BK virus reactivation increases the likelihood of hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplant (HCT). In this study, we aimed to identify predictive and risk factors associated with the increased occurrence of this condition following HCT. On a group of 124 patients aged ≤71 years old (median 40 years) who underwent HCT, we analyzed sex, age, time from diagnosis to transplantation, type of conditioning, donor’s relationship, age, and sex, the impact of immunosuppression with different drugs, and acute and chronic GVHD, BK viremia and viruria as potential factors increasing the risk of BK-related HC after HCT. HC occurred among 24 patients (24/124; 29.2%). A significant correlation was observed between HC incidences after HCT, BK viremia and viruria, and acute GVHD occurrence. Furthermore, the level of BKV DNA in serum at day +21 (>0.75 × 103) significantly impacted the patients’ survival time. According to our results, the likelihood ratio of BKV-DNA on day +21 in serum is 6.25, indicating that this diagnostic test has the potential to be utilized in a clinical setting. These findings may be used as a voice in the discussion on implementing an optimal preemptive treatment in BKV reactivation after allogeneic HCT.
Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies.
Anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) are two frequently utilised strategies in graft-versus-host disease (GvHD) prophylaxis following allogeneic hematopoietic cell transplantation (allo-HCT), currently approved for different recipient-donor settings. In addition, being efficacious in preventing GvHD owing to their T-cell depleting capacity, the employment of these two agents increases the risk of infections, including CMV reactivation, which stands as one of the most common and serious infections following allo-HCT. We performed a systematic literature review of articles published until 1 September 2023, through PubMed, MEDLINE, and Scopus, with the main endpoint being CMV reactivation after PTCy or ATG allo-HCT. The majority of the studies included in the analysis provide supporting evidence for a reduced risk of CMV reactivations following the use of PTCy compared to ATG, although not all findings reached statistical significance. Additionally, it appears that utilising a haploidentical donor leads to a higher incidence of CMV infections and clinically significant CMV infections (CS-CMVis) compared to other donor settings in PTCy allo-HCT. This study aims to compare the risk of CMV infections following allo-HCT in patients who have received either ATG or PTCy as GvHD prophylaxis and discuss other factors that could influence the infectious outcomes of patients who have undergone allo-HCT.
Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) - potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle. This makes leukemic stem cells resistant to most known treatment approaches. The role of HIFs in solid tumors and leukemia makes them almost ideal targets for an anticancer treatment. Although the first attempts with new molecules are encouraging, there is a need to investigate the ambiguous role of HIFs to develop a modern antileukemic treatment.