International Journal of Hematology最新文献

Letermovir is often administered for cytomegalovirus prophylaxis after allogeneic hematopoietic cell transplantation (HCT). Concomitant use of letermovir and azole antifungals affects tacrolimus concentration. Therefore, in HCT recipients taking fluconazole, letermovir may affect the optimal tacrolimus conversion ratios when switching from continuous intravenous infusion to oral administration. In this study, we retrospectively evaluated tacrolimus conversion ratios in 104 HCT recipients taking fluconazole with and without concomitant letermovir. The median tacrolimus concentration-to-dose (C/D) ratios with and without letermovir were 18.2 and 20.6 (ng/mL)/(mg/day), respectively, before conversion from continuous infusion (C/Dciv) (p = 0.21) and 2.9 and 1.9 (ng/mL)/(mg/day), respectively, after conversion (p < 0.01). The median (C/Dpo)/(C/Dciv) ratios with and without letermovir were 0.15 and 0.10, respectively (p < 0.01). These results suggest that in HCT recipients taking fluconazole, the optimal conversion ratio when switching from continuous intravenous infusion to oral administration is 0.7-fold lower with concomitant letermovir than without it.

In multiple myeloma, functional high risk (FHR) is a predictor of poor outcomes. It is defined as M protein reduction to ≤ 50% of normal, suboptimal response (SR), or progressive disease (PD) within 12 months (i.e., early PD). The clinical significance of anti-CD38 monoclonal antibody (MoAb) as second-line treatment for FHR myeloma remains unclear. We retrospectively investigated the efficacy of anti-CD38 MoAb as second-line treatment for FHR myeloma. We included 332 patients who were newly diagnosed with myeloma and received proteasome inhibitors and/or immunomodulatory drugs as first-line therapy. Their median age was 70 years, and 29.4% were FHR. At a median follow-up of 48.5 months, the overall survival (OS) in the FHR group was significantly shorter (hazard ratio [HR], 2.086; P < 0.001). However, the OS in the SR without early-PD group was comparable to that in the non-FHR group (HR, 1.659; P = 0.330). The OS in patients with FHR who received anti-CD38 MoAb as second-line treatment was similar to that in the non-FHR group (HR, 1.157; P = 0.660). Anti-CD38 MoAb as second-line treatment improved the outcome in our patients with FHR although FHR predicted a poor prognosis.

The incidence of leukemic conversion during the clinical course of paroxysmal nocturnal hemoglobinuria (PNH) has been reported to be 0.6-2.9%. Such an association is logically linked to the progression of PNH to acute leukemia, especially the M6 subtype of acute myeloid leukemia (AML-M6). In many of these cases (11/26, 42%), leukemic conversion from PNH is associated with development of AML-M6. A literature review including our cases showed that this leukemic conversion from PNH has two distinct development patterns. In type 1, leukemic clones were derived from non-PNH clones in most cases, and the PNH phenotype of erythrocytes disappeared with progression. In one of our cases, however, the patient was diagnosed with concomitant PNH and AML-M6, and leukemic cells were observed alongside CD55-negative and CD59-negative PNH clones. In Type 2 cases such as this one, conversion of PNH is characterized by the coexistence of leukemic cells with PNH clones. Flow cytometry revealed that CD34-positive blast cells were deficient in CD55 and CD59. In Type 2, PNH clones do progress into malignancies, albeit rarely, demonstrating a distinct second development pattern of leukemic conversion from PNH.

Rapid tapering of cyclosporine (CsA) in the early phase after allogeneic transplantation may induce a potent graft-versus-leukemia/lymphoma (GVL) effect. We retrospectively reviewed the outcomes of patients with high-risk hematological malignancies who underwent their first transplantation at our institution. The blood CsA concentration was maintained at around 300 ng/ml. Our planned schedule for tapering CsA in patients without graft-versus-host disease (GVHD) or with limited GVHD was to reduce the dose by 10% per week starting from day 30 for related HSCT or from day 50 for unrelated HSCT. In total, we began tapering CsA in 36, and classified them into 2 an "On-schedule group" or "Delayed group" based on the timing of starting tapering. The cumulative incidences of grade II-IV acute GVHD overall were 33.8% and 39.4% (P = 0.746) in the On-schedule and Delayed groups. The On-schedule group showed no significant difference in non-relapse mortality, but showed a trend toward a higher relapse rate, resulting in significantly worse overall survival (55.6% vs 72.2% at 1y, P = 0.025) and worse disease-free survival (38.9% vs 66.7% at 1y, P = 0.059). These findings suggest that early CsA tapering after HSCT in high-risk patients was not effective.

Background: Sickle cell anemia remains a major public health problem in Gabon, with high mortality. However, its prevalence is mainly documented in the capital city of Libreville, with few data for other areas.

Methods: We performed diagnostic testing by electrophoresis on 1534 individuals from two sites in eastern Gabon: Franceville and Koula-Moutou. We also screened 791 individuals from Koula-Moutou using a method that combines hemoglobin levels with leukocyte counts.

Results: The allelic frequency of the hemoglobin S and C genes were 18.5% and 0.07%, respectively, in areas of eastern Gabon. Also 3.7% of individuals had sickle cell disease, 29.8% had sickle cell trait and 0.1% was heterozygous for hemoglobin AC. The diagnostic orientation method used in our study showed a sensitivity of 100%, a specificity of 97.4%, and a negative predictive value of 100%.

Conclusion: This method using hemogram data has proved to be valuable in areas with high resource constraints, and could be used in other areas to aid diagnostic orientation. It would be interesting to similarly evaluate the frequency of sickle cell anaemia in the northern and southern regions of Gabon.

TAFRO syndrome is a systemic disease characterized by thrombocytopenia, anasarca, fever, systemic inflammation, reticulin fibrosis, renal insufficiency, and organomegaly. Although the pathogenesis of TAFRO syndrome remains unknown, it may be associated with cytokine storm and abnormal immune function. Herein, we present a case of a 65-year-old man who was diagnosed with myelodysplastic neoplasms (MDS) with repeating TAFRO syndrome-like symptoms. At ages 59 and 63 years, he developed TAFRO syndrome and was treated with immunosuppressive therapy, which improved these symptoms. At age 65 years, he had TAFRO syndrome-like symptoms with pancytopenia, chromosomal abnormalities, and dysplasia. The patient was subsequently diagnosed with MDS and treated with methylprednisolone, rituximab, bortezomib, and tocilizumab. His MDS-related and TAFRO syndrome-like symptoms simultaneously improved following treatment. Although the patient was not diagnosed with MDS at the first and second events, chromosomal abnormalities were detected, revealing increased clonal cells. MDS can be complicated by immune disorders associated with increased malignant clonal cells. Additionally, patients with MDS exhibit hypercytokinemia, including interleukin-6 and vascular endothelial growth factor. This case indicates that increased clonal cells and hypercytokinemia caused by MDS may lead to abnormal immune function and induce TAFRO syndrome-like symptoms.

Objective: The Glasgow prognostic score (GPS) is used to predict the prognosis of several cancers. This first systematic review and meta-analysis evaluated the role of GPS in predicting overall survival (OS) and progression-free survival (PFS) in patients with hematological malignancies.

Methods: Embase, PubMed, CENTRAL, Scopus, and Google Scholar were screened for studies evaluating the prognostic role of GPS in hematological malignancies.

Results: Twelve studies were eligible. Meta-analysis showed that patients with GPS of ≥1 and ≥2 had worse OS than those with GPS of 0. We noted that both GPS scores of ≥1 and ≥2 were associated with significantly poor PFS in patients with hematological malignancies. Results remained robust on sensitivity analysis.

Conclusion: GPS can be used as a predictor of OS and PFS in patients with hematological malignancies. High GPS scores can lead to a twofold higher risk of poor OS and PFS.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) has a wide range of clinical presentations and is sometimes life-threatening. It is often treated with systemic corticosteroids and etoposide, but no optimal treatment has been identified. Dexamethasone palmitate (DP) contains a combination of dexamethasone and a lipid emulsion and is selectively taken up by activated macrophages. Recently, a small case series reported the efficacy of dexamethasone palmitate (DP) in HLH. Here, we present the results of a nationwide survey in Japan detailing 14 cases of EBV-HLH treated with DP in children. One week after DP initiation, fever, cytopenia, and splenomegaly resolved in 77%, 38%, and 77% of patients (10, 5, and 10 of 13 patients, 1 missing). A 50% or greater reduction in ferritin levels was observed in 62% of patients (8 of 13 patients, 1 missing). In addition, the attending physician judged DP to be effective or partially effective in 12/14 (86%) patients. DP-related adverse events were uncommon, with only two infectious events reported. Thus, DP can be a therapeutic option for EBV-HLH.

We characterized the safety and efficacy of the bispecific antibody teclistamab in Japanese patients with relapsed/refractory multiple myeloma (RRMM). Patients were pretreated with a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 monoclonal antibody (mAb). The primary endpoint was frequency and type of treatment-emergent adverse events (TEAEs) in phase 1, and overall response rate (ORR; ≥ partial response [PR]) in phase 2. In phase 1, 14 patients received once-weekly (QW) subcutaneous teclistamab (0.72 mg/kg [n = 5]; 1.5 mg/kg [n = 5]; 3 mg/kg [n = 4]). No dose-limiting toxicities were observed. As of April 2024, 26 phase-2 patients received the recommended phase-2 dose (QW) (RP2D: 1.5 mg/kg) of teclistamab. Biweekly (Q2W) dosing was allowed after maintaining response for ≥ 6 months. At a median follow-up of 14.32 months, ORR was 76.9% (≥ very good PR: 76.9%; ≥ complete response: 65.4%). Median duration of response, progression-free survival, and overall survival were not reached. Common TEAEs included CRS (grade ≤ 2), neutropenia, and infections. No patient had immune effector cell-associated neurotoxicity syndrome (ICANS) and dose reductions. Teclistamab demonstrated deep and durable responses in Japanese patients with RRMM, consistent with the global pivotal MajesTEC-1 study, supporting the potential for a new standard of care for Japanese RRMM patients.