Negative impact of immunoparesis in response to anti-SARS-CoV-2 mRNA vaccination of patients with multiple myeloma.

Multiple myeloma reduces cellular and humoral immunity. Optimal prediction of antibody response to anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients with MM and related disorders is essential to prevent coronavirus disease 2019 (COVID-19) during the SARS-CoV-2 pandemic. This study analyzed the humoral response to the anti-SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccine and its associated factor in 83 patients from June to November 2021 at seven member institutions of the Kyoto Clinical Hematology Study Group.

Real-world data on induction therapy in patients with transplant-ineligible newly diagnosed multiple myeloma: retrospective analysis of 598 cases from Kansai Myeloma Forum.

To investigate the real-world clinical outcomes and management of novel drug-containing therapies for newly diagnosed multiple myeloma (MM) patients, we retrospectively analyzed data on the first-line treatment for newly diagnosed transplant-ineligible MM patients from Kansai Myeloma Forum, a registry network in Japan. A total of 598 patients treated with novel drugs between March 2007 and February 2018 were analyzed. Regimens used were VD (n = 305), Rd (n = 103), VMP (n = 97), VCD (n = 71), and VRd (n = 22).

Pretreatment serum level of interleukin-6 predicts carfilzomib-induced hypertension in relapsed/refractory multiple myeloma.

Carfilzomib (CFZ) constitutes powerful combinatory therapy for relapsed/refractory multiple myeloma (RRMM); however, cardiovascular adverse events (CVAEs) have been shown as major treatment obstacles with the use of CFZ. Along with our multi-institutional prospective observational study by the Kyoto Clinical Hematology Study Group on the efficacy and safety of CFZ-based treatments (UMIN000025108), we here performed an ad hoc analysis of CFZ-related CVAEs in 50 patients with RRMM. We analyzed the association between CFZ-related CVAEs and pre-planned examinations, including patients' background, electrocardiographic findings, echocardiographic findings, and serum/plasma levels of 18 potential candidate biomarkers.

Prognostic impact of resistance to bortezomib and/or lenalidomide in carfilzomib-based therapies for relapsed/refractory multiple myeloma: The Kyoto Clinical Hematology Study Group, multicenter, pilot, prospective, observational study in Asian patients.

Background: Combinatory strategies with carfilzomib (CFZ), a second-generation proteasome inhibitor, plus dexamethasone (DEX) with or without lenalidomide (LEN) have shown promising efficacy for patients with relapsed/refractory multiple myeloma (RRMM) in pivotal clinical trials. However, their effects on patients who were resistance to bortezomib (BTZ) and/or LEN have not been fully evaluated in a daily practice setting.

Aims: To evaluate the real-world efficacy and safety of CFZ-based treatments; that is, CFZ with LEN plus DEX (KRD therapy) and CFZ with DEX (KD therapy), in Asian patients, we conducted a multicenter pilot prospective observational study in the Kyoto Clinical Hematology Study Group.

Retrospective multi-center study of Adolescent and Young Adult (AYA) Multiple Myeloma in Kansai Myeloma Forum registry.

We retrospectively analyzed the clinical features and outcomes in a real-world cohort of adolescents and the young adult (AYA) patients (age between 16 and 39 years) with symptomatic multiple myeloma (MM) registered with the Kansai Myeloma Forum. 26 patients had been diagnosed as symptomatic MM out of 3284 patients. The prevalence of AYA-MM was 0.

Second primary malignancy after rituximab-containing immunochemotherapy for diffuse large B cell lymphoma.

Extended post-therapy long-term survival of patients with diffuse large B cell lymphoma (DLBCL) may also lead to an increase of late adverse events. We retrospectively investigated the frequency and clinical manifestation of second primary malignancy (SPM) after rituximab-containing immunochemotherapy in patients with DLBCL treated at seven institutes belonging to the Kyoto Clinical Hematology Study Group (KOTOSG) from the perspective of the existence of past or synchronous cancer history. In a median follow-up period of 899 days, 69 SPMs were observed in 58 of 809 patients.

Retrospective analysis of plasmacytoma in Kansai Myeloma Forum Registry.

We retrospectively analyzed 51 patients with solitary plasmacytoma diagnosed from October 2002 to September 2018 from a cohort of 3575 patients with plasma cell dyscrasias registered in the Kansai Myeloma Forum. Twenty-seven patients had solitary bone plasmacytoma (SBP) and 24 had extramedullary plasmacytoma (EMP), with prevalence of 0.8% and 0.

Effect of allogeneic hematopoietic cell transplantation for patients with T-prolymphocytic leukemia: a retrospective study from the Adult Lymphoma Working Group of the Japan Society for hematopoietic cell transplantation.

Alemtuzumab is the treatment choice for patients with T-prolymphocytic leukemia (T-PLL). However, patients with T-PLL have a poor prognosis, and the option of allogeneic hematopoietic cell transplantation (HCT) remains controversial in these patients. This study aimed to analyze the outcomes of allogeneic HCT among patients with T-PLL to identify the potential clinical efficacy of allogeneic HCT.

Combined rituximab, bendamustine, and dexamethasone chemotherapy for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma: a multicenter phase II study.

This multicenter phase II study (UMIN000008145) aims to investigate the efficacy and safety of six cycles of combination therapy (RBD) comprising rituximab, bendamustine, and dexamethasone (DEX) for relapsed or refractory (RR) indolent B-cell non-Hodgkin lymphoma (B-NHL) and mantle cell lymphoma (MCL). Although the initial study protocol comprised 20 mg/body DEX on days 1 and 2, and 10 mg/body on days 3-5 [high-dose (HD-) DEX group], the dose of DEX was later decreased to 8 mg/body on days 1 and 2 [low-dose (LD-) DEX group] due to frequent cytomegalovirus (CMV) antigenemia and recurrent retinitis. We enrolled 33 patients, and LD-DEX and HD-DEX were administered in 15 and 18 patients, respectively.

Immunosuppressive therapy with rabbit antithymocyte globulin therapy for acquired aplastic anemia: a multi-institutional retrospective study in Japanese adult patients.

We retrospectively analyzed efficacy and safety of therapy with rabbit antithymocyte globulin (rATG) in combination with cyclosporine A (CsA) in 30 Japanese adult patients with acquired aplastic anemia (AA) in the Kyoto Clinical Hematology Study Group. The median observation period was 31 months and the median age of the patients was 54 years. The objective response rates (ORRs) to rATG plus CsA increased over time until 18 months after the start of treatment; the rate of achievement of better than partial response at 18 months was 66.

Detection of chromosomal abnormalities by G-banding and prognostic impact in follicular lymphoma in the rituximab era.

Disease-specific cytogenetic abnormalities involving BCL2 gene rearrangement frequently co-exist with other cytogenetic abnormalities, contributing to disease progression in follicular lymphoma (FL). In the present study, we retrospectively investigated the prognostic impact of BCL2-unrelated cytogenetic abnormalities in FL. Of 139 consecutively diagnosed patients with FL at two independent institutes, metaphase spreads of tumor cells were obtained for use in G-banding analysis in 77 patients.

Quadruple Cancers of Non-producing Multiple Myeloma, Cholangiocellular Carcinoma, and Two Different Thyroid Cancers.

We report the case of a 72-year-old man who presented with non-producing multiple myeloma (MM) with three additional concomitant solid tumors that were identified by postmortem autopsy. The disease was refractory to anti-MM therapy including bortezomib and lenalidomide, and he finally died of bacterial pneumonia with diffuse alveolar damage 8 months after the diagnosis. An autopsy revealed that he was also affected by three other solid cancers, cholangiocellular carcinoma, medullary thyroid cancer and papillary thyroid cancer that were clinically asymptomatic and remained undiagnosed before death.

Phosphoinositide protein kinase PDPK1 is a crucial cell signaling mediator in multiple myeloma.

Multiple myeloma is a cytogenetically/molecularly heterogeneous hematologic malignancy that remains mostly incurable, and the identification of a universal and relevant therapeutic target molecule is essential for the further development of therapeutic strategy. Herein, we identified that 3-phosphoinositide-dependent protein kinase 1 (PDPK1), a serine threonine kinase, is expressed and active in all eleven multiple myeloma-derived cell lines examined regardless of the type of cytogenetic abnormality, the mutation state of RAS and FGFR3 genes, or the activation state of ERK and AKT. Our results revealed that PDPK1 is a pivotal regulator of molecules that are essential for myelomagenesis, such as RSK2, AKT, c-MYC, IRF4, or cyclin Ds, and that PDPK1 inhibition caused the growth inhibition and the induction of apoptosis with the activation of BIM and BAD, and augmented the in vitro cytotoxic effects of antimyeloma agents in myeloma cells.

Rheumatoid arthritis/methotrexate-associated primary cutaneous diffuse large B-cell lymphoma, leg type.

This report concerns a 62-year-old man with primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type that developed during methotrexate (MTX) treatment for rheumatoid arthritis (RA). Several tumors were observed on the left lower leg. A histological analysis showed diffuse proliferation of large neoplastic B-cells that were immunophenotypically CD10-/MUM1+/BCL6-/BCL2+ and cytogenetically had IgH/c-MYC translocation without translocation involving BCL6 or IgH/BCL2.

Azacitidine-associated acute interstitial pneumonitis.

Azacitidine is the first-line therapeutic option for myelodysplastic syndrome (MDS). This report describes a case of MDS in a patient who developed fatal acute interstitial pneumonitis (AIP) after the first seven-day course of intravenous azacitidine (75 mg/m(2)/day) treatment. A review of previous and present studies of azacitidine-associated AIP suggests that azacitidine may cause life-threatening AIP during or after the first seven-day course of treatment, with pyrexia commonly preceding AIP.

Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression leads to paracrine growth promotion of chronic myelogenous leukemia cells.

Galectin-3 is induced in chronic myelogenous leukemia (CML) cells by co-culture with bone marrow stromal cells, making paracrine growth promotion of CML cells in conditioned medium (CM) from galectin-3 overexpressing CML cells more potent. We used gel filtration chromatography to demonstrate that the bovine SERPINA1-fetal bovine serum albumin (BSA) complex was specifically suppressed in CM from galectin-3 overexpressing cells. The SERPINA1-BSA complex as well as human plasma SERPINA1 inhibited the growth of CML cells, while exogenous galectin-3 partly offset this effect.

Clinical manifestation of angioimmunoblastic T-cell lymphoma with exuberant plasmacytosis.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin lymphoma characterized by aggressive symptoms and various abnormal laboratory test results. One of the rare immunologic abnormalities in AITL is exuberant polyclonal plasmacytosis, but its clinical significance has not been evaluated. This report concerns three AITL cases with exuberant polyclonal plasmacytosis and investigates its clinical impact by comparison with 12 patients without plasmacytosis.

FTY720 induces apoptosis of chronic myelogenous leukemia cells via dual activation of BIM and BID and overcomes various types of resistance to tyrosine kinase inhibitors.

PP2A activator FTY720 has been shown to possess the anti-leukemic activity for chronic myelogenous leukemia (CML), however, the cell killing mechanism underlying its anti-leukemic activity has remained to be verified. We investigated the precise mechanisms underlying the apoptosis induction by FTY720, especially focusing on the roles of BH3-only proteins, and the therapeutic potency of FTY720 for CML. Enforced expression of either BCL2 or the dominant-negative protein of FADD (FADD.

Low ADAMTS-13 activity during hemorrhagic events with disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a life-threatening complication, and its control is essential for therapeutic success. Recombinant human soluble thrombomodulin alfa (rTM) is a novel therapeutic agent for DIC. The efficacy of rTM in the treatment of DIC is reportedly superior to that of conventional anti-DIC treatments, such as unfractionated heparin or low molecular weight heparin, but hemorrhagic events occasionally interfere with the therapeutic benefits of rTM.

Cyclosporine A and reduced-intensity conditioning allogeneic stem cell transplantation for relapsed angioimmunoblastic T cell lymphoma with hemophagocytic syndrome.

No standard therapeutic approaches have so far been established for the treatment of relapsed angioimmunoblastic T-cell lymphoma (AITL), a subtype of non-Hodgkin lymphoma. This case report describes an AITL patient who relapsed with hemophagocytic syndrome (HPS) two months after receiving high-dose chemotherapy (HDCT) supported by autologous peripheral blood stem cell transplantation (PBSCT). The patient was successfully treated with cyclosporine A (CsA) and subsequent allogeneic PBSCT with reduced intensity conditioning regimen (RIST).

RSK2(Ser227) at N-terminal kinase domain is a potential therapeutic target for multiple myeloma.

Multiple myeloma is an entity of cytogenetically and genetically heterogenous plasma cell neoplasms. Despite recent improvement in the treatment outcome of multiple myeloma by novel molecular-targeted chemotherapeutics, multiple myeloma remains incurable. The identification of a therapeutic target molecule in which various signaling for cell-survival converge is a core component for the development of new therapeutic strategies against multiple myeloma.