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.

Clonal hematopoiesis of a novel dic(18;20) clone following allogeneic hematopoietic stem cell transplantation.

A 55-year-old man in first complete remission of acute myeloid leukemia with a normal karyotype underwent allogeneic hematopoietic stem cell transplantation from a human-leukocyte-antigen-matched sibling. Bone marrow examination on day 28 confirmed complete remission, but G-banding analysis revealed a novel chromosomal abnormality, including dic(18;20)(p11.2;q11.2). The patient developed moderate chronic graft-versus-host disease on day 174, and the abnormal clones identified by dic(18;20) significantly increased after that point. Chimerism testing repeatedly confirmed complete donor type. Although next-generation sequencing showed no clonal hematopoiesis-related gene mutations, copy number analysis of the donor and the recipient revealed copy number deletion of 18p, 18q, and 20q. The patient has maintained remission for more than 2 years to date without developing a hematologic neoplasm or cytopenia. The distinctive clonal hematopoiesis with a dicentric chromosome seemed to have undergone the breakage-fusion-bridge cycle, which could cause the complex events of deletion, amplification, and inversion. These copy number alterations might have increased the number of clones with growth advantage, and the highly inflammatory environment in the recipient due to graft-versus-host disease might have contributed to the clonal selection.

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.

[Intestinal pneumatosis developed during the treatment of severe gastrointestinal graft-versus-host disease after cord blood transplantation].

A 62-year-old female developed stage4 gastrointestinal graft-versus-host disease (GVHD) on day 109 following an allogeneic cord blood transplant for relapsed refractory angioimmunoblastic T-cell lymphoma. GVHD went into remission 4 weeks after receiving the steroid (mPSL 1 mg/kg), but abdominal bloating started to emerge at the same time. A diagnosis of intestinal pneumatosis was made on day 158 after a CT scan revealed submucosal and serosal pneumatosis in the entire colon, and intestinal pneumatosis was identified as the cause. Fasting and reducing steroid use have helped. the abdominal symptoms, and the pneumatosis disappeared on day 175. No more flare-ups occurred, and the steroid was successfully stopped. After allogeneic transplantation, intestinal pneumatosis is a rather uncommon complications. Its pathogenesis is thought to be influenced by GVHD or steroids. Treatments for the disease may be incompatible with one another, and the response in individual cases needs to be studied in detail.

[Complete remission after standard induction therapy in a patient with acute myeloid leukemia associated with double-minute chromosomes].

Acute myeloid leukemia (AML) associated with double-minute chromosomes (dmin) is a rare condition and has a poor prognosis. A 68-year-old man with leukocytosis and thrombocytopenia was admitted to our hospital. Bone marrow aspiration showed that 79.5% of myeloblasts were positive for myeloperoxidase. The patient was diagnosed with acute myeloid leukemia (French-American-British classification: M2, World Health Organization classification: AML, not otherwise specified, AML with maturation). Chromosomal analysis revealed the presence of dmin: 45, X, -Y, 5-33 dmin. Fluorescence in situ hybridization revealed multiple MYC signals, and spectral karyotyping showed that dmin was derived from chromosome 8. These findings indicated resistance to chemotherapy alone. After the standard induction therapy with daunorubicin and cytarabine, the number of myeloblasts in the bone marrow decreased, and the amplified MYC signals disappeared. Then, the patient achieved complete remission. Reportedly, most patients with AML correlated with dmin have a complex karyotype, except for this case. Owing to the absence of a complex karyotype, the patient had good sensitivity to chemotherapy. Further studies with a larger population of patients with AML associated with dmin, but without complex karyotypes, should be conducted to accurately predict prognosis in such cases.

Severe tumor lysis syndrome during the induction therapy for the treatment of blastic plasmacytoid dendritic cell neoplasm arising from myelodysplastic/myeloproliferative neoplasms.

BPDCN shows clinically heterogeneous characteristics. And as other hematological malignancies, symptoms of BPDCN suggesting a high tumor burden, such as high white blood cell count or splenomegaly, should be carefully considered to prevent TLS.