[Rinsho ketsueki] The Japanese journal of clinical hematology最新文献

Recent advances in intensive treatment strategies have resulted in an overall treatment rate of approximately 70% for pediatric cancers. The most notable improvement in clinical outcomes has been observed for acute lymphocytic leukemia, with the cure rate increasing from approximately 10% 50 years ago to 90% at present. However, relapsed and refractory cases of childhood leukemia continue to have a poor prognosis, and there is no standard treatment strategy for many cases. Moreover, even in cases with favorable outcomes, growth retardation and endocrine disorders are major complications. To improve the cure rate of pediatric cancers, we have focused on the molecular mechanisms of leukemia, the most common type of pediatric cancer. In this symposium, recent findings on T-cell acute lymphocytic leukemia will be outlined.

Primary immunodeficiency diseases (PID) are caused by abnormalities in molecules involved in the immune system, and there are nearly 500 genes associated with PID. The symptoms are not only susceptibile to infectious diseases but also to autoimmune diseases, malignancies, autoinflammatory diseases, and allergies. Thus, these diseases are considered inborn errors of immunity (IEI) rather than PID. IEI is typically thought to occur in childhood because IEI is associated with a genetic variant, but there are also several adult-onset IEIs. The same 10 warning signs used to diagnose IEI in children are used to diagnose the condition in adults as well, who are then given a definitive genetic diagnosis after a 4-step diagnostic process. In addition to prophylactic antimicrobial agents and immunoglobulin replacement therapy, allogeneic hematopoietic cell transplantation (HCT) is performed as a curative therapy in some patients with IEI. However, in adult patients with IEI, HCT may have to be stopped due to complications. Adult patients with IEI need to be promptly assessed for HCT, and HCT must be done before complications increase.

A tyrosine kinase inhibitor (TKI) was used to treat the patient, a 35-year-old woman who was diagnosed with chronic myeloid leukemia at the age of 22 years. Since a four-year deep molecular response (DMR) was obtained, spontaneous pregnancy was planned under TKI withdrawal. Even though her disease had advanced to MR2.0 at the time of pregnancy confirmation, 2 months from TKI cessation, interferon α therapy was initiated in light of the patient's history. Later, the patient reached MR3.0, gave birth to a healthy baby, and maintained MR3.0-4.0. TKI was resumed after about 6 months of breastfeeding. Treatment-free remission (TFR) is required for natural conception despite the teratogenicity and miscarriage risks associated with BCR::ABL1 TKIs. When planning a pregnancy, it is also necessary to take the patients' backgrounds, disease states, and medical history into account.

A 62-year-old male patient was admitted for close monitoring of anemia (hemoglobin level, 8.2 g/dl). Hemolytic anemia was observed; however, the direct antiglobulin test (DAT) result (standard tube method) was negative. Nevertheless, autoimmune hemolytic anemia (AIHA) was still suspected; therefore, a DAT (Colum method) and quantifying levels of red-blood-cell bound immunoglobulin G were performed, resulting in a definite diagnosis of warm AIHA. The patient also had an acute kidney injury (AKI) from the time of admission, which was poorly improved by supplemental fluids therapy alone. Therefore, renal biopsy was performed. Renal biopsy revealed acute tubular injury due to hemoglobin columns, and a diagnosed AKI caused by hemolysis due to AIHA. Following the definitive diagnosis of AIHA, the patient was treated with prednisolone, and after approximately 2 weeks, the anemia and nephropathy completely improved, which is maintained to this day. We report this case as a rare case of AKI induced by hemolysis of AIHA and a successful case of renal salvage by early administration of steroid.

A 93-year-old woman was diagnosed with lymphoplasmacytic lymphoma (LPL) with circulating tumor cells in her peripheral blood after presenting with anemia. LPL progressed eight months later, with anemia worsening and tumor cells increasing to 66% of leukocytes. She began tirabrutinib at a low dose (80 mg daily: 17% of the standard dose) because she preferred to maintain her quality of life (QOL). Within three weeks, she was free of transfusion dependency and had a partial response with the disappearance of peripheral tumor cells. The dosage of tirabrutinib was increased to 240 mg daily because it was well tolerated. She has been on the treatment for 13 months with no adverse effects. Tirabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, has been reported to have promising efficacy for LPL, but it also has a high incidence of dermatological toxicity, which may impair QOL. Low-dose tirabrutinib initiation may be effective and assist elderly patients with LPL in maintaining their QOL.

A rare kind of malignant lymphoma, called primary effusion lymphoma (PEL) is associated with human herpesvirus 8 (HHV-8), and characterized by lymphomatous effusion in the bodily cavities. Although the initial clinical presentation of primary effusion lymphoma-like lymphoma (PEL-LL) is similar to that of PEL, PEL-LL is HHV-8 negative and has a favorable prognosis. A PEL-LL diagnosis was made after an 88-year-old man was admitted to our hospital with a pleural effusion. His disease regressed after effusion drainage. He demonstrated disease progression to diffuse large B-cell lymphoma after two years and ten months. Our example demonstrates that aggressive B-cell lymphoma can develop from PEL-LL.

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.

Large-scale in vitro red blood cell (RBC) production has been attempted in recent years. Potential cell sources for RBC production include hematopoietic stem/progenitor cells, pluripotent stem cells, and immortalized erythroid progenitor cell lines, which can induce enucleated RBCs with characteristics such as oxygen-carrying capacity and deformability. A phase I clinical study of cultured RBCs produced from hematopoietic stem/progenitor cells has revealed a similar in vivo half-life between cultured and native RBCs. Thus, the application of cultured RBCs in blood transfusion is gradually advancing. However, a single transfusion requires a large number of cells, unlike other cell therapies. Therefore, developing a method to mass-produce RBCs from a small culture volume at a low cost is important in the future. This review summarizes the current status and prospects concerning in vitro RBC production using each cell source, which can improve future transfusion medicine.