Influence of interruption of oral mycophenolate mofetil for graft-versus-host disease prophylaxis on outcomes after single cord blood transplantation.

Mycophenolate mofetil (MMF), in combination with a calcineurin inhibitor, is used as the prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). Compared to intravenous methotrexate (MTX), MMF is associated with a lower incidence of mucositis and shorter time for hematopoietic engraftment but comparable incidence of acute GVHD, resulting in the preferred use of MMF for GVHD prophylaxis in elderly patients or those undergoing cord blood transplantation (CBT). Although several studies have evaluated the clinical impact of MTX omission due to toxicity after allogeneic HCT, the impact of oral MMF interruption for GVHD prophylaxis on transplant outcomes remains unclear. Therefore, in this study, we retrospectively analyzed the consecutive data of adult patients who underwent single-unit unrelated CBT and received oral MMF in combination with cyclosporine for GVHD prophylaxis at our hospital. Among the 53 patients, the planned dose of MMF was interrupted in 14 with a median of 19.5 d (range, 3-27 d) of CBT. In multivariate analysis, MMF interruption, which was treated as a time-dependent covariate, was significantly associated with poorer overall survival (hazard ratio [HR], 5.41; 95% confidence interval [CI], 2.03-14.43; P < 0.001) and higher non-relapse mortality (HR, 7.56; 95% CI, 1.99-28.79; P = 0.002). Further studies with larger cohorts are necessary to confirm the clinical significance of oral MMF interruption in GVHD prophylaxis.

Evaluation of clinical effects of a multidisciplinary-collaborated cancer support team for gastrointestinal cancer chemotherapy: prospective observational study protocol of M-CAST study.

BACKGROUND: Although the multidisciplinary-collaborated team approach in cancer treatment has recently become popular, prospectively evaluated evidence is limited. We started a multidisciplinary-collaborated cancer support team (MCST) to facilitate cooperation across multidisciplinary medical staff in our hospital and established clinical evidence of supportive care. This study aimed to prospectively evaluate the clinical activity and effect of MCST in patients with gastrointestinal cancer receiving chemotherapy. METHODS: This is a single-center, single-arm, observational study. Patients with gastrointestinal cancer scheduled to receive chemotherapy are enrolled and supported by the MCST. The primary endpoints are the number of interventions by medical staff and the number of patients who showed improvement in side effects. The secondary endpoints are the severity of side effects, medical expenses, number of consultations, the acceptance rate of prescription recommendations, adjuvant chemotherapy completion rates, dose intensity, and time required for co-medical intervention. In addition, medical staff and attending physicians evaluate all adverse events. DISCUSSION: This study is expected to contribute to establishing new cancer-supportive care teams for patients with gastrointestinal cancer receiving chemotherapy and those with cancer receiving chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCT1030220495. The date of first registration, 29/11/2022, https://jrct.niph.go.jp/search.

Delayed Oxaliplatin-Related Severe Neurotoxicity in Metastatic Colorectal Cancer: A Case Report.

In patients receiving oxaliplatin-based chemotherapy, resulting in frequent peripheral neuropathy and requiring long-term management, anticancer drug-induced platinum-based peripheral neuropathy (mixed motor, sensory, and autonomic neuropathy) can result in the coasting phenomenon in which the symptoms worsen temporarily after two to three weeks, even after the cessation of the drug. The coasting phenomenon is difficult to manage due to the unpredictable nature of the symptoms. We encountered a patient with grade 3 peripheral neuropathy that developed rapidly in the second cycle after the treatment to switch from mFOLFOX6/bevacizumab to FOLFIRI/aflibercept. Supportive care with duloxetine was unsuccessful in this patient. Herein, we report the case.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Long-Term Incidence of Varicella Zoster Virus Disease in Adults Receiving Single-Unit Cord Blood Transplantation.

Although varicella zoster virus (VZV) disease is a common complication after allogeneic hematopoietic cell transplantation (HCT), research into the long-term incidence of VZV disease in adults receiving cord blood transplantation (CBT) has been limited. The objective of this study was to evaluate the incidence, risk factors, and clinical impact of VZV disease after CBT with long-term follow-up in our institution. We retrospectively analyzed the data for 156 adult patients who received single-unit CBT at our institution between 2007 and 2020 and who achieved neutrophil engraftment and survived at least 100 days without recurrence of the underlying disease. VZV disease occurred in 61 patients at a median of 608 days (range, 36 to 4090 days) after CBT. The cumulative incidence of VZV disease was 14% (95% confidence interval [CI], 9% to 20%) at 1 year post-CBT and 40% (95% CI, 31% to 48%) at 5 years post-CBT. Multivariate analysis identified the cessation of antiviral prophylaxis as an independent risk factor for an elevated risk of VZV disease (hazard ratio, 15.65; 95% CI, 6.59 to 37.21; P < .001). The cumulative incidence of VZV disease was significantly lower in the long-term antiviral prophylaxis group (who received prophylaxis for approximately 1 year after CBT or to the end of immunosuppressive therapy) compared with the short-term antiviral prophylaxis group (who received prophylaxis for 35 days after CBT) (P = .005). Among the patients who developed VZV disease, the median time to onset of VZV disease was significantly delayed in the long-term antiviral prophylaxis group compared with the short-term antiviral prophylaxis group (694 days versus 130 days; P < .001), but the median onset of VZV disease after the cessation of antiviral prophylaxis was not significantly different between the 2 groups (166 days versus 95 days; P = .087). These data demonstrate that the long-term incidence of VZV disease is relatively high in adult patients undergoing CBT. Given that the incidence of VZV disease remained high after the cessation of antiviral prophylaxis, additional interventions, such as recombinant zoster vaccine administration, could be required to prevent VZV disease in long-term adult survivors after CBT.

Severe thrombocytopenia induced by chemotherapy after total gastrectomy: A report of three cases.

Pancytopenia associated with vitamin B12 and folic acid deficiency has been reported in patients who have undergone total gastrectomy. Therefore, myelosuppression due to chemotherapy following total gastrectomy is considered to be more serious. We encountered three cases of severe thrombocytopenia in patients who received chemotherapy after total gastrectomy. The lowest platelet levels in these patients were 1.7 × 104/mm3, 2.3 × 104/mm3, and 0.9 × 104/mm3, respectively. None of the patients presented with vitamin B12 deficiency, and one patient presented with folic acid deficiency. The association between serum vitamin levels and chemotherapy-related adverse events is controversial. Since folic acid has a shorter half-life (6 hours) and cannot accumulate in the body, unlike vitamin B12 that is stored for a long time in the liver, folic acid deficiency is suspected to be associated with thrombocytopenia induced by post-total gastrectomy chemotherapy. However, serum folic acid levels fluctuate depending on the timing of evaluation and require a few days to evaluate. In conclusion, patients who undergo chemotherapy after total gastrectomy should be monitored for severe thrombocytopenia but serum vitamin B12 levels are not necessarily clinically important. By measuring serum folic acid levels at appropriate times, folic acid deficiency may prove to be a reference for predicting severe thrombocytopenia.

Thiamine Deficiency and Neurological Symptoms in Patients with Hematological Cancer Receiving Chemotherapy: A Retrospective Analysis.

Objectives Patients with hematological cancer receiving chemotherapy have a high risk of thiamine deficiency due to accelerated thiamine usage by tumor cells. Mild or severe thiamine deficiency can lead to varying degrees of neurological symptoms. We evaluated the relationship between thiamine deficiency and neurological symptoms, including mild or nonspecific symptoms, and the influence of chemotherapy on thiamine serum levels in patients with hematological cancer receiving chemotherapy. Materials and Methods We retrospectively identified 42 patients diagnosed with hematological cancer at our hospital, using electronic medical records collected from March 2019 to March 2020. We evaluated the risk factors associated with neurological symptoms (mild-to-severe cognitive impairment, attention impairment, and mood or emotional disorder), the relationship between the presence of neurological symptoms and thiamine serum levels, and changes in thiamine serum levels after chemotherapy. Results Thiamine deficiency was significantly associated with neurological symptoms. The thiamine serum levels in the group with neurological symptoms were significantly lower than those in the group without neurological symptoms. The Wilcoxon rank-sum test showed that thiamine serum levels after chemotherapy were significantly lower than those before administration of chemotherapy. Conclusion Thiamine serum levels in patients with hematological cancer may be used as a reference to maintain neurological status during chemotherapy.

Chemotherapy-related dysphonia: Similar and differentiating features of six cases.

Dysphonia has been reported with anti-angiogenic chemotherapy agents. Dysphonia in patients with cancer receiving chemotherapy tends to be overlooked in clinical practice since it is non-life-threatening. However, it reduces quality of life. Although inhibition of vascular endothelial growth factor receptor is the reported mechanism of dysphonia, it has not been elucidated. We report 6 cases of patients with dysphonia suspected to be due to panitumumab and nivolumab that have not been reported previously. Peripheral edema, a factor in dysphonia, can be seen with aflibercept, bevacizumab, panitumumab, and nivolumab. Therefore, chemotherapy drugs with peripheral edema may be related to dysphonia.

Association between thiamine decrease and neuropsychiatric symptoms in gastrointestinal and hematological cancer patients receiving chemotherapy.

BACKGROUND: Clinical evidence of thiamine-related neuropsychiatric symptoms, including the initial stage, is limited because serum thiamine levels tend to be evaluated only for patients who develop severe neuropsychiatric symptoms suspected to be related to severe thiamine deficiency. This study aimed to evaluate the relationship between thiamine decline and neuropsychiatric symptoms, including initial symptoms, and the effect of chemotherapy on serum thiamine levels in gastrointestinal and hematological cancer patients receiving chemotherapy. METHOD: We retrospectively identified 87 patients who were diagnosed with gastrointestinal and hematological cancers at our hospital. We evaluated the risk factors associated with neuropsychiatric symptoms, including initial symptoms (neuropsychiatric symptoms), the relationship between the presence of neuropsychiatric symptoms and serum thiamine levels, and changes in serum thiamine levels after chemotherapy. RESULTS: Logistic regression analysis identified thiamine decline as a significant factor associated with neuropsychiatric symptoms (p < 0.001, odds ratio = 0.040, 95% confidence interval [CI]: 0.010-0.163). The Mann-Whitney U test showed that patients with neuropsychiatric symptoms had significantly lower serum thiamine levels (19.5 ± 5.4 ng/mL, n = 39) than patients without neuropsychiatric symptoms (31.9 ± 14.2 ng/mL, n = 48) (p = 0.001). In hematological cancer patients, serum thiamine levels gradually declined after chemotherapy, with the lowest levels at 5-8 weeks (23.5 ± 7.6 ng/mL, P = 0.035 vs. 0 weeks, Wilcoxon rank sum test). CONCLUSION: Our study showed that a decrease in serum thiamine levels can be a risk factor for neuropsychiatric symptoms, and chemotherapy can lead to a decrease in serum thiamine levels.

Hyperammonemia-induced impaired consciousness following mFOLFOX6 therapy in a patient with recurrent rectal cancer.

OBJECTIVES: FOLFOX is a standard chemotherapy regimen used to treat colorectal cancer. Adverse events associated with FOLFOX treatment include peripheral neuropathy and myelosuppression. This report discusses the case of a 64-year-old man with rectal cancer who developed hyperammonemia and impaired consciousness following initiation of mFOLFOX6 as a postoperative adjuvant therapy. METHODS: This case study reports on the clinical disease progression of the aforementioned patient. RESULTS: Following preoperative chemoradiotherapy, the patient underwent low anterior resection for rectal cancer. mFOLFOX6 was then initiated as postoperative adjuvant therapy. During the 5th cycle of mFOLFOX6 treatment, the patient presented with impaired consciousness and upper extremity convulsions. Blood testing revealed marked hyperammonemia (349 µg/dL (normal range: 12 - 66 µg/dL)). Imaging did not reveal any intracranial lesions that could cause impaired consciousness. The patient recovered within a day after rehydration and BCAA substitution. CONCLUSION: Although impaired consciousness is a rare adverse reaction of FOLFOX, it has a major psychological impact on the patient and his/her family. Hyperammonemia should therefore be considered a potential cause of impaired consciousness during FOLFOX therapy and should be appropriately diagnosed and treated.

[Optimization of Preparation, and Stability of Indomethacin Mouth Wash for Oral Mucositis Caused by Cancer Therapy].

OBJECTIVE: Severe oral mucositis caused by chemo- and radio-therapy is a common adverse event in patients with cancer. In this study, we investigated the development of an indomethacin mouth wash(IM-MW)as a novel approach to treat pain due to oral mucositis. METHODS: We examined the appropriate preparation methods for IM-MW with suitable stability. IM- MW was made from bulk IM, controlled release IM capsules, and IM capsules. Dissolution in water was tested at water temperatures of 70℃, 90℃, and 98℃(n=3), and with a shaking time of 30 or 60s(n=3). We determined the IM concentration in IM-MW by HPLC-UV analysis(n=5)at time points between just after preparation and day 7, to estimate the shelf- life at 4℃ and 25℃. RESULTS: At 70℃, bulk IM did not dissolve, but at 90℃ and 98℃, bulk IM, controlled release IM capsules, and IM capsules all dissolved effectively. Shaking times of 30 and 60s were sufficient to dissolve bulk IM, controlled release IM capsules, and IM capsules. The stability of IM in IM-MW was 98.6±2.8%(bulk), 99.2±6.0%(controlled release capsule), and 98.5±6.0%(capsule)over 7 days at 4℃. However, at 25℃, IM stability in IM-MW decreased to 95.3±1.8% (bulk), 86.1±4.8%(controlled release capsule), and 83.6±1.6%(capsule). CONCLUSION: In this study, we identified the most suitable method for the preparation of IM-MW(90℃, shaking time of over 30s). IM-MW was stable when stored at 4℃ for at least 7 days after preparation.

Potential thiamine deficiency in elderly patients with gastrointestinal cancer undergoing chemotherapy
.

Gastrointestinal cancer and its treatment using fluorouracil-based anticancer agents are risk factors for thiamine deficiency (TD). Therefore, we aimed to determine the prevalence of TD among elderly patients with gastrointestinal cancer undergoing chemotherapy. We retrospectively reviewed the medical records of 12 elderly patients with gastrointestinal cancers who underwent chemotherapy. Median serum thiamine level was 22.5 ng/mL (range, 17 - 42 ng/mL). Four patients (33.3%) exhibited TD (< 20 ng/mL). We found that the prevalence of TD among elderly patients with gastrointestinal cancer undergoing chemotherapy was high. For these patients, careful monitoring of thiamine levels is warranted because TD may not produce overt clinical symptoms.

Potential thiamine deficiency and neurological symptoms in patients receiving chemotherapy for gastrointestinal cancer.

OBJECTIVES: The aim of this retrospective study was to search for risk factors for neurological adverse events in gastrointestinal cancer patients receiving chemotherapy and analyze the relationship between thiamine serum levels and neurological adverse events. MATERIALS AND METHODS: This is a single-center retrospective observational study. We enrolled patients who were diagnosed with gastrointestinal cancer at our hospital, for whom we measured the thiamine serum levels. We then performed a multivariate analysis (logistic regression) to identify risk factors for the neurological symptoms in our cohort. We then divided the patients into two groups, with and without neurological symptoms, based on their electronic medical records. By using the Mann-Whitney U-test, we performed a comparative analysis of the thiamine serum levels between the two groups. We also used descriptive statistics to examine the presence/absence of neurological symptoms or other potentially related clinical features in patients with decreased thiamine serum levels. RESULTS: The logistic regression analysis detected the decrease in thiamine serum levels as a statistically significant risk factor for neurological symptoms. The analysis of the relationship between the presence/absence of neurological symptoms and thiamine serum levels showed that the thiamine serum levels were significantly lower in the group presenting neurological symptoms. Descriptive statistics showed that all the patients with decreased thiamine serum levels had either cognitive decline, attention decline, or depression symptoms, and most of them were receiving the 5-fluorouracil anticancer drug and showing decreased serum albumin levels. We also observed a slight decrease in serum sodium, vitamin B12, and folate levels. CONCLUSION: When neurological symptoms occur in patients receiving chemotherapy for gastrointestinal cancer, the measurement of thiamine serum levels may become a standard reference for treatment indication.

Thiamine deficiency as a possible cofactor causing cognitive dysfunction in a patient with end-stage gastric cancer
.

We describe a case of a patient treated for cognitive dysfunction (CD) with suspected thiamine deficiency (TD). A 74-year-old man with gastric cancer presented with grade 3 diarrhea and grade 1 anorexia. He had been receiving trastuzumab plus tegafur (a chemotherapeutic fluorouracil prodrug), gimeracil, and oteracil (S-1) and oxaliplatin. On admission, cognitive function was assessed with the Hasegawa's Dementia Scale (HDS-R) because he had impaired short-term memory. His thiamine levels increased from 22 to 109 ng/mL after administration of 75 mg of thiamine. Furthermore, the patient's HDS-R score improved from 9 to 22, and cognitive and memory functions improved. TD should be considered in older CD patients receiving oral chemotherapy agents including fluorouracil.

Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients Undergoing Unrelated Cord Blood Transplantation.

Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive therapy and treatment of invasive fungal infections after cord blood transplantation (CBT). We retrospectively examined the efficacy and safety of low-dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our institute. Within the entire cohort, 42 patients (88%) received L-AMB as empirical or preemptive therapy. The median daily dose of L-AMB and the median cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and 30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L-AMB administration was 21.5 days (range, 1 to 313 days). A documented breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and 43 patients (90%) survived for at least 7 days after the end of L-AMB treatment. Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during L-AMB treatment. However, no patient developed an increase in serum creatinine levels of grade 3 or higher. In univariate analyses using a logistic regression model, a duration of L-AMB treatment of more than 21 days and a cumulative dose of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and effective in adult patients undergoing CBT.

[Effect of the Administration Period of Rasburicase in Japanese Adult Hematological Malignancy Patients at High-Risk for Tumor Lysis Syndrome].

Tumor lysis syndrome (TLS) is a life-threatening metabolic complication caused by the rapid breakdown of malignant cells. It is an oncologic emergency and occurs spontaneously after the initiation of chemotherapy for hematological malignancies. Therefore, the management of TLS is important. Rasburicase (RSB) has been shown to be effective for the management of TLS. We retrospectively investigated the optimal administration period of RSB (1 to 7 days) for 38 adult patients with a hematological malignancy who were at high risk for TLS. In all patients, the serum uric acid (sUA) value did not increase beyond the upper limit of normal. Clinical TLS did not occur in any patients. Seven patients were administered a single-dose of RSB and sUA remained within normal limits. These results suggested that single-dose RSB administration was efficacious for Japanese adult patients with hematological malignancies who are at high risk for TLS.