Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use.

A manual of Eustachian tube function tests-illustration of representative test results obtained from healthy subjects and typical disorders with suggestion of the appropriate test method of choice.

In the 19th century, Politzer devised a method to measure passage of the Eustachian tube (ET) by pressurizing the nasopharyngeal cavity, which marked the beginning of the ET function test. Since then, various examination methods have been developed. While ET function testing is important, recent advancements in diagnostic imaging and treatments have renewed interest on its importance. In Japan, the main objective methods used for examining ET function include tubotympanoaero-dynamic graphy (TTAG), sonotubometry, and the inflation-deflation test. The Japan Otological Society (JOS) Eustachian Tube Committee has proposed a manual of ET function tests, which presents typical patterns of the normal ear and typical diseases and suggests the ET function test of choice for each disease. However, the diagnosis of each disease should be made based on a comprehensive history and various examination findings, with ET function tests playing a supplemental role in the diagnosis.

Impact of cytogenetic abnormalities in symptomatic multiple myeloma; a Japanese real-world analysis from Kansai Myeloma Forum.

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis.

Clinical Significance of Controlling Nutritional Status (CONUT) Score in Patients With Colorectal Liver Metastases After Hepatectomy.

BACKGROUND/AIM: The prognostic outcome of the controlling nutritional status (CONUT) score in patients with colorectal liver metastases (CRLM) who underwent hepatectomy has not been investigated. The aim of this study was to investigate the prognostic value of preoperative CONUT score and other systemic inflammation-related biomarkers in patients who underwent hepatectomy for CRLM. PATIENTS AND METHODS: The subjects included 145 patients with CRLM who underwent hepatectomy and retrospectively investigated the association of preoperative CONUT score with disease-free survival (DFS), surgical failure-free survival (SFS), and overall survival (OS) using univariate and multivariate analyses. RESULTS: In this study, the cut-off of the CONUT score was 4. In the univariate analysis, the high CONUT score was associated with worse SFS and OS (p=0.01, 0.01). The multivariate analysis showed significant and independent predictors of OS were lymph node metastases (p=0.03) and a high CONUT score (p=0.04). In patients with a high CONUT score, postoperative complications due to infections were significantly more than in those with a low CONUT score (27% vs. 9%, p=0.04). CONCLUSION: The CONUT score can be useful for predicting not only short-term but also long-term outcomes in patients with CRLM after hepatectomy.

Mild Acute Graft-Versus-Host Disease Improves Outcomes After HLA-Haploidentical-Related Donor Transplantation Using Posttransplant Cyclophosphamide and Cord Blood Transplantation.

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.

Long-term survival after multidisciplinary treatments for HER2-positive advanced gastric cancer with multiple liver and lung metastases.

BACKGROUND: Trastuzumab-based chemotherapy is a standard treatment regimen for human epithelial growth factor 2 (HER2)-positive gastric cancer. This is a case of a patient who has survived 12 years after being diagnosed with advanced gastric cancer with multiple liver and lung metastases. CASE PRESENTATION: A woman in her 70s underwent total gastrectomy, cholecystectomy, and left hepatic lobectomy for gastric cancer with liver metastasis. One month after the surgery, multiple liver metastases appeared. After two courses of S-1 + CDDP chemotherapy, the liver metastases disappeared, and new lung metastases occurred. Because the primary tumor was HER2 positive, S-1 + CDDP + trastuzumab chemotherapy was performed. After one course of chemotherapy, the blood test showed pancytopenia, and CDDP was discontinued. S-1 + trastuzumab chemotherapy was then initiated, and as a result, the lung metastases disappeared. The patient is alive without recurrence 12 years after the surgery. CONCLUSIONS: We encountered a case of long-term survival after multidisciplinary treatments for HER2-positive advanced gastric cancer with multiple liver and lung metastases.

Efficacy of letermovir in HLA-haploidentical hematopoietic transplantation with posttransplant cyclophosphamide.

BACKGROUND: Cytomegalovirus reactivation (CMV-R) is a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HCT), especially in human leukocyte antigen-haploidentical transplantation (haplo-HCT) with posttransplant cyclophosphamide (PTCy). Prophylactic letermovir (LTV) prevents CMV-R in patients undergoing allo-HCT. However, evidence regarding its use in haplo-HCTs with PTCy is limited. Therefore, we aimed to investigate the efficacy of prophylactic LTV in haplo-HCT with PTCy. METHODS: We retrospectively analyzed 52 patients seropositive for CMV who underwent haplo-HCT with PTCy at our institution between January 2015 and June 2021 and compared patients who received LTV prophylaxis (LTV group: n = 29) with those who did not receive prophylaxis for CMV (control group: n = 23). The primary endpoint was the 100-day cumulative CMV-R incidence. We used Gray's test and the Fine and Gray test to compare the two groups. RESULTS: The 100-day cumulative CMV-R incidence was lower in the LTV group than in the control group (17.2% vs 81.8%, p < 0.001). Multivariate analysis revealed that prophylactic LTV reduced the 100-day cumulative CMV-R incidence (hazard ratio: 0.17, 95% confidence interval: 0.06-0.44, p < 0.001). CONCLUSIONS: Prophylactic LTV effectively prevents CMV-R in patients undergoing haplo-HCT for PTCy.

Objective assessment of nasal obstruction.

There are many methods and types of equipment for measuring the nasal airway, but there is no consensus regarding the results of various clinical studies on nasal obstruction. In this review, we discuss the two major methods of objectively assessing the nasal airway: rhinomanometry and acoustic rhinometry. The Japanese standard of rhinomanometry in Japanese adults and children was established by the Japanese Standardization Committee on Rhinomanometry in 2001 and 2018, respectively. However, the International Standardization Committee has proposed different standards because of differences in race, equipment, and social health insurance systems. The standardization of acoustic rhinometry in Japanese adults is making progress in several Japanese institutes, but the international standardization of acoustic rhinometry has not yet begun. Rhinomanometry is the physiological expression of nasal airway breathing, whereas acoustic rhinometry is the anatomic expression. In this review, we introduce the history and methods of the objective assessment of nasal patency and the physiological and pathological issues regarding nasal obstruction.

Effectiveness of fluorescence-guided methods using near-infrared fluorescent clips of robotic colorectal surgery: a case report.

BACKGROUND: This is the first report on the application of the Da Vinci-compatible near-infrared fluorescent clips (NIRFCs) as tumor markers to localize colorectal cancer lesions during robotic surgery. In laparoscopic and robotic colorectal surgeries, the accuracy of tumor marking is a critical issue that remains unresolved. This study aimed to determine the accuracy of NIRFCs in localizing tumors for intestinal resection. Indocyanine green (ICG) was also used to verify the feasibility of safely performing an anastomosis. CASE PRESENTATION: A patient diagnosed with rectal cancer was scheduled to undergo a robot-assisted high anterior resection. During colonoscopy 1 day prior to the surgery, four Da Vinci-compatible NIRFCs were placed intraluminally 90° around the lesion. The locations of the Da Vinci-compatible NIRFCs were confirmed using firefly technology, and ICG staining was performed before cutting the oral side of the tumor. The locations of the Da Vinci-compatible NIRFCs and the intestinal resection line were confirmed. Moreover, sufficient margins were obtained. CONCLUSIONS: In robotic colorectal surgery, fluorescence guidance with firefly technology offers two advantages. First, it has an oncological advantage, because marking with the Da Vinci-compatible NIRFCs allows for real-time monitoring of the lesion location. This enables sufficient intestinal resection by grasping the lesion precisely. Second, it reduces the risk of postoperative complications, because ICG evaluation with firefly technology prevents postoperative anastomotic leakage. Fluorescence guidance in robot-assisted surgery is useful. In the future, the application of this technique should be evaluated for lower rectal cancer.

Trajectories of the SARS-CoV-2 RNA load in patients with hematological malignancy.

OBJECTIVES: The higher risk of prolonged viral shedding in coronavirus disease (COVID-19) patients with hematological malignancies (HM) necessitates test-based de-isolation strategies. However, evidence to establish their appropriate isolation period is insufficient. This study investigated the factors affecting prolonged viral shedding and the requisite isolation period in these patients. METHODS: We retrospectively reviewed 14 COVID-19 patients with HM between January and April 2022, who were subjected to our test-based de-isolation strategy, followed by analysis of the viral load trajectory. The viral loads of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated using the cycle threshold (Ct ) of the reverse-transcription quantitative polymerase chain reaction. The trajectories were classified according to the time-interval from COVID-19 onset to the attainment of Ct values >30. RESULTS: The median interval between onset and attainment of a Ct value >30 was 22 days. Five patients with mild or moderate COVID-19 without intense treatment histories achieved Ct values >30 within 20 days. The other nine patients needed more than 20 days, including three patients who did not meet this criterion during the observation period. CONCLUSIONS: The SARS-CoV-2 viral load trajectories in patients with HM can be stratified by treatment history for the underlying HM and severity of COVID-19.

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study.

BACKGROUND: The effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. METHOD: This prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. RESULTS: A humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120-643) BAU/mL and 532 (95% CI 400-708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. CONCLUSION: Messenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.

Improved survival after single-unit cord blood transplantation using fludarabine and melphalan-based reduced-intensity conditioning for malignant lymphoma: impact of melphalan dose and graft-versus-host disease prophylaxis with mycophenolate mofetil.

We evaluated 413 adult patients with lymphoma who underwent unrelated cord blood transplantation (UCBT) with fludarabine and melphalan (FM)-based reduced-intensity conditioning between 2002 and 2017 to investigate longitudinal changes in outcomes and the optimal melphalan dose and graft-versus-host disease (GVHD) prophylaxis regimen. Outcomes were compared between FM80/100 (melphalan dose: 80 or 100 mg/m2) and FM140 (melphalan dose: 140 mg/m2), as well as between calcineurin inhibitor (CNI) plus methotrexate (MTX), CNI plus mycophenolate mofetil (MMF), and CNI alone. The 3-year overall survival (OS) and non-relapse mortality (NRM) rates improved over time (OS: 27% in 2000s vs. 42% in 2010s, p < 0.001; NRM: 43% in 2000s vs. 26% in 2010s, p < 0.001). Multivariable analysis showed that in the 2000s, melphalan dose and GVHD prophylaxis regimen did not affect any outcomes. In the 2010s, FM80/100 (vs. FM140) related to better OS (hazard ratio [HR] 0.62, p = 0.01) and NRM (HR 0.52, p = 0.016). MTX + CNI and CNI alone (vs. CNI + MMF) related to worse OS (CNI + MTX, HR 2.01, p < 0.001; CNI alone, HR 2.65, p < 0.001) and relapse/progression (CNI + MTX, HR 2.40, p < 0.001; CNI alone, HR 2.13, p = 0.023). In recent years, the use of FM80/100 and CNI + MMF significantly reduced the risk of NRM and relapse/progression, respectively, and resulted in better OS after UCBT for lymphoma.

Cold agglutinin anti-I antibodies in two patients with COVID-19.

BACKGROUND: Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID-19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID-19 is unclear. Here, we present two cases of CA identified in the context of COVID-19 without hemolytic anemia and clotting. CASE REPORT AND DISCUSSION: Two patients with no known risk factors for CA were diagnosed with COVID-19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti-I antibody. The two COVID-19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID-19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti-I antibodies in COVID-19 is unclear. The impact of CAS on clinical presentations in COVID-19 remains a matter of verification. CONCLUSIONS: A high CA titer was identified in COVID-19 patients without hemolytic anemia and clotting. Anti-I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID-19.

Clinical features and outcomes of duodenal-type follicular lymphoma: A single-center retrospective study.

Duodenal-type follicular lymphoma (FL) is a rare and newly recognized disease. Few data are available on the outcomes and treatment strategies for patients with duodenal-type FL. We aimed to investigate the clinical features and outcomes of duodenal-type FL. We defined duodenal-type FL as involvement of the duodenum, without nodal or extranodal lesions other than intestinal lesions, pathologically diagnosed as FL. We reviewed 26 patients with duodenal-type FL between January 2011 and December 2020 at Kobe City Hospital Organization, Kobe City Medical Center General Hospital. In particular, patients were selected for the watch and wait (WW) strategy and followed up with regular esophagogastroduodenoscopy about once a year at our institution. The patient characteristics were as follows: median age 63.5 years (range: 42-78), sex (male, 15; female, 11), stage (I, 26), and grade (I, 26). Regarding treatment strategies, 23 patients were selected for the WW strategy, and three patients received initial rituximab therapy. The median follow-up period was 65.5 months (range: 0.2-109). Five-year progression-free survival and 5-year overall survival rates were 86.3% and 100%, respectively. Among the 23 patients selected for the WW strategy, six had spontaneous complete regression, and 14 had stable disease, and three had progressive disease, including one with histologic transformation. The WW strategy for patients with duodenal-type FL could be an appropriate and safe treatment option. However, in several cases, disease progression was documented, and regular follow-up is important.

Transcatheter arterial embolization followed by surgical laparotomy for hemorrhagic shock due to intestinal bleeding: a case report.

BACKGROUND: Acquired jejunal diverticula are relatively rare conditions. While mostly asymptomatic, they can occasionally cause life-threatening complications requiring surgical treatment. We herein report a case of hemorrhagic shock due to jejunal diverticulum with intestinal amyloidosis that was successfully managed via transcatheter arterial embolization (TAE) and surgery. CASE PRESENTATION: An 80-year-old female presenting with hematochezia and hemorrhagic shock was transferred to our institution. Contrast-enhanced computed tomography revealed extravasation in the small bowel around the upper jejunum. Massive transfusion was performed with subsequently planning for TAE to control bleeding followed by surgical laparotomy to evaluate the ischemic intestine. First, the second jejunal artery was selectively embolized with a 1:3 mixture of N-butyl cyanoacrylate (NBCA) and iodize oil, after which laparotomy was performed. Multiple jejunal diverticula were detected near Treitz' ligament, and an induration of NBCA was palpable in the nearby mesentery. The intraoperative diagnosis was massive bleeding from acquired jejunal diverticula for which jejunectomy including the nearby diverticulum was performed to prevent future bleeding. Her postoperative course was stable. Histological examination of the specimen revealed several false diverticula with intestinal amyloidosis. CONCLUSION: Hemorrhagic shock due to jejunal diverticulum with intestinal amyloidosis is extremely rare. Combined treatment of TAE and surgical laparotomy appears to be effective, because the bleeding point can be identified by palpation of the embolic material.

Characterization of myeloid neoplasms following allogeneic hematopoietic cell transplantation.

We compared characteristics of myeloid neoplasms (MNs) following allogeneic hematopoietic cell transplantation (HCT) versus autologous HCT using a Japanese HCT registry database. Among 43 788 patients who underwent allogeneic (n = 18 874) or autologous HCT (n = 24 914) for non-myeloid malignancies or non-malignant diseases, 352 developed MNs. The cumulative incidence of MNs was lower after allogeneic HCT than after autologous HCT (0.3% vs. 1.8% at 10 years, respectively, p < .001). Compared with autologous HCT, MNs following allogeneic HCT developed in younger patients (median, 42 vs. 57 years old, respectively) and sooner after HCT (median, 16 vs. 33 months, respectively). Approximately half of MNs following allogeneic HCT were donor-derived and occurred later than recipient-derived MNs (median, 26 vs. 6 months, respectively, p = .003). In multivariate analysis, reduced-intensity conditioning and cord blood transplantation were associated with MN development after allogeneic HCT. Overall survival was similar in patients who developed MNs following allogeneic versus autologous HCT (18% vs. 22% at 5 years, respectively, p = .48). Patient age ≥ 55 years, the presence of previous HCT, AML subtype, and chromosome 5 or 7 abnormalities were adverse factors for overall survival after MN diagnosis. Further research is warranted to elucidate the mechanisms of MN development following allogeneic HCT.

Total body irradiation-containing conditioning regimens without antithymocyte globulin in adults with aplastic anemia undergoing umbilical cord blood transplantation.

Thus far, there have been no large cohort studies on total body irradiation (TBI)-containing conditioning regimens without antithymocyte globulin (ATG) in adults with aplastic anemia (AA) undergoing umbilical cord blood (UCB) transplantation (UCBT). We retrospectively analyzed 115 adults with idiopathic AA undergoing UCBT using TBI-containing reduced-intensity conditioning (RIC) regimens without ATG between 2000 and 2018 on behalf of the Adult Aplastic Anemia Working Group of the Japanese Society for Hematopoietic Cell Transplantation. We then compared transplantation outcomes between a fludarabine (Flu)- and melphalan (Mel)-based regimen (FM) and a Flu- and cyclophosphamide (Cy)-based regimen (FC). The median patient age at UCBT was 41 years. The median total nucleated cell and total CD34+ cell doses in a UCB unit at cryopreservation were 2.5 × 107/kg and 0.7 × 105/kg, respectively. The median follow-up period for survivors was 47 months. The cumulative incidence rate of neutrophil engraftment was 76.5%, and the 4-year overall survival (OS) rate was 64.3%. In multivariate analysis, the covariates that were significantly associated with a higher neutrophil engraftment were total CD34+ cell dose in an UCB unit (≥ 0.7 × 105/kg; hazard ratio, 0.57, P = 0.01) and total dose of TBI (4 Gy of TBI; hazard ratio, 0.32, P = 0.01). There was no significant difference in the cumulative incidence of neutrophil engraftment and the 4-year OS between the FM and FC groups. In conclusion, TBI-containing RIC regimens without ATG are suitable for adults with AA undergoing UCBT. There were no significant differences in transplantation outcomes between the FM and FC groups.