Peripheral Blood Stem Cell Research Articles

Gelofusine as alternative to Dextran40-based solution for washing cryopreserved hematopoietic stem cell products prior to infusion: Validation and application to clinical practice.

Cryopreservation is an essential step for autologous hematopoietic stem cell (HSC) transplantation and umbilical cord blood units (CBUs), and for allogeneic peripheral blood stem cells (PBSCs) or bone marrow (BM) when immediate infusion is not possible. However, the cryoprotectant dimethyl sulfoxide (DMSO) used for HSC cryopreservation can be toxic to cells post-thaw and to patients during infusion. The Rubinstein solution is validated to wash HSCs, but the unavailability of Dextran40 in Italy prompted a search for alternatives. This report discusses the use of Gelofusine, a 4% modified gelatin solution, as a substitute for Dextran40-based solutions in washing cryopreserved stem cell products. The study includes: (1) validation of Gelofusine in 10 CBUs unsuitable for transplantation; (2) outcomes of the first 93 transplanted units washed with Gelofusine; (3) comparisons of recovery and viability in five paired autologous PBSC products washed with Gelofusine and Rubinstein-solution; and (4) comparisons of engraftment times in patients receiving units washed with Gelofusine and Rubinstein-solution. For 10 CBUs washed with Gelofusine, CD34+ and TNC viability and recovery were 96%, 87%, 71%, and 75% respectively, higher than our reference values. In transplanted products, CD34+ and TNC viability and recovery were 96%, 89%, 82%, and 91% respectively. Comparisons with Rubinstein solution revealed similar TNC and CD34+ recovery but significantly higher TNC (89% vs. 68%) and CD34+ (97% vs. 89%) viability with Gelofusine. Engraftment times for both solutions were similar. These findings support Gelofusine as an effective and valid alternative to Rubinstein-solution for washing cryopreserved HSCs.

Addition of mycophenolate mofetil to a calcineurin inhibitor and post-transplant cyclophosphamide results in lower incidence of extensive chronic graft-versus-host disease in HLA-matched allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia in complete remission: a matched-pair analysis on behalf of the Acute Leukemia Working Party of the EBMT.

Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.e. age, adverse cytogenetics, Karnofsky performance status, patient and donor cytomegalovirus serology, conditioning intensity). Each group comprised 146 patients, with 63% in total undergoing matched unrelated-allo-HSCT. Median follow up was longer for PTCy+CNI (36 [IQR 31-39] months versus 25 [IQR 19-30] months for PTCy+CNI+MMF, p < 0.01). At 2 years, PTCy+CNI was associated with a higher incidence of extensive chronic GVHD (16% [95% CI 10-22] versus 6% [95% CI 3-12] for PTCy+CNI+MMF, p < 0.03) while no differences were observed for all the other transplant outcomes. Addition of MMF to PTCy and CNI may help to prevent extensive chronic GVHD in HLA-matched allo-HSCT with PBSC.

A multicenter study of allogeneic hematopoietic stem cell transplantation for stage 4/M neuroblastoma

Objective: To evaluate the effectiveness and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with stage 4/M neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter clinical trial conducted by Sun Yat-sen Memorial Hospital, Children's Hospital of Nanjing Medical University, Children's Hospital, Zhejiang University School of Medicine, the First Affiliated Hospital of Guangxi Medical University, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. From March, 2019 to August, 2023, 25 children with confirmed with stage 4/M NB and received allo-HSCT were enrolled. The patients received either unrelated cord blood transplantation (UCBT) or peripheral blood stem cell transplantation (PBSCT). Conditioning regimens for UCBT was fludarabine+busulfan+cyclophosphamide+topotecan, and for PBSCT was fludarabine+busulfan+melphalan+thiotepa+antithymocyte globulin, respectively. Until the last follow-up date of September, 2023, the overall survival (OS) rate and event free survival (EFS) rate were analyzed to evaluate efficacy. The engraftment rate and transplant-related complications were statistically assessed to evaluate safety. Survival analysis was performed using the Kaplan-Meier method. Results: Of the 25 patients, there were 15 males and 10 females. The age at transplantation was 5.7 (3.8, 7.3) years. The engraft rate was 100%, with recovery time of neutrophil as 15.7 (12.5, 17.0) d, and the recovery time of platelets as 33.5 (18.0, 48.0) d. Seventeen of the 25 children (68%) developed acute graft versus host disease (aGVHD), occurred at 18.0 (13.0, 22.5) d after transplantation, including 13 of grade Ⅲ-Ⅳ cases. The main sites of aGVHD were skin and intestinal tract. After treatment, 13 cases improved, 4 patients developed chronic graft-versus-host disease (cGVHD). After allo-HSCT, 14 children received maintenance therapy. Twenty of the 25 patients survived, the 2-year cumulative OS rate was (80±9)%, and 2-year EFS rate was (56±11)%. Nine cases (36%) relapsed, the time from allo-HSCT to disease relapse was 10.9 (5.5, 16.0) months. Five cases (20%) died. The hematopoietic stem cell transplantation associated mortality rate was 4% (1/25).The 2-year OS rate of patients who had partial remission prior to allo-HSCT was significant lower than those who had complete remission prior to allo-HSCT ((33±25)% vs. 100%, P=0.037). Conclusion: allo-HSCT is an effective treatment for patients with stage 4/M NB.

Granulocyte Colony-Stimulating Factor-Primed Bone Marrow Transplantation Experience in 350 Matched Sibling Donor Grafts for Severe Thalassemia.

Granulocyte Colony-Stimulating Factor-Primed Bone Marrow Transplantation Experience in 350 Matched Sibling Donor Grafts for Severe Thalassemia.

Incidence and Factors Associated with Graft-Versus-Host Disease in the First Year After Allogeneic Peripheral Blood Stem Cell Transplantation.

The use of allogeneic peripheral blood stem cell transplantation (allo-SCT) has increased in Latin America in recent years. In the absence of an matched-related donor (MRD), haploidentical transplantation has emerged as a potentially curative option with increasing availability in the region. Graft-versus-host disease (GVHD) is an important complication with variable incidence rates depending on the type of transplant. The aim of this study was to compare the incidence of acute and chronic GVHD between haploidentical and identical allo-SCT recipients and to analyze factors associated with the development of GVHD during the first year after transplantation. Our retrospective cohort study included adult patients with malignant and nonmalignant hematologic pathologies who received allo-SCT between 2014 and 2022 at a transplant center in Bogota, Colombia. Uni- and multivariate analyses were performed to determine factors associated with the development of GVHD. A total of 152 patients were analyzed, including 108 (71%) transplants from an MRD and 44 (28.9%) transplants from a haploidentical donor. The median age was 45 years. The most common indications for transplantation were acute myeloid leukemia (37.5%) and acute lymphoblastic leukemia (36.2%). The incidence of acute GVHD was greater in the haploidentical transplant group (63.0%) than in the MRD group (36.6%) (p < 0.05). There was no significant difference in the incidence of chronic GVHD between the two groups, with 18% and 33% in transplants from haploidentical donors and MRD, respectively (p = 0.09). The factors associated with the development of acute GVHD were relapse (odds ratio [OR] 0.41; 95% CI, 0.13-1.16), female sex (OR 2.34; 95% CI, 0.93-6.1), and age older than 50 years (OR 2.1; 95% CI, 0.81-5.71). The factors associated with the development of chronic GVHD were haploidentical donor status (OR 0.22; 95% CI, 0.05-0.75) and relapse (OR 0.16; 95% CI, 0.04-0.56). Our study revealed a higher rate of acute GVHD in transplant recipients from a haploidentical donor than in those from MRD, whereas no differences were found for chronic GVHD between the two groups. Sex, age, relapse, and type of transplant were identified as factors associated with the prevalence of GVHD.

Dose Effect of Anti-thymocyte Globulin or Post-transplant Cyclophosphamide in Haploidentical Peripheral Blood Stem Cell Transplantation: A Comparative Study: Dose effect of ATG or PTCy in haplo-PBSCT.

Dose Effect of Anti-thymocyte Globulin or Post-transplant Cyclophosphamide in Haploidentical Peripheral Blood Stem Cell Transplantation: A Comparative Study: Dose effect of ATG or PTCy in haplo-PBSCT.

Experience with T Cell–Depleted Allogeneic HSCT for Refractory sJIA Associated with Lung Disease

Background A subset of patients with systemic juvenile idiopathic arthritis (sJIA) develop sJIA-associated lung disease (sJIA-LD). Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment option for patients with refractory sJIA and can ameliorate associated lung disease. Infusion of T-replete grafts into sJIA-LD patients who have a high background of preexisting systemic and pulmonary inflammation may contribute to risks of inflammatory complications or graft versus host disease following allogeneic HSCT. We hypothesized that a T cell–depleted approach would achieve durable engraftment while minimizing the risks of GVHD, pulmonary complications, and TRM. Methods We report our single-center retrospective analysis of 4 pediatric patients with sJIA-LD who underwent allogeneic HSCT with reduced intensity conditioning (RIC) with alemtuzumab (days 14-12), fludarabine (150 mg/2 over days -8 to -4), melphalan (140 mg/m2 on day -3), and thiotepa (200 mg/m2 on day -2) and received either a CD34+-selected (n = 3) or TCR-αβ–depleted (n = 1) peripheral blood stem cell product. Results Patient and transplant characteristics are shown in Table 1. All patients had highly refractory disease and were heavily pretreated with a median of 8 (6-12) lines of sJIA-directed therapy. At the time of HSCT, three patients required respiratory support (supplemental O2 in n = 2, overnight BiPAP with supplemental O2 in n = 1). Table 1. Transplant characteristics All patients engrafted with &amp;gt;95% donor chimerism (range, 9-10 days post-HSCT). One patient experienced secondary graft failure on day +43 requiring a second HSCT with a haploidentical parental donor and post-transplant cyclophosphamide (Table 1). Second HSCT was complicated by grade 1 (skin) acute GVHD. None of the other patients developed acute or chronic GVHD or significant pulmonary complications. All had significant improvement in their pulmonary status and were able to discontinue their respiratory support (Figure 1). At a median follow up of 19.8 months (range, 6-36 months), all patients have 100% donor chimerism. None of the patients have had relapse of their sJIA. IL-18 levels declined post-HSCT to near normal levels in all patients (Table 1). Figure 1. Progress of pulmonary disease pre- and post-HSCT. High-resolution CT chest images of patient #1 pre- (A) and 2.5 years post- (B) HSCT. (C) This shows percent predicted FEV1 and FVC and lowest SpO2 in 6-minute walk test for patients #1-3 (patient 4 unable to reliably perform spirometry). Conclusions Our experience suggests that allogeneic HSCT with a T cell–depleted approach for patients with sJIA-LD offers durable engraftment with low risk of GVHD, pulmonary complications, and TRM.

Impact of single dose of pegfilgrastim on peripheral blood stem cell harvest in patients with multiple myeloma or malignant lymphoma

This phase 2 study evaluated the impact of pegfilgrastim, a single-dose, long-acting granulocyte colony-stimulating factor, on the steady-state mobilization of hematopoietic stem cells into peripheral blood in patients with multiple myeloma (MM) or malignant lymphoma (ML). Efficacy and safety, along with CD34-positive cell mobilization outcomes were assessed in patients with MM, who were randomly assigned to pegfilgrastim (n = 30) or daily filgrastim (n = 31), and ML (pegfilgrastim only, n = 13) cohorts. In the MM cohort, CD34-positive cell counts ≥ 2 × 106/kg were achieved in 100% of patients in the pegfilgrastim group and 96.7% in the filgrastim group (difference: 3.3%; 80% confidence interval: −0.9–7.5%), demonstrating the non-inferiority of pegfilgrastim to filgrastim. All patients in the ML cohort achieved ≥ 2 × 106/kg CD34-positive cell counts. The plerixafor administration rates in the MM cohort were 50.0% and 63.3% in the pegfilgrastim and filgrastim groups, respectively, and 91.7% in the ML cohort. There were no major differences in safety measures between the two groups. Although the sample size was small, particularly in the ML cohort, a single dose of pegfilgrastim demonstrated comparable efficacy and safety to daily doses of filgrastim, indicating its potential for clinical use while reducing patient burden.Trial Registration: jRCT2011210029, NCT05007652.

Unconditioned Hematopoietic Stem Cell Transplant in Hypomorphic RAG1-Associated Severe Combined Immunodeficiency Complicated by Cytomegalovirus Viremia and Inflammatory Bowel Disease

Introduction Managing hypomorphic RAG1-associated severe combined immunodeficiency (SCID) prior to hematopoietic stem cell transplant (HSCT) represents a unique therapeutic challenge as clinicians are charged with preventing and treating opportunistic infections while often simultaneously controlling the consequences of immune dysregulation. We describe a particularly challenging case of treatment-resistant cytomegalovirus (CMV) viremia and significant inflammatory bowel disease in a Mennonite infant with hypomorphic RAG1-associated SCID, ultimately treated with unconditioned HSCT. Case A Mennonite breastfed female with SCID secondary to homozygous RAG1 c.527G&amp;gt;T variants (older brother shared genotype) presented at 10 months old with an acute diarrheal illness, found to have cryptosporidium gastroenteritis and CMV viremia. She had rising CMV viral load despite treatment with ganciclovir, valganciclovir, foscarnet, and cidofovir sequentially, as well as 5 maternally derived CMV-specific cytotoxic T lymphocyte infusions. She had poor weight gain, chronic diarrhea, feed intolerance requiring parenteral nutrition, peri-rectal ulcers, and colonoscopy consistent with IBD. IBD was treated with triple antibiotic therapy alone given significant risk with further immunosuppression. B cell depletion with rituximab was pursued to eliminate potential anti–type I interferon antibody–producing B cells and augment CMV clearance. CMV-directed therapies were ultimately discontinued given continued treatment resistance and adverse side effects. She received an unconditioned haploidentical peripheral stem cell transplant with TCRαβ+/CD19+ cell depletion at 18 months old. Engraftment studies showed 34% donor chimerism in the T cell lineage at 3 months post-HSCT, which gradually increased to 80% at 1 year post-HSCT. At 1 year post-HSCT, immune phenotyping showed modestly increased naive T cells, normalized lymphocyte proliferative response to mitogen stimulation, and predominantly polyclonal TCR Vb repertoire. She remained with minimal B cell and myeloid donor engraftment and is maintained on immunoglobulin replacement therapy. Clinically, her GI disease improved with tolerance of complete enteral feeds since 10 months post-HSCT. At 1 year post-HSCT, her CMV viral load was undetectable. Conclusions We report a remarkably positive and unexpected outcome of rising T cell engraftment, clearance of previously treatment-resistant CMV viremia, and marked improvement in IBD symptoms after unconditioned HSCT for hypomorphic RAG1-associated SCID, adding to the field’s important and ever-growing experience in managing this challenging condition.

Coronary artery calcification score as a prognostic factor in younger patients with multiple myeloma undergoing autologous stem cell therapy

BackgroundCoronary artery calcification (CAC) scoring can be performed as a by-product of computed tomography (CT). CAC scoring may reflect the general cardiovascular risk profile of patients. The aim of the present study was to determine the impact of CAC on overall survival (OS) in patients with multiple myeloma (MM).MethodsA retrospective analysis was conducted on all patients with MM undergoing peripheral blood stem cell transplantation between the years 2009 and 2019. A total of 127 patients (50 female patients, 39.4%) with a mean age of 57.8 ± 7.6 years were included in the analysis. A whole-body CT scan was used to assess the CAC score for each patient. The Weston score as a surrogate for Agatston score was applied in the non-gated staging CT images.cResultsA total of 27 patients (22.0%) died during the course of the study. The CAC score did not differ between non-survivors and survivors in the discrimination analysis (mean 1.2 ± 2.4 versus 2.0 ± 2.8, p = 0.13). The CAC score showed no correlation with overall survival, with an HR of 0.92 (95% CI 0.78–1.09, p = 0.35). Of the patients without calcification (CAC score 0, n = 66, 51.9%), 18 died, while of those with calcification (CAC score 1 or higher, n = 61, 48.1%), nine died. The results of the Fisher’s exact test showed no statistically significant difference between the two groups (p = 0.20).ConclusionsThe presence of CT-defined coronary calcifications does not predict survival in younger patients with multiple myeloma undergoing autologous stem cell therapy and comparably short survival. The impact of CT-defined cardiovascular risk factors appears to be relatively modest in this heterogeneous disease.

Phase 1 study of quercetin, a natural antioxidant for children and young adults with Fanconi anemia.

Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure (BMF) and a predisposition to malignancy. Systemic reactive oxygen species (ROS) and increased sensitivity of FA hematopoietic progenitors to ROS play a key role in the pathogenesis of BMF. Treatment with antioxidants improve hematopoietic function in Fancc-/- mice. We report the safety, tolerability, and pharmacokinetics of quercetin, a naturally occurring antioxidant in the first dose-finding phase 1 study for patients with FA. Twelve patients (median age, 7 years [range, 3-21]) received oral quercetin twice daily for 4months. Quercetin was well tolerated at all dose levels. Allometrically bodyweight-adjusted dose with a maximum adult daily dose of 4000mg/d was established as the recommended dose of quercetin. Patients in an expansion cohort (n=18) were treated using this recommended dose for 6months. A subset of patients showed reduced ROS levels in the peripheral blood (PB) and bone marrow stem cell compartment. Patients in the analysis cohort treated with the recommended dose of quercetin achieved an a priori-defined optimal response of 25% reduction in the PB ROS level compared with baseline. Platelet counts remained stable to slightly improved over the study period (P=.06). Absolute neutrophil counts (P=.01) and hemoglobin levels gradually declined (P=.001). In those with evidence of BMF at baseline, 8 of 15 patients (53%) had a hematological response at some point after quercetin treatment. Fluctuations in counts are common in patients with FA, limiting accurate assessment of the impact of quercetin use in FA. This trial was registered at www.ClinicalTrials.gov as #NCT01720147.

Abstract 622: Age-dependent changes in cell cycle dynamics and hematopoietic responses to chemotherapy

Abstract Background: Precision medicine emphasizes individualized cancer treatment, particularly for elderly lung cancer patients facing unique chemotherapy challenges. Age-related changes in cell cycle dynamics significantly influence therapeutic outcomes, yet their role in optimizing personalized therapies remains underexplored. This study investigates these age-related dynamics to inform personalized therapeutic strategies for elderly lung cancer patients. Methods: Single-cell RNA sequencing data from 166 healthy individuals (aged 25-85 years) were analyzed to explore age-associated changes in cell cycle distribution, differentially expressed genes (DEGs), and enriched pathways. Young (9-11 weeks) and aged (17 months) mice received weekly cisplatin for four cycles. Peripheral blood and hematopoietic stem cells (HSCs) were monitored dynamically for cell cycle phases, DNA damage (γ-H2AX), and vascular leakiness using immunofluorescence. RNA sequencing of HSCs identified DEGs and enriched pathways after treatment cycles. Results: Single-cell analysis revealed a linear decrease in S-phase proportions with age (r=−0.681, p=0.0026) and identified 28 DEGs, including PAXB-AS1, BABAM1, and DONSON, enriched in immune regulation and cell cycle pathways. In murine models, aged mice showed impaired immune recovery, with persistently higher neutrophil proportions (post-cycle 1: 14.75% vs. 6.1%, p&amp;lt;0.05) and lower lymphocyte proportions (post-cycle 1: 65.73% vs. 79.98%, post-cycle 4: 60.5% vs. 63.8%) compared to young mice. Moreover, aged mice exhibited delayed neutrophil recovery (Day 4 vs. Day 2), accompanied by persistent G1-phase arrest in HSCs (Day 4: 86% vs. 82%) and reduced G2/M-phase proportions (Day 4: 3% vs. 6%). RNA sequencing of aged HSCs further revealed significant enrichment in the DNA_DAMAGE_TELOMERE_STRESS_INDUCED_SENESCENCE pathway after four treatment cycles (|NSE| = 1.98, p &amp;lt; 0.05), a pattern absent in young mice. Finally, γ-H2AX flow cytometry confirmed increased DNA damage in aged HSCs, while immunofluorescence demonstrated heightened bone marrow vascular leakiness in aged mice. Conclusion: Aging significantly alters cell cycle dynamics, hematopoietic recovery, and chemotherapy responses, highlighting the need to integrate cell cycle-based insights into personalized treatment strategies. These findings provide a foundation for future research on age-specific therapeutic interventions in lung cancer. Citation Format: Jianxing He,Yue Pan,Hao Liu,Ying Huang,Hongsheng Deng,Chao Yang,Qi Cai,Shan Xiong,Huiting Liu,Wenhua Liang. Age-dependent changes in cell cycle dynamics and hematopoietic responses to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 622.

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Severe Aplastic Anemia Patients.

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Severe Aplastic Anemia Patients.

Results of the Latin American Bone Marrow Transplantation Society (LABMT) activity survey 2019-2022: the impact of the COVID-19 pandemic and the increase in related haploidentical donors.

A total of 6767 first hematopoietic cell transplants (HCT), 4121 autologous (61%) and 2646 allogeneic (39%), were reported by 166 teams from 12 Latin American countries that answered the 2022 LABMT/WBMT activity survey. The transplant rate (TR) for Latin America in 2022 was 103 HCT/10 million inhabitants with a wide variation between the different countries. The main indication for allogeneic (allo)-HCT was acute lymphoblastic leukaemia (41%) for the pediatric population and acute myeloid leukemia (32%) for adults. The main indication for autologous (auto)-HCT was neuroblastoma (33%) in children and plasma cell disorders (57%) in adults. In alloHCT, the most used hematopoietic cell source was the bone marrow (54%) in pediatric while peripheral blood stem cells (PBSC) (87%) was in adults. PBSC was the source of choice for autoHCT in both ages. The main trends observed in the period 2019-2022 was a decrease in the number of procedures in 2020 in association with the start of the COVID-19 pandemic, resuming growth in the following years. AlloHCT had a greater growth compared to autoHCT, and it was mainly driven by the utilization of haploidentical related donors, which became the main source from 2020 onwards.

The impact of ABO compatibility on allogeneic hematopoietic cell transplantation outcomes: a contemporary and comprehensive study from the transplant complications working party of the EBMT.

The role of ABO blood group system mismatch on allogeneic hematopoietic cell transplantation (allo-HCT) outcomes is controversial since current publications of large datasets are lacking. We retrospectively analyzed 30,487 patients transplanted between 2010 and 2021 using the EBMT registry to assess ABO incompatibility's effect on non-relapse mortality (NRM), overall survival (OS), progression-free survival (PFS), relapse incidence (RI), acute GvHD (aGvHD), chronic GvHD (cGvHD), and neutrophil engraftment. Transplantations were classified as ABO-compatible (56.3%), major (18.1%), minor (20.1%), and bidirectional (5.5%) incompatibilities. Mainly peripheral blood stem cells (PBSC) were used as the cell source in 85.6% of cases. Multivariate analysis found no significant association between compatibility status, with the compatible group serving as the reference, and NRM, OS, PFS, RI or cGvHD. The incidence of non-engraftment was significantly higher in the major (HR 1.04, 95% CI 1.01-1.07, p = 0.021) and bidirectional (HR 1.09, 95% CI 1.03-1.15, p = 0.003) incompatibilities. At the same time, the risk of severe aGvHD grades III-IV was lower in the major incompatibility group (HR 0.85, 95% CI 0.77-0.94, p = 0.001). Our large contemporary study, showing no major impact on outcomes, suggests that the ABO blood group system should not be a primary consideration in donor selection for PBSC-based allo-HCT.

Intra-apheresis Cycling to Improve the Clinical Efficacy of Peripheral Blood Stem Cell Donations.

Peripheral blood stem cell (PBSC) donation is the primary procedure used to collect haemopoietic stem cells (HSCs) for transplantation in individuals with haematological malignancies. More than 90,000 HSC transplants take place globally each year, and there is an increasing need to guarantee HSC mobilisation, improve tolerability to apheresis, and optimise immune reconstitution. Currently, mobilisation of HSCs depends upon pharmacological agents, with donors inactive during their subsequent apheresis. A successful yield of HSCs is not always achieved, and greater efficiency of collection procedures would improve the donors' safety and experience, along with the overall functioning of apheresis departments. The mobilisation of immune cells during bouts of exercise has been increasingly studied over the past 40years. Exercise enriches peripheral blood with HSCs and immune cells such as cytolytic natural killer cells, and these may impact upon collection efficiency and patient outcomes following transplantation. Using exercise in conjunction with routine pharmaceutical agents may meet these needs. This article describes the impact of exercise on the quantity and engraftment potential of HSCs. Given that PBSC collections take on average 3-4h per day per donor, and often consecutive days to complete, particular attention is paid to adopting interval exercise in this setting. Moreover, practical and safety considerations for allogeneic and autologous donors are discussed. 'Intra-apheresis cycling' is proposed as a feasible adjunctive strategy to evoke clinically significant improvements in the quality of the immune graft. Further research is needed to validate this concept in conjunction with routine mobilisation agents.

Drug-induced liver injury due to granulocyte colony-stimulating factor in a healthy donor for allogeneic peripheral blood stem cell transplantation.

Granulocyte-colony stimulating factor (G-CSF) is commonly used for peripheral blood stem cell harvesting (PBSCH). Although its well-documented adverse effects include thrombocytopaenia and bone pain, drug-induced liver injury (DILI) is rare. We present the case of a 40-year-old male donor who developed DILI 4 days after G-CSF administration for PBSCH. Laboratory results indicated elevated hepatobiliary enzymes, with aspartate aminotransferase (AST) peaking at 171 U/L (×6 the upper limit of normal [ULN]) on Day 7 of G-CSF administration, alanine aminotransferase (ALT) at 244 U/L (×6 ULN) on Day 11, alkaline phosphatase (ALP) at 371 U/L (×3 ULN) on Day 5 and gamma-glutamyl transpeptidase (γ-GTP) 93 U/L (×1.5 ULN) on Day 9. The hepatobiliary dysfunction became evident after G-CSF administration had ended, despite other parameters-including white blood cell and platelet counts-remaining within acceptable ranges. DILI was confirmed by positive drug lymphocyte stimulation test results. The donor's liver function normalized within 1 month of supportive treatment, and the recipient achieved successful engraftment without G-CSF administration. As G-CSF allergy screening is not mandatory in current Japanese protocols, DILI due to G-CSF could present a risk during PBSCH. This case emphasizes the importance of vigilant monitoring and comprehensive risk assessment to ensure the safety of healthy donors.

Salvage HLA-haploidentical Peripheral Blood Stem Cell Transplantation Using Post-transplant Cyclophosphamide for Recurrent Hemophagocytic Lymphohistiocytosis-associated Graft Failure after Cord Blood Transplantations: A Case Report.

We describe a case of immunological rejection occurring twice after cord blood transplantation (CBT) for mixed phenotype blast phase chronic myeloid leukemia that was successfully salvaged by haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PT-Cy). Pre-engraftment immune reaction (PIR) and subsequent hemophagocytic lymphohistiocytosis (HLH), likely due to HLA mismatch in the graft-versus-host (GVH) direction, lead to poor graft function (PGF) and graft failure (GF). This case highlights the pathophysiology of PIR, HLH, PGF, and GF, collectively termed "post-transplant cytokine syndrome." PT-Cy haplo-PBSCT, with wide donor availability and reduced infection risk leading to HLH via rapid engraftment, may be a suitable salvage option for post-CBT cytokine syndrome-related GF.

Disseminated fusariosis successfully treated with empirical liposomal amphotericin B and voriconazole combination followed by ocular therapy in an allogenic hematopoietic stem cell transplant recipient.

We report the case of a 61-year-old man with chronic myelomonocytic leukemia, who underwent unrelated peripheral blood stem cell transplantation. Fusariosis was suspected prior to identification of the fungal species, and voriconazole and liposomal amphotericin B combination therapy were administered. The patient developed fusarium-related endophthalmitis, accompanied by eye pain. Despite vitrectomy, the endophthalmitis was poorly controlled, and the left eye was enucleated. No recurrence of fusariosis was observed until death following multiple-organ failure due to steroid-resistant graft-versus-host disease.

Allogeneic transplantation for CML blast phase: Learnings over last decade from a single centre in North India

Chronic myeloid leukemia in the blast phase (BP-CML) remains challenging despite advancements in tyrosine kinase inhibitors (TKIs). This study retrospectively assessed BP-CML patients who underwent allogeneic stem cell transplantation (allo-SCT) from June 2009 to December 2022. Thirty-three patients were included and the median age was 41 years, with a predominantly male cohort. Myeloablative conditioning and peripheral blood stem cells were used in the majority of the patients. The estimated 2-year overall survival (OS) was 48.3% of the cohort. Relapse occurred in 48.5% of patients, typically within 3 months post-transplant. Post-transplant TKI maintenance showed a significant association with improved OS (p-value = 0.001). The study highlights the need for early intervention and optimized post-transplant maintenance to improve outcomes.