Clinical Benefit of Low-Dose Antithymocyte Globulin-Thymoglobulin as Graft-versus-Host Disease Prophylaxis in Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation from HLA-Identical Donors.

Graft-versus-host disease (GVHD) is a major complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Previous randomized studies have already shown that the use of several types of antihuman T lymphocyte immune globulin (ATG) as GVHD prophylaxis can reduce the incidence of acute GVHD and chronic GVHD. However, the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG remain unclear. This study aimed to clarify the efficacy and safety of PBSCT from HLA-identical donors with low-dose ATG compared with PBSCT from HLA-identical donors without ATG. To do so, we retrospectively analyzed the outcomes of patients who underwent allogeneic PBSCT from HLA-identical donors with low-dose ATG-thymoglobulin (ATG-T; 2.5 mg/kg) versus those who did not receive ATG-T. Patient data were collected retrospectively from the medical records of Anjo Kosei Hospital. This study was conducted from 2009 to the final follow-up in October 2022. Forty-seven of 91 patients received ATG-T between January 2009 and March 2020. ATG-T reduced the incidence rates of moderate-to-severe chronic GVHD (hazard ratio [HR], .15; 95% confidence interval [CI], .057 to .41; P < .0010) and nonrelapse mortality (HR, .21; 95% CI, .0058 to.75, P = .016) without increasing the risk of relapse. Overall survival did not differ significantly between the 2 groups; however, the low-dose ATG-T group had better moderate-to-severe chronic GVHD-free, relapse-free survival rates (HR, .47; 95% CI, .27 to .80, P = .0054) than the non-ATG-T group. In addition, multistate analysis revealed that the low-dose ATG-T group had better current GVHD-free, relapse-free survival at 24 months after transplantation (45% [95% CI, 29% to 63%)] versus 21% [95% CI, 9.1% to 34%]; P = .015). Low-dose ATG-T was not associated with increased incidence of infections or adverse events. Our findings suggest that low-dose ATG-T can be beneficial for patients receiving PBSCT from HLA-identical donors. © 2023 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Feasibility of trimethoprim/sulfamethoxazole desensitization therapy in hematological diseases.

The effectiveness and safety of trimethoprim/sulfamethoxazole (TMP/SMX) desensitization therapy is insufficiently evaluated in hematological diseases. From 2002 to 2019, we retrospectively analyzed 112 patients with hematological diseases who underwent desensitization therapy after TMP/SMX prophylaxis withdrawal due to adverse events. They orally started TMP/SMX at 0.4 mg/2 mg, which was then increased daily to 80 mg/400 mg for 5 or 9 days. Eighty-eight patients (79%) had complete desensitization, and the major reason for failure was rash seen in 21 cases (19%). The cause of desensitization and reasons for failure matched in 22 cases (92%). Pneumocystis pneumonia was not observed throughout the study. In the failure group, the number of eosinophils and alanine aminotransferase (ALT) levels were significantly increased after desensitization. In particular in the failure group, the slight increase in eosinophils was seen through the beginning to halfway during desensitization (36/µL (0-900/µL) and 48/µL (0-2560/µL), respectively, p = 0.025). These data show that TMP/SMX desensitization therapy is effective and safe in hematological diseases. The recurrence of adverse events could help predict desensitization success.

[A case report of complete response by S-1/docetaxel combination chemotherapy for advanced gastric cancer].

A 52-year-old male patient with advanced gastric cancer and multiple lymph node metastasis was treated by S-1/docetaxel combination chemotherapy from April, 2004. As of January 2005, after the tenth course, a scarred tumor was observed with an endoscope, and negative neoplastic cells were found on endoscopic biopsy. After the sixteenth course in July, 2005, CT scan showed that the lymph node metastasis had disappeared. The primary and metastatic lesions were regarded to have responded completely. A total of 26 courses of chemotherapies were undergone until March, 2006. We are taking a wait and see approach at this writing without treatment since then. The patient has had a recurrence-free survival for about five years since the onset. The results suggested that the S-1/docetaxel chemotherapy for metastatic gastric cancer had confirmed feasibility and sufficient efficacy while maintaining the patient's quality of life.

5-Fluorouracil-related gene expression in primary sites and hepatic metastases of colorectal carcinomas.

UNLABELLED: The aim of this study was to investigate the correlation of the mRNA expressions of 5-fluorouracil (5FU)-related genes in the primary sites and liver metastases of colorectal carcinomas. PATIENTS AND METHODS: Patients with liver metastases from colorectal carcinomas were included (n = 43). The expression ratios to beta-actin of mRNA of thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and oroteta phosphoribosyl transferase (OPRT) were measured in primary and liver metastases of colorectal carcinomas by laser-captured microdissection and real time PCR. RESULTS: The ratios for the expression of TS, DPD, TP and OPRT mRNAs were significantly correlated between paired primary sites and liver metastases. The mRNA expression ratios of DPD and TP showed a significant correlation both in primary sites and in liver metastases. CONCLUSION: Enzymes of the primary colorectal carcinomas can be used in predicting the therapeutic efficacy of 5FU against liver metastases.

5-Fluorouracil-related gene expression in hepatic artery infusion-treated patients with hepatic metastases from colorectal carcinomas.

AIM: To predict the therapeutic efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil (5FU) for patients with liver metastases from colorectal carcinomas, 5FU-related gene expressions were examined in primary colorectal carcinomas. PATIENTS AND METHODS: Thirty-eight patients with liver metastases from colorectal carcinoma received HAI of 5FU. The expressions of the mRNAs for thymidine synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and oroteta phophoribosyl transferase (OPRT) in primary colorectal carcinomas were measured by RT-PCR. RESULTS: The response rate was 52.6% (20/38). The overall median survival time was 29.1 months. DPD and TP expression was significantly higher in the progressive disease (PD) group than in the complete response (CR) or partial response (PR) group (p = 0.032, p = 0.014), respectively. The levels of DPD and TP mRNAs showed a significant correlation (r = 0.76, p = 0.0001). CONCLUSION: The expression of DPD and TP mRNAs in primary colorectal carcinomas was significantly predictive of the therapeutic response to 5FU HAI.

C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn's disease.

BACKGROUND: The ability of serum infliximab level to predict clinical outcome in infliximab therapy in Crohn's disease is unclear. Here, we aimed to clarify the correlation between the timing of loss of response (LOR) to treatment and a decrease in serum infliximab level, and, in addition, to identify an indicator of infliximab level. METHODS: The study used data from a previous clinical study of infliximab for Crohn's disease, in which infliximab was initially given at 0, 2, 6 weeks at 5 mg/kg, and then at 8-week intervals to 62 week-10 responders. Of these 62, here we analysed data from 57 in whom Crohn's disease activity index and serum infliximab level were evaluated at week 14. RESULTS: Twelve patients showed a clinical response despite an infliximab level <1 µg/mL at week 14; of these, 8 (67 %) experienced LOR by week 54. A decrease in infliximab level preceded LOR in 6 (75 %). In receiver operating characteristic curve analysis, C-reactive protein (CRP) showed better performance in detecting an infliximab level <1 µg/mL. Infliximab level was <1 µg/mL in 60-80 % of patients with CRP >0.5 mg/dL. Time to LOR (median: 22.0 weeks) was significantly longer than that to a decrease in infliximab level to <1 µg/mL (14.0 weeks, p < 0.05) or to an increase in CRP to >0.5 mg/dL (14.0 weeks, p < 0.01). CONCLUSIONS: A decrease in serum infliximab level preceded LOR, and was easily detected by an increase in CRP. The CRP may be an indicator of serum infliximab level in predicting LOR.

Retrieval of serum infliximab level by shortening the maintenance infusion interval is correlated with clinical efficacy in Crohn's disease.

BACKGROUND: Infliximab has shown beneficial effects in the treatment of Crohn's disease (CD). The aim of this study was to assess 1) the clinical efficacy of shortening the infusion interval from 8 to 4 weeks when patients had shown loss of response during maintenance therapy, and 2) the association between the serum trough level and clinical efficacy. METHODS: This was an open-label prospective multicenter study. Infliximab was administered at 5 mg/kg to patients with active CD at weeks 0, 2, and 6. Week 10 responders received infliximab every 8 weeks thereafter. In those with loss of response after week 14 the interval was switched to every 4 weeks. Co-primary endpoints were the rate of patients achieving clinical response and remission at week 54. Serum level of infliximab was measured at each visit. RESULTS: Fifty-seven patients who responded to induction treatment received maintenance therapy after week 14. Thirty-seven patients continued at the 8-week interval and 20 patients were switched to a 4-week interval. The overall clinical response and remission rates at week 54 were 82.5% and 61.4%, respectively. For those with loss of response, treatment at the 4-week interval resulted in clinical response and remission rates of 83.3% (15/18) and 55.6% (10/18), respectively, at week 54. A correlation between clinical efficacy and serum trough level was found (P < 0.01, overall). CONCLUSIONS: A treatment strategy with an option of shortening the dosing interval of infliximab retrieves its trough level and may be useful for maintaining its efficacy.