Antonio Martin Jimenez Jimenez

The ACCESS trial is a prospective, multicenter phase 2 trial evaluating peripheral blood stem cell (PBSC) transplantation using 4/8 to 7/8 HLA-mismatched unrelated donors (MMUD) with posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first hematopoietic cell transplantation (HCT) with myeloablative conditioning or reduced-intensity conditioning (RIC)/nonmyeloablative conditioning (NMA) were enrolled. This expanded analysis includes all enrolled adult PBSC HCT recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA-match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 MMUD grafts. Median follow-up among survivors was 11.9 months. At 1 year, overall survival was 78.6% (95% confidence interval [CI], 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, nonrelapse mortality, and graft-versus-host disease (GVHD)–free relapse-free survival were 17.1%, 13.7%, and 51.1% vs 22.8%, 8.4%, and 54.6%, in the 7/8 and <7/8 cohorts, respectively. The cumulative incidence of grade II to IV and grade III to IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort vs 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% vs 7.7% in the 7/8 and <7/8 cohorts, respectively. Among adult ACCESS trial participants treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. This trial was registered at www.clinicaltrials.gov as NCT04904588.

Background/Objectives: Autologous stem cell transplantation (ASCT) remains a standard frontline treatment for eligible patients with multiple myeloma and is associated with improved progression-free survival and sustained treatment responses. In addition to medical eligibility factors, pre-treatment psychosocial variables such as depression and anxiety as well as cognitive functioning may influence short- and long-term transplant outcomes. This study examined the relationship between pre-transplant psychosocial and cognitive functioning and clinical outcomes in patients with multiple myeloma undergoing ASCT. Methods: Participants (n = 245) undergoing a standardized protocol for ASCT in Miami, Florida received pre-transplant psychosocial and neuropsychological assessments. Patient-reported clinical variables and cognitive performance were related to transplant success and transplant recovery outcomes, including time to engraftment, length of hospital stay post-engraftment, and survival across four timepoints. Results: While most patients achieved engraftment within a similar timeframe, the duration of hospitalization following engraftment varied considerably. Only higher baseline trait anxiety was associated with longer post-engraftment hospital stays. In multivariate Cox regression analyses, post-engraftment length of stay was independently associated with long-term mortality when modeled as a continuous variable. In a secondary analysis using an empirically derived cutoff corresponding to stays longer than the 80th percentile (≥7 days post-engraftment), both prolonged post-engraftment hospitalization and poorer baseline delayed memory was independently associated with mortality. Descriptive survival analyses further showed that patients with prolonged post-engraftment hospitalizations had higher overall mortality and shorter survival than those with shorter post-engraftment hospital stays. Conclusions: Patients who demonstrated poorer delayed memory performance pre-transplant and prolonged hospital admission post-transplant may be most vulnerable to dying when examined at long-term follow-up. Pre-transplant psychiatric assessments provide an opportunity to identify and potentially implement supportive care interventions for patients at increased risk for cognitive impairment.

From the 2026 National Summit on Hematologic Cancers

Myelodysplastic syndromes (MDS) in young adults are uncommon and underrepresented in transplant cohorts. We evaluated 697 patients aged 18–40 years who underwent first allogeneic hematopoietic cell transplantation (allo-HCT) reported to the EBMT between 2016 and 2021. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and graft-versus-host disease (GVHD). With a median follow-up of 2.8 years, 3-year OS and PFS were 69% (95% CI, 65–73) and 62% (58–66), respectively. At 3 years, CIR and NRM were 20% (16–23) and 18% (15–21). Grade II–IV acute GVHD occurred in 28% (25–32) by day +100, while chronic GVHD and extensive chronic GVHD occurred in 38% (34–42) and 18% (14–21) at 3 years. In multivariable analysis, very-poor cytogenetic risk was associated with inferior OS (HR 2.81, 95% CI 1.77–4.45). Haploidentical donors and reduced-intensity conditioning were also associated with inferior survival. Patients younger than 30 years had superior PFS, whereas outcomes with matched sibling and matched unrelated donors were comparable. These findings support the feasibility of allo-HCT in young adults with MDS and may help inform risk-adapted transplant approaches.

HLA-mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) has emerged as an effective therapy for adult patients with hematologic malignancies. The MMUD ACCESS trial, which incorporated posttransplant cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis, demonstrated a combined overall survival of 81% in enrolled patients, 59% of whom were from ethnically diverse groups. Given that PTCy is also associated with significant bacterial and viral infections, we defined infection burden in the full adult cohort (N = 268) using infections graded according to an international standard (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0). Infection density (number of infections per 100 days at risk), cumulative incidence of infection, and frequency of pathogen types were categorized by post-HCT time, conditioning intensity, level of donor HLA mismatch, and presence of acute GvHD (aGvHD). Of 465 CTCAE grade 2 to 5 infections recorded in 183 (68%) adults, 176 (38%) were significant or life-threatening, and most (296 [64%]) occurred within the first 100 days. Infection density at days 0 to 30 was significantly higher than at other times and was similar by conditioning and level of HLA mismatch, as were pathogen types and isolates. Multivariable analysis showed that aGvHD is significantly associated with infection. Finally, 21 (7.8%) patients died of infection. Results show significant infection burden using standard-dose PTCy in the MMUD HCT setting, irrespective of conditioning and level of donor HLA mismatch, and serve as a benchmark for trials investigating reducing infection burden after MMUD HCT. This trial was registered at www.clinicaltrials.gov as NCT04904588.

Background/Objectives: Autologous stem cell transplantation (ASCT) remains a standard frontline treatment for eligible patients with multiple myeloma and is associated with im-proved progression-free survival and sustained treatment responses. In addition to medi-cal eligibility factors, pre-treatment psychosocial variables such as depression and anxiety as well as cognitive functioning may influence short and long-term transplant outcomes. This study examined the relationship between pre-transplant psychosocial and cognitive functioning and clinical outcomes in patients with multiple myeloma undergoing ASCT. Methods: Participants (N = 245) undergoing ASCT in Miami, Florida completed routine pre-transplant psychosocial and neuropsychological assessments. Patient-reported clini-cal variables and cognitive performance were examined in relation to transplant success and transplant recovery outcomes, including time to engraftment, length of hospital stay post-engraftment, and survival across four timepoints. Results: While most patients achieved engraftment within a similar timeframe, the duration of hospitalization follow-ing engraftment varied considerably. Higher baseline trait anxiety was associated with longer post-engraftment hospital stays. In multivariable Cox regression analyses, post-engraftment length of stay was independently associated with long-term mortality when modeled as a continuous variable. In a secondary analysis using an empirically de-rived cutoff corresponding to stays longer than the 80th percentile (≥7 days post-engraftment), both prolonged post-engraftment hospitalization and poorer baseline delayed memory were independently associated with mortality. Descriptive survival analyses further showed that patients with prolonged post-engraftment hospitalizations had higher overall mortality and shorter survival than those with shorter post-engraftment hospital stays. Conclusions: Patients who demonstrated delayed memory performance pre-transplant and prolonged hospital admission post-transplant may be most vulnerable to dying when examined at long-term follow-up. Pre-transplant psychiatric assessments provide an opportunity to identify potentially implement supportive care interventions for patients at increased vulnerability for cognitive impairment.

To prevent graft-versus-host disease (GVHD) in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation (alloHSCT), a calcineurin inhibitor plus methotrexate is routinely used. Early phase studies suggested improved outcomes with Orca-T, an allogeneic T-cell immunotherapy that uses purified donor regulatory T cells to prevent GVHD with significantly less immunosuppression. This phase 3 trial randomized adult patients (N = 187) with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning to receive either Orca-T with tacrolimus or a conventional allograft with tacrolimus and methotrexate (Tac/MTX), using granulocyte colony-stimulating factor–mobilized peripheral blood from HLA-matched donors. The primary end point was survival free from moderate-to-severe chronic GVHD (cGVHD; cGFS). Using a stratified log-rank test, cGFS was significantly higher in the Orca-T arm than in Tac/MTX (hazard ratio, 0.26; 95% confidence interval, 0.14-0.47; P< .001). One-year estimates were as follows: cGFS was 78.0% with Orca-T vs 38.4% with Tac/MTX; cumulative incidence of moderate-to-severe cGVHD was 12.6% with Orca-T and 44.0% with Tac/MTX (Gray test P< .001); overall survival was 93.9% with Orca-T vs 83.1% with Tac/MTX (P = .12); GVHD-free and relapse-free survival was 63.1% and 30.9% in the Orca-T and Tac/MTX arms (P< .001), respectively; nonrelapse mortality (NRM) was 3.4% with Orca-T vs 13.2% with Tac/MTX (P = .03). Orca-T met the primary end point of improved survival free from cGVHD compared with Tac/MTX prophylaxis and should be considered a new therapeutic option with low toxicity for GVHD prophylaxis. Moreover, significantly less toxicity was observed with Orca-T patients, including fewer serious infectious complications and less NRM. This trial was registered at www.clinicaltrials.gov as NCT05316701.

Background: Despite important advancements in diagnostic modalities, routine use of therapeutic drug monitoring (TDM) and newer antifungal therapies, there is a paucity of contemporary data regarding clinical characteristics and outcomes of invasive aspergillosis (IA) in the United States. Methods: Single-center, retrospective cohort study of hospitalized patients between 2015 and 2020, who had active hematological malignancy (HM) or had undergone transplantation and cellular therapy (TCT) and had probable or proven IA. Results: Sixty-two patients with probable or proven IA, including 21 HM and 41 TCT, were identified. Forty-four percent of the cases corresponded to breakthrough IA. Bronchoalveolar lavage galactomannan was ≥ 1 in 71% and ≥ 0.5 in 88%, while serum galactomannan was ≥ 0.5 in only 34%. Among assessable patients (n = 59), 90-day partial or complete response to antifungal therapy occurred in 39%. All-cause mortality for the entire cohort was 22% at 30 days and 46% at 90 days. IA attributable mortality was 18% at 30 days and 38% at 90 days. Achieving therapeutic antifungal serum levels was associated with a reduction in all-cause mortality, while prior clinically significant CMV infection (aOR 9.65, 95% CI 1.34–69.6; P = 0.025) and relapsed/refractory hematological disease (aOR 8.5, 95% CI 2.23, 32.4; P = 0.002) were associated with higher IA attributable mortality. Conclusions: Despite advancements in diagnosis and treatment, IA remains associated with poor outcomes in hematological patients in the contemporary era. Newer antifungals and improved strategies for monitoring and prevention of IA in these vulnerable patient populations are urgently needed.

This brief communication summarizes the joint session of the Brazilian Cellular Therapy and Bone Marrow Transplantation Society (SBTMO) and the Brazilian Histocompatibility and Immunogenetics Association (ABHI), held during the 2025 SBTMO Annual Meeting. The joint session focused on how post-transplant cyclophosphamide (PTCy) is redefining donor selection in contemporary allogeneic hematopoietic cell transplantation (HCT). In three lectures with experts in the field, several topics concerning PTCy were addressed, including the effectiveness of PTCy in overcoming the HLA barrier, the increased use of mismatched unrelated donors (MMUD) under PTCy, which significantly broadens HCT access for underserved ethnic minorities, and strategies for reducing the dose of PTCy. The impact of donor-specific HLA antibodies in allogeneic HCT, the importance of HLA serotypes (associated antigens) in improving the accuracy of virtual crossmatch during MMUD searches, and the utility of novel bioinformatics tools to enhance serotype evaluation for MMUD selection under PTCy were also discussed. Additionally, the present report outlines the discussions among the speakers, session chairs, and audience members.