replacing acute GvHD II to IV), and rate of infection was added to our list of secondary outcomes. We included nine RCTs with a total of 1521 participants. Overall, the risk of bias in the included studies was low. Median participant age across studies ranged from 21 to 45 years, and studies took place in Canada, the USA, New Zealand, Brazil, Australia, Egypt, and across Europe. Bone marrow transplantation (BMT) compared with peripheral blood stem cell transplantation (PBSCT) likely results in little to no difference in overall survival (hazard ratio (HR) for all-cause death 1.07, 95% CI 0.91 to 1.25; 6 studies, 1330 participants; moderate-certainty evidence). There may be little to no difference between BMT and PBSCT in terms of disease-free survival (HR for disease recurrence or all-cause death 1.04, 95% CI 0.89 to 1.21; 6 studies, 1225 participants; low-certainty evidence) and non-relapse or transplant-related mortality (HR 0.98, 95% CI 0.76 to 1.28; 3 studies, 758 participants; low-certainty evidence). BMT compared with PBSCT likely results in lower rates of extensive chronic GvHD (HR 0.69, 95% CI 0.54 to 0.90; 4 studies, 765 participants; moderate-certainty evidence) and overall chronic GvHD (HR 0.72, 95% CI 0.61 to 0.85; 4 studies, 1121 participants; moderate-certainty evidence). BMT compared with PBSCT may reduce the incidence of acute GvHD grades III to IV, although the 95% CI of the HR is also compatible with no effect (HR 0.75, 95% CI 0.55 to 1.02; 3 studies, 925 participants; moderate-certainty evidence). Evidence from two trials that used different quality of life assessment instruments suggests that BMT compared with PBSCT may be associated with higher quality of life five years after transplantation. Moderate-certainty evidence suggests little to no difference in overall survival following allo-HSCT using bone marrow versus peripheral blood stem cells (the current clinical standard stem cell source). Low-certainty evidence suggests little to no difference between the stem cell sources in terms of disease-free survival and non-relapse or transplant-related survival. BMT likely reduces the risk of extensive chronic GvHD and overall chronic GvHD compared with PBSCT. Evidence from two RCTs suggests that BMT compared with PBSCT may result in higher long-term quality of life, possibly due to the lower chronic GvHD incidence. With this update, we aimed to supply the most recent data on the choice of stem cell source for allo-HSCT in adults by including new evidence published up to November 2022. We identified no new ongoing studies and no new RCTs with published results. Further research in this field is warranted.

Comparison of HLA-haploidentical donors with post-transplant cyclophosphamide versus HLA-matched unrelated donors in peripheral blood stem cell transplantation for acute myeloid leukaemia.

HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo) is emerging as an effective alternative due to donor availability and safety. We conducted a nationwide retrospective study comparing the outcomes of PTCy-haplo with both anti-thymocyte globulin (ATG)-free and ATG-administered matched unrelated donors (MUD) transplantation, using peripheral blood stem cells as the first transplantation for acute myeloid leukaemia (AML). Our study showed a lower and slower haematopoietic recovery and a higher incidence of infection-related deaths after PTCy-haplo than after MUD transplantation. In addition, we revealed an increased risk of acute and chronic graft-versus-host disease (GVHD) in ATG-free MUD transplantation in comparison to PTCy-haplo. For grades III-IV acute GVHD, the hazard ratio (HR) was 2.71 (95% CI, 1.46-5.01), and for extensive chronic GVHD, the HR was 3.11 (95% CI, 2.07-4.68). There was no significant difference regarding overall survival amongst the groups. In addition, GVHD-free relapse-free survival (GRFS) was lower in ATG-free MUD transplantation than in PTCy-haplo (HR, 1.46; 95% CI, 1.17-1.82). Notably, ATG-administered MUD transplantation showed no significant difference in GRFS from PTCy-haplo, negating the advantage of PTCy. Our results suggest that PTCy-haplo could be viable for AML patients without an HLA-matched related donor.

Post-transplant cyclophosphamide with post-engraftment anti-thymocyte globulin reduce moderate to severe chronic graft-versus-host disease in peripheral stem cell transplantation from HLA-matched unrelated and haploidentical donors.

Post-transplantation cyclophosphamide (PTCy) has unique advantages for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this single-center retrospective landmark analysis, we evaluated chronic GVHD (cGVHD) and clinical outcomes in patients receiving PTCy, tacrolimus, and post-engraftment low-dose anti-thymocyte globulin (PTCy-ATG) as GVHD prophylaxis after HLA-matched unrelated or haploidentical donor transplantation. Two historical patient groups receiving calcineurin inhibitor-based GVHD prophylaxis were used as control groups. A total of 71 patients with myeloid malignancies undergoing allo-HSCT with myeloablative conditioning regimens were included in the analysis. The 3-year cumulative incidences of cGVHD and moderate to severe cGVHD (M/S cGVHD) were 39.2% (95%CI 27.4%-51.0%) and 11.5% (95%CI 4.1%-18.9%), respectively, in the PTCy-ATG group, and only one instance of bronchiolitis obliterans (BO) was observed. The disease-free survival (DFS), overall survival (OS), and GVHD-free and relapse-free survival rates were 94.0% (95%CI 88.3%-99.7%), 93.0% (95%CI 87.1%-98.9%) and 83.8% (95%CI 75.0%-92.6%) respectively. Of note, the PTCy-ATG group presented with a significantly lower incidence of M/S cGVHD and BO, which translated into superior OS in multivariate analysis. In this retrospective analysis, we observed that PTCy-ATG-based GVHD prophylaxis was associated with a lower incidence of M/S cGVHD and better transplantation outcomes beyond day 100, which invites prospective evaluation.

Infectious Complications in Pediatric Hematopoietic Stem Cell Transplantation Recipients in Northeast Mexico

Abstract Background Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for an increasing number of neoplastic and hematological diseases. However, these patients are at high risk of acquiring infections due to a complex interaction involving organ dysfunction, tissue damage, pathogen exposure, pathogen virulence, and the overall state of dynamic immunosuppression varying according to different phases of immunologic reconstitution after HSCT, and the need for immunosuppressants to prevent and treat non-infectious complications such as graft-versus-host disease (GVHD). Methods All patients under 16 years old who underwent HSCT at the “Dr. José Eleuterio González” University Hospital, a referral center in Northeast Mexico, from March 2019 to October 2023, were included. Clinical, epidemiological, and analytical characteristics of the patients and infectious episodes during pre-engraftment, early engraftment, and late engraftment periods were analyzed. Results In the studied period, a total of 75 patients underwent HSCT, of whom 52 (69%) experienced infectious events (IEs). A total of 136 IEs were documented, averaging 2.5 IEs per patient. Among these, 40% were viral infections, 33% bacterial, 6.6% fungal, 0.7% parasitic, and 19.3% were indeterminate. The most prevalent baseline diagnoses were acute lymphoblastic leukemia (52%), acute myeloid leukemia (19%), and aplastic anemia (12%). Seventy-two percent of the patients underwent a haploidentical stem cell transplantation, and the graft was sourced from peripheral blood stem cells in 75% of the population. Bacterial infections were predominant in the pre-engraftment period, whereas viral infections were more frequent in early and late engraftment. The distribution of these IEs by period is shown in Figure 1. Among bacterial infections, bloodstream infections (BSIs) accounted for 56%, followed by skin and soft tissue infections (14%) and gastroenteritis (13%). Of the 26 BSI events, 73% were caused by Gram-negative bacilli, including 8 cases of Escherichia coli (42%), 6 cases of Pseudomonas aeruginosa (32%), 2 cases of Klebsiella pneumoniae (11%), and 1 case each of Acinetobacter calcoaceticus, Salmonella enterica and Stenotrophomonas maltophilia (5%). 44% of these exhibited extended-spectrum beta-lactamase (ESBL), and 19% were carbapenem-resistant. The remaining 27% of BSI were caused by Gram-positive cocci: Staphylococcus epidermidis (43%), Streptococcus viridans group (29%), Staphylococcus aureus, and Rothia mulcilaginosa (14% each). 17% of all BSI were central line associated bloodstream infection (CLABSI). Among viral infections, cytomegalovirus (CMV) was the most frequent agent at 46%, followed by SARS-CoV-2 and BK virus at 14% and 11%, respectively. Among the fungal infections, we identified 9 cases of invasive fungal disease (IFD), four cases of possible IFD, two of probable IFD and three cases of proven IFD were identified, including one case each of mucormycosis (zygomycetes), Candida tropicalis fungemia, and Aspergillus niger pneumonia. Additionally, one case of intestinal giardiasis, was identified, accounting for 0.7% of the total. Conclusion Infections represent one of the major adverse events in patients undergoing HSCT. It is essential to understand the local epidemiology in each hospital center to tailor international guidelines to the available resources in each institution, which is crucial in improving strategies for preventing, detecting, and providing timely treatment for these infectious complications and their clinical outcomes. Figure 1. Distribution of infectious events among the post-HSTC periods.

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 106/kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

Comparison of the efficacy of a generic plerixafor versus Mozobil as adjunct peripheral blood stem cell mobilization agents in multiple myeloma patients.

Plerixafor is an adjunct peripheral blood stem cell (PBSC) mobilization agent with well-demonstrated safety and efficacy. The routine use of the originator brand drug (Mozobil) has been limited by cost. This retrospective study was conducted to compare the mobilization efficacy of a lower-cost generic plerixafor and Mozobil in multiple myeloma (MM) patients. The study included two near-concurrent cohorts of MM patients mobilized with brand (n = 64) or generic (n = 61) plerixafor in addition to filgrastim. Collection and early engraftment outcomes were compared. The two cohorts had comparable distributions of sex, age, and weight. Previous treatment histories and proportions of upfront versus just-in-time plerixafor use were similar. There was no significant difference in their median overall cumulative total yield (106 CD34+ cells/kg) (brand, 5.91; generic, 5.80; p = .51). However, the generic cohort had a significantly higher median yield after the first dose (4.79 vs. 3.78, p = .03), and consequently lower median numbers of plerixafor doses (p = .001) and collection days (p = .002). Only 31.1% of patients in the generic arm required more than one dose versus 59.4% of patients in the brand arm (p = .006). All transplanted patients in the brand and generic arms (90.6% and 85.2% respectively, p = .42) achieved engraftment. There was no significant difference in their median times to platelet and neutrophil engraftment, nor their transfusion requirements during the first 30 days post-transplant. The generic plerixafor produced comparable cumulative collection yields and early engraftment outcomes as Mozobil, but fewer doses and collection days were needed to reach collection goal.

Selected stem cell populations in pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is characterized by a disturbed maturation of hematopoietic stem cells (HSCs) resulting in development of a malignant clone. Despite relatively positive outcome, there are still instances of disease relapse occurring due to ineffective disease eradication or primary leukemic clone alterations. Unclear significance of stem cells in the course of ALL led us to investigate and establish crucial changes in two stem cell populations - very small embryonic-like stem cells (VSELs) and HSCs during the induction phase of treatment. In a retrospective study selected stem cells in peripheral blood and bone marrow of 60 pediatric ALL subjects and 48 healthy controls were subjected to flow cytometric analysis at 4 different time points. Both VSELs and HSCs were elevated at the moment of ALL diagnosis compared to healthy controls, but profoundly decline until day 15. Further observations revealed an increase in HSCs with a concomitant depletion of VSELs until week 12. ALL patients with high HSCs showed positive correlation with bone marrow blasts at diagnosis. Patients with lower VSELs or HSCs at diagnosis had slightly improved response to applied therapy. We observed higher initial bone marrow lymphoblast values in patients with lower VSELs or higher HSCs in the high-risk group. The significance of VSELs in predicting treatment outcome can be illustrated by lower day 15 MRD level of patients with lower VSELs at diagnosis. We found HSCs and VSELs to be valid participants in pediatric ALL with possible contribution in the neoplastic process and prediction of initial treatment outcome.

Quality Assessment of Cryopreserved Peripheral Blood Stem Cell Products: Evaluation of Two Methods for Flow Cytometric Viability Testing

ABSTRACTIntroductionThe standard flow cytometry method for viability testing using 7‐aminoactinomycin D (7‐AAD) determines cells in necrosis and late apoptosis. The colony‐forming unit (CFU) assay, which evaluates the proliferation ability of HSCs, is also used in graft quality assessment despite known deficiencies that make this assay impractical in routine clinical settings. The aim was to compare the effectiveness of the flow cytometry 7‐AAD/annexin V method with the 7‐AAD method in assessing the quality of HSCs in autologous and allogeneic peripheral blood stem cell (PBSC) products.MethodsThirty autologous and 30 allogeneic fresh and thawed cryopreserved PBSC products were included in this study. The viability of HSCs was determined using the 7‐AAD method and 7‐AAD/annexin V method on a flow cytometer, while their clonogenic capacity was assessed by CFU assay.ResultsThere was an excellent correlation for CD34+ cell viability between the 7‐AAD and the 7‐AAD/annexin V method for fresh samples (Rs = 0.930, p < 0.001) and a good correlation for thawed PBSC samples (Rs = 0.739, p < 0.001). Excellent correlation was observed for post‐thaw CD34+ cell recovery between the two methods for viability (Rs = 0.980, p < 0.001). Statistical analysis showed a weak correlation between CFU‐GM recovery and CD34+ cell recovery, regardless of which viability testing method was used (7‐AAD method p = 0.021, Rs = 0.298; 7‐AAD/annexin V method p = 0.029, Rs = 0.282).ConclusionsResults of this study showed that in the quality assessment of cryopreserved PBSC product viability, the 7‐AAD/annexin V method had no added value compared to the 7‐AAD method, which was suitable enough for routine quality control of cryopreserved autologous and allogeneic PBSC samples.

The transplantation effect of pegylated granulocyte colony-stimulating factor mobilized hematopoietic stem cells may be superior to that of G-CSF mobilized hematopoietic stem cells in haploidentical allogeneic hematopoietic cell transplantation

Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells have become the preferred source of hematopoietic stem cells. We compared the effectiveness of G-CSF and pegylated G-CSF (peg-G-CSF) for hematopoietic stem cell mobilization in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) donors, and evaluated the transplant outcomes. We conducted a matched retrospective cohort study. Donors mobilized with peg-G-CSF (n = 70) and G-CSF (n = 70). 140 consecutive patients diagnosed with acute leukemia who underwent haplo-HSCT were included in this study. The findings revealed that the peg-G-CSF cohort exhibited significantly elevated myeloid-derived suppressor cells (MDSCs) levels in their grafts when compared to the G-CSF cohort (P < 0.001). The 100-day cumulative incidence (CI) of grade III-IV acute graft-versus-host disease (GVHD) and 1-year CI of moderate-to-severe chronic GVHD were 4.3% vs 14.3 % (P = 0.047) and 11.2% vs 27.4 % (P = 0.023), in the peg-G-CSF group and G-CSF group. Patients reveiving mobilized stem cell with peg-G-CSF had a significantly greater likelihood of 1-year GVHD-free relapse-free survival (GRFS) compared to patients reveiving mobilized stem cell with G-CSF (74.9% vs 37.9 %, P < 0.001). The higher graft MDSCs proportion was associated with lower grade II-IV aGVHD, cGVHD (P < 0.05) and higher GRFS in the univariate analysis (P < 0.05). Multivariate analysis showed that MDSCs proportion higher than 11.36 % (HR, 0.305; 95 % CI, 0.154–0.606; P = 0.001) and peg-G-CSF for stem cell mobilization (HR, 0.466; 95 % CI, 0.251–0.865; P = 0.016) were independent prognostic factors of GRFS. The superior survival rates observed in recipients of peg-G-CSF-mobilized cells are likely due to reduced acute GVHD, potentially mediated by the increased MDSCs within the grafts.

Preemptive Approach to Plerixafor Use Is Optimal in Patients With Relapsed/Refractory Germ Cell Tumors Undergoing Peripheral Blood Hematopoietic Stem Cell Collection: Effect on Collection Days, Yields, and Cost.

Evidence describing the use of plerixafor in the off-label population of relapsed/refractory germ cell tumors (GCT) is limited. Weaim to describe the effect of rescue versus preemptive plerixafor use on apheresis collection days, collection yields, and cost. We retrospectively collected data on 77 consecutive patients (at least 15 years of age) with GCT who underwent peripheral blood stem cell (PBSC) collection for autologous stem cell transplant between January 1, 2020 and May 1, 2022. Depending on insurance approval, plerixafor was given either as "rescue" (after a first apheresis collection of < 5 × 106 CD34+ cells/kg) or as "preemptive" on Day 4 of granulocyte-colony stimulating factor (G-CSF) prior to the first apheresis collection, if the Day 4 peripheral blood CD34+ count was < 40 cells/μL. A total of 66% of patients who received preemptive plerixafor completed collection in 1 day, similar to good mobilizers who only needed G-CSF (71%, p = 0.366). In contrast, all poor mobilizers in the rescue group required at least 2 days of collection and had lower CD34+ cell yields than the preemptive group (7.15 vs. 9.81 × 106/kg, p = 0.0055). A cost analysis revealed that preemptive plerixafor may save approximately $7000 per patient compared with a rescue approach. Preemptive plerixafor in GCT patients undergoing PBSC collection allows relatively poor mobilizers to collect in fewer days and with lower overall cost. Fewer apheresis procedures result in less risk to the patient, increased patient satisfaction, and the ability to schedule more patients within the constraints of staffing.

Genetic profiles and clinical features in subcutaneous panniculitis-like T-cell lymphomas.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare peripheral T-cell lymphomacharacterized by cutaneous lesions and immunologic manifestations. The five-year survival rate of SPTCL has been reported to be over 80%, indicating a favorable prognosis. Recent studies have uncovered recurrent germline variants in HAVCR2, encoding an immunomodulator. In this study, we integrated whole-exome sequencing data from 60 samples collected from 36 SPTCL patients, encompassing six patients of our cohort and 30 patients of publicly available data. We identified 138 somatic mutations in skin tumors of 24 patients and HAVCR2 germline mutations in 23 of 29 patients. HAVCR2 p.Tyr82Cys mutations were identified in four of six Japanese patients. During the clinical courses of four patients, cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone were administered to all patients, but it resulted in incomplete responses in all four patients. However, disease conditions of all patients remained stable with additional treatment, including autologous peripheral blood stem cell transplantation. Over a 7.5-year median follow-up, one patient developed autoimmune-related diseases, while one developed other hematological malignancy, resulting in death. To our knowledge, this is the first report of recurrent HAVCR2 germline mutations in Japanese patients, suggesting the necessity for long-term follow-up.

Post-thaw CD34+ cell recovery likely degraded under extreme graft platelet concentrations.

Impaired post-thaw CD34 cell (postCD34) viability in autologous haematopoietic stem cell transplant (ASCT) could indicate delayed engraftment where multiple factors might complicate the relationship. Despite of a couple of unconfirmed reports of a negative correlation of platelet concentration with postCD34 viability, how platelets might be involved in the relationship is largely unknown. Therefore, this question was addressed in this retrospective study of 82 ASCT patients with a total of 150 collections of peripheral blood stem cells in New Zealand. A significant negative correction between platelet concentration and postCD34 recovery (r = -0.18, p = 0.028) was observed overall, but upon further analysis only confirmed in the subset with graft platelets 1500-2000 ×109/L. Importantly, the postCD34 recovery was clearly reduced in the subgroups with either the lowest or the highest platelet concentration. The lowest subgroup was enriched with collections from patients with Hodgkin or non-Hodgkin lymphoma, whereas the highest subgroup from patients with multiple myeloma, both with clearly male preponderance. We hypothesized that graft platelet concentrations probably indicated CD34 cell state (e.g. cell cycle and cell adhesion highly related to platelet functions) that sustained when platelet concentrations were within a niche range but went out of kilter otherwise.

The Interactions of T Cells with Myeloid-Derived Suppressor Cells in Peripheral Blood Stem Cell Grafts.

The interaction of myeloid-derived suppressor cells (MDSCs) with T cells within G-CSF-mobilized peripheral blood stem cell (PBSC) grafts in patients undergoing autologous or allogeneic hematopoietic stem cell transplantation remains to be elucidated. Through studying allo- and auto-PBSC grafts, we observed grafts containing large numbers of T cells and MDSCs with intergraft variability in their percentage and number. T cells from autologous grafts compared to allografts expressed relative higher percentages of inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, TIGIT and BTLA. Autograft T cells had decreased cell proliferation and IFN-γ secretion, which supported the possible presence of T cell exhaustion. On the contrary, graft monocytic MDSCs (M-MDSCs) expressed multiple inhibitory receptor ligands, including PD-L1, CD86, Galectin-9, HVEM and CD155. The expression of inhibitory receptor ligands on M-MDSCs was correlated with their corresponding inhibitory receptors on T cells in the grafts. Isolated M-MDSCs had the ability to suppress T cell proliferation and IFN-γ secretion and/or promote Treg expansion. Blocking the PD-L1-PD-1 signaling pathway partially reversed the functions of M-MDSCs. Taken together, our data indicated that T cells and M-MDSCs in PBSC grafts express complementary inhibitory receptor-ligand pairing, which may impact the quality of immune recovery and clinical outcome post transplantation.

MM-518 Outcome of Non-Cryopreserved DMSOFree Peripheral Blood Stem Cells in Autologous SCT in Multiple Myeloma: An Attempt to Overcome Financial Toxicity of Cryopreservation

MM-518 Outcome of Non-Cryopreserved DMSOFree Peripheral Blood Stem Cells in Autologous SCT in Multiple Myeloma: An Attempt to Overcome Financial Toxicity of Cryopreservation

Higher survival following transplantation with a mismatched unrelated donor with posttransplant cyclophosphamide-based graft-versus-host disease prophylaxis than with double unit umbilical cord blood in patients with acute myeloid leukemia in first complete remission: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

Seven-years post allogeneic hematopoietic stem cell transplantation pure red cell aplastic anemia cured with daratumumab: A case report and review of literature

BACKGROUND Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is currently the only viable method of curing patients with acute myeloid leukaemia. In 30% to 50% of patients, donors and recipients have some level of ABO blood group incompatibility. ABO blood group incompatibility can cause antibodies against the donor's red blood cells to persist in the recipient's body, resulting in a delay of several months in the recovery of red blood cells. A number of different treatments have been reported for post-transplant pure red cell aplastic anaemia (PRCA), such as plasmapheresis, donor lymphocyte infusions, anti-thymocyte globulin, rituximab and steroids. CASE SUMMARY A 41-year-old female diagnosed with acute myeloid leukaemia underwent peripheral blood allogeneic haematopoietic stem cell transplantation in November 2013 from an HLA matched unrelated donor. The donor was AB-positive and the recipient was O-positive. The patient was diagnosed with PRCA three months after receiving the donor stem cell transplant. After failing multiple lines of therapy, the patient applied for daratumumab. After receiving three doses of daratumumab, the patient developed a reticulocyte response and no longer required blood transfusions. CONCLUSION The use of daratumumab anti-CD38 for the remove of plasma cells is safe and effective and may be tried for refractory patients with PRCA after undergoing allo-HSCT for ABO incompatibility.

Outcome of Non-Cryopreserved DMSO-Free Peripheral Blood Stem Cells in Autologous SCT in Multiple Myeloma: An Attempt to Overcome Financial Toxicity of Cryopreservation

Outcome of Non-Cryopreserved DMSO-Free Peripheral Blood Stem Cells in Autologous SCT in Multiple Myeloma: An Attempt to Overcome Financial Toxicity of Cryopreservation

Effectiveness of oral calcium to prevent citrate-related toxicity during peripheral blood hematopoietic stem cell collection – An experience from a tertiary care center

Abstract: BACKGROUND: Apheresis procedures use citrate as an anticoagulant to ensure the fluidity of extracorporeal blood. Citrate-related toxicities are common adverse effects in peripheral blood stem cell (PBSC) collections as they are lengthy procedures resulting in prolonged citrate exposure. Intravenous (IV) calcium administration during therapeutic apheresis procedures is commonly used to reduce the citrate-related toxicity in adults and pediatric population. Very few literature on the use of oral calcium for the prevention of citrate toxicity during PBSC collection are present. OBJECTIVE: The objective of this study was to evaluate the effect of prophylactic oral calcium in reducing citrate-related toxicities during PBSC collections. MATERIALS AND METHODS: A prospective cross-sectional study was carried out at a tertiary care hospital of Southern India. All participants received calcium carbonate – 1 g before and at each 100 ml of collection. Preprocedure, interim, and postprocedure serum calcium were measured. All procedures were done using Spectra Optia. The ACD (acid-citrate-dextrose) rate were between 1:8 to 1:14 and were adjusted for inlet draw rate. The total blood volume processed between 2.5 to 3 based on body weight. Reduction in calcium levels and adverse reactions due to hypocalcemia were observed. Data were analyzed using SPSS 23 software. RESULTS: The majority of the procedures were undisturbed and tolerable to oral calcium. A total of 97.3% of the study subjects did not experience any symptoms of hypocalcemia. Only 2.7% (One autologous and one allogenic donor) had symptoms attributable to hypocalcemia though they had preprocedure calcium &gt;9 mg/dl. Pre- and postprocedure calcium were compared using a paired t-test which was statistically significant. CONCLUSION: Prophylactic oral calcium in PBSC collection is an effective and easy way to the prevention of citrate-related adverse effects without affecting technical performance and product efficacy.