Allogeneic Peripheral Blood Stem Cell Research Articles

Complications and the impact of hematological parameters in donors involved in allogenic peripheral blood stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplantation (HSCT) is a vital treatment option for many hematological malignancies, offering a more convenient alternative to bone marrow transplantation. In allogeneic HSCT, donors provide hematopoietic stem cells for transplantation into patients, necessitating careful consideration of the donor's health and hematological parameters to ensure successful engraftment and treatment outcomes. In a study involving 20 adult donors at Apeksha Hospital, Sri Lanka key hematological parameters, comorbidities, clinical histories, and medications were analyzed. Diabetes mellitus and hypertension were the most prevalent comorbidities among donors, while anemia, primarily linked to iron and vitamin B12 deficiencies, was common. Although baseline coagulation abnormalities were rare and no significant complications occurred during transplantation, early clinical issues such as pain and paresthesia correlated with abnormal peripheral blood smear findings. Notably, a 4-day single daily G-CSF dosing schedule was favored over a 5-day twice daily regimen due to fewer reported problems. While anemia and thrombocytopenia were infrequent, these findings underscore the critical importance of meticulous donor selection and vigilant monitoring throughout the transplantation process to optimize outcomes.

Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation from a sibling donor for pediatric patients.

Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.

Pyogenic spondylitis after Corynebacterium striatum blood stream infection following allogeneic hematopoietic stem cell transplantation for malignant lymphoma

Patient 1 was a 70-year-old woman with refractory diffuse large B-cell lymphoma who received allogeneic peripheral blood stem cell transplantation from an HLA-haploidentical related donor. Upper back pain appeared on day63, and Th8-Th9 pyogenic spondylitis was diagnosed based on magnetic resonance imaging (MRI). Blood culture on day14 identified Corynebacterium striatum as the causative bacteria of blood stream infection (BSI). The pyogenic spondylitis resolved after treatment with daptomycin for 2 months. Patient 2 was a 65-year-old man with relapsed angioimmunoblastic T-cell lymphoma who received bone marrow transplantation from an HLA-DR single-antigen-mismatched unrelated donor. Lower back pain appeared on day30, and L4-L5 pyogenic spondylitis was diagnosed based on MRI. Blood culture was negative. Daptomycin and clindamycin were selected for treatment based on the drug susceptibility of bacteria that had caused pre-engraftment BSI (Escherichia coli on day3 and Corynebacterium striatum on day9), and the pyogenic spondylitis resolved after 6 months of this treatment. Pyogenic spondylitis should be considered in the differential diagnosis of back pain accompanied by BSI before engraftment in allogeneic hematopoietic stem cell transplant recipients.

Haploidentical and Matched Sibling Transplantation for Acute Myeloid Leukemia: A Hospital-Based Study.

Allogeneic peripheral blood stem cell transplantation (PBSCT) has been increasing for the last years in Latin America. The objective of this study was to describe clinical outcomes in acute myeloid leukemia (AML) receiving allogeneic PBSCT between 2013 and 2019 in a single center of Cali, Colombia. A retrospective cohort study was conducted in Fundacion Valle del Lili. Patients diagnosed with AML who received an allogeneic PBSCT between 2013 and 2019 using human leukocyte antigen (HLA)-matched sibling donors (MSDs) or haploidentical related donors (HRDs) with myeloablative conditioning regimen were included. Cases with diagnosis of promyelocytic leukemia, myelodysplastic syndrome-related AML and therapy-related AML were excluded. Data were obtained directly from the hospital PBSCT database and clinical records. A total of 50 patients were included (HRD, n = 32; MSD, n = 18). Sixty-two percent was in the first complete remission (CR1) at the time of the transplant, of which 26% were MSD and 74% were HRD. The European Group for Blood and Marrow Transplantation (EBMT) risk score was: 44% vs. 50% low, 28% vs. 28% intermediate and 28% vs. 22% high for MSD vs. HRD, respectively. Overall survival at 5 years for MSD was 62% (95% confidence interval (CI): 31-83%) and 43% (95% CI: 25-60%) for HRD. Event-free survival was 56% (95% CI: 26-78%) and 35.6% (95% CI: 18-53%), respectively. Non-relapse mortality at day-100 was 6% (95% CI: 0.8-35%) and 20% (95% CI: 9-39%). Relapse at5 years was 18% (95% CI: 4-58%) and 25% (95% CI: 10-52%). Overall mortality rate was 46%. The grade II-IV, III-IV acute graft-versus-host disease and severe chronic graft-versus-host disease was 44%, 11% and 12% for MSD, and 43%, 9% and 0% for HRD. These results underline that MSD remains the first donor choice for AML patients in CR1 when available. HRDs are still our next option among alternative donors. It is necessary to find strategies that have a positive impact on those outcomes that markedly affect the quality of allogeneic PBSCT and the prognosis of patients. Comparative, randomized, prospective studies with longer follow-up of haploidentical allogeneic PBSCT with other donor types are required to definitely establish its role among alternative donors.

The impact of cryoprotectant exposure time on post-thaw viability of autologous and allogeneic hematopoietic stem cells and leukocyte subpopulations.

Although the use of cryoprotectant dimethyl sulfoxide (DMSO) is the gold standard in cryopreservation of hematopoietic stem cells, it is well known that it has a negative effect on cell viability. The aim of this prospective study was to examine how the length of post-thaw exposure to DMSO affects the cell viability and stability of peripheral blood stem cell (PBSC) samples. Additionally, the effects of donor type and pre-cryopreservation storage time on post-thaw viability during the stability study were evaluated. In 30 autologous and 30 allogeneic PBSC samples viable CD34+, CD14+, CD19+, CD16+/56+, and CD3+ cells were determined immediately after thawing, and one-and three-hours post-thaw. Analysis of the absolute count of viable cells in thawed samples showed a significant difference between all measurement points for CD34+ (p < 0.001), CD14+ (p < 0.001), and CD19+ cells (p < 0.001). No significant differences were observed for post-thaw stability of allogeneic samples analysed between products stored before cryopreservation ≥ 24 hours (N = 20), and those stored < 24 hours (N = 10), except for viable CD3+/CD4+ cells after three hours post-thaw (p = 0.028). In conclusion, DMSO had different effects on leukocyte subpopulations in cryopre-served PBSC samples. The type of donors and the length of storage before cryopreservation did not affect the post-thaw stability of cryopreserved PBSC samples.

Unrevealing Hematopoietic Reconstruction Discrepancies after Allo-UCBT and Allo-PBSCT at Single Cell Resolution

Umbilical cord blood (UCB) and G-CSF mobilizing peripheral blood stem cell (G-PBSC) are the main sources of hematopoietic stem cells for transplantation on clinic. Clinical data have shown that hematopoietic reconstruction in allogeneic cord blood transplantation (allo-UCBT) is significantly delayed compared with allogeneic peripheral blood stem cell transplantation (allo-PBSCT), suggesting that the cellular composition and reconstruction dynamics of UCB are significantly different from that of G-PBSC. Following on the heels of our recently study that found HSC/MPPs show differentiation bias to megakaryocytic-erythroid lineage and strong proliferation tendency, and defined a neutrophil progenitor population named S100A hi Neu2 which is inversely associated with the incidence of GVHD after allo-PBSCT (Yingying Huo et al, Science Immunology 2023), we next aimed to analyze the differences of hematopoietic reconstitution between allo-UCBT and allo-PBSCT and the causes of delayed hematopoietic reconstitution after allo-UCBT. In this study, we collected peripheral blood (PB) and bone marrow (BM) samples from 8 patients with bone marrow failure syndrome (BMFs) who received allo-UCBT (n=4) or allo-PBSCT (n=4) at different time points (d14, d21, d30, d60, d90, d180, d365) after transplantation. At the same time, UCB, G-PBSC and BM of normal children were collected as controls. Lin -CD34 + cells from BM, G-PBSC and UCB were separated by FACS for STRT-seq, the total nucleated cells (TNCs) of all samples were isolated for 10X transcriptome sequencing. We used 276628 hematopoietic cells to map the single cell transcriptome profiles of hematopoietic reconstruction by different transplantation methods and annotated 44 cell types. Compared with the G-PBSC, the immunogenicity of HSC/MPPs in Lin -CD34 + cells derived from UCB decreased, the proportion increased, and the differentiation bias of HSC/MPPs to monocytic and erythroid lineage was stronger, but the differentiation ability to myeloid and megakaryocytic lineage was decreased, the proportion of EBM, MEP and CMP decreased. For TNCs, the proportion of T cells and NK cells increased, and NK_CD56dim_CD16 had a stronger immune function. Compared with allo-PBSCT, the differentiation of HSC/MPPs and CMP into neutrophils in the early stage after allo-UCBT was weakened. The proportion of MEP cells decreased, and the differentiation ability of HSC/MPPs to MEP, HSC/MPPs and MEP to Mk was weakened. In summary, we found that the delayed reconstruction of neutrophils and platelets in patients with allo-UCBT are related to the nature of the graft, suggesting the importance of reasonable intervention of HSC derived from UCB to accelerate platelet implantation.

Higher Infused CD34+ Cell Dose Does Not Influence Clinical Outcomes in Allogeneic Peripheral Blood Stem Cell Transplantation Using Post-Transplant Cyclophosphamide in Children with High-Risk Leukemia

Background: The impact of infused graft cell dose on outcomes, including graft-versus-host disease (GVHD) and relapse, which have been major challenges in allogeneic hematopoietic stem cell transplantation (HSCT), remains unclear. Post-transplant cyclophosphamide (PTCy) has emerged as an effective and safe GVHD prophylaxis strategy, with improved GVHD incidence and relapse-free survival (RFS). Early practice of unmanipulated peripheral blood stem cell transplantation (PBSCT) using PTCy was commonly performed with a restriction on the CD34 + cell dose to minimize the risk of GVHD. However, recent studies demonstrated the protective effect of CD34 + cells on relapse, with no association with GVHD, thereby raising questions about the optimal cell dose. In this context, we aimed to study the impact of infused cell dose on outcomes in children with high-risk leukemia who underwent allogeneic PBSCT using PTCy. Methods: A retrospective analysis was conducted on 50 pediatric patients (median age at diagnosis : 9.3 years, range, 0.3-17.3) with hematologic malignancy (33 acute myeloid leukemia, 12 acute lymphoblastic leukemia, and 4 myelodysplastic syndrome/myeloproliferative neoplasm, 1 other) in first or second remission between 2019 and 2023. They received their first allogeneic PBSCT and donors included matched or mismatched unrelated donors (n=12) and haploidentical family donors (n=38). Conditioning was myeloablative, and PTCy-based GVHD prophylaxis (50mg/kg/day on days 3 and 4) was used for all patients. The patients were divided into three groups based on infused CD34 + cell dose: high dose group (&amp;gt;10 × 10 6/kg, N=10), intermediate dose group (5-10 × 10 6/kg, N=24), and low dose group (&amp;lt;5 × 10 6/kg, N=16). Results: The median age at HSCT was 11.6 years (range, 0.7-24.9). The median dose of infused CD34 + cells and CD3 + cells was 6.5 x 10 6/kg and 48.6 x 10 7/kg, respectively. There was a tendency for the mean dose of infused CD3 + cells to increase in the group with higher infused CD34 + cell dose: 47.6 x 10 7/kg for low dose group, 57.5 x 10 7/kg for intermediate dose group, and 73.4 x 10 7/kg for high dose group ( P=0.053). Patients receiving a higher dose of CD34+ cells had significantly shorter median time to neutrophil engraftment (13 days in high dose group vs. 14 days in intermediate dose group vs. 17 days in low dose group, P&amp;lt;0.001). The time to platelet engraftment was similar among the three groups. There was no difference among high dose, intermediate dose, and low dose groups in the cumulative incidence (CI) of day+100 grades II-IV acute GVHD and moderate to severe chronic GVHD (grades II to IV acute GVHD: 60.0% vs. 63.6% vs. 73.3% [ P=0.988], respectively; moderate to severe chronic GVHD: 22.2% vs. 29.2% vs. 25.0% [ P=0.961], respectively). With a median observation period of 20.4 months (range, 3.0-46.8) from transplant, RFS and overall survival (OS) showed a non-significant trend towards a higher survival rate in the high dose group compared to the other groups (RFS: 76.2% in high dose group vs. 62.1% in intermediate dose group vs. 62.6% in low dose group, P=0.694; OS: 88.9% in high dose group vs. 63.0% in intermediate dose group vs. 76.0% in low dose group, P=0.788). Conclusions: Higher number of infused CD34 + cell dose was associated with faster neutrophil engraftment. For patients in the high dose group (CD34 + cell dose &amp;gt; 10 x 10 6/kg with a relatively higher number of CD3 + cells), a non-significant trend toward a higher survival rate was observed, with no detrimental impact on GVHD. PBSCT in a pediatric patient from an unrelated or haploidentical adult donor may result in a high infused cell dose. Our findings suggest that restricting the number of infused CD34 + cell dose may not be necessary in the setting of allogeneic PBSCT with PTCy. Larger cohort studies are needed to confirm the potential benefits and drawbacks of a higher cell dose in children who receive PBSCT within a PTCy setting.

Azacitidine Combined with Interferon α for Preemptive Treatment of AML/MDS after Allogeneic Peripheral Blood Stem Cell Transplantation：a Prospecitive Phase II Study

Objective : this study investigated the efficacy and safety of azacitidine and interferon α preemptive treatment in the post-transplant in patients with AML/MDS. Methods: between Octorber 1, 2019 and July 31, 2022, a total of 49 patients aged 17 to 62 years were enrolled into this prospective clinical study of post-transplant azacitidine combined with interferon α preemptive treatment. Patients with minimal residual disease (MRD) positive and / or mixed chimerism were scheduled to receive azacitidine, given as 32 mg/m 2 per day subcutaneously for 5 days, and interferon α 3 million units/m 2 per day from 8th day and continued for 28th day for 1 cycle. Results: patients who acquired treatment response were 34 (69.4%), of which turned MRD-negative and obtained complete chimerism were 22 (44.9%) and 5 (10.2%) at 1 cycle, respectively. Median follow-up time after preemptive intervention was 440(range, 45 to 927) days. Cumulative incidences of relapse (CIR) and no relapse mortality (NRM) were 36.7% and 4.1%, respectively. Probabilities of event-free survival (EFS) and overall survival (OS) were 55.1% and 71.4%, respectively. The most common adverse events were graft-versus-host disease (GVHD) (38.8%), liver toxicity (46.9%) and neutropenia (28.6%). Conclusion: these data support the notion that azacitidine combined with interferon α is better used as the preemptive therapy against relapse tendency for patients after allo-HSCT performed for AML/MDS. Side effects were mainly GVHD, reversible cytopenia and hepatic toxicity. This prospective trial in the post-transplant setting was feasible and safe but challenging. This trial was registered at www.clinicaltrials.gov as#NCT04078399.

Comparison of Biosimilar Filgrastim (Nivestym) Versus Originator Filgrastim (Neupogen) for Peripheral Blood Stem Cell Mobilization for Allogeneic Hematopoietic Stem Cell Transplantation

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an optimal and potentially curative therapy for patients with hematologic malignancies. Granulocyte colony-stimulating factor (G-CSF) is used for the mobilization of peripheral blood stem cells (PBSCs) in allogeneic donors, and an optimal CD34 cell dose plays a critical role in successful transplantation. Nivestym, a biosimilar G-CSF to the originator Filgrastim (Neupogen), is now used by multiple institutions as it has become more available; however, there is a lack of data in this regard among healthy donors for allogeneic HSCT mobilization. In this study, we aim to compare the efficacy of Nivestym compared to Neupogen for allogeneic donor PBSC mobilization. Methods: For this retrospective single-center study, we included all (n=541) adult allogeneic HSCT donors at the University of Kansas Medical Center receiving Nivestym (January 2013-July 2020) or Neupogen (July 2020-June 2023) for donor PBSC mobilization. We conducted a bivariate analysis utilizing the ANOVA test. Statistical analyses were performed using SPSS version 28. Statistical significance was determined at p&amp;lt;0.05. Results: Our study included 541 allogeneic HSCT donors who received Neupogen (n=345, 64%) or Nivestym (n=196, 36%) for PBSC mobilization. The median age was 47 (range 17-76) years. The median donor weight was 86 (95% CI 87-91) kilograms. Donors receiving Neupogen had similar pre-GCSF WBC count (median 45 vs 47 K/uL, p=0.739), pre-GCSF CD34 percentages (median 17% vs 17%, p=0.527), and pre-GCSF circulating CD34 count (median 74 vs 74 million cells/kg, p=0.842) compared to donors receiving Nivestym. Neupogen recipients had similar median PBSC product total neutrophil count (TNC, 6.8 vs 6.5 K/uL, p=0.347), product CD34 percentage (75% vs 79%, p=0.068), absolute CD34 count (503 vs 533 million cells, p=0.636), and final CD34 dose (6.1 vs 6.3 million cells/kg, p=0.365) compared to Nivestym recipients. Seven percent (n=28) of donors needed two days of PBSC collection to achieve the target PBSC dose, with a statistically similar proportion noted in Neupogen (n=25, 7.3%) and Nivestym (n=13, 6.6%) cohorts. In a subgroup analysis stratified by age, donors aged 35 or older (n=154) had similar responses in all mentioned variables (p&amp;gt;0.05); however, for donors under the age of 35 years, the CD34 dose was higher in donors receiving Neupogen compared to Nivestym (median 6.9 vs 6.3 million cells/kg, p=0.044). Most of the PBSC collections (98%) were completed in one day, except for five donors in both Neupogen (5%) and Nivestym (8.5%) cohorts. Conclusions: Biosimilar G-CSF (Nivestym) demonstrated similar efficacy for peripheral blood stem cell mobilization compared to the originator G-CSF (Neupogen) among allogeneic HSCT donors. In donors aged 35 years or younger, a slightly lower PBSC product CD34 count was noted with Nivestym compared to Neupogen.

Low-Dose ATG Has the Same Risk of CMV Reactivation after Allogeneic PBSCT As Ptcy, but Letemovir Is Effective in Preventing CMV Reactivation

[Introduction] Allogeneic peripheral blood stem cell transplantation (allo-PBSCT) is a curative treatment for hematological malignancies but has a risk of a chronic graft-versus-host disease (GVHD) compared to other donor sources. Post-transplant cyclophosphamide (PTCY) has been spread rapidly worldwide from HLA haploidentical-SCT (Haplo-SCT) to HLA matched-SCT. Although PTCY was theoretically thought to preserve non-alloreactive T cells which can contribute to fight infection, recent studies showed that PTCY was associated with the increased incidence of cytomegalovirus (CMV) infection. Letermovir (LTV), a novel anti-CMV agent, was useful for the prevention of CMV reactivation after SCT including Haplo-SCT using PTCY. On the other hand, low-dose antithymocyte globulin (ATG) is an alternative and useful option for GVHD prophylaxis in allo-PBSCT and often used in Japan. However, the risk of post-transplant CMV reactivation and the protective effect of LTV when using low-dose ATG remain to be elucidated. [Methods] We retrospectively analyzed 222 recipients who received allo-PBSCT using PTCY or low-dose ATG at Hokkaido University Hospital from January 2013 to July 2021. Of the 121 patients who underwent PBSCT with PTCY, 69 (all patients underwent Haplo-PBSCT) were without LTV prophylaxis and 52 (34 patients, Haplo-PBSCT) were with LTV. On the other hand, of the 101 patients who underwent PBSCT with low-dose ATG, 66 (12 patients, Haplo-PBSCT) were without LTV and 35 (2 patients, Haplo-PBSCT) were with LTV. LTV was administered on the day 0 at a dosage of 480 mg daily. All patients were monitored for CMV reactivation by using the anti-CMV pp65 monoclonal antibody HRP-C7 assay at least weekly from neutrophil engraftment to discharge and after discharge monthly until day 180 after SCT. CMV reactivation was defined as the start of CMV preemptive therapy, generally initiated when there are 2 or more CMV antigen positive cells per 50000 white blood cells. Moreover, CMV disease was defined by organ dysfunction attributable to CMV. [Results] Baseline characteristics of the patients are summarized in Table 1. Although more patients in ATG group compared to PTCY group received myeloablative conditioning regimen significantly, there was no significant difference between the groups in terms of sex, age, underlying disease, disease risk at SCT, and CMV serostatus. GVHD prophylaxis in PTCY consisted of CY (40-50 mg/kg on day 3 and 4), tacrolimus (from day 5), and mycophenolate mofetil (from day 5), whereas that in ATG consisted of ATG at a total dose of 2-3 mg/kg around day -2, tacrolimus (from day -1) and short-term methotrexate. LTV prophylaxis significantly reduced the cumulative incidence of CMV reactivation at 180 days after SCT in PTCY group (69.6% without LTV vs. 22.4% with LTV, p&amp;lt;0.001) and ATG group (62.6% without LTV vs. 18.9% with LTV, p&amp;lt;0.001; Figure 1.). Importantly, although CMV disease were occurred in 2 patients in PTCY (1 gastritis and 1 retinitis) and 8 focuses in 7 patients (3 pneumoniae, 3 enteritis, 1 retinitis, and 1 glossitis) in ATG without LTV prophylaxis, none of the patients receiving LTV developed CMV disease in both group. Moreover, LTV did not affect overall survival, the cumulative incidence of non-relapse mortality, relapse, acute GVHD, and engraftment of neutrophil and platelet. Interestingly, the cases of early CMV reactivation within 100 days after SCT under LTV prophylaxis was significantly more frequent in ATG than in PTCY (p=0.0345). [Conclusion] CMV reactivation occurred with similar frequency after allo-PBSCT with low-dose ATG as after that with PTCY. LTV was effective for prevention of CMV reactivation in both GVHD prophylaxis methods. CMV breakthrough reactivation may be likely to occur in PBSCT with low-dose ATG compared to that with PTCY even under LTV prophylaxis, and careful CMV monitoring may be required.

Comparison between Post-Transplant Cyclophosphamide Use and Conventional Prophylaxis of Graft-Versus-Host Disease: A Retrospective Study

Introduction: In order to modify the immune response balance between donor and recipient in the context of haploidentical transplantation, the use of post-transplant cyclophosphamide (PTCy), which reduces the population of recipient alloreactive T cells, has become the preferred strategy for graft-versus-host disease (GVHD) prophylaxis. Recently, this approach has also been tested and validated in HLA-matched related or unrelated transplants, as well as in unrelated transplants with HLA mismatch. However, high doses of PTCy can cause cardiac toxicity, hemorrhagic cystitis, and potentially increase the incidence of viral infections. Therefore, comparative studies are needed to evaluate the outcomes of PTCy use compared to other conventional GVHD prophylaxis strategies. Objective: To evaluate the outcomes of patients undergoing allogeneic peripheral blood stem cell transplantation (PBSCT) and to compare the use of post-transplant cyclophosphamide with other GVHD prophylaxis strategies. Patients and Methods: Retrospective analysis of consecutive patients transplanted between March 2014 and March 2023 at two transplant centers. The median follow-up was 24 months (range: 3-116 months). Results: A total of 118 adult patients undergoing PBSCT were included. There were 70 HLA-matched related donors, 28 HLA-matched unrelated donors, and 20 unrelated donors with one HLA mismatch. The median age was 52 years (range: 18 to 80), with a majority being male (51%). The most common diagnoses were acute myeloid leukemia (37%), acute lymphoblastic leukemia (18%), and myelodysplastic syndrome (18%). The disease risk index (DRI) was considered low or intermediate in 53% of cases, high in 31%, and very high in 16%. The majority of patients (76%) had a low risk of transplant-related complications (HCT-CI). Most patients received reduced-intensity conditioning regimens (78%), and the majority (72%) received some sort of T-cell depletion, with 36 (31%) patients receiving PTCy and 49 (41%) receiving ATG. No significant differences were found between the groups (PTCy vs. non-PTCy) in overall survival at 24 months (65% vs. 61%, p = 0.71, respectively), disease-free survival at 24 months (55% vs. 53%, p = 0.76), non-relapse mortality at 24 months (21% vs. 23%, p = 0.84), relapse rate at 24 months (24% vs. 24%, p = 0.61), neutrophil engraftment at 30 days (89% vs. 93%, p = 0.49), and incidence of grade II-IV acute GVHD at 100 days (31% vs. 29%, p = 0.99), grade III-IV acute GVHD at 100 days (6% vs. 12%, p = 0.22), chronic GVHD at 24 months (42% vs. 50%, p = 0.51), and moderate/severe chronic GVHD at 24 months (19% vs. 23%, p = 0.66). There was also no difference in the incidence of infections, including viral infections and cytomegalovirus reactivation. Conclusions: The use of PTCy demonstrated similar clinical outcomes to other GVHD prophylaxis strategies, without an increased risk of infections or mortality. Therefore, PTCy can be considered a viable, safe, and cost-effective option for GVHD prophylaxis in the context of HLA-matched and HLA-mismatched transplants.

A Case of Multiple Eccrine Poromas with a History of Chemotherapy and Allogeneic Peripheral Blood Stem Cell Transplantation

A "poroid cell neoplasm" is a general term used to describe nodular tumors that consist of poroid cells and cuticular cells. Eccrine poroma, the most common type of poroid cell neolplasm, is a tumor continuous with the epidermis and extends into the dermis in a cord-like fashion. This tumor is almost always seen as a single lesion, with cases of multiple eccrine poromas (eccrine poromatosis) being exceedingly rare. In fact, there have only been about 20 reported cases of multiple eccrine poromas worldwide; all of which were associated with some immunosuppressive state. Here we report another case of eccrine poromatosis; this time in a patient who received an allogeneic peripheral blood stem cell transplant for acute lymphocytic leukemia 18 years prior. Our case of eccrine pormatosis is particularly rare that it involved a truncal tumor distribution, whereas the other reported cases were generally isolated to the extremities.

Aortitis after administration of pegfilgrastim to a healthy donor for peripheral blood stem cell collection

A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of pegfilgrastim (Day 4) and 4.32 × 106 /kg of CD34-positive cells per recipient body weight were obtained. Fever of 38 ℃ or higher and left submandibular pain appeared on Day 6. Ultrasonography and contrast-enhanced computed tomography (CT) showed wall thickening of the carotid artery and the abdominal aorta. We carefully excluded the possibilities of cardiovascular and autoimmune diseases by thorough examination, and ultimately diagnosed pegfilgrastim-induced aortitis. The patient’s fever resolved rapidly after treatment with prednisolone (PSL) 1 mg/kg. We began to taper PSL after eight days. Sixty-one days after starting PSL, we confirmed that abdominal aortic wall thickening had improved by contrast-enhanced CT. We continued to taper off PSL and stopped 141 days later with no relapse thereafter. This is the first case report of pegfilgrastim-induced aortitis in an allo-PBSCT donor. Careful monitoring is warranted when administering pegfilgrastim to donors even without past medical history.

Successful Pre- and Post-transplant Administration of Gilteritinib in a Patient with Relapsed and Refractory Acute Myeloid Leukemia Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation.

Patients with acute myeloid leukemia (AML) harboring FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication mutation are associated with a poor survival outcome, even those receiving allogeneic stem cell transplantation (Allo-SCT). An additional treatment strategy with allo-SCT is therefore required to reduce relapse in these patients. Gilteritinib is a specific FLT3 inhibitor that has shown clinical benefit for patients with relapsed and refractory (R/R) AML harboring FLT3 mutation. We herein report a 49-year-old woman with R/R AML who was successfully treated with pre- and post-transplant gilteritinib. Post-transplant gilteritnib yielded a durable response with possible exacerbation of graft-versus-host disease.

Peripheral Blood Allogeneic Stem Cell Mobilization: Can We Predict a Suboptimal Mobilization?

Allogeneic peripheral blood stem cells mobilization is now the basis of most stem cell transplants. In a very limited number of cases, mobilization is suboptimal leading to further collection procedures, to suboptimal cell doses infusion with delayed engraftment time, increased risks of transplant procedure and of related costs. To date we have no recognized and shared criteria for early estimating the probability of poor mobilization in healthy donors. We then analyzed allogeneic peripheral blood stem cell donations performed at the Fondazione Policlinico Universitario A.Gemelli IRCCS Hospital from January 2013 to December 2021 in order to identify premobilization factors associated with successful mobilization. The following data were collected: age, gender, weight, complete blood cell count at baseline, G-CSF dose, number of collection procedures, CD34+ cell count in peripheral blood on the first day of collection, CD34+ cell dose per kg body weight of recipient. Mobilization efficacy was defined according to the number of CD34+ cells in peripheral blood on day +5 of G-CSF administration. We classified donors as sub-optimal mobilizers or good mobilizers according to the achievement of the 50 CD34+ cell/μL threshold. We observed 30 suboptimal mobilizations in 158 allogeneic peripheral blood stem cell donations. Age and baseline white blood cell count were factors significantly associated with negative or positive impact on mobilization, respectively. We did not find significant differences in mobilization based on gender or G-CSF dose. Using cut-off values of 43 years and 5.5×109/L WBC count, we built a suboptimal mobilization score: donors who reach 2, 1 or 0 points have a 46%, 16% or 4% probability of suboptimal mobilization, respectively. Our model explains 26% of the variability of mobilization confirming that most of the mobilization magnitude depends on genetically determined factors; however, suboptimal mobilization score is a simple tool providing an early assessment of mobilization efficacy before G-CSF administration begins in order to support allogeneic stem cells selection, mobilization and collection. Through a systematic review, we looked for confirmation of our findings. According to the published articles, all the variables we included in our model are confirmed to be strongly related to the success of mobilization. We believe that score system approach could be applied in clinical practice to assess the risk of mobilization failure at baseline allowing for a priori intervention.

Successful Bridging to Allogeneic Hematopoietic Stem Cell Transplantation by Azacitidine and Venetoclax in a Case of Acute Myeloid Leukemia With t(3;3)(q21.3;q26.2) Developed Early After Orthotopic Heart Transplantation

A 48-year-old male patient developed acute myeloid leukemia (AML) with t(3;3)(q21.3;q26.2) chromosomal mutation 8 months after orthotopic heart transplantation from a human leukocyte antigen-unmatched brain-dead donor for cardiac sarcoidosis. He had sequelae of stroke and chronic renal failure at the time of AML diagnosis. He received 3 cycles of azacitidine and venetoclax induction therapy and achieved complete hematological remission with incomplete count recovery without causing severe complications, including infection. He sequentially underwent allogeneic peripheral blood stem cell transplantation from a HLA-8/8 matched, ABO-blood matched, unrelated female donor and successfully achieved donor cell engraftment. His transplanted heart was viable, and the coronary vessels were not damaged even after allogeneic peripheral blood stem cell transplantation. Although AML relapsed afterward, azacytidine/venetoclax was a tolerable bridging therapy even for early-onset AML after heart transplantation.

The Effect of the COVID-19 Pandemic on Unrelated Allogeneic Hematopoietic Donor Collections and Safety.

The COVID-19 pandemic profoundly influenced unrelated donor (UD) allogeneic peripheral blood stem cell (PBSC) collections. Changes included efforts to minimize COVID-19 exposure to donors and cryopreservation of products. The extent to which the efficacy and safety of PBSC donations were affected by the pandemic is unknown. Prospective cohort analysis of PBSC collections comparing pre-pandemic (01 April 2019-14 March 2020) and pandemic (15 March 2020-31 March 2022) eras. Of a total of 291 PBSC collections, cryopreservation was undertaken in 71.4% of pandemic donations compared to 1.1% pre-pandemic. The mean requested CD34+ cell dose/kg increased from 4.9 ± 0.2 × 106 pre-pandemic to 5.4 ± 0.1 × 106 during the pandemic. Despite this increased demand, the proportion of collections that met or exceeded the requested cell dose did not change, and the mean CD34+ cell doses collected (8.9 ± 0.5 × 106 pre-pandemic vs. 9.7 ± 0.4 × 106 during the pandemic) remained above requested targets. Central-line placements were more frequent, and severe adverse events in donors increased during the pandemic. Cryopreservation of UD PBSC products increased during the pandemic. In association with this, requested cell doses for PBSC collections increased. Collection targets were met or exceeded at the same frequency, signaling high donor and collection center commitment. This was at the expense of increased donor or product-related severe adverse events. We highlight the need for heightened vigilance about donor safety as demands on donors have increased since the pandemic.

Safety of Cryopreserved Stem Cell Infusion through a Peripherally Inserted Central Venous Catheter

The management of patients undergoing stem cell transplantation requires a multipurpose central venous catheter (CVC) to facilitate drug administration, parenteral nutrition, transfusion of blood products, and collection of blood samples. Peripherally inserted central venous catheters (PICCs) appear to meet these requirements but are rarely used for stem cell infusion. We aimed to retrospectively assess the safety and feasibility of stem cell infusion through PICC and to evaluate its impact on transplantation kinetics. We retrospectively analyzed the outcomes of peripheral blood stem cell (PBSC) transplantation in patients receiving cryopreserved autologous or allogeneic PBSC by PICCs and compared the results with patients receiving transplants through a conventionally inserted central venous catheter (CICC). Despite statistically significant differences in CD34+ dose, infusion rate, and total length of administration, the clinical outcomes of transplantation, exemplified by platelet and neutrophil engraftment, along with the length of hospitalization, were not affected by the prolonged infusion time and lower infusion velocity in the PICC group. Our study showed that the clinical outcomes of PBSC transplantation did not differ between the PICC and CICC groups, suggesting that both types of catheters can be implemented in a PBSC transplantation setting.

Clinical Benefit of Low-Dose Antithymocyte Globulin-Thymoglobulin as Graft-versus-Host Disease Prophylaxis in Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation from HLA-Identical Donors

Graft-versus-host disease (GVHD) is a major complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Previous randomized studies have already shown that several types of antihuman T-lymphocyte immune globulin (ATG) as GVHD prophylaxis can reduce the incidence of acute GVHD and chronic GVHD. However, the efficacy and safety of PBSCT from human leukocyte antigen (HLA)-identical donors with low-dose ATG remain unclear. This study aimed to clarify the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG compared to PBSCT from HLA-identical donors without ATG. We retrospectively analyzed the outcomes of allogeneic PBSCT from HLA-identical donors with low-dose ATG-thymoglobulin (ATG-T: 2.5 mg/kg) versus PBSCT without ATG-T. Patients' data were collected retrospectively from the medical records of Anjo Kosei Hospital. This study was conducted from 2009 to the final follow-up in October 2022. In total, 47 of 91 patients received ATG-T between January 2009 and March 2020. ATG-T reduced the incidence of moderate-to-severe chronic GVHD (hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.057-0.41, p < 0.0010) and non-relapse mortality (HR: 0.21, 95% CI: 0.0058-0.75, p = 0.016) without increasing the risk of relapse. The overall survival did not differ significantly between the two groups. However, the low-dose ATG-T group had better moderate-to-severe chronic GVHD-free, relapse-free survival rates (HR: 0.47, 95% CI: 0.27-0.80, p = 0.0054) than the non-ATG-T group. In addition, the multistate analysis revealed that the low-dose ATG-T group had better current GVHD-free, relapse-free survival at 24 months after transplantation than the non-ATG group (45% [95% confidence interval, CI: 29%-63%) and 21% (95% CI: 9.1%-34%)], respectively, p = 0.015). Low-dose ATG-T did not increase the incidence of infections and adverse events. Low-dose ATG-T could be beneficial for patients receiving PBSCT from HLA-identical donors.

The Impact of Graft CD3+ T-Cell Dose on the Outcome of T-Cell Replete Human Leukocyte Antigen-Mismatched Allogeneic Hematopoietic Peripheral Blood Stem Cells Transplantation.

Data on whether the graft CD3-positive (CD3+) T-cell dose in T-cell-replete human leukocyte antigen (HLA)-mismatched allogeneic hematopoietic peripheral blood stem cells transplantation (PBSCT) influences post-transplant outcomes are controversial. Using King Hussein Cancer Center (KHCC) Blood and Marrow Transplantation (BMT) Registry database, 52 adult subjects, receiving the first T-cell-replete HLA-mismatched allogeneic hematopoietic PBSCT for acute leukemias or myelodysplastic syndrome, were identified, from January 2017 to December 2020. The cutoff value of graft CD3+ T-cell dose was identified using the receiver operating characteristic (ROC) formula and Youden's analysis. Subjects were divided into two cohorts: cohort 1 with low CD3+ T-cell dose (n = 34) and cohort 2 with high CD3+ T-cell dose (n = 18). Correlative analyses were performed between CD3+ T-cell dose and the risk of graft-versus-host disease (GvHD), relapse, relapse-free survival (RFS), and overall survival (OS). P-values were two-sided and considered significant when P < 0.05. Subject covariates were displayed. Subject's characteristics were comparable, except for higher nucleated cells and more female donors in the high CD3+ T-cell cohort. The 100-day cumulative incidence of acute GvHD (aGvHD) was 45±7% and 3-year cumulative incidence of chronic GvHD (cGvHD) was 28±6.7%. There was no statistically significant difference between the two cohorts in aGvHD (50% vs. 39%, P = 0.4) or cGvHD (29% vs. 22%, P = 0.7). The 2-year cumulative incidence of relapse (CIR) was 67.5±16.3% for low compared with 14.3±6.8% for high CD3+ T-cell cohort (P = 0.018). Fifteen subjects relapsed and 24 have died, 13 due to disease relapse. There was an improvement in 2-year RFS (94% vs. 83%; P = 0.0022) and 2-year OS (91% vs. 89%; P = 0.025) in low CD3+ T-cell cohort compared with high CD3+ T-cell cohort. Graft CD3+ T-cell dose is the only significant risk factor for relapse (P = 002), and OS (P = 0.030) in univariate analysis which was maintained in multivariate for relapse (P = 0.003), but not for OS (P = 0.050). Our data suggest that high graft CD3+ T-cell dose is associated with lower risk of relapse, and might improve long-term survival, but has no influence on the risk of developing aGvHD or cGvHD.