Chronic graft-versus-host disease (cGVHD) remains a leading cause of late morbidity after allogeneic hematopoietic cell transplantation (HCT), but its phenotype under modern prophylaxis with post-transplant cyclophosphamide (PTCy) is not well characterized. We conducted a prospective, single-center study of 600 consecutive adults undergoing HCT with PTCy- based prophylaxis to assess incidence, clinical manifestations, treatment response, prognostic factors, and outcomes. Donors included matched siblings (36%), matched unrelated (34%), haploidentical (24%), and mismatched unrelated (6%). The 1-year cumulative incidence of moderate-to-severe cGVHD was 22% (95% confidence interval [CI]: 19-26%). The mouth was the most frequently involved organ (64%), with lichen planus-like changes as the predominant diagnostic feature, whereas sclerotic forms were uncommon. Notably, 27% of moderate-to-severe cases were managed successfully without systemic corticosteroids. The cumulative incidence of systemic therapy requirement was 15% at 1 year, with risk significantly higher in donors ≥30 years and in female-to-male transplants. Among 105 patients requiring systemic steroids, 64% achieved complete response, 32% discontinued immunosuppression, yet 18% developed cGVHD-related sequelae. Mouth ulcers and erythema, as well as a lung score ≥2 at steroid initiation independently predicted shorter failure-free survival. At 2 years, overall survival, cGVHD-free relapse-free survival, and GVHD-free relapse-free survival were 76% (95% CI: 72-79), 63% (95% CI: 60-68), and 57% (95% CI: 53-62), respectively. In conclusion, after HCT with PTCy-based prophylaxis, systemic therapy was required in only a minority of patients, with risk influenced by donor age and sex mismatch rather than donor type. While corticosteroids were generally effective, a substantial subset required salvage therapy, underscoring the burden of refractory cGVHD and the need for steroid-sparing approaches and novel interventions.

BACKGROUND:Secondary malignancies (SM) are a well-recognized long-term complication after hematopoietic cell transplantation (HCT), increasingly contributing to morbidity and mortality as post-transplant survival improves. However, the incidence, spectrum, and outcomes of SM remain incompletely defined in the context of evolving transplant practices and a growing population of long-term survivors. OBJECTIVE:To evaluate the incidence, risk factors, and outcomes of SM in a contemporary cohort of autologous and allogeneic HCT recipients. STUDY DESIGN:Observational, retrospective, single-center study including all consecutive patients undergoing a first autologous or allogeneic HCT from any donor type at the Hospital Universitario y Politécnico La Fe (Valencia, Spain) between January 2007 and December 2024. RESULTS:Among 2098 patients, 103 (4.9%) developed non-cutaneous SM, including 56 solid tumors (ST), 25 post-transplant lymphoproliferative disorders (PTLD), 15 therapy-related myelodysplastic syndromes/acute myeloid leukemia (t-MDS/AML), 2 donor cell leukemia, and 5 other hematologic malignancies. PTLD occurred earlier after allogeneic transplantation (median 3.9 months) than t-MDS/AML (median 47.0 months) and ST (median 51.5 months). Risk factors for ST included a history of prior malignancy (hazard ratio [HR] 2.96, 95% confidence interval [CI] 1.46 to 6.00; p = .003), allogeneic HCT (HR 2.44, 95% CI 1.29 to 4.60), and patient age ≥50 years (HR 1.89, 95% CI 1.07 to 3.35), whereas the risk of t-MDS/AML was higher among patients with a prior malignancy (HR 2.96, 95% CI 1.47 to 5.98). In the allogeneic setting, the use of post-transplant cyclophosphamide as graft-versus-host disease prophylaxis did not affect the risk of SM in multivariate analysis. SM ranked as the second and third leading causes of death after autologous and allogeneic HCT, respectively. Overall survival (OS) differed among SM subtypes entities, being particularly adverse for PTLD (1-year OS 19%, 95% CI 9 to 43) and better for solid tumors (5-year OS 43%, 95% CI 29 to 64). CONCLUSION:SM are a significant determinant of post-transplant mortality, with risk shaped by prior malignancy, older age, and transplant type, and outcomes varying markedly according to subtype.

Background: Platelet transfusion can be life-saving in some situations, but, if unnecessary, it puts the patients at risk and increases health system costs. Previous reports of audits performed on platelet transfusion practice in hospitals from different countries show a low adherence of physicians to the current recommendation. The objective of this article is to describe our patient blood management strategy to improve platelet transfusion practice of hematologic inpatients and outpatients, focusing on the impact on platelet transfusion activity and appropriateness rate. Methods: We developed a specific platelet transfusion guideline for hematological patients at our hospital. Platelet transfusion activity was audited after implementing the guide in mid-2024 and mid-2025, and these data were compared to the previous audits performed before the intervention. We also reviewed the platelet transfusion activity and adverse effects related to from 2021 to 2024. Results: Audit 1 reviewed 128 inpatients and 49 outpatients transfused from March 2022 to September 2023. Audit 2 studied 130 inpatients and 45 outpatients requiring platelet transfusion from March 2025 to July 2025. Annual platelet transfusions decreased from 8028 before intervention to 6880 in 2024 (14% decrease). In the hematological area, where the intervention has been made, the reduction in platelet transfusions was of 15.6% in hospitalized patients and 34.5% in outpatients as compared to 2023 (p < 0.001). The platelet supply decreased from 8407 in 2023 to 7138 in 2024. Adverse events related to PLT transfusion occurred in 51 patients in 2023 and 35 patients in 2024. Conclusions: Implementing patient blood management strategies focused on platelets led to a more rational and standardized use of platelet transfusions and decreased transfusion burden. Each organization should establish thresholds for platelet transfusion based on available evidence and guidelines, and also audit adherence to guidelines. In view of the scarce available evidence, research on platelet transfusion practice is mandatory.

This study assessed 552 allogeneic hematopoietic cell transplantation (HCT) recipients with posttransplant cyclophosphamide (PTCy) to evaluate the incidence, characteristics, risk factors, and impact of early posttransplant cytokine release syndrome (CRS) on outcomes. The cohort included 36% matched sibling donors (MSD), 34% matched unrelated donors (MUD), 27% haploidentical donors, and 4% mismatched unrelated donors (MMUD). CRS was observed in 182 patients, with the highest incidence in haploidentical transplants (80%) compared to MMUD (32%), MUD (23%), and MSD (8%). Most CRS cases were mild, with 93% classified as grade 1 and 6% as grade 2, with only one severe case of grade 3. In haploidentical transplants, CRS was linked to a lower risk of severe chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM), leading to improved overall survival. In contrast, among HLA-matched recipients (MSD and MUD), there were no significant differences in outcomes between those with or without CRS. However, subgroup analysis revealed that CRS in patients with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, was associated with a reduced relapse rate, improving survival outcomes. In conclusion, while CRS is typically mild and short-lived, it significantly impacts survival, particularly in haploidentical transplants and HLA-matched patients with myeloid malignancies.

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023. Data were collected on transplant procedures, complications, and GIB incidents, with UGIB cases undergoing endoscopic and histologic examination. Out of 559 patients, 38 (6.6%) experienced UGIB, with 27 cases (70%) attributed to GVE. GVE typically presented as melena or hematemesis at a median time of 68 d (range, 29 to 125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-mo cumulative incidence of GVE was 5.1%. Older age (≥60 yr) and diagnosis of myelodysplastic/myeloproliferative neoplasm were significant risk factors. All cases resolved with no attributable mortality with supportive measures including transfusions, proton-pump inhibitors, and sirolimus withdrawal in some cases. GVE is a notable cause of UGIB in HSCT recipients on PTCY-based GVHD prophylaxis, presenting significant morbidity but favorable outcomes with appropriate management. The potential role of sirolimus and conditioning agents in GVE pathogenesis warrants further investigation.

We analyzed the outcomes of 217 acute myeloid leukemia patients in complete remission who underwent allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning and post-transplant cyclophosphamide-based graftversus- host disease prophylaxis, aiming to assess the prognostic significance of genetic risk categories. In the overall cohort, the 2-year overall survival (OS) and event-free survival (EFS) were 77% (95% confidence interval [CI]: 71-83) and 72% (95% CI: 66-78), respectively. European LeukemiaNet (ELN)2022 risk stratification lacked prognostic value in HCT. Instead, we identified four risk categories with distinct impact on OS: standard risk (ELN2022 favorable/intermediate and adverse risk without high-risk genetic risk under the defined subcategories), intermediate risk (≥2 myelodysplasia-related gene mutations) (hazard ratio [HR]=2.23; 95% confidence interval [CI]: 1.14-4.92), adverse risk (complex karyotype, monosomal karyotype, inv(3)/t(3;3), KMT2A rearrangement) (HR=4.24; 95% CI: 2.00-9.02), and very adverse risk (TP53 mutations) (HR=6.81; 95% CI: 3.00-15.5). These categories demonstrated similar predictive power for EFS and cumulative incidence of relapse. Moreover, integrating pre-transplant measurable residual disease (MRD) refined risk stratification, identified MRD-negative patients with ≥2 myelodysplasia-related gene mutations whose OS and EFS were comparable to standard-risk patients. This refined classification improves the prognostic value of ELN2022 for acute myeloid leukemia patients undergoing allogeneic HCT with modern platform by integrating genetic features and MRD status to better guide post-transplant management.

Engraftment syndrome (ES) is a non-infectious febrile complication of hematopoietic cell transplantation (HCT), with diagnostic challenges, particularly in the allogeneic setting. The increasing use of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease prophylaxis highlights the need for a re-examination of ES in this contemporary context. To evaluate the incidence and clinical presentation of ES, as well as its impact on transplant outcomes in the era of PTCy-based prophylaxis. We retrospectively analyzed 552 allogeneic HCT patients receiving PTCy, sirolimus, and mycophenolate mofetil across various donor types. To improve ES diagnosis in this setting, we proposed new criteria in which peri-engraftment fevers (PEFs) (d -4 to d +3 before and after myeloid engraftment) were classified as follows: definite ES (PEF meeting Spitzer, Maiolino, or Grant criteria); probable ES (PEF plus ≥1 additional ES sign); and possible ES (PEF without additional signs). Among the 80 patients (14.5%) who developed PEF, 24 (30%) fulfilled criteria for definite ES, 14 (17.5%) for probable ES, and 42 (52.5%) for possible ES. The 30-d cumulative incidence of overall ES was 15% (95% confidence interval [CI], 12 to 18), comprising 4.4% (95% CI, 2.9 to 6.4) for definite ES, 2.6% (95% CI, 1.5 to 4.2) for probable ES, and 7.8% (95% CI, 5.7 to 10) for possible ES. In addition to fever, the most frequently observed ES-related symptoms included diarrhea (n = 18), weight gain (n = 14), skin rash (n = 11), hepatic dysfunction (n = 8), and pulmonary infiltrates (n = 7). Risk factors associated with the development of ES were younger age (defined as <40 yr), underlying lymphoproliferative neoplasms, haploidentical donor transplantation, and a history of prior cytokine release syndrome. Importantly, ES resolved within 48 h in 75 of the 80 cases (94%), and no deaths were attributed to PEF or ES episodes. Interestingly, the presence of ES was significantly associated with improved overall survival and event-free survival, potentially reflecting a composite effect of trends toward lower relapse rates and reduced non-relapse mortality in affected patients. ES in PTCy-based allogeneic HCT is frequent but rarely meets traditional criteria, highlighting the potential value of a refined three-category classification. Our findings suggest an unexpected survival benefit, possibly linked to the immunomodulatory effects of PTCy, and underscore the need for further studies to validate this classification and investigate the underlying biological mechanisms.

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a serious complication following allogeneic hematopoietic cell transplantation (HCT). Although post-transplant cyclophosphamide (PTCy) is increasingly used for graft-versus-host disease prophylaxis, data on its impact in the context of SOS/VOD remain limited. This study aimed to assess the incidence, clinical characteristics, prognostic factors, treatment approaches, and outcomes of SOS/VOD in HCT recipients receiving GVHD prophylaxis with PTCY, sirolimus or tacrolimus, and mycophenolate mofetil (MMF) across all donor types. This single-center observational study included all 532 consecutive adults who underwent HCT with PTCy between January 2017 and February 2024. Patient demographics, transplant procedures, toxicities, and complications were prospectively collected. Clinical charts were reviewed as needed to address inconsistencies or missing information. Myeloablative conditioning was administered to 96% of recipients, who received grafts from matched sibling donors (MSD, 36%), matched unrelated donors (MUD, 34%), haploidentical donors (26%), or mismatched unrelated donors (MMUD, 4%). SOS/VOD was diagnosed in 35 patients and classified according to EBMT criteria as probable (n = 10), clinical (n = 23), or proven (n = 2). Classical SOS/VOD occurred in 21 patients (60%), while 14 (40%) had late-onset disease. EBMT severity grading showed 3% mild, 20% moderate, 37% severe, and 40% very severe cases. The 100-day cumulative incidence was 6.6% (95% CI:4.7 to 8.9). Multivariable analysis identified prior transplantation, prior antibody-drug conjugates and higher CD3+ cell dose as risk factors. Patients with very severe or severe SOS/VOD (based on clinical features but not those upgraded solely due to the presence of risk factors) received defibrotide. Four patients (11.4%) died from SOS/VOD; all classified as very severe, and three of them had undergone prior transplantation (two autologous, one allogeneic). Despite high severity, SOS/VOD analyzed as a time-dependent variable showed no association with overall survival or nonrelapse mortality. SOS/VOD remains a challenging but clinically manageable complication with a modest incidence following HCT with PTCy. Although many cases were classified as severe or very severe, the associated mortality rate was relatively low. The identification of key risk factors, such as prior transplantation, antibody-drug conjugate exposure, and higher CD3⁺ cell doses, along with the notable proportion of late-onset cases, underscores the need for vigilant monitoring and individualized management strategies.

Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) and the frequent involvement of infections, evidence concerning patients receiving post-transplant cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis in the molecular diagnostic era is limited. This study aimed to evaluate the characteristics, incidence, risk factors, and outcomes impact of infectious enterocolitis in patients with hematologic malignancies undergoing HCT from matched sibling, matched unrelated, and haploidentical donors using PTCy as GVHD prophylaxis. Retrospective analysis of infectious enterocolitis episodes in 399 patients undergoing HCT at a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity. Levofloxacin was used prophylactically until myeloid engraftment. Infectious enterocolitis episodes were diagnosed by both molecular-based techniques and stool cultures. Infectious enterocolitis affected 21% of patients, with 19% having more than one episode. The median onset and duration was of 83 and 13 days, respectively, 20% were nosocomial and 58% were managed ambulatorily. The 1-year cumulative incidence was 19%, with 39% occurring beyond day 100, and was similar for Clostridioides difficile infection (CDI; 7%), non-CDI bacterial (8%), and viral enterocolitis (6%), with no differences in clinical features. However, toxin-positive CDI lasted longer (22 days) than toxin-negative cases (10 days, P = .03) Bone marrow HCT significantly increased the risk of overall infectious enterocolitis, while moderate-severe chronic GVHD increased all-cause and viral enterocolitis incidence. Infectious enterocolitis did not significantly impact overall survival, GVHD disease-free relapse-free survival, and non-relapse mortality. Approximately one-fifth of PTCy-based HCT recipients develop infectious enterocolitis in the first year, typically resolving within 2 weeks, with higher incidence in bone marrow recipients and those with moderate-severe chronic GVHD. CDI, non-CDI bacterial, and viral infections had similar incidences and clinical features. While infectious enterocolitis does not significantly impact transplant outcomes, its diagnosis remains challenging.

What is the potential of Human Umbilical Cord Platelet-rich Plasma (hUC-PRP) as a therapeutic option for endometrial tissue regeneration in women with endometrial pathologies? Human umbilical cord platelet-rich plasma (hUC-PRP) hysteroscopy injection produce a remarkable increase and improvement in the endometrial lining and pattern in women with endometrial pathologies. Endometrial pathologies, such as Asherman’s syndrome (AS) or thin endometrium /endometrial atrophy (TE/EA), are major contributors to infertility, with conventional treatments such as hormonal therapy often yielding limited efficacy. This has prompted the exploration of alternative treatments at improving reproductive outcomes. Platelet-rich plasma (PRP) has demonstrated potential in tissue repair, remodelling and increasing endometrial thickness, with favourable results documented in various studies. Recently, hUC-PRP has attracted interest due to its higher concentration of growth factors and anti-inflammatory properties observed across multiple medical fields. However, its application in gynaecology remains unstudied, presenting a promising therapy for endometrial pathologies. Firstly, 38 hUC-PRP samples were collected from postpartum donors and its use was approved by the Spanish Agency of Medicines and Medical Devices (AEMPS, Nº EudraCT 2020-005717-40). Before patient treatment, analysis related with viral safety, blood types and Rh of donor hUC blood were performed. This multicenter pilot clinical trial included 15 women with endometrial pathologies (AS, TE and EA). Endometrial thickness and pattern were evaluated before and after hUC-PRP administration. Compatibility between donors and patients was verified as we previously described. All patients (n = 15) followed these inclusion criteria: women aged 18 to 48, with a BMI ranging from 18 kg/m² to 35 kg/m², and an endometrial thickness of less than 5 mm despite 10 days of oestrogen administration and/or evidence of AS. The treatment was based on the hysteroscopy injection of hUC-PRP in the endometrium. Endometrial thickness and patterns were assessed by ultrasonography. Analysis of hUC-PRP demonstrated a significantly higher platelet concentration compared to hUC blood (p-value <0.0001). Proteomic analysis revealed differences between PRP samples of different age groups (18-65 years) and hUC-PRP. Interestingly, all hUC-PRP samples were more homogenous between them than PRP samples of different age groups, suggesting that all hUC-PRP samples are equally suitable for endometrial treatment. All patients showed a marked increase in endometrial thickness following hUC-PRP treatment, from 2.6-4.7mm pre-treatment to 3.7-8.2 mm post-treatment, with a statistical significant difference (p-value <0.0001). Regardless of endometrial pathologies, hUC-PRP therapy resulted effective in all cases, being statistically significant in both AS (n = 6, p-value = 0.0020) and TE/EA patients (n = 9, p-value = 0.0016). These results pre and post-treatment were consistent in both centers participating in this clinical trial (center 1: n = 8, p-value = 0.0009 and center 2: n = 7, p-value = 0.0025). Beyond thickness improvements, notable pattern changes were observed in the endometrial tissue. Surprisingly, 90% of patients with non-trilaminar or atrophic endometrium exhibited a transition to a tri-laminar pattern after hUC-PRP treatment. These findings indicate an increasing in the endometrial lining and a restoration of the endometrial pattern after the hUC-PRP administration, which is critical for successful implantation and improved fertility outcomes. This pilot clinical trial has some limitations. The small sample size of 15 patients limits the ability to confirm the conclusions. Additionally, long-term efficacy in fertility outcomes should be investigated. Further studies with larger samples and extended follow-up are also needed. These results highlight the potential of hUC-PRP as an innovative therapy in women with endometrial pathologies (AS/TE/EA), restoring endometrial lining and pattern and offering possible benefits in fertility outcomes. If validated in larger studies, this treatment could become a breakthrough alternative to conventional therapies, improving clinical management and reproductive success. Yes

Bacterial bloodstream infections (BSI) are an important contributor to morbidity and mortality after hematopoietic cell transplant (HCT). Its specific characteristics with the use of post-transplant cyclophosphamide (PTCy) remain poorly defined, particularly in the HLA-matched setting. The objectives were to evaluate the characteristics, incidence, risk factors, and clinical impact of bacterial BSI in patients with hematologic malignancies undergoing HCT from matched related (MSD), matched unrelated (MUD), and haploidentical donors using PTCy-based graft-versus-host disease (GVHD) prophylaxis. We conducted a retrospective single-center analysis of bacterial BSI in 456 patients undergoing HCT. Quinolone prophylaxis was administered during neutropenia, and screening for bacterial colonization was performed during hospitalization, regardless of transplant timing. Median age at HCT was 55 yr, with 63% diagnosed with acute leukemia. HCT was performed with MSD in 40%, MUD in 34% and haploidentical donors in 26%. A total of 159 bacterial BSI episodes were observed in 128 patients. The cumulative incidence of first BSI was 28% at 2 yr at a median time of 11 d (range, 1-694). Regarding timelines, 60% of episode occurred until d +30, 19% between d +31 and +100, 14% between d +100 and one year, and 7% beyond the first year. There was a predominance of gram-negative bacterial infections, particularly in haploidentical HCT during the first 30 d. Multidrug resistance criteria was met in 55% of gram-negative and 47% of gram-positive bacteria. Haploidentical donors were independently associated with early BSI, while grade II-IV acute GVHD increased the risk after d +30. BSI-related mortality accounted for 9% of deaths, and late-onset BSI was associated with inferior OS. In conclusion, bacterial BSI affects over one-fourth of PTCy-based HCT recipients, particularly in the early post-transplant period, with a predominance of gram-negative microorganisms. Haploidentical donors and acute GVHD were independent risk factors for BSI, and late-onset BSI was associated with worse OS.

Post-transplantation cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis regimens may increase the incidence of mold invasive fungal infections (IFI). Nevertheless, data on prophylaxis strategies and donor modalities are heterogeneous, and reports on posaconazole prophylaxis remain limited. The objectives were to characterize mold IFI incidence, risk factors, and impact on outcomes in patients with hematologic malignancies undergoing PTCy-based HCT from matched sibling, matched unrelated, and haploidentical donors under posaconazole prophylaxis. This is a single-center retrospective study of mold IFI episodes in 435 patients undergoing HCT at a single institution. Daily 300 mg posaconazole dosage was given between days +7 and +90 or during GVHD on steroids. Mold IFI affected 6% of patients (16 possible, 8 probable, and 2 proven), with 73% of breakthrough infections. Only Aspergillus spp. was identified. With a median onset of 88 days, the 2-yr cumulative incidence was 5.6% overall and 2.1% for probable/proven mold IFI. Grade II-IV acute GVHD and a higher HCT comorbidity index increased the risk for probable/proven mold IFI. One patient died from mold IFI, although 7% of deaths occurred with active mold IFI. Probable/proven mold IFI negatively impacts on overall survival (OS). Mold IFI is an infrequent complication in allogeneic HCT with PTCy under posaconazole prophylaxis, although acute GVHD significantly increases its risk. While direct mortality is low, OS is negatively impacted by probable/proven mold IFI.

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

Background: Selective IgA deficiency (IgA-D) has been historically considered a high-risk entity for developing allergic/anaphylactic reactions after blood transfusion (AATRs). However, it has been suggested that the IgA-D-related anaphylactic transfusion reaction is not evidence-based. Methods: We conducted three different approaches to collect evidence about epidemiology, AATRs, and transfusion management of patients with IgA-D at La Fe University Hospital. Firstly, we analysed the prevalence of IgA-D in a population of patients diagnosed with acute leukaemia, The second approach consisted of collecting transfusion data from IgA-D patients. Finally, we reviewed the IgA levels of patients recorded in the hemovigilance system suffering an AATR. Results: IgA-D prevalence was 1 in 334 patients. At least one blood component was transfused to 23 patients diagnosed with IgA-D. Plasma was transfused to eight IgA-D patients, while six patients received red blood cells, platelets, and plasma. No adverse reactions were reported in any patient. AATRs occurred in 325 men and 264 women with a median age of 52 years. Severe reactions occurred in 56 patients (1/14,520 components). Mean IgA levels were 215 mg/dL (4–5570) for mild reactions and 214 mg/dL (14–824) for severe reactions (p = ns). Washed platelets were administered to two patients who developed severe and repeated AATRs. Both had normal IgA levels. Conclusions: Since the AATRs related to IgA-D are extremely low, as reported in current hemovigilance systems, IgA-D should not be considered a high-risk entity to develop AATRs. On the contrary, our findings support standard transfusion management of IgA-D patients.

Single-unit red blood cell (1-RBC) transfusion policy has shown to effectively reduce transfusion burden while maintaining comparable clinical outcomes in hematological patients compared to the classical double-unit policy. However, its effects specifically after autologous stem cell transplantation (ASCT) have not been previously studied. We aimed to evaluate the impact of the 1-RBC policy on transfusion burden in a homogeneous cohort of patients undergoing ASCT. We retrospectively compared the transfusion requirements and the clinical outcomes of 187 patients transplanted from May 2019 to December 2022 under a 1-RBC policy, with a historical cohort of 153 patients transplanted from January 2016 to April 2019 under a double-unit policy. The 1-RBC policy was associated with a 32% reduction in RBC utilization and lower number of RBC transfusions at day 30 after transplantation (median 2 versus 3 units; P<0.0001), with an odds ratio of 0.49 in multivariate analysis (P=0.03). However, the number of transfusion episodes remained similar (median of 2 in both arms; P=0.34). No significant differences in length of stay, hemoglobin levels at discharge or 30‐day mortality were observed. In conclusion, transitioning to the 1-RBC represents a straightforward action in current practice that significantly reduces blood transfusions in patients undergoing ASCT, without negatively impacting clinical outcomes.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections.We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type.Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Post-transplant cyclophosphamide, sirolimus and mycophenolate mofetil (PTCy/siro/MMF) constitutes an innovative and well-tolerated acute graft-versus-host disease (aGVHD) prophylaxis after allogeneic stem cell transplantation (allo-HSCT), but risk factors for aGVHD incidence and therapy failure in this setting are scarce. The study prospectively registered all consecutive adult patients with hematologic malignancies who received an allo-HSCT using PTCy/siro/MMF prophylaxis at our institution between 2017 and 2023. A total of 439 patients were included, of whom 40% were transplanted from matched sibiling donors, 34% from matched unrelated donors (MUD) and 26% from haploidentical donors. The 100-day cumulative incidence of grade II-IV and grade III-IV aGVHD was 22% (95% confidence interval [CI] 18–26%) and 11% (95% CI 8–14%), respectively. The use of MUD was associated with decreased risk of severe aGVHD while a diagnosis of myelodysplastic or myeloproliferative neoplasms (MDS/MPN) was deleterious. Among 92 patients receiving first-line systemic corticosteroids, 51% achieved a sustained complete response, while 22% and 23% developed steroid-dependent (SD-aGVHD) and steroid-refractory aGVHD (SR-aGVHD), respectively. Only grade III-IV aGVHD was a predictor of steroid failure. SR-aGVHD was associated with worse salvage treatment response and overall survival compared to SD-aGVHD. The 1-year cumulative incidence of aGVHD-related mortality was 5.7% (95% CI, 3.7–8.2). Risk factors for aGVHD-related mortality included haploidentical donors, older donors, diagnosis of MDS/MPN, and grade IV aGVHD. This study confirms a low incidence aGVHD with PTCy/siro/MMF prophylaxis. SR-aGVHD showed poorer response to salvage therapies and worse survival, while haploidentical donors and older donor age were negative predictors for aGVHD-related deaths.