CCL22 mutations in large granular lymphocytic leukemia.

Not available.

Successful treatment by glecaprevir/pibrentasvir followed by hepatoprotective therapy of acute chronic hepatitis exacerbation caused by daratumumab-based regimen for multiple myeloma: Case report and review of the literature.

Hepatitis C virus (HCV) exacerbation is relatively rare as compared with hepatitis B virus reactivation in patients treated with immunosuppressive or anticancer drugs. We herein present the first reported case of acute exacerbation of chronic hepatitis in a patient with HCV persistent infection caused by combination treatment with daratumumab (DARA), bortezomib, and dexamethasone (DVd therapy). A 79-year-old woman diagnosed as having chronic HCV infection 11 years prior without successful viral elimination was referred to our hospital for the treatment of acute liver injury. Multiple myeloma (MM; IgG-κ type) was diagnosed two years before referral and subjected to several treatments. She had commenced DVd therapy four months prior to admission. Since her liver enzymes did not normalize with drug discontinuation and hepatoprotective therapy, we suspected HCV exacerbation and began direct-acting antiviral (DAA) treatment with glecaprevir/pibrentasvir (GLE/PIB). Soon afterwards, her liver enzymes normalized, and she achieved a sustained virological response after 8 weeks of treatment. Clinicians should bear in mind HCV exacerbation when encountering chronic HCV with acute liver injury under MM treatment including a DARA-based regimen. In such cases, DAA therapy is an option when other urgent treatments are needed.

[Successful treatment of X-linked sideroblastic anemia with ALAS2 R452H mutation using vitamin B6].

A 45-year-old man presented with fatigue and pain in the finger joints. Despite having a history of suspected sideroblastic anemia since the age of 18 years, he had not been followed up for years. Upon presentation, laboratory data revealed microcytic anemia and elevated serum ferritin levels. In addition, ringed sideroblasts were increased in the bone marrow. A liver biopsy revealed hemochromatosis and cirrhosis. Furthermore, genetic analysis revealed that he harbored the ALAS2 R452H mutation, leading to the diagnosis of X-linked sideroblastic anemia (XLSA). Accordingly, oral folate or vitamin (Vit) B12 was administered, but his anemia did not respond. However, his hemoglobin level increased from 7 to 11 g/dl with an additional prescription of oral VitB6, which facilitated the patient to undergo phlebotomy to ameliorate organ dysfunctions caused by iron overload. Previous research has revealed that ALAS2 R452 mutations confer poor responses to VitB6 therapy. Hence, accrual of patients with an unexpectedly better response, which was observed in our case, may help elucidate the pathogenesis of and therapies for XLSA.

Acute leukemias in pregnant women: Results of a retrospective study at a local tertiary-care hospital in Japan.

Leukemia may rarely develop in a woman during pregnancy, posing clinical challenges to the patient, fetus, family, and medical staff managing malignancy and pregnancy. We retrospectively analyzed cases of pregnancy-associated leukemia consecutively diagnosed and treated at a local tertiary-care hospital in Nagano, Japan, over the past 20 years. Five cases were identified among 377,000 pregnancies in the area (one in every 75,000 pregnancies), all involving acute leukemia (three acute myelogenous leukemia [AML] and two acute lymphoblastic leukemia [ALL]). The cases were diagnosed in the first trimester (n = 1), second trimester (n = 3), or third trimester (n = 1). There were no apparent pregnancy-associated delays in diagnosing and treating the cases. Three patients underwent induction chemotherapy during pregnancy, two of whom eventually delivered healthy babies. One of the five patients chose abortion before chemotherapy initiation. Two cases showing high-risk features at the diagnosis (AML with an FLT3-ITD mutation [n = 1] and relapsed ALL [n = 1]) eventually died despite consolidative allogeneic hematopoietic stem cell transplantation. Our results suggested that patients with pregnancy-associated acute leukemia can be treated similarly to nonpregnant patients, although pregnancy imposes particular clinical challenges that should be resolved with multidisciplinary care.

T cell clonal expansion and STAT3 mutations: a characteristic feature of acquired chronic T cell-mediated pure red cell aplasia.

Acquired chronic pure red cell aplasia (PRCA) develops idiopathically or in association with other medical conditions, including T cell large granular lymphocytic leukemia (T-LGLL) and thymoma. T cell dysregulation is considered a cardinal pathogenesis of PRCA, but genetic-phenotypic associations in T cell abnormalities are largely unclear. We evaluated an extended cohort of 90 patients with acquired PRCA, including 26 with idiopathic, 36 with T-LGLL-associated and 15 with thymoma-associated PRCA, for their T cell immuno-phenotypes, clonalities and STAT3 mutations. TCR repertoire skewing of CD8+ T cells was detected in 37.5% of idiopathic, 66.7% of T-LGLL-associated and 25% of thymoma-associated PRCA patients, and restriction to Vß1 was most prominent (41%). Clonalities of TCRß or γ chain and STAT3 mutational status were statistically associated (P = 0.0398), and they were detected in all three subtypes. The overall response rate to cyclosporin A was 73.9%, without significant difference by subtypes nor STAT3 mutational status. The T cell dysregulations, such as TCR repertoire skewing with predominant Vß1 usage, clonality and STAT3 mutations, were frequently found across the subtypes, and the close associations between them suggest that these T cell derangements reflect a common pathophysiological mechanism among these PRCA subtypes.

Comparative analysis of humoral responses to BNT162b2 vaccine among patients with hematologic disorders and organ transplant recipients.

Vaccination against SARS-COV-2 is considered the most promising approach to curbing the pandemic. Patients with an immunocompromised state, such as those with hematological malignancies and organ transplantation recipients, are considered more susceptible to infection, but these at-risk patients were underrepresented in early clinical trials for vaccination. Although a growing body of studies suggests that the humoral response to COVID-19 vaccination in each of these at-risk groups of patients may be suboptimal in comparison to healthy controls, a clinical and strategic information for the further comparative analysis among these groups is not fully described. The humoral responses after two doses of BNT162b2 vaccination were evaluated in a total of 187 patients either with allogeneic hematopoietic transplantation, with renal transplantation, with anti-CD20 antibody therapy, or with anti-CD38 antibody therapy, and in 66 healthy controls. The early response at one to three months after vaccination was significantly inferior among patients with renal transplantation, patients with anti-CD20 antibody therapy, and patients with anti-CD38 antibody therapy in comparison to healthy control. But the patients with allogeneic hematopoietic transplantation showed early humoral response comparable to healthy control. The late response at 6 months after vaccination was still suboptimal among patients with renal transplantation and patients with anti-CD20 therapy. Among our patient group, renal transplant recipients had the lowest antibody titers after vaccination regardless of timing of vaccination. Patients who had received allogeneic hematopoietic transplantation attained a comparable serological response to the control group especially if they are vaccinated >300 days after transplantation, but the response was suboptimal if the vaccination was within 300 days after transplantation. Our results may provide policy makers with critical information for the further stratification of at-risk groups, helping contribute to a better allocation of resources, including additional booster vaccination.

A novel germline GATA2 frameshift mutation with a premature stop codon in a family with congenital sensory hearing loss and myelodysplastic syndrome.

GATA2 is a zinc-finger transcription factor regulating early hematopoiesis and developmental processes. Heterozygous germline mutations in GATA2 underlie a pleiotropic autosomal dominant disorder, GATA2 deficiency syndrome. The wide spectrum of its clinical features involves familial predisposition to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) and multiorgan dysfunction, including congenital sensorineural hearing loss (CSHL). We herein report a pedigree with a novel germline frameshift mutation presenting as CSHL and familial MDS. The proband was a 46-year-old man, and his daughter also presented with an identical set of clinical syndromes. Target DNA sequencing identified a novel eight-nucleotide duplicative insertion at exon 5 (NM_032638.4:c.1126_1133dup:p.Lys378Asnfs*12)　of the GATA2 gene. RT-PCR and subcloning analysis showed that the frameshift might result in a truncated mutation with an early stop codon without interfering with the predicted splice site. The predicted mutant protein had 388 amino acids and in silico analysis showed the variant was considered deleterious. This mutation was not detected in unaffected family members. Its deleterious effect is highly likely to have portended the familial MDS and CSHL in this pedigree. Genetic testing among suspected individuals may be warranted for adequate management, including timely transplantation.

Magnetic Resonance Imaging-negative, Rituximab-resistant Neurolymphomatosis as a Paradoxical Presentation of Relapsed Primary Adrenal Lymphoma.

Primary adrenal lymphoma (PAL) is rare and known to have a predilection for central nervous system (CNS) relapse. A 70-year-old man with a 2-year history of primary aldosteronism presented because of a fever. He was hypotensive, and his adrenal glands were unequivocally enlarged. PAL was diagnosed. Despite showing an initial response to immunochemotherapy, progressive paralysis ensued. Magnetic resonance imaging findings were negative, and rituximab was ineffective. His debilitated condition hindered further chemotherapy. A postmortem examination revealed lymphoma relapse in the systemic peripheral nerves. The sequential presentation of two rare lymphomas implies that PAL might have a predilection for not only the CNS but also peripheral nerves.

Persistent Infection of Drug-resistant Influenza A Virus during Chemotherapy for Malignant Lymphoma.

We herein report the case of an 80-year-old man with malignant lymphoma who became persistently infected with influenza A virus. Although he was repeatedly treated with NA inhibitors, such as oseltamivir or peramivir, nasal cavity swab tests for influenza A antigen continued to be positive for more than 2 months. Virological analyses revealed that he was infected with the NA inhibitor-resistant A (H3N2) virus possessing an R292K substitution in the NA protein. These findings suggest that a drug-resistant influenza virus strain might selectively survive antiviral therapy in elderly patients with refractory malignant lymphoma undergoing multiple chemotherapies.