Peripheral Blood Stem Cell Research Articles

Autologous non-myeloablative hematopoietic stem cell transplantation for diffuse cutaneous systemic sclerosis: identifying disease risk factors for toxicity and long-term outcomes in a prospective, single-arm trial.

Two randomized trials for patients with diffuse systemic sclerosis (SSc) demonstrated an overall survival (OS) and event-free survival (EFS) advantage of autologous hematopoietic stem cell transplantation (AHSCT) using CD34+ selected peripheral blood stem cells (PBSC) compared to monthly cyclophosphamide. We asked if an unmodified PBSC graft followed by maintenance mycophenolate mofetil (MMF) after AHSCT, instead of CD34+ selected graft, could provide comparable AHSCT outcomes. 20 patients with high-risk SSc were enrolled in a prospective, single-arm trial with cyclophosphamide 200 mg/kg and horse anti-thymocyte globulin (CY200/ATG), followed by unmanipulated autologous PBSC, then MMF maintenance starting at 2 months after AHSCT. Point estimates of OS and EFS at 5 years after AHSCT were 85% (95% CI, 60.4%-94.9%) and 75% (95% CI, 50%-88.7%), respectively. Median follow-up was 7.5 years (range, 5.6-11.6) after transplant for living patients. Eight patients (40%) required intensive care unit treatment early after transplant. Early transplant-related mortality occurred in 2 patients (10%). Five patients developed relapse/progression of SSc after AHSCT. Four of 9 patients with anti-RNA polymerase-III antibody had both prior scleroderma renal crisis and the lowest quartile of estimated glomerular filtration rate (eGFR) upon study entry; all 4 patients developed prolonged organ failure/death early post-transplant. We observed favorable OS and EFS after AHSCT for SSc patients, using CY200/ATG, unmanipulated PBSC and MMF post-transplant maintenance, that was comparable to trials with CD34+ graft selection. We identified a possible risk factor, pretransplant low eGFR, for adverse outcome after AHSCT.

PTCy-based graft-versus-host disease prophylaxis for matched sibling donor allogeneic hematopoietic cell transplantation

AbstractPosttransplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GVHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear. We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into 4 groups: group I (calcineurin inhibitor [CNI] + methotrexate [MTX] or mycophenolate mofetil [MMF]), group II (CNI + MTX or MMF + antithymocyte globulin [ATG]), group III (PTCy + ATG + CNI), and group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade 2 to 4 (hazard ratio [HR], 0.6; P = .01) and grade 3 to 4 acute GVHD (HR, 0.2; P = .001) and all-grade (HR, 0.5; P = .007) and moderate-to-severe chronic GVHD (HR, 0.4; P = .001) compared with CNI + MTX (or MMF)–containing regimens. PTCy did not increase relapse risk; PTCy reduced nonrelapse mortality (NRM; HR, 0.3; P < .002), leading to improved GVHD-free/relapse-free survival (GRFS; HR, 0.4; P < .001). PTCy was also associated with improved overall survival (HR, 0.56; P = .01). Bloodstream infections are increased with PTCy (HR, 1.5; P = .001). The addition of ATG to PTCy did not further improve GRFS and was associated with a higher incidence of clinically significant cytomegalovirus (csCMV; HR, 2.16; P = .002) and Epstein-Barr virus (csEBV) reactivation (HR, 9.5; P < .001) and a numerical increase in NRM (HR, 1.7; P = .2). PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted.

Different impacts of granulocyte colony-stimulating factor administration on allogeneic hematopoietic cell transplant outcomes for adult acute myeloid leukemia according to graft type.

We retrospectively evaluated the impacts of using granulocyte colony-stimulating factor (G-CSF) and its timing on posttransplant outcomes for 9766 adults with acute myeloid leukemia (AML) between 2013 and 2022 using a Japanese database. We separately evaluated three distinct cohorts based on graft type: 3248 received bone marrow transplantation (BMT), 3066 received peripheral blood stem cell transplantation (PBSCT), and 3452 received single-unit cord blood transplantation (CBT). Multivariate analysis showed that G-CSF administration significantly accelerated neutrophil recovery after BMT, PBSCT, and CBT. However, it was associated with a higher risk of grades II-IV acute graft-versus-host disease (GVHD) across all graft types. Moreover, an increased incidence of overall chronic GVHD was observed with G-CSF administration in BMT and CBT patients, but not in PBSCT patients. G-CSF administration significantly improved overall survival (OS) and leukemia-free survival (LFS) only following CBT. Regarding the timing of G-CSF, in comparison with late initiation of G-CSF (Days 5-10), early initiation (Days 0-4) did not provide benefits for hematopoietic recovery regardless of graft type. In contrast, late initiation was significantly associated with a lower risk of grades II-IV acute GVHD and better OS and LFS in CBT patients. These data demonstrated that G-CSF administration accelerated neutrophil recovery and increased the risk of grades II-IV acute GVHD across all graft types, but significantly improved survival outcomes but only following CBT. Therefore, routine use of G-CSF should be considered for CBT in adult patients with AML.

Immunological reconstitution and infections after alloHCT - a comparison between post-transplantation cyclophosphamide, ATLG and non-ATLG based GvHD prophylaxis.

Immunological reconstitution after allogeneic hematopoietic cell transplantation (alloHCT) is critical for patient survival. We compared short- and long-term immune reconstitution and clinical endpoints in adult recipients of haploidentical or mismatched T cell replete peripheral blood stem cell transplants (PBSCT) with post-transplant cyclophosphamide as GvHD prophylaxis (PTCY, n = 68) to: (a) patients receiving matched unrelated grafts and anti-T lymphocyte globulin (ATLG) (MUD/ATLG, n = 280); (b) patients with a mismatched donor and ATLG (MM/ATLG, n = 54); and (c) recipients of matched related grafts without ATLG (MRD/NoATLG, n = 97). PTCY was associated with delayed neutrophil engraftment, low NK-cell counts on day 30 and reduced CD8+ cells on days 60-80. In terms of long-term reconstitution, PTCY recipients demonstrated significantly higher CD4+ counts from day 100-365, primarily derived from naïve T cells. Additionally, B-lymphocyte counts at one year were highest in the PTCY group. Early morbidity and mortality due to infectious complications (viral reactivation, (blood stream) infections) were most frequent in PTCY patients during the first three months. However, beyond three months, no PTCY patient suffered a fatal infection. Our study highlights the pattern of early immunodeficiency followed by robust long-term immune reconstitution in PTCY recipients, identifying critical time periods of risk that could be targeted to optimise patient survival and reduce infectious complications.

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

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

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

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

Clinical Response and Peripheral Blood Stem Cell Mobilization with MINE±Obinutuzumab Regimen in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma

Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of malignant tumors. Although the R-CHOP regimen significantly improves the prognosis for patients with DLBCL, 40% of cases experience relapse or become refractory. The MINE regimen (Ifosfamide, Mitoxantrone Hydrochloride Liposome, and Etoposide), with or without obinutuzumab, is a viable second-line chemotherapy option for relapsed or refractory DLBCL. However, there is currently limited research on clinical response and peripheral blood stem cell mobilization related to treating relapsed/refractory DLBCL (R/R DLBCL) with this regimen. Aims: This study evaluated the clinical response and peripheral blood stem cell mobilization associated with treating R/R DLBCL using the MINE regimen with or without Obinutuzumab as the second-line chemotherapy. Methods: We enrolled first-time R/R DLBCL patients from our hospital in China from January 2023 to April 2024. We collected clinical information, overall response rates, and adverse events for all patients. The MINE±obinutuzumab regimen included obinutuzumab (1000 mg), Mitoxantrone Hydrochloride Liposome (20 mg/m²) on day 1 of each cycle, and Ifosfamide (1.33 mg/m²) and Etoposide (65 mg/m²) once daily on days 1 through 3 of each of the first four cycles. Results: Twenty-one patients with first-time R/R DLBCL were enrolled, with a median age of 53 years (range 25-65). The male-to-female ratio was 11:10. Based on the Ann Arbor staging system, 81.0% of patients were classified as stage III/IV, and 71.4% had an International Prognostic Index (IPI) score of ≥3. Additionally, 66.7% of patients had at least one extranodal lesion. Elevated levels of lactic dehydrogenase and β2 microglobulin were found in 76.2% and 85.7% of patients, respectively. According to the Hans algorithm, 81.0% of patients were in the non-GCB group, and the median Ki-67 value was 80% (range 50%-90%). Only one patient was CD5 positive, and 57.1% of patients were diagnosed with double-expression lymphoma. Among the cohort, 71.4% of patients exhibited P53 protein expression greater than 50%. Ten cases were primary refractory diseases, and eight patients had early recurrence disease (relapse within one year). All patients completed at least two cycles of the MINE±obinutuzumab regimen. The overall response rate (ORR) was 95.2%, with a complete response rate (CRR) of 38.1% at the end of the second cycle. By the end of treatment, the ORR was 85.7%, and the CRR was 64.5%. After 2 cycles of this regimen, 80.0% of patients successfully collected peripheral blood stem cells, but after four cycles, only 16.7% of patients were successful. The most common adverse events were hematologic toxicities, with 76.2% of patients experiencing grade 3/4 granulocytopenia after two cycles. Conclusion: The MINE±obinutuzumab regimen demonstrated good response rates and acceptable safety in treating first-time R/R DLBCL patients. For those requiring autologous stem cell transplantation, it is recommended to collect peripheral blood stem cells as soon as possible after two cycles.

Sociodemographic and Patient-Related Determinants of Outcomes after Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia and Myelodysplastic Syndromes

Background: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a curative therapy for several high-risk hematologic disorders. Sociodemographic determinants (age, gender, and ethnicity) and patient-related factors (frailty and comorbidities) significantly impact post-transplant outcomes. We aimed to investigate the impact of sociodemographic and patient-related factors on allo-HCT outcomes. Methods: A retrospective multicenter analysis was conducted, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Cox regression was performed to compare overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic graft-versus-host disease (GVHD), and platelet and neutrophil engraftment. Multivariate analyses were performed for recipient age, gender, ethnicity, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and adjusted for significant variables identified in the univariate analysis. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p &amp;lt;0.05. Results: We included 7545 allo-HCT recipients. The median age at the time of transplant was 56 years, and 58% were men. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), Asian (5%), and others (5%). The primary disorders included acute myeloid leukemia (47.2%), myelodysplastic syndrome (34.4%), and acute lymphoblastic leukemia (18.4%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34.1%), and cord blood (16.4%). Graft sources were peripheral blood stem cells (68%), umbilical cord blood (16%), and bone marrow (16%). GVHD prophylaxis regimens included tacrolimus or cyclosporine-based (87%), post-transplant cyclophosphamide-based (9%), CD34 selection (2%), and others (2%). The KPS was 90% or higher (57%), 80-89 (29%), and &amp;lt;80 (14%). The HCT-CI was 0 (20%), 1-2 (30%), 3-4 (31%), and five or higher (19%). In the multivariate analyses adjusted for all significant predictors identified in the univariate analyses, significant predictors of outcomes included - inferior OSwas predicted by older age (HR 1.01, 95% CI 1.01-1.10, p&amp;lt;0.001), male gender (HR 1.08, 95% CI 1.00-1.15, p=0.030), lower KPS (HR 1.33, 95% CI 1.20-1.46, p&amp;lt;0.001), and higher HCT-CI (HR 1.71, 95% CI 1.53-1.92, p&amp;lt;0.001); lower DFSwas predicted by older age (HR 1.013, 95% CI 1.010-1.016 p&amp;lt;0.001), lower KPS (HR 1.30,95% CI 1.12-1.50, p&amp;lt;0.00), and higher HCT-CI (HR 1.66, 95% CI 1.41-1.95, p&amp;lt;0.001); higher NRMwas predicted by older age (HR 1.01, 95% CI 1.01-1.02, p&amp;lt;0.001), male gender (HR 1.13, 95% CI 1.00-1.28), lower KPS (HR 1.23, 95% CI 1.04-1.46, p=0.018), and higher HCT-CI (HR 2.17, 95% CI 1.77-2.65, p&amp;lt;0.001); higher rate of relapsewas predicted by older age (HR 1.01, 95% CI 1.01-1.01, p&amp;lt;0.001), lower KPS (HR 1.23, 95% CI 1.10-1.38, p&amp;lt;0.001), and higher HCT-CI (HR 1.15, 95% CI 1.02-1.30, p=0.020); higher incidence of chronic GVHD was predicted by older age (p&amp;lt;0.001, HR 1.01, 95% CI=1.0008-1.012), male gender (HR 1.12, 95% CI 1.04-1.20, p=0.003), and lower KPS (HR 1.134, 95% CI 1.01-1.27, p=0.028); and delayed neutrophil engraftment was predicted by older age (HR 1.01, 95% CI 1.01-1.01, p&amp;lt;0.001). No other significant associations were observed between these factors and post-transplant outcomes. Conclusion: The analyses identified sociodemographic factors (older age, male gender), frailty, and higher comorbidities as predictors of post-transplant outcomes, including inferior overall and disease-free survival, higher risk of relapse and non-relapse mortality, and increased incidence of chronic graft-versus-host disease in patients with acute leukemia and myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplantation. Our findings highlight the relevance of developing patient-centered interventions and a tailored selection of disease- and transplant-related factors to improve post-transplant outcomes.

Impact of Systemic Antibiotics Use on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Post-transplant complications lead to significant morbidity and mortality in the management of patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT). Broad-spectrum systemic antimicrobials and better prophylaxis strategies have reduced infection-related morbidity and mortality in allo-HCT patients. However, broad-spectrum antibiotic use disrupts the microbiome and immunome, which may result in poor post-transplant outcomes. We aimed to evaluate the impact of systemic antibiotics on allo-HCT outcomes. Methods: A retrospective multicenter analysis was conducted, including allo-HCT patients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2013 to 2018 using P5646 data by Ramathan et al. Chi-square and t-tests were used to compare categorical and continuous baseline demographics. Multivariate Cox regression analyses were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), engraftment, and infection-related mortality between the two groups. Statistical analysis was conducted using R version 4.16, with statistical significance defined as p &amp;lt;0.05. Results: Among 7524 allo-HCT patients, 5779 were administered broad-spectrum systemic antibiotics (SA) while 1745 were not given systemic antibiotics (NSA). The median age was 58.58 years (range: 2.03-82.67) in the SA group and 56.18 years (range: 2.00 - 77.86) in the NSA group, and 58% were men in both groups. Ethnicities were Caucasian (76%), Hispanic (8%), African American (6%), and others (10%). The primary disorders included acute myeloid leukemia (47%), myelodysplastic syndrome (35%), and acute lymphoblastic leukemia (18%). Myeloablative conditioning was used in 53% of patients. Donor types were matched unrelated (49.5%), matched related (34%), and cord blood (16%). Graft sources were bone marrow (15%), peripheral blood stem cells (68%), and cord blood (16%). GVHD prophylaxis regimens included Tacrolimus and Cyclosporine-based (77%), post-transplant Cyclophosphamide-based (9%), Ex vivo T-cell depletion or CD34 selection (3%), and others (11%). In the multivariate regression analyses, systemic antibiotics independently predicted poor OS (55% SA vs 57% NSA; HR 1.13, 95% CI 1.01-1.22, p=0.026). Higher incidence of NRM (19% SA vs 15% NSA; HR 1.32, 95% CI 1.12-1.55, p=0.001), grade 2-4 aGVHD (41% SA vs 34% NSA; HR 1.24, 95% CI 1.12-1.38, p&amp;lt;0.001), and cGVHD (40% SA vs 39% NSA; HR 1.12, 95% CI 1.01-1.24, p=0.040) were observed with SA use. The two groups had no significant difference in DFS, relapse, infection-related mortality, and engraftment rates. The outcomes analyses were adjusted for the significant predictors identified in the univariate analyses. Conclusion: Systemic antibiotics use in allo-HCT patients is associated with higher morbidity and mortality. Judicious use and de-escalation of systemic antibiotics when safe may help to improve post-transplant outcomes. Future research exploring microbiome restoration could result in better post-transplant outcomes.

The Impact of the Absolute Lymphocyte Count before Anti-T-Lymphocyte Globulin (ATLG) Administration on Transplant Outcomes in Matched Unrelated Peripheral Blood Stem Cell Allogeneic Stem Cell Transplantation

Background: Data on optimal ATLG dosing in MUD-PBSC-allo-SCT is limited. Conventional weight-based dosing may excessively deplete T-cells and lead to unfavorable outcomes. ALC-based dosing on ATLG administration day has been proposed as an alternative. We conducted a retrospective study at University Medical Center Hamburg-Eppendorf (UKE) and University Medical Center Bologna to investigate the impact of ALC and ATLG dose on transplant outcomes. Methods: We included 378 (UKE n=251, Bologna n=127) patients who underwent allo-SCT (years 2018-2023) with PBSCs from UD (97% HLA 10/10, 3% HLA 9/10) and received ATLG at a total dose of 30 mg/kg between days -4 and -1 in the UKE cohort and days -6 to -2 in the Bologna Cohort. Patients were categorized based on the median ALC 0.32Mrd/L (range 0-13.85) into the “low-ALC” group with (ALC ≤ 0.32Mrd/L) and the “high-ALC” group with measurable lymphocytes (ALC &amp;gt; 0.32Mrd/L) on the first day of ATLG administration, allowing for a comparison of transplant outcomes between these groups. Results: Median follow-up was 12 months (range 1-56). Median days to neutrophil engraftment was 11 (range 6-21) in the low-ALC group and 13 (range 8-27) in the high-ALC group (p&amp;lt;0.001). In univariate analysis, no significant differences in 2-year NRM were observed between low-ALC (16% [95%CI: 11-22%]) and high-ALC groups (12% [95%CI: 8-17%]; p=0.24), whereas allo-SCT year (≤ 2020: 18% vs &amp;gt;2020 10%, p=0.02), conditioning intensity (MAC 9% vs RIC 19%) p=0.005), disease status at transplant (CR: 10% vs not CR 18%, p=0.03) significantly affected NRM. In Multivariate analysis (MVA) only ALC (per 1 point increase HR 1.03 [95%CI: 1.0-1.1]; p=0.04) and conditioning intensity (RIC vs. MAC: HR 2 [95%CI: 1-3.8]; p=0.038) significantly impacted NRM. There was a trend for higher cumulative incidence of relapse (CIR) at 2 years in the low-ALC group (21% [95%CI: 16-27%]) when compared to the high-ALC group (16% [95%CI: 11-21%]), p=0.09. On UVA only Patient age (≤66 years 22% vs &amp;gt; 66 years 14%, p=0.02), TBI (No TBI 18% vs TBI 38%, p=0.003) affected CIR. On MVA only ALC (HR 0.98 [95%CI: 0.96-0.99]; p=0.013) TBI vs no TBI (HR 2.14 [95%CI: 1.3-3.5]; p=0.003) significantly affected CIR. A trend toward decreased 2-year OS was noted in patients with low-ALC (62%) compared to those with high-ALC (74%) p=0.06. On UVA disease status at transplant (CR: 74% vs not CR 61% p=0.004) conditioning intensity (MAC: 75% vs RIC: 62% p=0.01) and Immunosuppression significantly impacted OS. MVA revealed lower OS for non-CR patients (HR 2.68 [95%CI 1.6-4.49], p=0.024) and improved OS for MDS (HR 0.34 [95%CI 0.18-0.64]) and PMF (HR 0.04 [95%CI 0.01-0.35]), compared to AML and TAC+MMF led to reduced OS versus CSA+MMF (HR 5.99 [95%CI 1.91-18.82], p=0.002) PFS at 2 years was significantly lower in the low-ALC group (56%) compared to the high-ALC group (67%), p=0.038. Factors affecting PFS included ATLG dosing schedule (D-6 to -3: 70% vs D-4 to -1: 57% , p=0.02), patient age (≤66 years: 61% vs &amp;gt;66 years: 63%, p=0.04), disease status (CR: 68% vs not CR: 55%, p=0.005), and conditioning intensity (MAC: 67% vs RIC: 57%, p=0.048). MVA showed that females had higher PFS than males (HR 0.66 [95%CI: 0.45-0.97], p=0.037), non-CR status lower PFS (HR 2.51 [95%CI: 1.58-3.98], p&amp;lt;0.001), and MDS or PMF higher PFS over AML (HR 0.3 [95%CI: 0.17-0.55] and HR 0.08 [95%CI: 0.02-0.40], p&amp;lt;0.001, p=0.002). GRFS at 2 years was significantly lower in patients with low-ALC (31%) compared to those with high-ALC (48%) p=0.005). On UVA ATLG dosing-schedule (D-6 to -3: 52% vs D-4 to -1: 33%, p=0.001), donor CMV serology (negative: 47% vs positive: 33%, p=0.013), disease status (CR: 48% vs not CR: 28%, p=0.0002), and conditioning intensity (MAC: 44%vs RIC: 35%). Multivariate analysis showed non-CR status was associated with lower GRFS (HR 2.68 [95%CI: 1.6-4.49], p&amp;lt;0.001), transplantation for MDS (HR 0.34 [95%CI: 0.18-0.64], p&amp;lt;0.001) and PMF (HR 0.04 [95%CI: 0.01-0.35], p=0.003) higher GRFS compared to AML. We observed no significant differences in the cumulative incidence of aGVHD grade III-IV (8% in bopth groups, p=0.87) and cGVHD moderate/severe between the groups (at 2 years low-ALC 22% [95%CI 16-28] vs high-ALC 16% [95%CI 11-22] p=0.16). Conclusion: Higher ALC at ATLG administration may improve transplant outcomes after allo-SCT. These findings suggest tailoring ATLG doses based on ALC and earlier administration could optimize allo-SCT outcomes.

Immune Reconstitution after Allogenic Stem Cell Transplantation in Patients with Myelofibrosis

Background Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for patients (pts) diagnosed with myelofibrosis (MF). Despite several improvements over time, post-transplant complications can still be severe and significantly affect pts' survival. Inflammation and bone marrow fibrosis may hinder immune reconstitution (IR) in MF pts, but there is limited data available. This study aimed to evaluate IR in MF pts undergoing alloHSCT and its impact on their outcomes. Methods We retrospectively evaluated IR in MF pts who underwent alloHSCT at the Bone Marrow Transplantation Unit of Spedali Civili di Brescia between April 2017 and April 2024. Absolute lymphocyte counts (ALC) and lymphocyte subtypes were assessed at +3, +6, +9, +12, +18, and +24 months (M) post-transplant. IR was evaluated by flow cytometry using fresh whole blood samples. Monoclonal antibodies were employed to evaluate main lymphocyte populations, CD4/CD8 ratios, and T-cell subset (CD45RA; CD45RO). Lymphocyte recovery was defined as ALC &amp;gt;500/uL at M+3, and ALC &amp;gt;750/uL from M+6 onward. The recovery of subtypes CD3+CD4+, CD3+CD8+ and CD19+ was classified as absolute counts &amp;gt;200/uL. Results Since April 2017, 33 MF pts were transplanted at our Institution. The median age was 60.7 years (range 44-71), with 76% (25) being male. Seventeen out of 29 evaluable pts (59%) had an unfavorable karyotype. Twenty-four pts were JAK2 mutated, while 8 were CALR+ and 1 MPL+. Overall, 13 on 28 evaluable pts harbored a high molecular risk mutation. Five pts had DIPSS intermediate-1, 20 pts had intermediate-2, and 8 had high risk. Twenty-eight pts received JAK2 inhibitor before alloHSCT. Regarding transplant features, 16 pts received a myeloablative conditioning, and 27 received double-alkylators regimens (Thiothepa-Busulfan-Fludarabine). Donors were sibling, unrelated or haploidentical in 18.2%, 48.5% and 33.3% of cases, respectively. HCT-CI was high in 15 pts. Almost all pts (85%) received peripheral blood stem cell grafts. In haploidentical alloHSCT, pts received post-transplant cyclophosphamide, while the other pts received GvHD prophylaxis with cyclosporine and methotrexate (or mycophenolate); 21 pts received rabbit antithymocyte globulin (ATG). After a median follow-up of 15.9 months (IQ 8-43), 12 pts had died (5 relapse, 4 infections, 3 acute GVHD) for a 5-year CIR, NRM and OS of 27.2% (95%CI 10.8-46.7), 19% (95%CI 7.5-34.6) and 54.3% (95%CI 28.5-74.4), respectively. Serial ALC assessments showed a gradual increase from M+3 to M+18. Median counts reached 426/uL (115-1758) at M+3, 587/uL (254-2794) at M+6, 891/uL (148-3181) at M+9, and 1643/uL (438-4978) at M+18, representing 41%, 42%, 53% and 83% of recovered pts, respectively. Similarly, CD4+ recovery improved over time, with median CD4+ counts surpassing 200/uL only at M+9. CD4+ reconstitution at M+3 varied significatively according to donor type: haploidentical alloHSCT had a median of 104/uL, whereas sibling and MUD transplants were 171/uL and 142/uL, respectively (p 0.01). ATG treatment was not related to CD4+ reconstitution. CD4+CD45RA+ cells, more likely naïve cells, significatively increase at each time point, peaking at 37.7/uL at M+18. Conversely, CD3-CD56+/CD16+ NK cells significatively decreased from M+3 to M+24. Pts not reconstituting CD4+ and ALC at M+9 were associated with a higher relapse rate (p 0.05) and showed a trend towards worse overall survival. At M+24, the cumulative incidence of relapse was 33% in pts with less than 200 CD4+/uL at M+9, compared to 0% in those with recovered CD4+ counts (p 0.05). Similarly, pts not recovering ALC at M+9 had relapse CI of 40% at M+24, compared to 0% in those with recovered ALC. ALC and CD4+ recovery at M+9 also impacted the maintenance of chimerism (p 0.05). CD4+ recovery at M+3 and M+6 was associated with a trend towards fewer infections. Additionally, not achieving CD4+ recovery at M+3 was linked to a higher risk of chronic GVHD. Conclusion MF pts exhibit slow immune reconstitution after alloHSCT, with median CD4+ count exceeding 200/uL only after 9 months, and CD4CD45RA+ counts peaking at 18 months. ALC and CD4+ recovery at 9 months is associated with lower late-relapse rates and lower chimerism loss. Despite being influenced by various factors (e.g., donor type), IR after alloHSCT in MF pts can be a valuable tool for assessing the risk of infections, GVHD development, and relapse.

Sociodemographic Determinants of Allogeneic Hematopoietic Stem Cell Transplant Outcomes

Background: Allogeneic hematopoietic stem cell transplant (allo-HCT) is a curative therapy for several high-risk hematologic disorders. While clinical factors significantly impact post-transplant outcomes, socio-demographic determinants such as age, gender, and ethnicity play a crucial role in the success of allo-HCT. Furthermore, performance status and comorbidities also affect the outcomes. We aimed to investigate the influence of socio-demographic determinants on allo-HCT outcomes. Methods: For this retrospective single-center study, we included all patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-SCT at the University of Kanas Medical Center from August 2016 to July 2021. Cox regression analysis compared overall survival (OS) and disease-free survival (DFS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Logistic regression was performed to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Odds ratios (0R) with 95% CI were calculated. Linear regression was performed to compare platelet and neutrophil engraftment, and the correlation coefficient (R) was calculated. Multivariate analyses were performed for recipient age, gender, ethnicity, Karnofsky's performance status (KPS), and Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p&amp;lt;0.05. Results: A total of 452 patients were included, of which 276 had MUD allo-HCT while 176 had haplo allo-HCT. The median age of the recipients was 57 years (18-77), of which 61% were male (n=277). Ethnicity was Caucasians (n=381, 84%), Hispanics (n=28, 6%), African Americans (n=20, 5%), and others (n=23, 5%). KPS was 60-80% in 67% (n=304) patients and 90% or higher in 33% (n=148) of patients. Fifty-six percent of patients (n=251) had an HCT-CI score of 3 and above. Myeloablative and reduced-intensity conditioning were performed in 169 (37%) and 283 (63%) recipients. The graft source was bone marrow in 224 (49.6%) and 228 (50.4%) had peripheral blood stem cell grafts. The median graft cell dose was 4 million CD34 cells/kg. GVHD prophylaxis included tacrolimus/methotrexate (n=241, 53%) and post-transplant cyclophosphamide-based (n=211, 47%). Hematologic diagnoses included myeloid (n=322, 71%), lymphoid (n=101, 22%), and others (n=29, 7%). In univariate analyses for recipient age, gender, ethnicity, KPS, and HCT-CI, predictors include OS: age (years, HR 1.03, 95% CI 1.01-1.04, p&amp;lt;0.001), HCT-CI (≥3 vs 0-1: HR 1.40, 95% CI 1.03-1.91, p=0.030), and KPS (60-80% vs ≥90%: HR 1.61, 95% CI 1.14-2.26, p=0.006); DFS: age (years, HR 1.02, 95% CI 1.01-1.03, p&amp;lt;0.001) and KPS (60-80% vs ≥90%: HR 1.41, 95% CI 1.04-1.90, p=0.028); GRFS: None; Relapse: None; NRM: age (years, HR 1.02, 95% CI 1.01-1.04, p=0.001); acute GVHD: gender (male vs female, HR 0.59, 95% CI 0.40-0.87, p=0.007); chronic GVHD: KPS (60-80% vs ≥90%: HR 0.64, 95% CI 0.43-0.96, p=0.029); engraftment: None. Multivariate models were adjusted for all significant predictors identified in the univariate analyses. After adjusting for confounders, higher recipient age significantly predicted inferior OS (HR 1.10, 95% CI 1.01-1.04, p=0.0084), inferior DFS (HR 1.02, 95% CI 1.01-1.03, p=0.0012), and higher NRM (OR 1.03, 95% CI 1.01-1.04, p=0.005). Male gender significantly predicted lower risk of acute GVHD ((OR 0.59, 95% CI 0.40-0.86, p=0.007). African American ethnicity compared to Caucasians significantly predicted inferior OS (HR 1.90, 95% CI 1.01-3.58, p=0.046). KPS was a significant predictor of a higher risk of chronic GVHD (HR 0.62, 95% CI 0.40-0.95, p=0.028). HCT-CI did not predict any of the outcomes. No other significant associations were observed between these factors and post-transplant outcomes. Conclusion: In this single-center study, recipient age significantly affected OS, DFS, and NRM. The recipient's gender had a notable impact on acute GVHD, while ethnicity influenced OS. KPS was associated with chronic GVHD; interestingly, HCT-CI had no impact on post-transplant outcomes. Our findings suggest the need for larger studies to explore and mitigate the sociodemographic determinants of transplant outcomes.

Cryotherapy Prevents Hair Loss in Multiple Myeloma Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation

Cryotherapy Prevents Hair Loss in Multiple Myeloma Patients Undergoing Autologous Peripheral Blood Stem Cell Transplantation

Efficacy and Safety of Reduced-Doses of Post-Transplant Cyclophosphamide in Matched Peripheral Blood Stem Cell Transplantation, a Multicenter Study

Efficacy and Safety of Reduced-Doses of Post-Transplant Cyclophosphamide in Matched Peripheral Blood Stem Cell Transplantation, a Multicenter Study

Impact of Donor Age and Gender on Allogeneic Hematopoietic Stem Cell Transplantation

Background: Allogeneic hematopoietic stem cell transplant (allo-SCT) is critical in managing hematologic disorders. Donor age and gender are essential factors for post-transplant outcomes, and younger male donors have been associated with improved outcomes. We aimed to investigate the impact of donor age and gender on outcomes in patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-SCT. Methods: For this retrospective single-center study, we included allo-SCT recipients who received a MUD (n=276) or haplo (n=176) SCT at the University of Kanas Medical Center from August 2016 to July 2021. Cox regression analysis compared overall survival (OS) and disease-free survival (DFS). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Logistic regression was performed to compare relapse, non-relapse mortality (NRM), acute and chronic graft versus host disease (GVHD), and GVHD-free Relapse-free survival (GRFS). Odds ratios (0R) with 95% CI were calculated. Linear regression was performed to compare platelet and neutrophil engraftment, and the correlation coefficient (R) was calculated. Multivariate analyses were performed for donor age as a continuous and categorical variable (&amp;lt;30 years vs 30 years and above). SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p&amp;lt;0.05. Results: We included 452 Allo-SCT recipients who received a MUD (n=276) or Haplo (n=176) SCT. The median recipient age was 57 (18-77) years and 277 (61%) were male. The median age of the donor was 28 (10-65) years, with 57% of donors being younger than 30 years. Seventy-one percent (n=331) of donors were male. Myeloablative and reduced-intensity conditioning were performed in 169 (37%) and 283 (63%) recipients. The graft source was bone marrow in 224 (49.6%), and 228 (50.4%) had peripheral blood stem cell grafts. The median graft cell dose was 4 million CD34 cells/kg. GVHD prophylaxis included tacrolimus/methotrexate (n=241, 53%) and post-transplant cyclophosphamide-based (n=211, 47%). Hematologic diagnoses included myeloid (n=322, 71%), lymphoid (n=101, 22%), and others (n=29, 7%). After adjusting for significant variables in the multivariate regression models, OS was not affected by the donor age (HR 1.005, 95% CI 0.991-1.021, p=0.476) and donor age &amp;lt;30 years (HR 0.923, 95% CI 0.681-1.252, p=0.608). Donor age had a marginal association with relapse (donor age: OR 0.974, 95% CI 0.950-0.997, p=0.032; donor age &amp;lt;30 years: OR 1.760, 95% CI 1.131-2.775, p=0.013) and NRM (donor age: OR 1.025, 95% CI 1.001-1.048, p=0.034; donor age &amp;lt;30 years: OR 0.656, 95% CI 0.417-1.031, p=0.067). The donor's age did not affect GRFS, DFS, acute and chronic GVHD, and engraftment. Allo-SCT with male donors had superior OS (HR 0.626, 95% CI 0.452-0.868, p=0.0049) compared to female donors. Faster platelet engraftment was observed using male donors (R -4.212, -7.90 to -0.517, p=0.0250). GRFS, Relapse, DFS, NRM, acute and chronic GVHD, and neutrophil engraftment were not affected by donor gender. Conclusion: The use of male donors was associated with superior overall survival and faster platelet engraftment, while donor age did not significantly impact post-transplant outcomes. Our findings suggest improved survival with the use of male donors regardless of donor age, and these findings should be validated in a larger contemporary cohort.

Donor Neutrophil Subsets in G-CSF Mobilized Peripheral Blood Stem Cell to Predict the Risk of Agvhd

Donor Neutrophil Subsets in G-CSF Mobilized Peripheral Blood Stem Cell to Predict the Risk of Agvhd

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

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

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

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

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

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

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

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