Guillain-Barr Syndrome Caused by Cytomegalovirus after Multiple Myeloma Treatment.

BACKGROUND: Both humoral and cell-mediated immunity of the patient affected by multiple myeloma (MM) are impaired; thus, infection is the main cause of the onset of symptoms and death caused by MM. Bortezomib is a first-line drug approved for patients with multiple myeloma (MM) and has significantly increased their overall survival. However, bortezomib-induced peripheral neuropathy (PN) remains a significant side effect that has led to its discontinuation in some patients. Guillain-Barre syndrome (GBS) is thought to be related to immune damage, and most patients have cytomegalovirus (CMV), Epstein-Barr virus (EBV), or mycoplasma infection before onset. Cases of GBS secondary to MM are rare. METHODS: We provide a case of GBS caused by cytomegalovirus infection after MM treatment, and briefly review the existing literature. RESULTS: Secondary GBS after MM. This patient received active treatment. The clinical symptoms are gradually improving. CONCLUSIONS: The use of bortezomib has the risk of reactivating the virus. It is more about the reactivation of hep-atitis B virus. Nonetheless, cytomegalovirus and Epstein-Barr virus shall have our attention. Patients with MM need to monitor CMV, regularly, especially during the treatment of bortezomib. At the same time, they also need to closely monitor the symptoms and signs of the nervous system to guard against the occurrence of GBS.

Surgical treatment outcomes of acetabular posterior wall and posterior column fractures using 3D printing technology and individualized custom-made metal plates: a retrospective study.

BACKGROUND: Fractures involving the posterior acetabulum with its rich vascular and neural supply present challenges in trauma orthopedics. This study evaluates the effectiveness of 3D printing technology with the use of custom-made metal plates in the treatment of posterior wall and column acetabular fractures. METHODS: A retrospective analysis included 31 patients undergoing surgical fixation for posterior wall and column fractures of the acetabulum (16 in the 3D printing group, utilizing 3D printing for a 1:1 pelvic model and custom-made plates based on preoperative simulation; 15 in the traditional group, using conventional methods). Surgical and instrument operation times, intraoperative fluoroscopy frequency, intraoperative blood loss, fracture reduction quality, fracture healing time, preoperative and 12-month postoperative pain scores (Numeric Rating Scale, NRS), hip joint function at 6 and 12 months (Harris scores), and complications were compared. RESULTS: The surgical and instrument operation times were significantly shorter in the 3D printing group (p < 0.001). The 3D printing group exhibited significantly lower intraoperative fluoroscopy frequency and blood loss (p = 0.001 and p < 0.001, respectively). No significant differences were observed between the two groups in terms of fracture reduction quality, fracture healing time, preoperative pain scores (NRS scores), and 6-month hip joint function (Harris scores) (p > 0.05). However, at 12 months, hip joint function and pain scores were significantly better in the 3D printing group (p < 0.05). Although the incidence of complications was lower in the 3D printing group (18.8% vs. 33.3%), the difference did not reach statistical significance (p = 0.433). CONCLUSION: Combining 3D printing with individualized custom-made metal plates for acetabular posterior wall and column fractures reduces surgery and instrument time, minimizes intraoperative procedures and blood loss, enhancing long-term hip joint function recovery. CLINICAL TRIAL REGISTRATION: 12/04/2023;Trial Registration No. ChiCTR2300070438; http://www.chictr.org.cn .

Clinical outcomes of pomalidomide-based and daratumumab-based therapies in patients with relapsed/refractory multiple myeloma: A real-world cohort study in China.

BACKGROUND: Comparative investigations evaluating the efficacy of pomalidomide-based (Pom-based) versus daratumumab-based (Dara-based) therapies in patients with relapsed/refractory multiple myeloma (RRMM) remain scarce, both in randomized controlled trials and real-world studies. METHODS: This retrospective cohort study included 140 RRMM patients treated with Pom-based or Dara-based or a combination of pomalidomide and daratumumab (DPd) regimens in a Chinese tertiary hospital between December 2018 and July 2023. RESULTS: The overall response rates (ORR) for Pom-based (n = 48), Dara-based (n = 68), and DPd (n = 24) groups were 57.8%, 84.6%, and 75.0%, respectively (p = 0.007). At data cutoff on August 1, 2023, the median progression-free survival (PFS) was 5.7 months (95% CI: 5.0-6.5) for the Pom-based group, 10.5 months (5.2-15.8) for the Dara-based group, and 6.7 months (4.0-9.3) for the DPd group (p = 0.056). Multivariate analysis identified treatment regimens (Dara-based vs. Pom-based, DPd vs. Pom-based) and Eastern Cooperative Oncology Group performance status (ECOG PS) as independent prognostic factors for PFS. In the subgroups of patients aged >65 years, with ECOG PS ≥2, lines of therapy ≥2, extramedullary disease or double-refractory disease (refractory to both lenalidomide and proteasome inhibitors), the superiority of Dara-based regimens over Pom-based regimens was not evident. A higher incidence of infections was observed in patients receiving Dara-based and DPd regimens (Pom-based 39.6% vs. Dara-based 64.7% vs. DPd 70.8%, p = 0.009). CONCLUSIONS: In real-world settings, Pom-based, Dara-based, and DPd therapies exhibited favorable efficacy in patients with RRMM. Dara-based therapy yielded superior clinical response and PFS compared to Pom-based therapy.

Simultaneous removal of ammonia and sulfur odorants in biotrickling filters and N2O production.

Research on the stability evaluation of biotrickling filters (BTFs) under harsh conditions and the bacterial adaptation process still needs to be improved. Herein, BTFs with polypropylene plastic (PP) and ceramic raschig rings (CRR) were investigated for a better understanding of the biodegradation of ammonia (NH3), hydrogen sulfide (H2S), and dimethyl sulfide (DMS). The results showed an excellent performance in removal efficiency (RE) for NH3 (91.6 %-99.9 %), H2S (RE: 55.3 %-99.5 %), and DMS (RE: 10.6 %-99.9 %). It was found that a more apparent positive correlation between N2O emission and pressure drop in CRR BTF (R2 = 0.92) than in PP BTF (R2 = 0.79) (P < 0.01). Low temperature promotes an increase in the abundance ofComamonasandBacillus. The polysaccharides in PP and CRR reactors decreased by 78.6 % and 68.1 % when temperature reduced from 25℃ to 8℃. This work provides a novel insight into understanding bacterial survival under harsh BTF environments.

Role of plasma EBV-DNA load and EBER status on newly diagnosed peripheral T-cell lymphoma.

PURPOSE: To explore the prognostic and therapeutic role of Epstein-Barr Virus (EBV) on peripheral T-cell lymphoma (PTCL). METHODS: Totally 262 newly diagnosed PTCL patients who were hospitalized from January 2014 to December 2022 were retrospectively enrolled. Molecular analysis included 31 eligible patients. EBV-encoded RNA (EBER) presence in tumor tissue and EBV DNA levels in patients at baseline (DNA1) and after 4 cycles of chemotherapy (DNA4) were assessed. RESULTS: Our findings revealed that the EBER-positive cohort exhibited significant differences compared to counterparts in overall survival (OS, P = 0.047) and progression-free survival (PFS, P = 0.009). Both DNA1 and DNA4 were significantly associated with inferior OS. Multivariate analysis demonstrated that DNA4 independently affected PTCL prognosis for OS (hazard ratio = 5.1617; 95% confidence interval 1.1017-24.1831; P = 0.037). Treatment with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus azacytidine regimen showed a better OS compared to CHOP or CHOP plus etoposide for patients with partially positive EBER and EBER positive statuses (P = 0.192), although the improvement was not statistically significant. This study delineated the genetic paradigm of PTCL, comparing genetic differences by EBV status and found that EBER partially positive plus positive patients were more likely to have DNMT3A (P = 0.002), RHOAG17V (P = 0.023), and TET2 mutations (P = 0.032). CONCLUSION: EBER, DNA1, and DNA4 emerged as sensitive markers for prognosis. CHOP plus azacytidine might present a preferable option for PTCL patients with DNA methylation due to EBV infection.

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Impact of myelofibrosis on patients with myelodysplastic syndromes following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. METHODS: We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. RESULTS: The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%-17.7%), 16.3% (95% CI 10.2%-23.6%), 76.6% (95% CI 69.0%-85.1%), and 72.8% (95% CI 65.0%-81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%-32.9%), 14.7% (95% CI 5.3%-28.7%), 71.8% (95% CI 57.6%-89.6%), and 68.4% (95% CI 53.6%-87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25-5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10-4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. CONCLUSIONS: In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.

The ratio of serum urea nitrogen to albumin is a better predictor of OS in MM patients than urea nitrogen alone.

Introduction Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, Kaplan‒Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with ß2-microglobulin (ß2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. ß2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost ß2-MG and LDH's predictive value and sUAR had a higher predictive value. Conclusion This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with ß2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.

Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia.

BACKGROUND: AML1/ETO fusion confers favorable prognosis in acute myeloid leukemia (AML) treated with intensive chemotherapy (IC). However, the impact of AML1/ETO fusion on the efficacy of venetoclax in the treatment of AML is unclear. OBJECTIVE: The aim of this study was to evaluate the efficacy of venetoclax plus hypomethylating agents (VEN/HMAs) in patients with AML1/ETO-positive AML. PATIENTS AND METHODS: Patients with newly diagnosed AML in two centers were reviewed and divided into three cohorts: AML1/ETO-positive AML treated with frontline VEN/HMA (Cohort A), AML1/ETO-negative AML treated with frontline VEN/HMA (Cohort B), or AML1/ETO-positive AML treated with frontline IC (Cohort C). The response and survival were compared between the cohorts. RESULTS: A total of 260 patients were included in the study. Patients in Cohort A had a significantly lower overall response rate (ORR) than patients in Cohort B (40.9% vs 71.2%, p = 0.005). The median event-free survival (EFS) in Cohort A and Cohort B was 2.7 months and 7.7 months, respectively, with no significant difference. The ORR and median EFS in Cohort C were 80.8% and 14.9 months, respectively, which were significantly superior to those in Cohort A, and the advantages remained significant after propensity score matching. ORR and EFS in KIT-mutated patients with AML1/ETO-positive AML receiving VEN/HMA were much inferior to those in KIT wild-type patients (ORR 0.0% vs 81.8%, p = 0.001; EFS 1.2 months vs not reached, p < 0.001). CONCLUSIONS: Newly diagnosed AML patients with AML1/ETO fusion had a poor response to frontline VEN/HMA treatment. When determining induction therapy for patients with AML1/ETO-positive AML, IC should be preferred over VEN/HM.

Evaluation of the association between glutathione S-transferase polymorphisms and susceptibility to cutaneous melanoma: a systematic review and meta-analysis.

Introduction: Glutathione S-transferase (GST) enzymes play a crucial role in detoxification by catalysing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Polymorphisms in GST genes may influence the susceptibility to various cancers, including melanoma. Aim: We reported a systematic review and meta-analysis to evaluate the association between GST polymorphisms and susceptibility to cutaneous melanoma. Material and methods: A comprehensive search of four databases, namely PubMed, Scopus, Cochrane Library, and Web of Science, was conducted to gather pertinent studies up until 24 August 2023. No restrictions were imposed during the search. The analysis included 32 studies and was broken down into subgroups based on ethnicity, control source, control matching, quality score, and sample size. Results: The forest plot analyses on GSTM1, GSTT1, combined GSTM1/GSTT1, and GSTP1 polymorphisms in relation to melanoma risk showed no statistically significant differences between the case and control groups, except for the recessive model of GSTP1 polymorphism. The analysis revealed significant associations between GSTM1 polymorphisms and melanoma risk in Asians and in studies with a sample size of less than 200. For the combined GSTM1/GSTT1 polymorphisms, a significant association was found in hospital-based controls. Conclusions: While this study enhances our understanding of the genetic factors influencing melanoma risk, it also highlights the need for further research. The current evidence is not sufficient to confirm or reject the intervention effect. Future research should consider gene-gene and gene-environment interactions, which could offer a more comprehensive understanding of the complex biology of melanoma.

VLDL and LDL Subfractions Enhance the Risk Stratification of Individuals Who Underwent Epstein-Barr Virus-Based Screening for Nasopharyngeal Carcinoma: A Multicenter Cohort Study.

Serological tests for Epstein-Barr virus (EBV) antibodies have been widely conducted for the screening of nasopharyngeal carcinoma (NPC) in endemic areas. Further risk stratification of NPC can be achieved through plasma lipoprotein and metabolic profiles. A total of 297 NPC patients and 149 EBV-positive participants are enrolled from the NCT03919552 and NCT05682703 cohorts for plasma nuclear magnetic resonance (NMR) metabolomic analysis. Small, dense very low density lipoprotein particles (VLDL-5) and large, buoyant low density lipoprotein particles (LDL-1) are found to be closely associated with nasopharyngeal carcinogenesis. Herein, an NMR-based risk score (NRS), which combines lipoprotein subfractions and metabolic biomarkers relevant to NPC, is developed and well validated within a multicenter cohort. Combining the median cutoff value of the NRS (N50) with that of the serological test for EBV antibodies, the risk stratification model achieves a satisfactory performance in which the area under the curve (AUC) is 0.841 (95% confidence interval: 0.811-0.871), and the positive predictive value (PPV) reaches 70.08% in the combined cohort. These findings not only suggest that VLDL-5 and LDL-1 particles can serve as novel risk factors for NPC but also indicate that the NRS has significant potential in personalized risk prediction for NPC.

A Novel Conchal Cartilage Harvesting Technique.

BACKGROUND: Conchal cartilage is generally favored in rhinoplasty with a satisfied aesthetic outcome. However, patients may suffer from postoperative donor auricle deformities. OBJECTIVES: This study introduced a novel conchal cartilage harvesting technique which can minimize the deformity of auricle and harvest the sufficient amounts of grafts. METHODS: This study proposed preservation of the concha cymba and cavum support structures to minimize the deformity of auricle and harvest of cartilage hidden in the craniofacial region to obtain the sufficient amounts. The medical records of 60 patients who underwent the novel conchal cartilage harvesting were reviewed retrospectively. Postoperative aesthetic outcomes were assessed by comparing pre- and postoperative photographs according to the deformation extent of auricular subunits (cymba concha, cavum concha, antihelix, helix crus and intertragal notch) on a four-point Likert scale. Additionally, function and complications were analyzed. RESULTS: 56 patients performed unilateral conchal cartilage harvesting (8 with right-side and 48 with left-side) and 4 performed bilateral harvesting. The average aesthetic score, rated on a four-point Likert scale (1 = significant deformation, 2 = moderated deformation, 3 = slight deformation, 4 = complete no deformation), were 3.83 ± 0.03 points, respectively. The functional scores, rated on a four-point Likert scale (1 = significant damage, 2 = moderated damage, 3 = slight damage, 4 = complete no damage), was 3.94±0.03. Complications included hematoma, delayed wound healing and hypopigmentated scar in six ears (9.4%). CONCLUSIONS: This novel technique can minimize the deformity of auricle, as shown by the outcome scores, and allows for sufficient amount of grafting material acquired. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Advancements in tissue engineering for articular cartilage regeneration.

Articular cartilage injury is a prevalent clinical condition resulting from trauma, tumors, infection, osteoarthritis, and other factors. The intrinsic lack of blood vessels, nerves, and lymphatic vessels within cartilage tissue severely limits its self-regenerative capacity after injury. Current treatment options, such as conservative drug therapy and joint replacement, have inherent limitations. Achieving perfect regeneration and repair of articular cartilage remains an ongoing challenge in the field of regenerative medicine. Tissue engineering has emerged as a key focus in articular cartilage injury research, aiming to utilize cultured and expanded tissue cells combined with suitable scaffold materials to create viable, functional tissues. This review article encompasses the latest advancements in seed cells, scaffolds, and cytokines. Additionally, the role of stimulatory factors including cytokines and growth factors, genetic engineering techniques, biophysical stimulation, and bioreactor systems, as well as the role of scaffolding materials including natural scaffolds, synthetic scaffolds, and nanostructured scaffolds in the regeneration of cartilage tissues are discussed. Finally, we also outline the signaling pathways involved in cartilage regeneration. Our review provides valuable insights for scholars to address the complex problem of cartilage regeneration and repair.

Comparison of long-term outcomes between imatinib and dasatinib prophylaxis after allogeneic stem cell transplantation in patients with Philadelphia-positive acute lymphoblastic leukemia: A multicenter retrospective study.

BACKGROUND: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation. METHODS: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared. RESULTS: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation. CONCLUSIONS: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib.

Graft CD8 T-cell-based risk system predicts survival in antithymocyte globulin-based myeloablative haploidentical peripheral blood stem cell transplantation.

Objective: This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Methods: Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021. Results: A higher dose of graft CD8+ T cells (≥ 0.85 × 108 kg-1) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P = 0.002) and disease-free survival (DFS; HR, 1.751; P < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P = 0.038) and DFS (HR, 1.532; P = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8+ T-cell risk system based on graft CD8+ T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8+ T-cell dose was negatively correlated with donor age (P < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation (P < 0.001). Conclusion: A higher CD8+ T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk.

Successful Treatment of Systemic Light Chain Amyloidosis with Liver Involvement using Low-Frequency Daratumumab: A Case Report.

BACKGROUND Systemic light chain (AL) amyloidosis is a disease characterized by the deposition of amyloid fibrils throughout tissues due to the production of misfolded immunoglobulin light chains by clonally expanded populations of CD38+ plasma cells. Some patients can have liver involvement, which typically presents with nonspecific symptoms. Daratumumab, a human CD38-targeting antibody, has shown efficacy in improving hematological parameters and organ function in patients with AL amyloidosis. Low-frequency daratumumab can reduce financial burden, but whether it is effective for patients with liver involvement has not been reported. CASE REPORT We present the case of a 64-year-old man admitted to our hospital with fatigue and recurrent fever. Histological analysis of a liver biopsy demonstrated AL amyloidosis. Bone marrow biopsy demonstrated the presence of abnormal plasma cells. Laboratory test results demonstrated increased levels of circulating free kappa (kappa) light chains, which were also seen on blood and urine immunofixation electrophoresis. Based on these findings, AL amyloidosis of the kappa light chain type with liver, cardiac, and renal involvement was diagnosed. The patient ultimately achieved hematological stringent complete response, liver remission, renal complete response, and cardiac very good partial response after 2 cycles of the low-frequency daratumumab, bortezomib, and dexamethasone regimen and 4 cycles of daratumumab and dexamethasone regimen chemotherapy. CONCLUSIONS The case indicates that low-frequency daratumumab treatment can have efficacy in AL amyloidosis with liver involvement.

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors.

KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.

Enhancer of Zeste Homolog 2 Inhibitor SHR2554 in Relapsed or Refractory Peripheral T-cell Lymphoma: Data from the First-in-Human Phase I Study.

PURPOSE: Patients with peripheral T-cell lymphomas (PTCL) in the relapsed or refractory (r/r) setting have only a limited number of therapies available, and the prognosis is extremely poor. SHR2554 is an oral inhibitor against EZH2, a rational therapeutic target for lymphomas. PATIENTS AND METHODS: This was a multicenter, two-part, phase I study of SHR2554 in r/r mature lymphoid neoplasms. In part I, 350 mg twice daily was established as the recommended phase II dose (RP2D) based on the findings during dose escalation and expansion; subsequently, selected lymphoma subtypes were recruited in clinical expansion cohorts to receive SHR2554 at RP2D. Here, we provide an in-depth assessment of SHR2554 at RP2D in subpopulation with r/r PTCL. RESULTS: Twenty-eight patients were included for analysis (17 angioimmunoblastic T-cell lymphoma and 11 not otherwise specified). Eighteen (64%) patients had received ≥2 lines of previous anticancer therapies. The objective response rate was 61% [95% confidence interval (CI), 41-78]. Responses were still ongoing in 59% (10/17) of the responders; estimated median duration of response was 12.3 months (95% CI, 7.4-not reached). Median progression-free survival was 11.1 months (95% CI, 5.3-22.0), and 12-month overall survival rate was 92% (95% CI, 72-98). The most common grade 3 or 4 treatment-related adverse events were decreased platelet count [nine (32%)] as well as decreased white blood cell count, decreased neutrophil count, and anemia [four (14%) for each]. No treatment-related deaths were reported. CONCLUSIONS: This extended follow-up analysis further supports SHR2554 as a therapeutic opportunity for patients with r/r PTCL.

Ibrutinib Efficacy, Safety, and Pharmacokinetics in Chinese Patients with Relapsed or Refractory Waldenström's Macroglobulinemia: A Multicenter, Single-Arm, Phase 4 Study.

INTRODUCTION: Waldenström's macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM. METHODS: This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM. RESULTS: Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively. CONCLUSIONS: Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04042376.