Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity following allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP), which exposes mononuclear cells to ultraviolet A irradiation in the presence of a photosensitizing agent, has shown efficacy in the treatment of GVHD. Recent observations in molecular and cell biology have revealed the mechanisms by which ECP can reverse GVHD, including lymphocyte apoptosis, differentiation of dendritic cells from circulating monocytes, and modification of the cytokine profile and T cell subpopulations. Technical innovations have made ECP accessible to a broader range of patients; however, logistical constraints may limit its use. In this review, we scrutinize the development of ECP from its origins to recent insights into the biology underlying ECP efficacy. We also review practical aspects that may complicate successful ECP treatment. Finally, we analyze how these theoretical concepts translate into clinical practice, summarizing the published experiences of leading research groups worldwide.

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.

The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1–2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4–5 events. The 9-year CI of grade 1–2 cardiac failure was 1.3%, grade 3–4 was 15%, and grade 5 was 2.1%; of grade 1–2, arrhythmia was 1.9%, grade 3–4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3–4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis. Furthermore, we analyze risk factors for BK-HC and its impact on renal function and transplant outcomes. Retrospective analysis of BK-HC episodes in patients undergoing HSCT from 167 MSD, 129 MUD and 103 HAPLO from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus and mycophenolate mofetil was given, irrespective of donor type or conditioning intensity, and mesna was used prophylactically with PTCy. The incidence of grade 2-4 BK-HC was 23%, with a higher prevalence of grades 3-4 in HAPLO (19%), compared to MSD (11%) and MUD (8%) recipients (p=0.02). BK-HC was diagnosed at a median of 29 days after HSCT and symptoms persisted for a median of 27 days, with longer duration in grade 3-4 cases (p=0.02). Additionally, higher grades were associated with a greater transfusion burden (p<0.001). JC virus coinfection was detected in 24%, and cytomegalovirus viruria in 17%, which was not treated. BK antiviral treatment beyond supportive care was used in only two patients, while antibacterial treatments were prescribed in 28% for urinary symptoms and in 57% for concomitant infections in other sites. Younger age and HAPLO donors were significant risk factors for developing higher-grade BK-HC. No interaction was seen between age and conditioning intensity. Importantly, BK-HC did not significantly impact overall survival or graft-versus-host disease-free relapse-free survival as a time-dependent variable, as well as non-relapse mortality. Furthermore, BK-HC patients maintained stable creatinine renal clearance at 1 year post-transplant. BK-HC is a relatively early frequent complication in allogeneic HSCT with PTCy, especially in HAPLO recipients, with symptoms typically lasting a median of three weeks. Supportive care remains the mainstay of treatment, while specific antiviral treatments are rarely needed. The role of cidofovir and concomitant CMV viruria treatment are yet to be established. Our findings suggest that BK-HC does not significantly impact transplant outcomes and renal function.