Cytomegalovirus-driven early-onset lymphocytosis in hematopoietic allogeneic transplant mimicking a T-cell lymphoma progression.

Hepatosplenic T-cell lymphoma (HSTCL) is an uncommon and highly aggressive subtype of peripheral T-cell lymphoma characterized by liver, spleen, and bone marrow involvement. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment for HSTCL, but it carries a significant risk of relapse. Cytomegalovirus (CMV) reactivation is a frequent complication after alloHSCT, particularly in patients undergoing lymphocyte-toxic therapies. A 27-year-old man diagnosed with HSTCL underwent an alloHSCT with active disease after six lines of therapy. A CMV reactivation was successfully treated with foscarnet. A sudden reappearance of symptomatic lymphocytosis (15,550/µL) by day +20, prior to engraftment, raised suspicion of disease progression. A comprehensive diagnostic work-up revealed an oligoclonal expansion of donor lymphocytes along with complete donor chimerism, leading to an alternative diagnosis of a CMV-driven T-cell expansion. This was confirmed by an in vitro assay testing T-cell specificity against CMV. The patient achieved both complete response and complete donor chimerism despite persisting lymphocytosis, but ultimately relapsed. This case highlights the importance of diagnostic tools in understanding disease progression and guiding treatment decisions.

Acute hemolytic reaction by anti-Wra: Case report and review of the hemovigilance database of a tertiary care hospital.

Wra is the most common LIA in white population. The incidence of Wra antigen in Spanish population has been estimated to be 1 in 785 in blood donors, while anti-Wra was found in 2.7 % and 3.6 % of healthy donors and transfused patients respectively. Severe, even fatal hemolytic transfusion reactions and hemolytic disease of the newborn caused by anti-Wra have been reported. Since the reagent red blood cells used for antibody screening usually lack Wra antigen, the anti-Wra is not detected and hemolytic reaction could occur if transfusion is performed by type and screen approach. We report an acute hemolytic reaction due to anti-Wra in a patient with negative antibody screening. We have also reviewed the records of the hospital hemovigilance database in order to collect the previous hemolytic cases due to anti-Wra. During a 21-year period 461,539 red blood cell units have been transfused to 81,614 patients in our hospital. Alloimmnunization was detected in 3840 patients (0.83 %) and anti-Wra was detected in 22 patients (1/3709), 10 of whom had other alloantibodies, and only in 1 occasion (this case) has been implicated in mild hemolytic acute transfusion reaction. In our experience, the risk of fatal hemolytic reaction due to LIA in hospitals with blood services using the type and screen policy is extremely low.

Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Gastric Bleeding in Stem Cell Transplantation: A Focus on Gastric Vascular Ectasia Under Post-Transplant Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil Prophylaxis.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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 days (range, 29-125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-month cumulative incidence of GVE was 5.1%. Older age (≥60 years) 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. CONCLUSIONS: 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.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

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.