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Biomedical subjects

Hiroshi Miyata

Publications and source records attributed to Hiroshi Miyata.

At least 19 recordsLinked to original sources

Real-world outcomes of ipilimumab plus nivolumab in esophageal squamous cell carcinoma: a multi-institutional large cohort study.

BACKGROUND: Combination immune checkpoint inhibition with ipilimumab plus nivolumab (NIVO + IPI) has shown promising efficacy in advanced esophageal squamous cell carcinoma (ESCC) in the CheckMate648 trial. However, real-world evidence regarding its safety, efficacy as first-line therapy, and host-related biomarkers relevant to immunotherapy remains limited. METHODS: This multicenter retrospective study evaluated a large cohort of 111 patients with unresectable advanced or recurrent ESCC who received first-line NIVO + IPI therapy. Treatment response, treatment-related adverse events, and prognostic factors were analyzed. RESULTS: The objective response and disease control rates in cases with target lesions were 44.0% and 70.7%, respectively. Treatment-related adverse events ≥ Grade 2 occurred in 58 (52.3%) patients, including one Grade 4 event (type 1 diabetes) and two Grade 5 events (biliary infection and myocarditis). The median overall survival (OS) and progression-free survival were 22 months (95% confidence interval [CI]: 13-not reached) and 5 months (95% CI 3-8), respectively. OS was significantly affected by lymph node metastasis in unresectable advanced disease and by liver metastasis in recurrent disease. Multivariate analysis of OS identified the C-reactive protein-to-albumin ratio (CAR), a marker of host immune-inflammatory status, as the only independent prognostic parameter (hazard ratio = 2.99, 95% CI 1.35-6.63, P = 0.0071). CONCLUSIONS: In this large real-world cohort, first-line NIVO + IPI therapy demonstrated meaningful clinical activity and an acceptable safety profile in advanced ESCC. Treatment outcomes varied according to metastatic patterns, suggesting an influence of organ-specific immune microenvironments, and CAR emerged as a simple and robust prognostic biomarker. These findings support the real-world applicability of dual immune checkpoint blockade and highlight the importance of host immune context in patient selection.

Humans↗

Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood mononuclear cells of cancer patients undergoing surgery.

Patients undergoing surgery often develop symptoms of circadian rhythm disorders such as insomnia or delirium. However, the effect of surgery on the biological clock remains unknown. The present study examines the expression of clock genes in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone concentrations in patients with esophageal cancer and early gastric cancer who underwent surgery. Six blood samples per day were collected from 9 patients with esophageal cancer before and after esophagectomy and from 9 patients with early gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG). The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real-time RT-PCR. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the day and plasma cortisol levels changed after surgery. The acrophase of clock gene expression was altered after surgery as follows: hPer1, from 6:19+/-1:50 to 13:59+/-0:59 (p=0.0003) and from 7:47+/-1:27 to 12:33+/-1:30 (p=0.0043) and hPer2, from 5:01+/-2:59 to 19:30+/-2:15 (p<0.0001) and from 6:49+/-1:59 to 13:39+/-3:06 (p=0.0171) in patients with esophageal and early gastric cancer, respectively. The post-operative phase change of hPer2 was more prominent after esophagectomy than after LADG. Our results suggest that surgical stress affects the peripheral clock as well as endogenous hormones in humans.

Cell Cycle Proteins↗

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site.

Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.

Aged↗

A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis in recurrent laryngeal nerve chain nodes.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of intra-operative genetic diagnosis of RN node micrometastasis in the decision-making of 3FL for thoracic esophageal cancers. METHODS: Eighty-nine patients with middle and lower thoracic esophageal cancer were enrolled in a prospective study, in which 3FL was performed when RN node metastasis was revealed by intra-operative histological examination and/or genetic analysis using real-time RT-PCR assay. For other cases, 2FL was performed. RESULTS: Of the 89 patients, 3FL was performed for 33 patients and 2FL for 56 patients. In the 3FL group, RN node metastasis was both histologically and genetically positive in 19 patients, histologically negative and genetically positive in 11, and histologically positive and genetically negative in 3, with cervical node metastasis being detected in 7, 3, and 0 patients, respectively. In the 2FL group, only one patient had cervical node recurrence during the follow-up period. The post-operative survival in this study was equivalent to that of the historical controls (3-year survival rates 63.9% vs. 52.3%, P = 0.1513) of 66 3FL patients when 3FL was the first choice for thoracic esophageal cancers. CONCLUSIONS: Intra-operative histological and genetic diagnosis of RN node metastasis may help avoid unnecessary cervical node resection. A Phase III trial should be done.

Aged↗

Clinical significance of the second cycle response to cisplatin-based chemotherapy as preoperative treatment for esophageal squamous cell carcinoma.

BACKGROUND: Repeating two cycles of cisplatin-based chemotherapy is standard protocol for preoperative treatment for advanced esophageal squamous cell carcinoma (ESCC). However, the second cycle of chemotherapy is often less effective than the first. METHODS: Forty-six patients with advanced ESCC underwent two (41) or one (5) cycle of chemotherapy, consisting of cisplatin, adriamycin, and 5-fluorouracil (5-FU), followed by surgery. RESULTS: The tumor reduction rates (RR) for the first and second cycles of chemotherapy were 33.3 +/- 22.5% versus 11.5 +/- 42.6%, with the second showing less effectiveness and larger deviation. The second cycle RR was closely correlated with the pathological findings of the surgical specimens, including the effect of chemotherapy, tumor depth, and lymph node metastases, and with postoperative survival rates, which were 75.2% and 26.8% (P = 0.0028) at 3 years for good and poor responders. The first cycle RR showed correlation with neither. The second cycle RR was the only independent prognostic factor among the preoperative parameters in multivariate analysis. CONCLUSIONS: The second cycle of cisplatin-based chemotherapy in ESCC is less effective, but more closely related with postoperative survival than the first. Treatment other than surgery should be considered for ESCC resistant to second cycle chemotherapy.

Adult↗

Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma.

BACKGROUND: The transcriptional factor hypoxia-inducible factor 1alpha (HIF-1alpha) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1alpha is induced by hypoxia. Increased HIF-1alpha expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types. METHODS: We investigated the association between HIF-1alpha expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1alpha, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer. RESULTS: Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1alpha, p53, and VEGF expression, respectively. The increased expression of HIF-1alpha protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer. CONCLUSION: Our results indicate that overexpression of HIF-1alpha correlates significantly with p53 and VEGF protein expression in patients with gastric cancer; however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity.

Adenocarcinoma↗

Granulocyte functions and changes in ability with age in newborns; Report no. 2: activation of granulocyte functions by cytokines.

BACKGROUND: The aim of the present study was to examine the function of granulocytes in newborns from the perspective of granulocyte activation by cytokines. METHODS: Granulocytes were stimulated with tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor, and the reactivity of granulocytes to these substances was then compared between newborns (umbilical cord blood, peripheral blood obtained at age 5 days and at age 1 month) and peripheral blood obtained from adults. In addition, the expression of cytokine receptors on the surface of granulocytes was measured for each age group. RESULTS: The amplification of CD11b expression on the surface of granulocytes and suppression of l-selectin expression were weaker for cord blood regardless of which cytokine was added. In addition, the increases in the activity of intracellular elastase when stimulated with tumor necrosis factor-alpha or GM-CSF were significantly lower for cord blood. Moreover, the expression of GM-CSF receptors and granulocyte colony stimulating factor receptors on the surface of granulocytes was lower for cord blood, and this expression approached the level found in adults as age increased. CONCLUSION: Granulocytes during early infancy exhibit low reactivity to inflammatory cytokines, and this was considered to be one of the factors contributing to the higher incidence of serious bacterial infections in infants.

Adult↗

Granulocyte functions and changes in ability with age in newborns; Report no. 1: flow cytometric analysis of granulocyte functions in whole blood.

BACKGROUND: Serious bacterial infections occur with higher frequency in the first weeks of life than in other age groups and this may be, in part, related to functional impairment of neonatal granulocytes. The purpose of the present study was to estimate the characteristics of granulocyte function during the neonatal period. METHODS: The expression of adhesive molecules on the surface of granulocytes present in umbilical cord blood and peripheral blood obtained at 5 days and 1 month after birth, H(2)O(2) production and protease activity in granulocytes were studied by comparison with adult blood. RESULTS: Although there were no significant differences observed with respect to the expression of CD11b on the surface of granulocytes between each age group and adults, l-selectin was significantly lower in cord blood as compared with adult blood. Production of H(2)O(2) by granulocytes was significantly lower for cord blood than peripheral blood from 1 month old infants or that from adults in the presence of either phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine stimulation. The intracellular activity of elastase and collagenase within granulocytes exhibited a higher tendency for cord blood as compared with adult blood. CONCLUSIONS: Decreased functions of part of the phagocyte system during early infancy were clearly observed.

Adult↗

Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer.

Docetaxel, one of the most effective anticancer drugs for gastric cancer, targets beta-tubulin, the major protein in mitotic spindles. Eight isotypes of beta-tubulin, with tissue and organ-specific expression, have been identified in mammalian cells. We examined class III beta-tubulin expression in gastric cancer and assessed its relationship with sensitivity to docetaxel-based chemotherapy. A total of 115 paraffin-embedded gastric tumors were analyzed by immunohistochemistry for class III beta-tubulin expression. Twenty patients with advanced gastric cancer received preoperative docetaxel-based chemotherapy. Their biopsied specimens, obtained by endoscopy before chemotherapy were examined for class III beta-tubulin expression. The relationship between expression and chemosensitivity was assessed. Forty-two (36.4%) of 115 cases were confirmed to be positive for class III beta-tubulin expression. There was no association between clinicopathological status and prognosis. Among the patients positive for class III beta-tubulin expression, only 16.7% showed no response to chemotherapy, while 64.3% responded to the chemotherapy in the negative group. Our results suggest that class III beta-tubulin is a simple and useful predictive marker for the clinical response to docetaxel-based chemotherapy in gastric cancer.

Adult↗

[A phase I study of combination chemotherapy using TS-1 and weekly paclitaxel for advanced gastric cancer].

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.

Adult↗

Bile acid promotes the proliferation of squamous cell carcinoma of the esophagus, independent of its inducing COX-2 expression.

BACKGROUND: We have reported G1 progression and cyclooxygenase-2 (COX-2) induction during carcinogenesis of the squamous epithelium of the esophagus. As bile acid induces COX-2 expression and promotes carcinogenesis in the digestive tract, we investigated the effect of bile acid on the proliferation of squamous cell carcinoma of the esophagus (ESCC). MATERIALS AND METHODS: MTT assay, Western blot analysis of COX-2 and cell cycle-related molecules in the G1 phase (Rb, CDC25A, cyclin D1), and CDK2 kinase assay were performed on chenodeoxycholic acid (CDCA) exposure to ESCC cell lines (TE2R, TE3, TE13, TE15). RESULTS: In the presence of gradient bile acid concentration (up to 100 microm), growth of ESCC cell lines was stimulated at a low concentration (maximally at 20-30 microm), but suppressed at a higher concentration. Only a low dose of bile acid induced the expression of cyclin D1 and CDC25A and showed high Rb phosphorylation and high CDK2 kinase activity. In contrast, bile acid progressively induced COX-2 expression in a dose-dependent manner, regardless of its biphasic effects on cell proliferation, and a COX-2 specific inhibitor (JTE-522) did not suppress growth stimulation by a low dose of bile acid. CONCLUSIONS: Bile acid at a low dose stimulates the proliferation of ESCC by inducing G1-regulating molecules. However, COX-2 expression, which is also induced by bile acid, does not affect cell proliferation. Further work is needed to elucidate its role in carcinogenesis.

Bile Acids and Salts↗

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Aged↗

Correlation between histological effects on the main tumors and nodal status after chemoradiotherapy for squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemoradiotherapy is equally effective against metastatic lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. RESULTS: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and 1 responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients.

Adult↗

A simple technique for performing laparoscopic purse-string suturing during circular stapling anastomosis.

An esophagojejunostomy using a circular stapler requires the fixing of an anvil at the esophageal stump. When this placement procedure is laparoscopically performed, purse-string suturing is difficult, and there is a risk of loosening when a conventional needle driver is used. We herein present a simple but effective technique for performing laparoscopic purse-string suturing of the esophageal stump using a semiautomatic suturing device called the Endostitch. Gastrointestinal anvil placement was laparoscopically performed for 10 patients who underwent an esophagojejunostomy following a total gastrectomy. After the lumen of the esophagus was expanded using bowel forceps, the Endostitch was used to place approximately 12 encircling purse-string sutures. An anvil was positioned with support of the esophageal wall at three points with forceps. The Endostitch was used for the ligation with a sufficient degree of tension applied by extracorporeally pulling the sutures through the abdominal wall. The time for placement of the anvil averaged approximately 8 min. The ring formation following anastomosis was favorable in all patients. As a result, we consider our technique to be simple but very effective.

Anastomosis, Surgical↗

A mouse model of early-stage peritoneal metastasis: optimal RT-PCR-based method for detection of peritoneal micrometastases.

The presence of peritoneal micrometastasis in the abdomen is a poor prognostic factor in advanced gastric cancer. However, there is no standardized method for detection of peritoneal micrometastases. The aim of this study was to establish an animal model mimicking early phase peritoneal dissemination of advanced gastric cancer and then to use this model to compare the sensitivity and specificity of reverse transcription-polymerase chain reaction (RT-PCR) with peritoneal lavage fluid, randomly collected omentum with or without milky spots stained with activated carbon particles for detection of disseminated cancer cells. MKN-45-EGFP gastric cancer cells (1 x 10(3), 5 x 10(3) and 1 x 10(4)) were injected intraperitoneally into 4-week-old female BALBc nu/nu mice on day 0. Mice were sacrificed at 7 or 14 days postinjection. Peritoneal seeding was assessed by fluorescence stereomicroscopy. The sensitivities of RT-PCR with peritoneal lavage fluid, omentum with or without milky spots, were compared. Peritoneal seeding was confirmed in 8 of 10 mice injected with 1 x 10(4) MKN-45-EGFP cells by fluorescence stereomicroscopy. On days 7 and 14, the rate of the detection of CEA mRNA was 0, 50.0, and 87.5% in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. On days 7 and 14, the average level of CEA mRNA was 0, 51113+/-28225, and 3556+/-2842 in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. Molecular diagnosis using peritoneal lavage fluid is more sensitive than that using the omentum.

Animals↗

Preoperative intraperitoneal chemotherapy for patients with serosa-infiltrating gastric cancer.

BACKGROUND AND OBJECTIVES: Serosa-infiltrating gastric cancer poses a high risk for peritoneal recurrence. This study examined the feasibility and efficacy of preoperative intraperitoneal (i.p.) chemotherapy for such cancer. METHODS: Patients with serosa-infiltrating tumors, diagnosed by conventional examinations as well as by staging laparoscopy, were enrolled in this study. Those with unresectable T4 tumors, visible peritoneal metastasis or distant organ metastasis were excluded. Twenty-five eligible patients received preoperative i.p. chemotherapy, which consisted of i.p. injection of 20 mg of mitomycin C on day 1 and 10 mg of cisplatin for 5 days, followed by surgery. RESULTS: Of the 25 patients, 24 underwent gastrectomy with lymph node dissection and 1 underwent palliative gastrojejunostomy. The curability of the surgery was curability A in 6, B in 16, and C in 3. Preoperative T stages (T3 in 21 and T4 in 4) were downstaged postoperatively (T1 in 1, T2 in 10, T3 in 11, and T4 in 3). The 1- and 2-year overall survival was 83.3 and 51.3%, respectively. The median survival time was 24.4 months. The toxicity of the preoperative treatment was tolerable and no serious postoperative complication was seen. CONCLUSIONS: Preoperative i.p. chemotherapy seems to be a safe and effective therapy for serosa-infiltrating gastric cancer. Randomized clinical trials comparing preoperative i.p. chemotherapy followed by surgery and surgery alone are needed.

Adenocarcinoma↗

Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma.

PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. EXPERIMENTAL DESIGN: VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. RESULTS: Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups. CONCLUSION: This study demonstrated the prognostic significance of VCP expression in ESCC.

Adenosine Triphosphatases↗

Experience with the use of salazosulfapyridine for intractable diarrhea after hematopoietic stem cell transplantation.

We encountered 2 children with intractable diarrhea after allogeneic hematopoietic stem cell transplantation (SCT). In both cases, salazosulfapyridine (SASP) was administered to treat the diarrhea. One patient was a 14-year-old male with acute myelogenous leukemia who received SCT from a related HLA-identical donor. The leukemia recurred early, and a second SCT from the same donor was performed approximately half a year later. Because intestinal graft-versus-host disease (GVHD) was observed, steroids and octreotide were administered, but the symptoms were not improved. Thereafter, SASP was administered, and the symptoms remitted 9 days later. The other patient was a 12-year-old male with chronic myelogenous leukemia who received SCT from an unrelated HLA-identical donor. Diarrhea and abdominal pain developed early after engraftment and did not respond to either steroids or tacrolimus. Oral administration of SASP was initiated on day 236, and the diarrhea remitted 4 days later without recurrence thereafter. SASP may be effective in children for the digestive system symptoms of chronic GVHD.

Adolescent↗