Successful treatment of acyclovir-resistant herpes simplex virus infection with amenamevir in a patient who received umbilical cord blood transplantation for T-cell prolymphocytic leukemia.

A 34-year-old woman received umbilical cord blood transplantation for refractory T-cell prolymphocytic leukemia after salvage therapy with alemtuzumab. She developed right angular cheilitis on the 46th day after transplantation, which worsened after receiving systemic steroid therapy for extensive chronic graft versus host disease. The treatment dosage of acyclovir (ACV), ganciclovir, and vidarabine ointment was not effective due to ACV-resistant mutations of the herpes simplex virus type 1 (HSV-1) in the thymidine kinase domain. Foscarnet is expected to be effective against ACV-resistant HSV-1 infection. However, it could not be used because the patient developed renal dysfunction. Several viral thymidine kinase mutations related to ACV resistance were found in the patient's sample. Nevertheless, amenamevir, a helicase-primase complex inhibitor, was effective in our patient who was significantly immunocompromised after allogeneic hematopoietic stem cell transplantation (allo-HSCT). ACV-resistant HSV infection after allo-HSCT is an rare but important complication in the era of low-dose long-term ACV prophylaxis. To date, there is no established treatment against ACV-resistant HSV infection. This case report showed that amenamevir could be a promising treatment option for ACV-resistant HSV infection in patients with renal failure after allo-HSCT.

Three cases of suspected pleuroparenchymal fibroelastosis after allogeneic hematopoietic cell transplantation.

This article reports the clinical course and imaging findings of three cases of suspected pleuroparenchymal fibroelastosis (PPFE) after allogeneic hematopoietic cell transplantation (HCT). All patients complained of dyspnea more than 5 years after HCT, had progressive restrictive deficits on respiratory function tests, and presented with pneumothorax, pleural thickening, or exacerbation of consolidation in the upper lobe of the lung. Though lung biopsy was not done in all three cases, the clinical findings and results of spirometry were compatible with those of PPFE. PPFE has been sporadically reported as a pulmonary complication of allogeneic HCT; however, clinical diagnostic criteria other than histological diagnosis and treatment methods have not yet been established. The accumulation of more cases is necessary to improve the prognosis of PPFE complications.

Clinical Benefit of Low-Dose Antithymocyte Globulin-Thymoglobulin as Graft-versus-Host Disease Prophylaxis in Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation from HLA-Identical Donors.

Graft-versus-host disease (GVHD) is a major complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Previous randomized studies have already shown that the use of several types of antihuman T lymphocyte immune globulin (ATG) as GVHD prophylaxis can reduce the incidence of acute GVHD and chronic GVHD. However, the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG remain unclear. This study aimed to clarify the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG compared with PBSCT from HLA-identical donors without ATG. To do so, we retrospectively analyzed the outcomes of patients who underwent allogeneic PBSCT from HLA-identical donors with low-dose ATG-thymoglobulin (ATG-T; 2.5 mg/kg) versus those who did not receive ATG-T. Patient data were collected retrospectively from the medical records of Anjo Kosei Hospital. This study was conducted from 2009 to the final follow-up in October 2022. Forty-seven of 91 patients received ATG-T between January 2009 and March 2020. ATG-T reduced the incidence rates of moderate-to-severe chronic GVHD (hazard ratio [HR], .15; 95% confidence interval [CI], .057 to .41; P < .0010) and nonrelapse mortality (HR, .21; 95% CI, .0058 to.75, P = .016) without increasing the risk of relapse. Overall survival did not differ significantly between the 2 groups; however, the low-dose ATG-T group had better moderate-to-severe chronic GVHD-free, relapse-free survival rates (HR, .47; 95% CI, .27 to .80, P = .0054) than the non-ATG-T group. In addition, multistate analysis revealed that the low-dose ATG-T group had better current GVHD-free, relapse-free survival at 24 months after transplantation (45% [95% CI, 29% to 63%)] versus 21% [95% CI, 9.1% to 34%]; P = .015). Low-dose ATG-T was not associated with increased incidence of infections or adverse events. Our findings suggest that low-dose ATG-T can be beneficial for patients receiving PBSCT from HLA-identical donors. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Treatment strategies for relapse after CAR T-cell therapy in B cell lymphoma.

Clinical trials of anti-CD19 chimeric antigen receptor T (CART19) cell therapy have shown high overall response rates in patients with relapsed/refractory B-cell malignancies. CART19 cell therapy has been approved by the US Food and Drug Administration for patients who relapsed less than 12 months after initial therapy or who are refractory to first-line therapy. However, durable remission of CART19 cell therapy is still lacking, and 30%-60% of patients will eventually relapse after CART19 infusion. In general, the prognosis of patients who relapse after CART19 cell therapy is poor, and various strategies to treat this patient population have been investigated extensively. CART19 failures can be broadly categorized by the emergence of either CD19-positive or CD19-negative lymphoma cells. If CD19 expression is preserved on the lymphoma cells, a second infusion of CART19 cells or reactivation of previously infused CART19 cells with immune checkpoint inhibitors can be considered. When patients develop CD19-negative relapse, targeting different antigens (e.g., CD20 or CD22) with CAR T cells, investigational chemotherapies, or hematopoietic stem cell transplantation are potential treatment options. However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.

Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response.

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.