Autologous peripheral blood stem cell mobilization and apheresis in pediatric patients with cancer: A single-center report of 64 procedures.

BACKGROUND: The published experience concerning autologous peripheral blood stem cell collection in children is very limited. METHODS: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively. RESULTS: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5-19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1-4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8-54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter-related infections (n:10, 20.8%), followed by catheter-related thrombosis in eight patients (16.7%). CONCLUSIONS: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers.

Peripheral blood stem cell transplantation using HLA-haploidentical donor with post-transplant cyclophosphamide versus HLA-matched sibling donor for lymphoma.

Data comparing HLA-haploidentical donors and HLA-matched sibling donors (MSDs) in peripheral blood stem cell transplantation (PBSCT) for lymphoma are scarce. We retrospectively analyzed 465 patients with lymphoma aged 16 years or older who underwent PBSCT using haploidentical donors with post-transplant cyclophosphamide (PTCy-haplo) (n = 166) or MSDs with calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis (n = 299). Two-year overall survival (OS), progression-free survival (PFS), and GVHD-free, relapse-free survival (GRFS) in the PTCy-haplo and MSD groups were 49.2% versus 51.9% (P = 0.64), 38.0% versus 39.9% (P = 0.97), and 27.7% versus 18.5% (P = 0.006), respectively. In multivariable analyses, PTCy-haplo recipients had slower neutrophil recovery (hazard ratio [HR], 0.62; P < 0.001) and platelet recovery (HR, 0.54; P < 0.001), lower risk of chronic GVHD (HR, 0.64; P = 0.038) and extensive chronic GVHD (HR, 0.45; P = 0.008), and better GRFS (HR, 0.66; P = 0.003) than MSD transplant recipients. OS, PFS, relapse or progression, and non-relapse mortality were similar between the groups. The difference might be mainly due to PTCy use rather than donor type; however, the results suggested that PTCy-haplo could be a possible option as an alternative to conventional MSD transplantation for lymphoma in PBSCT.

Sirolimus Is an Acceptable Alternative to Tacrolimus for Graft-versus-Host Disease Prophylaxis after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT.

A Clinic Study on Long-term Efficacy and Safety of Autologous Peripheral Blood Stem Cell Transplantation in Patients with Decompensated Hepatitis B Cirrhosis.

Objective: To investigate the long-term safety and efficacy of autologous peripheral blood stem cell transplantation (APBSCT) in treating decompensated hepatitis B cirrhosis. Methods: In this study, a retrospective analysis was conducted on a cohort of 84 patients diagnosed with decompensated hepatitis B cirrhosis between January 2011 and December 2012. The patients were categorized into two groups based on their treatment approach: the transplantation group, consisting of 34 cases who received APBSCT in addition to medical treatment, and the comprehensive medical treatment (CMT) group, comprising 50 cases who solely received CMT. EPI Data software was used for data input and verification. Survival curves were drawn by Kaplan-Meier method and analyzed by log-rank test. Paired t test and independent sample t test were used for intra-group and inter-group mean comparison of measurement data, respectively. The Mann-Whitney U test is used for non-normally distributed data. Results: After the ten-year follow-up period, it was found that overall survival (OS) in the transplantation group was markedly higher than that in the CMT (56% vs. 16%, P < .001). Albumin (ALB), prothrombin time (PT), and indocyanine green retention at 15 min (ICG R15) were significantly improved in sequence at 4 to 12 weeks of early treatment in APBSCT group; subsequently, the Acoustic radiation force impulse (ARFI) index and spleen length significantly decreased at 48 weeks. Compared with the CMT group, ALB and PT levels in the APBSCT group continued to recover and eventually stabilize at normal or low-risk levels at subsequent follow-ups up to 8 years. The ten-year prevalence of hepatocellular carcinoma (HCC) in the APBSCT group was markedly lower than that in the CMT group (26% vs. 62%; P = .025). Moreover, APBSCT significantly reduced ascites (χ2 = 6.997, P = .041) and was not associated with any significant adverse events during APBSCT. Based on clinical evidence, APBSCT is a safe and effective treatment for decompensated hepatitis B cirrhosis, resulting in a favorable long-term prognosis with no significant adverse events. Conclusions: APBSCT is a relatively safe and effective treatment for decompensated hepatitis B cirrhosis.

Posttransplant cyclophosphamide in unrelated and related peripheral blood stem cell transplantation from HLA-matched and 1 allele mismatched donor.

Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been increasingly used in HLA-haploidentical transplantation and recent studies also demonstrated the efficacy of PTCy in HLA-matched transplantation. We conducted a prospective multicenter phase II study to evaluate the safety and efficacy of PTCy with tacrolimus and mycophenolate mofetil in 43 patients who underwent HLA-matched (n = 21), 1 allele mismatched (n = 20), or 2 allele mismatched (n = 2) peripheral blood stem cell transplantation (PBSCT) following myeloablative (n = 28) or reduced-intensity (n = 15) conditioning. The incidence of grade III-IV acute GVHD at 100 days was 2.3%. The incidences of grades II-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 16.3%, 14.0%, and 4.7%, respectively. Overall survival, disease-free survival, and non-relapse mortality at 2 years were 75.3%, 74.0%, and 7.0%, respectively. GVHD-free, relapse-free survival at 2 years was 67.0%. The rate of off-immunosuppressants in patients who survived without relapse at 2 years was 85.4%. These results indicate that PTCy is a valid option for GVHD prophylaxis in both HLA-matched and HLA 1-2 allele mismatched PBSCT.

Impact of stem cell selection between bone marrow and peripheral blood stem cells for unrelated hematopoietic stem cell transplantation for hematologic malignancies: on behalf of the Donor/Source Working Group of the Japanese Society for Transplantation and Cellular Therapy.

BACKGROUND AIMS: This study aimed to comprehensively assess the impact of stem cell selection between bone marrow (BM) and peripheral blood (PB) in unrelated hematopoietic stem cell transplantation (HSCT) for hematological malignancies. Our objective was to identify specific factors associated with better transplant outcomes. METHODS: A retrospective analysis was conducted using data from the Japanese HSCT registry. Inclusion criteria were patients aged 0-70 years who underwent their first unrelated HSCT with BM or PB, with an 8/8 or 7/8 allele HLA match for hematological malignancies between 2010 and 2020. RESULTS: Among 10 295 patients, no significant difference was observed in overall survival, relapse, graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) or non-relapse mortality between the groups. Patients who received PB showed no clear difference in acute GVHD but had a greater rate of chronic GVHD, resulting in poor chronic GVHD-free, relapse-free survival (CRFS). Subgroup analyses highlighted the importance of patient-specific factors in source selection. Patients with non-Hodgkin lymphoma and a greater hematopoietic cell transplantation-comorbidity index showed better CRFS and GRFS when BM was the preferred source. Similar trends were observed among patients with standard-risk disease for CRFS. However, no such trends were evident among patients aged 0-24 years, indicating that both sources are viable choices for young patients. CONCLUSIONS: This real-world retrospective analysis showed similar basic outcomes for BM and PB in an unrelated setting. The results support that BM may still be preferred over PB, especially when the long-term quality of life is a major concern. A consideration of individual factors can further optimize transplant success. Further research is warranted to explore the long-term implications of stem cell source selection.

Non-Cryopreserved Peripheral Blood Stem Cell Graft for Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma and Lymphoma Patients.

BACKGROUND Hematopoietic stem cell transplantation (HSCT) using cryopreserved grafts is time-consuming, expensive treatment, and may associated with dimethyl sulfoxide (DMSO) toxicity. Here, we assess the clinical utility and safety of non-cryopreserved peripheral blood stem cell graft in autologous HSCT. MATERIAL AND METHODS Medical data of multiple myeloma or lymphoma patients who underwent autologous non-cryopreserved HSCT were reviewed. RESULTS A total of 58 patients (40 myeloma and 18 lymphoma) were reviewed. The median myeloma and lymphoma CD34⁺ cell doses were 7.59 and 6.9 million/kg, respectively, with good viability after storage. The median times in neutrophil and platelet engraftment were 9 and 13 days and 11 and 14 days in myeloma and lymphoma, respectively. Only 5 patients in this cohort developed serious post-transplant complications. After transplantation, the cumulative incidence of relapse at 5 years was 34.4% in myeloma versus 19.1% in lymphoma patients. Notably, the mortality incidence rate rapidly increased within the first year and reached a plateau after 4 years, with cumulative incidence of 5.9% and 30.9% in myeloma and lymphoma, respectively. With a median follow-up time of 60 months, the median progression-free survival (PFS) and overall survival (OS) for lymphoma patients was 123.8 and 130 months, respectively. For the myeloma group, the median follow-up time was 38.6 months, the median PFS was 99.5 months, and OS was 157 months. CONCLUSIONS Non-cryopreserved HSCT is effective and safe. The long-term survival outcomes could be achieved by the shortening the duration of neutrophil and platelet engraftments and the complication rates are acceptable.

Impact of GVHD prophylaxis on CMV reactivation and disease after HLA-matched peripheral blood stem cell transplantation.

The kinetics of early and late cytomegalovirus (CMV) reactivation after hematopoietic cell transplantation using various methods of graft-versus-host-disease (GVHD) prophylaxis are poorly defined. We retrospectively compared CMV reactivation and disease among 780 seropositive patients given HLA-matched peripheral blood stem cell (PBSC) grafts and calcineurin inhibitor plus posttransplantation cyclophosphamide (PTCy; n = 44), mycophenolate mofetil (MMF; n = 414), or methotrexate (MTX; n = 322). Transplantation occurred between 2007 and 2018; CMV monitoring/management followed uniform standard practice. Hazards of CMV reactivation at various thresholds were compared. Spline curves were fit over average daily viral load and areas under the curve (AUC) within 1 year were calculated. PTCy and MMF were associated with an increased risk of early (day ≤100) CMV reactivation ≥250 IU/mL after multivariate adjustment. The viral load AUC at 1 year was highest with MMF (mean difference = 0.125 units vs MTX group) and similar between PTCy and MTX (mean difference = 0.016 units vs MTX group). CMV disease risk was similar across groups. There was no interaction between GVHD prophylaxis and CMV reactivation on chronic GVHD risk. Despite PTCy-associated increased risk of early CMV reactivation, the CMV disease risk by 1 year was low in HLA-matched PBSC transplant recipients. In contrast, MMF was associated with higher overall CMV viral burden in the 1 year posttransplant. Although different mechanisms of immunosuppressive agents may affect CMV reactivation risk, effective prevention of GVHD may reduce corticosteroid exposure and mitigate infection risk over time.

Severe short-term adverse events in related bone marrow or peripheral blood stem cell donors.

The incidence of severe adverse events (SAEs) and associated risk factors in hematopoietic cell transplantation donors needs to be clarified for related donors (relatives of the transplant recipient), whose criteria for donation are more lenient than for unrelated donors. Data from related donors registered in the Japanese national data registry database between 2005 and 2021 were evaluated to determine the association of short-term SAE incidence with donor characteristics at registration.Fourteen of 4339 bone marrow (BM) donors (0.32%) and 54 of 10,684 peripheral blood stem cell (PBSC) donors (0.51%) experienced confirmed SAEs during the short donation period. No deaths were observed. Past medical history was a common risk factor for SAEs in both BM and PBSC donors. Age of 60 years or older and female sex were identified as risk factors for SAEs in PBSC donors. Female sex was also a risk factor for poor mobilization, which resulted in discontinuation of PBSC collection.Although donors should be selected carefully, a certain level of safety is ensured for related donors in Japan. Donor safety should be further increased by improving the selection method for related donors and extending the follow-up period.

Safety and efficacy of high-dose cytarabine MEAM therapy and other treatments for auto-peripheral blood stem cell transplantation: A retrospective comparative study.

AIM: The MEAM regimen consisting of ranimustine (MCNU), etoposide (ETP), cytarabine (Ara-C), and melphalan (MEL) is widely used before auto-peripheral blood stem cell transplantation (auto-PBSCT) for malignant lymphoma in Japan. The MEAM regimen generally consists of 200-400 mg/m2 for 4 days, but we decided to increase the dosage of Ara-C from the standard to 2 g/m2 for 2 days with the aim of increasing drug transferability to the central nervous system. We evaluate the safety and therapeutic efficacy of high-dose Ara-C MEAM therapy. METHODS: The high-dose Ara-C MEAM protocol consisted of MCNU 300 mg/m2 on day -7, ETP 200 mg/m2 on days -6, -5, -4, -3 and Ara-C 2 g/m2 on day -4 -3, and MEL 140 mg/m2 on day -2. We retrospectively analyzed 37 cases of malignant lymphoma at our institution between May 2014 and July 2020. RESULTS: All patients got engraftment and there were no cases of treatment-related mortality. In all cases, the 3-year overall survival (OS) and progression-free survival (PFS) after transplantation were 80.6% and 65.7%, respectively. Twenty-one cases of diffuse large B-cell lymphoma recurrence, for which there is proven usefulness of auto-PBSCT, showed good results after transplantation, with the 3-year OS and PFS after transplantation being 100% and 74.3%, respectively. CONCLUSION: The safety and efficacy of high-dose Ara-C MEAM therapy were demonstrated, but the expected therapeutic effect on central nervous system lesions could not be fully evaluated owing to the small number of cases.

Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT.

In this registry-based study which includes acute myeloid leukemia patients who underwent a matched unrelated donor allogeneic peripheral-blood stem cell transplantation in complete remission and received post-transplant cyclophosphamide (PTCY) as graft-versus-host disease (GvHD) prophylaxis, we compared 421 recipients without anti-thymocyte globulin (ATG) with 151 patients with ATG. The only significant differences between PTCY and PTCY + ATG cohorts were the median year of transplant and the follow-up period (2017 vs 2015 and 19.6 vs 31.1 months, respectively, p < 0.0001). Overall, 2-year survival was 69.9% vs 67.1% in PTCY and PTCY + ATG, respectively, with deaths related to relapse (39% vs 43.5%), infection (21.9% vs 23.9%) or GvHD (17.1% vs 17.4%) not differing between groups. On univariate comparison, a significantly lower rate of extensive chronic GvHD was found when ATG was added (9.9% vs 21%, p = 0.029), a finding which was not confirmed in the multivariate analysis. The Cox-model showed no difference between PTCY + ATG and PTCY alone with respect to acute and chronic GvHD of all grades, non-relapse mortality, relapse, leukemia-free survival, overall survival, and GvHD-free-relapse-free survival between study cohorts. Our results highlight that the addition of ATG in PTCY does not provide any extra benefit in terms of further GvHD reduction, better GRFS or better survival.

Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients.

BACKGROUND AIMS: In allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants. METHODS: The authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs. RESULTS: In 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group. CONCLUSIONS: The authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors.

Defibrotide combined with triple therapy including posttransplant cyclophosphamide, low dose rabbit anti-t-lymphocyte globulin and cyclosporine is effective in prevention of graft versus host disease after allogeneic peripheral blood stem cell transplantation for hematologic malignancies.

Endothelial dysfunction and damage play important roles in the pathophysiology of graft versus host disease (GvHD) and hepatic venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS). Preliminary evidence suggests that defibrotide (DF) may decrease the risk of GvHD. We speculated that DF prophylaxis may have a synergistic effect with other immunosupressive agents by decreasing the incidence of GvHD and retrospectively evaluated the impact of a DF prophylaxis on the development of GvHD. Thirty-eight adult patients with various hematological neoplasms who underwent peripheral blood allogeneic hematopoietic stem cell transplantation from all donor types were included. All patients received DF for prevention of VOD/SOS. GvHD prophylaxis included rabbit anti-T lymphocyte globulin (rATLG), posttransplant cyclophosphamide (PTCy) and cyclosporine (CsA). The median follow-up of the surviving patients was 484 (365-814) days. The cumulative incidence of grade III-IV acute GvHD and moderate/severe chronic GvHD requiring systemic immunosupression at 1 year were 20.6 % and 5.3 %, respectively. Non-relapse mortality, GvHD-relapse-free survival, and overall survival of the study cohort at 1-year were 21.1 %, 44.7 % and 57.9 %, respectively. Our preliminary results suggest that DF may act as a global endothelial protectant and decrease the risk of GvHD in combination with rATLG, PTCy and CsA.

HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning with very low-dose antithymocyte globulin for relapsed/refractory acute leukemia in pediatric patients: a single-institution retrospective analysis.

The prognosis of relapsed/refractory (R/R) pediatric acute leukemia is extremely poor. We retrospectively reviewed 20 consecutive pediatric patients with R/R acute leukemia who underwent a first HLA-haploidentical peripheral blood stem cell transplantation following reduced-intensity conditioning (haplo-RIC-PBSCT) with very low-dose antithymocyte globulin (ATG) between 2012 and 2019. Of these 20 patients, 7 patients had acute lymphoblastic leukemia, and 13 had acute myeloid leukemia. At the time of haplo-RIC-PBSCT, 15 patients had active disease. The median follow-up duration for survivors was 56 months (range 22-108 months). Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus, short-term methotrexate, methylprednisolone, and ATG 1.25 mg/kg on day-2. The 2-year cumulative incidence of transplant-related mortality and relapse were 5.0% [95% confidence interval (CI) 0.7-30.5%)] and 57.8% (95% CI 37.4-79.6%), respectively. Among the 20 patients, 16 (80.0%) developed grade III-IV acute GVHD, and 2 developed severe chronic GVHD. The 2-year event-free survival and overall survival rates were 40.0% (95% CI 19.3-60.0%) and 50.0% (95% CI 27.1-69.2%), respectively. Although the sample size is small, the survival outcomes of the present study are encouraging.

Effects of cell concentration, time of fresh storage, and cryopreservation on peripheral blood stem cells: PBSC fresh storage and cryopreservation.

INTRODUCTION: Peripheral blood stem cells are widely used in autologous or allogeneic transplantation. The quality of the product directly impacts clinical outcomes, and the cell quality and/or functionality may be influenced by the storage conditions as time, temperature, total nucleated cells (TNC) concentration and cryopreservation requirement. OBJECTIVE: To verify the effects of time, cell concentration, and cryopreservation/thawing in the viability and functionality of stem cells for transplantation. METHODS: We evaluated TNC, CD45+ viable cells, CD34+ viable cells, and cell viability and functionality of 11 samples. Measurements were performed immediately and 24 h, 48 h, 72 h, and 96 h after sample collection at high and low TNC concentrations. The same parameters were also evaluated after cryopreservation and thawing of the samples. RESULT: Duration of storage and TNC concentration exhibited a negative effect on cell quality (CD45+ viable cells, CD34+ viable cells and functionality). Moreover, the association of these parameters increased the negative effect on graft quality. Cryopreservation and thawing also negatively affected the collected sample regarding viable CD34+ cells (recovery 66.2 %), viable CD45+ cells (recovery 56.8 %), and 7-AAD viability. No significant losses in viable CD45+/CD34+ cells and functionality were observed in the first 24 h in both TNC conditions. CONCLUSION: These results emphasize the importance to consider carefully the storage conditions until transplantation, measuring TNC/µL until 24 h after collection (diluting the product when TNC > 300 × 103/µL) and infusing fresh graft as soon as possible.

Hematopoietic Progenitor Cell Donation from Healthy Female Donors During Pregnancy: A Report of 10 Cases.

The golden rule when collecting hematopoietic progenitors (HPs) from healthy volunteers is "donor safety." Pregnancy is an absolute contraindication for HP collection from unrelated donors; however, collection from a related pregnant donor is sometimes considered based on the urgency of the indication for transplantation and the available alternatives. Data on the safety and efficacy of this practice are limited. We conducted a retrospective chart review of an institution's transplantation database to characterize the safety and efficacy of HP donation from pregnant donors. Ten cases of HP donation from pregnant donors were identified, including 6 bone marrow grafts and 4 peripheral blood stem cell grafts. The median age of donors was 27.5 years. The median volume of the collected product was 521 mL (range, 128 to 1160 mL), the median number of total nucleated cells (TNCs) in the graft was 252 × 108 (range, 30.5 to 794 × 108), the median TNC concentration in the graft was 37 × 106 per mL (range, 4.7 to 214.6 × 106 per mL). The median number of CD34 cells in the graft was 142 × 106 (range, 6 to 763 × 106), and the median CD34 concentration in the graft was 20 × 104 per mL (range, 2 to 206 × 104 per mL). There were no safety issues or signals related to the procedure. HP collection from pregnant donors is relatively safe. This case series provides valuable information for practicing transplant physicians on how to counsel pregnant donors when this scenario is encountered in clinical practice.

Efficacy of peripheral arterial access for peripheral blood stem cells collection.

BACKGROUND: Transplantation of peripheral blood stem cells (PBSCs) mobilized by cytokines is increasingly applied to treat patients with hematologic diseases, such as lymphoma, multiple myeloma, leukemia, etc. Successful hematopoietic stem cell transplantation (HSCT) increasingly depends on the collection of hematopoietic stem cells (HSCs) from peripheral blood. Peripheral vein (PV) is the most common type of blood access. When the blood vessels are not well filled and the blood flow is insufficient, the machine will appear repeated low pressure alarm or pipeline coagulation, which seriously affects the collection efficiency. A peripheral artery (PA) is utilized for drawing blood, while a peripheral vein is used for blood return, that is a way to perform apheresis. The advantages of PA are that it ensures adequate extracorporeal circulation blood flow, stable blood flow rate, simple operation, and relatively low price. However, there are very few studies on the efficacy of peripheral arterial access for HSCs collection. Therefore, this retrospective study was conducted to assess the effectiveness of PA and PV access for PBSCs collection. METHODS: We performed a retrospective analysis of 150 apheresis procedures on 26 patients and 95 healthy donors collected by PV or PA access from March 1, 2020 to March 1, 2021. We compared the CD34+ cell count, collection efficiency (CE), duration of processing a single blood volume, number of low-pressure alarms, average blood flow rate and number of punctures between the two groups. Also, we analyzed adverse events. RESULTS: There was no significant difference in the quality of apheresis blood components between the PA group and the PV group. The CD34+ cells collected was 274.16 ± 216.31 × 106 in the PV group and 246.63 ± 127.94 × 106 in the PA group. The CE in the PA group was 49.50 ± 9.88%, higher than 42.39 ± 14.62% in the PV group. The duration of processing a single blood volume was 90.67 ± 15.35 min in the PV group and 79.68 ± 10.28 min in the PA group. The number of low-pressure alarms in the PA group was 0.38 ± 0.98, <2.42 ± 1.76 in the PV group, and the average blood flow rate in the PA group was 59.27 ± 2.18, higher than 54.21 ± 3.41 in the PV group. The difference was statistically significant (P < .05). The Number of punctures was 1.35 ± 0.75 in the PA group and 1.41 ± 1.01 in the PV group. There was no statistically significant difference. CONCLUSION: Peripheral artery is a safe, reliable, economical, convenient, and fast vascular access, which opens a new way to the establishment of vascular access for PBSCs collection.

An innovation in stem cell harvesting: Heparin use.

BACKGROUND AND OBJECTIVES: Stem cell transplantation is a growing treatment strategy for most malignant and non- malignant hematological diseases. Plerixafor and granulocyte colony stimulating factor (G-CSF) are usually used in mobilization regimens to increase the CD34+ cell count in the harvest. Heparin is a sulphated glycosaminoglycated polymer with 12-15 kDa mass. Heparin inhibits the CXCR4/SDF1 axis, as does plerixafor. In this study, our aim was to investigate the effect of using heparin on stem cell mobilization and harvesting. MATERIALS AND METHODS: We administered 5000 units of unfractioned heparin intravenously in 150 mL (mL) of isotonic sodium chloride solution, 15 min before the stem cell harvesting procedure to 141 patients who underwent bone marrow transplantation between the years of 2018 and 2019 at our Stem Cell Transplantation Unit. Thirty patients were included as a control group, and they were not given heparin. The study population included patients with multiple myeloma and lymphoma equally in each group. RESULTS: In all patients hematopoeitic stem cells were successfully harvested in a single cycle of apheresis. In multiple myeloma patients who received heparin, the mean collected CD34+ cell number was 8 × 106/kg, and the mean CD34+ cell number yield was 12,555/µl. In the control group, the mean collected CD34+ cell number was 4,2 × 106/kg, and mean CD34+ cell number in yield was 492/µl. In lymphoma patients who received heparin, the mean collected CD34+ cell number was 6,8 × 106/kg, and the mean CD34+ cell number was 1421/µl. In the control group the mean collected CD34+ cell number was 4,3 × 106/kg, and the mean CD34+ cell number was 358/µl. The effect of heparin on the collected stem cell number in both myeloma and lymphoma patients was statistically significant (p < 0.01). CONCLUSIONS: Our results have shown that heparin increases harvested stem cell numbers significantly. Heparin may be a promising agent for stem cell harvesting.

Epstein-Barr virus (EBV) deletions as biomarkers of response to treatment of chronic active EBV.

Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV+ haematological clones that are lost on successful treatment.