Juan Montoro

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. The increasing use of post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) has expanded beyond haploidentical transplantation to matched related (MRD) and unrelated donor (MUD) settings, although real-world GVHD incidence in this context is not well characterized. We performed a nationwide retrospective study including 1544 alloHSCTs conducted in Spain between 2018 and 2020. PTCy-based prophylaxis was used in 65.6% of transplants, being almost universal in haploidentical procedures (96.9%) and predominant in mismatched donors (72.4%), with notable use in MRD (43.5%) and MUD (56.8%). The cumulative incidence of grade II-IV acute GVHD at day +100 and 1 year was 28.4% and 30.7%, respectively, while grade III-IV occurred in 6.9% and 8.0%. Despite the prevalent use of peripheral blood stem cells, chronic GVHD at 2 years was 36.7%, with 23.5% moderate-to-severe. Acute GVHD was strongly associated with inferior survival (HR 2.40; P < 0.001), particularly grade III-IV disease (HR 4.34; P < 0.001). This large nationwide real-world study highlights the shift in GVHD prophylaxis in modern alloHSCT and underscores the need to define new studies based on this evolving landscape.

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) may occur after allo-HSCT. This retrospective study of 793 allo-HSCT performed in adult patients analyzes the impact of clinical risk factors and the EASIX score on the incidence and outcomes of SOS/VOD using Real-World data (GETH-TC registry). Severity and clinical risk factors were defined according to the EBMT-2023 criteria. The EASIX score was calculated at three time points after allo-HSCT (EASIX-day 0, d + 7, d + 14). SOS/VOD developed in 79 patients (10%), at a median time of 15 days. The cumulative incidence of SOS/VOD at 30 and 90 days post-HSCT was 8.58% and 9.97%, respectively. Defibrotide was used in 44 patients (56%) who developed SOS/VOD. Patients with SOS/VOD experienced an increased risk of NRM (HR 5.56; p < 0.001). Multivariate analysis confirmed the prognostic value for SOS/VOD incidence of second or subsequent HSCT, use of parenteral nutrition, high tacrolimus/sirolimus levels, INR > 1.5 before SOS, as well as day 0 EASIX ≥ 2 (sHR 1.67; p = 0.036), d + 7 EASIX ≥ 6 (sHR 2.86; p < 0.001), and d + 14 EASIX ≥ 6 (sHR 2.87; p = 0.003). In conclusion, SOS/VOD incidence is similar to previous series and significantly impacts NRM. EASIX score was validated as a risk factor of SOS/VOD.

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). Although post-transplant cyclophosphamide (PTCy) and antithymocyte globulin (ATG) have reshaped prophylactic strategies, contemporary real-world data on GVHD incidence under current practice are limited. We conducted a nationwide retrospective study including 1 544 alloHSCTs performed in Spain (2018-2020) to characterize current prophylaxis patterns and the epidemiology of GVHD. PTCy-based prophylaxis was used in 65.6% of transplants, being nearly universal in haploidentical donors (96.9%) and predominant in mismatched unrelated (72.4%), matched unrelated (58.6%), and matched related donors (43.5%). The cumulative incidence of acute GVHD grades II-IV was 28.4% at day +100 and 30.7% at 1 year; grade III-IV occurred in 6.9% and 8.0%, respectively. Chronic GVHD at 2 years was 36.7%, with 23.5% moderate-to-severe cases. Acute GVHD was independently associated with inferior survival (HR 2.40, p<0.001), particularly grade III-IV disease (HR 4.34, p<0.001). These findings define the contemporary real-world burden of GVHD in a high-volume European country and provide an updated epidemiologic framework to inform preventive strategies, clinical trial design, and healthcare planning in modern alloHSCT.

Introduction: Patients undergoing hematopoietic stem cell transplantation (HSCT) are at an increased risk of secondary skin neoplasms. However, detailed clinicopathological and therapeutic descriptions are limited. Methods: We conducted a prospective, observational, single‐center study including HSCT recipients. Patients with actinic keratosis or skin/mucosal malignancies were evaluated by expert dermatologists, with a histological review. Management followed standard protocols, and patients were stratified according to the National Comprehensive Cancer Network (NCCN) guidelines. Results: Of the 2042 HSCT recipients, 96 (4%) developed any actinic keratosis or skin cancer, with a median latency period of approximately three years. The most common lesions were basal cell carcinoma (BCC, 35%), actinic keratosis (30%), and squamous cell carcinoma (SCC, 22%), followed by melanoma (9%). The lesions predominantly appeared on the face and scalp. Almost 20% of invasive SCCs or BCCs exhibited high‐risk histopathological features, most commonly micronodular BCC and deep invasion in SCC. Surgical excision was the primary treatment; however, a high percentage of positive margins was found, especially in SCCs. At follow‐up, 47% of patients developed subsequent lesions, typically of the same histological subtype or actinic keratosis, with a median time to recurrence of 9.5 months. One patient died from metastatic SCC of the lip. Conclusion: This study provides the most detailed clinicopathological description of post‐HSCT cutaneous lesions to date. While most tumors were non‐aggressive, the high prevalence of high‐risk features and recurrence highlights the need for dermatological surveillance. Nearly half of patients develop new lesions within months of the first diagnosis, so regular follow‐up is warranted.

Haploidentical hematopoietic cell transplantation (HCT) is widely used in high-risk acute lymphoblastic leukemia (ALL), yet optimal donor selection remains unclear. We retrospectively analyzed 933 ALL patients receiving post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to evaluate the impact of donor characteristics on outcomes. Donors had a median age of 36 years; 38% were female, including 23% who donated to male recipients. Peripheral blood (PB) was the graft source in 69%, and CMV-seronegative donors were used in 16% of CMV-negative recipients. Multivariate analysis showed that PB grafts were associated with inferior overall survival (OS) and GVHD-free/relapse-free survival. CMV-matched seronegative pairs had reduced non-relapse mortality and improved OS. Chronic GVHD was more frequent with older donors and in male recipients of female donor grafts, the latter also increasing extensive cGVHD risk. In conclusion, donor and graft selection significantly influence outcomes after haplo-HCT with PTCy. When feasible, bone marrow should be favored over PB grafts, and CMV-seronegative donors prioritized for CMV-seronegative recipients. Older donor age and female-to-male sex mismatch were associated with increased chronic GVHD risk.

Hematotoxicity after anti‐CD19 chimeric antigen receptor T‐cell therapy has drawn attention for potential long‐term effects, and yet, recovery of lymphocyte subsets and immunoglobulin levels beyond B‐cell aplasia remains poorly understood. We retrospectively analyzed 76 consecutive axicabtagene ciloleucel (axi‐cel) recipients with relapsed/refractory aggressive B‐cell lymphoma between 2020 and 2024, focusing on basic immune recovery patterns and their impact on outcomes. Median CD8 ⁺ T and NK cells increased to >300/mm ³ and >100/mm ³ , respectively, within 2 months after infusion. CD4 ⁺ T‐cell recovery was slower, with 42% cumulative incidence of >200/mm ³ cell count at 12 months. B‐cells were detectable in 18% at 12 months. Immunoglobulin levels initially declined and then plateaued, with 51% incidence of immunoglobulin G (IgG) levels > 400 mg/dL at 12 months. Modified EASIX > 2.00 was associated with delayed kinetics of CD3 ⁺ T‐cells, CD4 ⁺ T‐cells, and CD8 ⁺ T‐cells, and cumulative dexamethasone dose > 120 mg with delayed recovery of CD4 ⁺ T‐cells, NK cells, and IgG. At 1 month post‐infusion, low CD4 ⁺ T‐cell count and high CAR‐HEMATOTOX predicted worse 12‐month progression‐free survival (hazard ratio [HR] 2.81 and 3.34) and overall survival (HR 3.21 and 4.41), respectively. After axi‐cel, CD4 ⁺ T‐cells and IgG recovered slowly during the first year, while CD8 ⁺ T and NK cells increased rapidly. A higher modified EASIX score may predict slower cellular recovery, while corticosteroids may delay both cellular and humoral recovery. Lower CD4 ⁺ T‐cell count was associated with worse outcomes.