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

A 69-year-old man presented with lumbago and was diagnosed with multiple myeloma (IgD-λ type, R-ISS stage II) with bone-destructive lesions in the lumbar spine and sacrum. Chromosome analysis showed t (8;14)(q24;q32) and t (11;14)(q13;q32). Treatment with daratumumab, lenalidomide, and dexamethasone resulted in partial response, but the disease relapsed, with a copy number increase in t (11;14) and abnormal amplification of the 1q21 region. The patient was treated for CMV enteritis, and was admitted to the hospital due to sudden abdominal pain. Gastrointestinal perforation was diagnosed by CT scan showing free air and wall thickening in the small intestine. Emergency surgery was performed, and the tumors in the perforated area were positive for CCND1 but negative for MYC on immunostaining. The patient's general condition did not improve after the surgery and he died. Pathological autopsy revealed extramedullary infiltration of multiple organs in addition to the small intestine. Extramedullary infiltration is thought to be caused by clonal evolution, and further research is warranted to clarify its pathogenesis and establish effective therapeutic strategies in high-risk patients.

A 43-year-old man with pancytopenia was diagnosed with acute promyelocytic leukemia (APL). On the first day of induction therapy with all-trans retinoic acid (ATRA) alone, he presented with high fever and was found to have coronavirus disease 2019 (COVID-19) infection by SARS-CoV2 antigen test. While it is generally recommended to delay treatment for APL patients with COVID-19 unless urgent APL treatment is required, this patient needed to continue treatment due to APL-induced disseminated intravascular coagulation (DIC). Considering the challenge of distinguishing between differentiation syndrome (DS) and COVID-19 exacerbation, the ATRA dosage was reduced to 50%. The patient was able to continue treatment without development of DS or exacerbation of DIC, leading to his recovery from COVID-19 and remission of APL.

The addition of the thrombopoietin receptor agonist eltrombopag to immunosuppressive therapy (IST) with horse antithymocyte globulin and cyclosporin A has improved response to initial therapy for aplastic anemia, but about one-third of patients still require allogeneic hematopoietic stem cell transplantation (HSCT) due to resistance or relapse. Allogeneic HSCT as initial therapy is indicated when the patient is younger than 40 years of age (especially <20 years) and has an HLA-matched sibling donor. On the other hand, fulminant aplastic anemia, in which the neutrophil count is 0 even with G-CSF administration, requires transplantation regardless of donor type. When an HLA-matched donor is not available and an early transplant is needed, cord blood transplantation and haploidentical transplantation are options. In the past few years, haploidentical transplantation with post-transplantation cyclophosphamide (PTCY) as GVHD prophylaxis has been shown to produce favorable outcomes in patients with aplastic anemia. A retrospective study in Japan also showed a good engraftment rate after haploidentical transplantation with PTCY. This review discusses transplant indications for aplastic anemia and selection of donor type and conditioning regimen.

Primary central nervous system lymphoma (PCNSL) is a B-cell lymphoma confined to the CNS. In general, early initiation of treatment after diagnosis is considered to be associated with improved prognosis in patients with malignancy. However, the prognostic impact of the time from diagnostic brain biopsy to initiation of treatment in patients with PCNSL remains unclear. In this study, we retrospectively analyzed how time from diagnostic biopsy to rituximab-containing treatment correlated with prognosis in 19 patients with PCNSL. Patients with a better prognostic score defined by age and performance status at diagnosis tended to have a better prognosis if chemotherapy was initiated sooner after brain biopsy. In conclusion, earlier chemotherapy initiation after brain biopsy and definitive diagnosis should be considered in the treatment of PCNSL.

Myelodysplastic neoplasms (MDS) are clonal hematological malignancies arising from gene mutations. Immunosuppressive therapies (IST) are effective in lower-risk MDS (LR-MDS) with characteristics such as hypoplastic marrow with low blasts or low ring sideroblasts, and with a small increase of PNH clones or decrease of megakaryocytes. Differential diagnosis of these LR-MDS cases from AA can be difficult, and precise diagnosis requires careful evaluation of bone marrow cellularity and dysplasia. To decide on an appropriate treatment strategy for LR-MDS, it is important to evaluate the underlying pathology, and preferentially select IST as first-line therapy in patients with features that indicate immune-mediated bone marrow failure.

The prognosis of hematopoietic diseases has been improving over the past several decades, and measures to fulfill patients' wishes to have children are needed to improve survivors' quality of life. In Japan, the Japan Society for Fertility Preservation has taken the lead in developing guidelines, a national registry, and a nationwide uniform subsidy system. When considering fertility preservation in patients with hematopoietic diseases, interdisciplinary collaboration between oncology and onco-fertility is necessary to solve problems specific to hematopoietic diseases, such as the short time window between the onset of disease and the start of treatment, complications associated with fertility preservation treatment such as bleeding or ovarian hyperstimulation syndrome, and contamination of collected tissue with hematopoietic tumor cells. This article outlines the basic concept of fertility preservation in patients with hematopoietic diseases and recently established strategies for women with chronic myelogenous leukemia. It will also share some treatment innovations that can be considered in cases when fertility preservation treatment may be challenging.

Tisagenlecleucel, a commercially available CD19-targeted CAR-T cell product, has dramatically changed the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). Tisagenlecleucel infusion has been linked to distinct acute adverse events, including cytokine release syndrome, neurotoxicity, hemophagocytic lymphohistiocytosis and prolonged pancytopenia, which are rare with cytocidal chemotherapy. In addition, recent retrospective studies have revealed pre-infusion prognostic factors including high tumor burden (bone marrow leukemia cell fraction ≥5%) and non-response to blinatumomab, another CD19-targeting agent. Not only physicians providing CAR-T cell therapy but also those referring patients for this therapy should thoroughly understand the indications and limitations, characteristic acute complications, pre-treatment factors affecting prognosis, and late complications. This article outlines the current understanding regarding the use of tisagenlecleucel in children and adolescents with B-ALL.

Flow cytometry (FCM) remains an essential test in the diagnosis of leukemia despite advances in genomic testing. However, the role of FCM results as a risk factor is already extremely limited. International diagnostic criteria for leukemia already prioritize diagnosis based on genetic abnormalities, with FCM diagnosis only serving as an aid to morphological diagnosis for subtypes without genetic abnormalities. However, rapid lineage diagnosis of leukemia by FCM remains important for selecting initial treatment. FCM is also an important tool for evaluating response to molecular targeted therapy, which requires repeated measurements and rapid results. Furthermore, FCM enables prediction of specific genetic abnormalities by immunophenotypic patterns, which could make it useful for verifying the clinical impact of genetic abnormalities detected by multi-gene panel testing.

Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Survival outcomes for FL have improved since the introduction of anti-CD20 monoclonal antibodies, such as rituximab, and median overall survival has reached 15-20 years. However, FL is an incurable disease that subsequently progresses or relapses, and progression-free and overall survival tend to shorten with repeated relapses. For patients with limited-stage disease, radiation therapy is generally the treatment of choice and results in a median survival of approximately nearly 20 years. For advanced-stage patients with low tumor burden, watchful waiting continues to be the appropriate strategy at present. It remains unclear whether rituximab monotherapy might change this watchful waiting approach and result in a benefit from early intervention in patients with low tumor burden. For advanced-stage patients with high tumor burden, chemoimmunotherapy including rituximab or obinutuzumab followed by maintenance therapy is the standard treatment. For relapsed or refractory patients, treatment options such as chemoimmunotherapy, lenalidomide-rituximab, tazemetostat, chimeric antigen receptor T-cell therapies, and CD3/CD20 bispecific antibodies are available or in development. This review presents current standard treatments, recent advances, and future perspectives on the management of FL.

EVI1 is a zinc finger transcription factor encoded by the MECOM locus and is essential for the development and maintenance of hematopoietic stem cells. However, overexpression of EVI1 in various myeloid malignancies is associated with aggressive clinical behavior and poor outcome. The locus encodes multiple isoforms that are differentially acting and independently regulated. EVI1 interacts with a variety of transcription and epigenetic factors via different domains. It also regulates cell survival, differentiation, and proliferation through a variety of mechanisms, including transcriptional activation and repression, regulation of other transcription factors' activity, and chromatin remodeling. While the mechanism by which 3q26 translocation leads to high EVI1 expression through enhancer hijacking of genes active in myeloid development is now better understood, regulation of EVI1 expression in the absence of chromosomal translocations and in normal hematopoiesis remains unclear. Recent studies have provided insight into the regulatory mechanisms of EVI1 expression and action, which may lead to development of targeted therapies in the near future.