2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Defining the clinical benefits of adding a neurokinin-1 receptor antagonist to control chemotherapy-induced nausea and vomiting in moderately emetogenic chemotherapy: a systematic review and meta-analysis of the clinical practice guidelines for antiemesis 2023 from the Japan society of clinical oncology.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC). METHODS: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT3RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model. RESULTS: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events. CONCLUSIONS: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy.

Efficacy and safety of dexamethasone sparing for the prevention of nausea and vomiting associated with highly emetogenic risk antineoplastic agents: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023 from the Japan Society of Clinical Oncology.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) are common side effects, classified according to timing and severity. Conventional agents such as dexamethasone are effective but have various side effects. For moderately emetogenic chemotherapy, dexamethasone-sparing antiemetic therapies have been developed to minimize these side effects. This systematic review evaluated the efficacy and safety of dexamethasone-sparing antiemetic therapy for highly emetogenic chemotherapy (HEC). METHODS: We performed a thorough literature search for studies related to dexamethasone-sparing antiemetic therapy with neurokinin-1 antagonists (NK1RA) for HEC using the PubMed, Cochrane Library, and Ichushi-Web databases. A qualitative analysis of the combined data was performed and risk differences with confidence intervals were calculated. RESULTS: Two reviewers independently assessed the 425 records and 12 full-text articles were evaluated for eligibility. Two studies were included in the qualitative and meta-analyses. These studies included anthracycline-cyclophosphamide (AC) regimens and cisplatin-based regimens, with palonosetron as the serotonin receptor antagonist. In the two studies, no difference was found in the prevention of vomiting (delayed complete response). However, non-inferiority was not demonstrated in the subgroup that received cisplatin-containing regimens. Delayed complete control showed different results for nausea prevention; however, there was no significant difference in the meta-analysis. Only one report has shown non-inferiority for delayed total control. Although the strength of evidence for individual outcomes varied, there was no difference in the duration of dexamethasone administration. CONCLUSIONS: This systematic review and meta-analysis revealed that dexamethasone-sparing antiemetic therapy with NK1RA and palonosetron can be used to prevent CINV in HEC, limited to AC combination therapy.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Efficacy and safety of dexamethasone sparing for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy: a systematic review and meta-analysis of Clinical Practice Guidelines for Antiemesis 2023 from Japan Society of Clinical Oncology.

BACKGROUND: Palonosetron, a second-generation 5-HT3 receptor antagonist (5-HT3RA), is more effective than first-generation 5-HT3RA. Several studies have investigated whether dexamethasone (DEX), when combined with palonosetron as a 5-HT3RA, can be spared in the delayed phase after moderately emetogenic chemotherapy (MEC). In this systematic review, we aimed to determine which between 1- and 3-day DEX administration, when combined with palonosetron, is more useful in patients receiving MEC. METHODS: The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant studies published between 1990 and 2020. We included studies that compared the efficacy of 1- and 3-day DEX administration in preventing nausea and vomiting associated with MEC. Outcomes were "prevention of vomiting (complete response rate and no vomiting rate)," "prevention of nausea" (complete control rate, total control rate, no nausea rate, and no clinically significant nausea rate)" in the delayed phase, "prevention of blood glucose level elevation," and "prevention of osteoporosis." RESULTS: Eight studies were included in this systematic review. The no vomiting rate was significantly higher in the 3-day DEX group than in the 1-day DEX group. However, the other efficacy items did not significantly differ between the two groups. Meanwhile, insufficient evidence was obtained for "prevention of blood glucose level elevation" and "prevention of osteoporosis." CONCLUSIONS: No significant differences in most antiemetic effects were found between 1- and 3-day DEX administration. Thus, DEX administration could be shortened from 3 days to 1 day when used in combination with palonosetron.

Clinical significance of the immunoglobulin G heavy-chain repertoire in peripheral blood mononuclear cells of adult T-cell leukaemia-lymphoma patients receiving mogamulizumab.

'Monitoring of immune responses following mogamulizumab-containing treatment in patients with adult T-cell leukaemia-lymphoma (ATL)' (MIMOGA) is a multicentre prospective clinical study (UMIN000008696). In the MIMOGA study, we found that a lower percentage of CD2- CD19+ B cells in peripheral blood mononuclear cells (PBMC) was a significant unfavourable prognostic factor for overall survival (OS). Accordingly, we then analysed the immunoglobulin G (IgG) heavy-chain repertoire in PBMC by high-throughput sequencing. Of the 101 patients enrolled in the MIMOGA study, for 81 a sufficient amount of PBMC RNA was available for repertoire sequencing analysis. Peripheral IgG B cells in patients with ATL had a restricted repertoire relative to those in healthy individuals. There was a significant positive correlation between the Shannon-Weaver diversity index (SWDI) for the IgG repertoire and proportions of B cells in the PBMC of the patients. Multivariate analysis identified two variables significantly affecting OS: a higher serum soluble interleukin-2 receptor level, and a lower SWDI for the IgG repertoire [hazard ratio, 2·124; 95% confidence interval, 1·114-4·049; n = 44]. The present study documents the importance of humoral immune responses in patients receiving mogamulizumab-containing treatment. Further investigation of strategies to enhance humoral immune responses in patients with ATL is warranted.

Surveillance of the current situation regarding influenza vaccination according to medical oncologists in Japan.

This study aimed to clarify the attitude of oncologists toward influenza vaccination and the current situation and issues regarding influenza vaccination for patients on chemotherapy in Japan. A web-based survey of medical oncologists certified by the Japanese Society of Medical Oncology was conducted between November 1 and December 31, 2019. Of the 1369 medical oncologists who were invited to participate, 415 (30.3%) responded to our survey. The questionnaire comprised 4 sections: "oncologist characteristics," "oncologist attitude toward influenza vaccines and the current status of influenza vaccination for cancer patients undergoing chemotherapy," "incidence of influenza infection and associated treatment complications," and "treatment policy for influenza infection." In total, 153 (36.9%) physicians replied that they did not actively encourage influenza vaccination for patients undergoing chemotherapy. The primary reasons given were lack of evidence (48/153, 31.4%) and uncertainty of appropriate timing (46/153, 30.1%). There was diverse variation in the timing of vaccination and in the levels of encouragement based on the cancer location and medication type. Two hundred eighty-three (68.2%) oncologists reported that their cancer patients had experienced influenza infection while undergoing chemotherapy, and 169 (40.7%) responded that their patients had experienced an administration delay or discontinuation of medication because of influenza infection. Our surveillance revealed some oncologists considered evidence regarding the administration of influenza vaccine to cancer patients undergoing chemotherapy (particularly the optimal timing and level of recommendation by cancer location and medication) to be lacking. It also exposed the adverse impact of influenza infection in cancer patients.

Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: Update summary of the 2015 Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis.

Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).

[Risk Assessment of Hematologic Malignancy Treatment of the Elderly].

Along with the aging society in Japan, the number ofelderly cancer patients is increasing, and hematological malignancy is no exception. Treatment ofhematological malignancy is mainly chemotherapy and furthermore it is necessary to keep its dose intensity. In the elderly, adverse events may be strong due to deterioration oforgan function, comorbidity, etc., and it is difficult for individual differences to decide chemotherapy regimen and dose. Geriatric assessment(GA)used in the field of geriatric medicine is reported to be useful for risk assessment of chemotherapy. The usefulness of GA is also shown in hematological malignancy. In non-Hodgkin's lymphoma, attempts have been made to determine the treatment method by stratifying the risk using the results of GA.

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary.

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

[The survey for anti-emetic guideline by using questioner].

BACKGROUND: Japan Society of Clinical Oncology published a guideline for anti-emetic therapy two years ago. This guideline was a first evidence based guideline of anti-emetic treatment for the patients who received chemotherapy in Japan. To investigate a current situation of anti-emetic treatment in Japan, we analyzed the data from nationwide questionnaire. MATERIAL: Questionnaire analysis; From June 2012 to August 2012, we gave 24 questionnaires on the Japan Society of Clinical Oncology Website and collected the response from the member of 5 major academic oncology societies. The questionnaires included degree of recognition, penetration, usefulness, problems and user type of medial stuff for the anti-emetic guideline published by (JSCO). RESULTS: Questionnaire; 1,529 medical stuff responded to our questionnaire. 1,308 (85.5%) stuffs recognized JSCO guidelines, 586 (51%) had regard for guideline and 489 (42.6%) referred to the guideline. 899 (78.3%) changed their practice in clinic to recommended practice by the guideline. But 385 (33.5%) complained high medical cost of recommended anti-emetic therapy. CONCLUSIONS: Degree of recognition and penetration of our guideline for anti-emetic therapy were very high in Japan.

Direct endoscopic probing for congenital lacrimal duct obstruction.

BACKGROUND: The most common treatment for congenital lacrimal duct obstruction is standard probing without dacryoendoscopy. However, the lacrimal duct cannot be observed in this procedure. If the probing procedure allows the observation of the lacrimal duct, it could be more successful and safer. To use endoscopic probing to view the lacrimal duct in cases of congenital lacrimal duct obstruction 6 months post-surgery and to evaluate the condition of the lumen while simultaneously performing direct endoscopic probing. DESIGN: This is a retrospective, non-comparative case series. PARTICIPANTS: The study participants were 10 children aged 14-74 months, including three children with bilateral obstruction. In total, 13 congenital lacrimal duct obstruction were probed. METHODS: The patients underwent direct endoscopic probing with dacryoendoscopy instead of blind probing, that is, standard probing without dacryoendoscopy under brief total anaesthesia. MAIN OUTCOME MEASURES: During the procedure, outcomes were assessed as the endoscope reached the nasal cavity. A successful probing outcome was defined as an absence of tearing and discharge. RESULTS: Twelve congenital lacrimal duct obstruction were successfully treated by direct endoscopy, whereas one was not. There were various sites of obstruction and various conditions such as oedematous thickening of the mucosa of the lacrimal duct and fibrous tissue because of chronic inflammation. The subjective outcome from their parents by telephonic interview was obtained. Epiphora disappeared in 12/13 (92.3%) of the eyes treated by endoscopy; however, 5/13 (38.5%) of the patients reported occasional discharge from the eyes. CONCLUSIONS: Direct endoscopic probing is effective and safe to treat cases of congenital lacrimal duct obstruction in children.

Comprehensive geriatric assessment as a useful tool in predicting adverse events in elderly patients with diffuse large B-cell lymphoma.

We conducted a multicenter prospective study on whether a comprehensive geriatric assessment (CGA) can predict the adverse events (AEs) of chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients aged ≥ 65 years with newly diagnosed DLBCL underwent a pretreatment baseline CGA consisting of six assessment tools: activities of daily living (ADL), instrumental ADL (IADL), mood, nutritional status, comorbidities, and cognitive function. An attending physician chose each patient's treatment but was blind to CGA results. Patients were grouped as "dependent" or "independent" according to the CGA. The primary endpoint was to evaluate the association between chemotherapy-induced grade 3-4 toxicity and CGA. Of 86 patients, 78 completed the designated CGA. The median age was 79 years (65-89). Seventy-two patients were treated with a cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP-like) regimen, and six were treated with low-toxicity regimens. Forty-one patients were classified as dependent and 37 as independent. In multivariate analysis, an impairment of IADL was independently associated with grade 3-4 leukopenia (odds ratio [OR] 0.63; 95% confidence interval [CI] 0.43-0.92, p = 0.017) and anemia (OR 0.67; 95% CI 0.50-0.90, p = 0.008). The presence of a comorbidity was also associated with grade 3-4 non-hematological toxicity (OR 2.17; 95% CI 1.37-3.43, p = 0.001). The 4-year survival rate tended to be longer in the independent (72.7%) compared to dependent (56.9%) group. Overall, a CGA may be a useful tool for predicting serious AEs associated with chemotherapy in elderly patients with DLBCL.

Focal segmental glomerulosclerosis and concurrent glomerular microangiopathy after long-term imatinib administration.

A 79-year-old Japanese man was admitted to our hospital because of proteinuria and kidney dysfunction. He was diagnosed with chronic myeloid leukemia 13 years before and was treated with imatinib. Deep molecular response was achieved but he developed 1+ proteinuria in the first year, which gradually worsened thereafter. Imatinib was discontinued 12 years later but proteinuria and kidney dysfunction were progressive. Percutaneous kidney biopsy revealed mild mesangial hyper-cellularity and matrix increase, swelling of endothelial cells, and partial double contours of glomerular tufts. Subendothelial edema in the interlobular artery was also noted. Immunofluorescence was not remarkable. Electron microscopy revealed endothelial injury with severe sub-endothelial edema. Since imatinib had already been discontinued, conservative therapy with maximal dose of azilsartan was administered. A second biopsy was performed 1 year later because of further deterioration of kidney function, which revealed markedly increased global glomerulosclerosis and severe interstitial fibrosis and tubular atrophy. Segmental glomerulosclerosis with podocyte hyperplasia was also observed. Electron microscopy revealed glomerulosclerotic changes and partially attenuated endothelial injury. Two and a half years later, proteinuria reduced, progression of kidney dysfunction slowed, and he was independent on dialysis therapy. Molecular response of chronic myeloid leukemia was also maintained. The clinical course suggested that endothelial and podocyte injuries were induced by imatinib, and that the nephrotoxic effects lasted for a few years after discontinuation.

Operative Complications of Glaucoma Drainage Implant Tube Insertion Through the Sulcus for Pseudophakic Eye.

PRECIS: Malposition of the tube through the ciliary sulcus is more frequently observed with the Ahmed glaucoma valve (AGV) than the Baerveldt drainage implant (BDI) due to the weaker rigidity of the Ahmed tube. PURPOSE: To report intraoperative and early postoperative complications of ciliary sulcus tube insertion of glaucoma drainage implants (GDIs). PATIENTS AND METHODS: We performed retrospective analysis of 104 eyes of 94 patients with GDI tube insertion through the ciliary sulcus were performed. The rigidities of tubes were also examined using a microcompression tester. RESULTS: The mean observation period was 20.0 (range, 6 to 60) months. Thirteen eyes were treated with the BDI and 91 were with the AGV. The mean age of the patients was 69.3 (34 to 90) years. The mean intraocular pressure was 27.9 mm Hg before surgery and 12.9 mm Hg after surgery (P<0.01). Upon tube insertion 42/91 eyes (46%) with the AGV required reinsertion of the tube due to malpositioning, whereas only 1/13 (8%) eyes with BDI did (P<0.01). Transient hyphema (12 eyes) and hypotony (12 eyes) were observed as early postoperative complications with the AGV. Seven eyes with hypotony were treated by proline stenting of the tube. We could not accomplish sulcus insertions in 4 eyes. Microcompression analysis of the tubes showed that the BGI tube was more rigid than that of the AGV. CONCLUSIONS: Ciliary sulcus insertion of the tube is an effective method to control intraocular pressure. The tube of the AGV was more difficult to insert through the sulcus than the BDI due to its weaker rigidity.

[Extranodal NK/T-cell lymphoma arising from soft tissue of the left forearm].

A 72-year-old man with extranodal natural killer cell lymphoma (ENKL) presented with a painless swelling of the left forearm. He was initially diagnosed as having a bacterial cellulitis and received antimicrobial therapy. However, his left arm became increasingly swollen in association with fever and redness of the lesion. Therefore, he underwent focal dissection. Because of persistent swelling, the left arm was rebiopsied 9 months later, and a diagnosis of ENKL developing in the subcutis was established. He was treated with focal radiation therapy in combination with dexamethasone, etoposide, ifosfamide, methotrexate and L-asparaginase. The lesion was significantly reduced in size but did not disappear completely. Two months later the lesion became necrotic, although swelling of the forearm lesion, left axillary and cervical lymph nodes were kept under control. We then performed amputation of the left forearm since it could not be saved medically. The patient currently remains alive and well without progression 2 years after amputation. When evaluating panniculitis, which is difficult to cure, ENKL should be considered in the differential diagnosis and treated appropriately.

Efficacy of oral levofloxacin monotherapy against low-risk FN in patients with malignant lymphoma who received chemotherapy using the CHOP regimen.

The safety and feasibility of oral fluoroquinolone monotherapy in patients with low-risk febrile neutropenia (FN) were demonstrated in recent studies. Levofloxacin (LVFX) is a commonly prescribed antibiotic; however, evidence for its efficacy against FN is limited. Therefore, in this study, we retrospectively investigated the efficacy of LVFX against low-risk FN in patients with malignant lymphoma at our institution. Treatment success was defined as recovery from fever and neutropenia without alteration of the initial regimen. We recruited 29 patients between January 2013 and December 2018. The median age of the cohort was 64 (range: 21-87) years; 13 (44.8%) were aged over 65 years. In total, 22 patients had diffuse large B-cell lymphoma (DLBCL). Therapy was successful in 24 (82.8%) patients, whereas 5 had treatment failure requiring a change from LVFX to intravenous broad-spectrum antibacterial agents. No deaths related to FN were observed. Two patients required FN-related chemotherapy dose reduction in subsequent cycles. Although this cohort comprised many elderly patients, our study confirmed the efficacy of LVFX in patients with low-risk FN. This may improve the treatment of low-risk FN and malignant lymphoma.

Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study.

Monitoring of Immune Responses Following Mogamulizumab-Containing Treatment in Patients with Adult T-Cell Leukemia-Lymphoma (ATL) (MIMOGA) is a multicenter prospective observational study to establish the most effective and safe treatment strategy using mogamulizumab for ATL patients (UMIN000008696). Mogamulizumab-naive patients were enrolled (n = 102), of whom 101 received mogamulizumab-containing treatment (68 acute, 18 lymphoma, 12 chronic, and 3 smoldering subtypes). At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD8+ T cell subset, but there was not a correlation with cytomegalovirus pp65-specific cytotoxic T lymphocytes (CMV-CTLs). The overall response rate was 65%, and median progression-free survival and overall survival (OS) were 7.4 and 16.0 months, respectively. A higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or in the CD8+ T cell subset was significantly associated with longer survival. Multivariate analysis identified the clinical subtype (acute or lymphoma type), a higher sIL-2R level, and a lower percentage of CD2-CD19+ B cells in peripheral blood mononuclear cells as significant independent unfavorable prognostic factors for OS. This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment. In conclusion, the MIMOGA study has demonstrated that mogamulizumab exerts clinically meaningful antitumor activity in ATL. The patient's immunological status before mogamulizumab was significantly associated with treatment outcome. Further time series immunological analyses, in addition to comprehensive genomic analyses, are warranted.

Severe Hemorrhagic Cystitis Caused by Cyclophosphamide and Capecitabine Therapy in Breast Cancer Patients: Two Case Reports and Literature Review.

Combined oral cyclophosphamide and capecitabine (XC) chemotherapy is used for metastatic breast cancer (MBC) patients. We report herein two MBC patients who developed severe hemorrhagic cystitis after XC therapy. Case 1: A 67-year-old woman with MBC had received XC therapy for 2.5 years. After a sudden onset of lower abdominal pain and gross hematuria, cystoscopy revealed a urinary bladder mucosa showing diffuse dilation of the capillaries and a large blood clot. A total dose of 60.8 g cyclophosphamide had been given and the XC regimen was discontinued immediately. The patient experienced frequent episodes of bladder tamponade over 18 months and underwent continuous bladder irrigation and cystoscopic fulguration. Hyperbaric oxygen therapy (HBOT) provided only temporary relief and the patient subsequently developed hemorrhagic shock. A bilateral ureterostomy was eventually performed. Case 2: A 65-year-old woman with MBC was given XC for 3 years, but this was discontinued after she developed new lung lesions. The patient was given a total dose of 78.4 g of cyclophosphamide. A month later, the patient complained of intermittent gross hematuria, which progressed to persistent macroscopic hematuria for 1 week. She underwent continuous bladder irrigation with saline, without an improvement in her bladder tamponade. Subsequently, the bleeding ceased completely after HBOT. Some MBC cases can be controlled for a long time with XC therapy. For those cases, we need to realize that severe hemorrhagic cystitis may occur. Even at a low dose, requires testing periodically for occult blood in the urine to detect the early stages of cystitis.