Biomedical subjects

H Sakamaki

Publications and source records attributed to H Sakamaki.

At least 19 recordsLinked to original sources

PubMed2005

Comparison between reduced intensity and conventional myeloablative allogeneic stem-cell transplantation in patients with hematologic malignancies aged between 50 and 59 years.

To evaluate the efficacy of reduced-intensity stem-cell transplantation (RIST), we retrospectively compared outcomes of 207 consecutive Japanese patients aged between 50 and 59 years with hematologic malignancies who received RIST (n=70) and conventional stem-cell transplantation (CST) (n=137). CST recipients received total body irradiation (TBI)-based or busulfan/cyclophosphamide-based regimens. RIST regimens were purine analog-based (n=67), 2 Gy TBI-based (n=2), and others (n=1). Most CST recipients (129/137) received calcineurin inhibitors and methotrexate as graft-versus-host (GVHD) prophylaxis, while 32 RIST recipients received cyclosporin. In all, 23 CST and five RIST recipients died without disease progression within 100 days of transplant. Grade II to IV acute GVHD occurred in 56 CST and 38 RIST recipients. There was no significant difference in overall survival (OS) and progression-free survival between CST and RIST. On multivariate analysis on OS, five variables were significant: preparative regimens (CST vs RIST) (hazard ratio=1.92, 95% confidence interval, 1.25-2.97; P=0.003), performance status (2-4 vs 0-1) (2.50, 1.51-4.16; P<0.001), risk of underlying diseases (1.85, 1.21-2.83; P=0.004), acute GVHD (2.57, 1.72-3.84; P<0.001), and CML (0.38, 0.21-0.69; P=0.002). We should be careful in interpreting results of this small-sized retrospective study; however, reduced regimen-related toxicity might contribute to better survival in RIST. The low relapse rates following RIST suggest a strong antitumor activity through allogeneic immunity.

Female↗

PubMed2005

Myeloablative allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: significant roles of total body irradiation and chronic graft-versus-host disease.

Disease-free survival in Philadelphia chromosome-positive ALL (Ph + ALL) is very poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently considered the only procedure with curative potential. To identify factors affecting transplant outcome, we analyzed the data from 197 Ph + ALL patients aged 16 years or older who had undergone allo-HSCT. The 5-year survival rates were 34% for patients in first complete remission (CR), 21% for those in second or subsequent CR, and 9% for those with active disease (P < 0.0001). Multivariate analysis showed four pre-transplant factors as significantly associated with better survival: younger age, CR at the time of transplantation, conditioning with total body irradiation, and HLA-identical sibling donor (P < 0.0001, P < 0.0001, P = 0.0301, P = 0.0412, respectively). Severe acute GVHD increased the risk of treatment-related mortality (TRM) without diminishing the risk of relapse, whereas chronic GVHD reduced the risk of relapse without increasing the risk of TRM. Thus, patients who developed extensive chronic GVHD had better survivals (P = 0.0217), and those who developed grade III-IV acute GVHD had worse survivals (P = 0.0023) than did the others.

Adolescent↗

PubMed2005

Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS). The object of this study was to evaluate the impact of chemotherapy before allo-SCT. We analyzed the data of 283 patients who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidence of grade II-IV acute GVHD was 33%. Overall survival (OS) at 5 and 10 years was 48.8 and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81). The proportion of patients with a poor karyotype was equivalent between the two groups (P=0.44). Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.

Adolescent↗

PubMed2004

Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation.

To evaluate the clinical significance of a cytomegalovirus (CMV) antigenemia assay in the prediction and diagnosis of CMV gastrointestinal (CMV-GI) disease after hematopoietic stem cell transplantation (HSCT), 19 allogeneic HSCT recipients developing CMV-GI disease were retrospectively reviewed. All patients were monitored by a CMV antigenemia assay, at least once weekly after engraftment. The median onset of CMV-GI disease occurred 31 days post transplant (range: 19-62). Only four of 19 patients (21%) developed a positive CMV antigenemia test before developing CMV-GI diseases. Although all 19 patients subsequently developed positive CMV antigenemia tests during their clinical courses, the values remained at a low-level in nine (47%) patients. Among the 14 patients in whom results of real-time polymerase chain reaction (PCR) were available, seven (50%) yielded positive results of real-time PCR before developing CMV-GI disease. In contrast to the values of CMV antigenemia, all 14 patients exclusively yielded high viral loads (median: 2.8 x 10(4) copies/ml plasma). We conclude that CMV antigenemia testing has limited value in prediction or early diagnosis of CMV-GI disease, and that real-time PCR could have a more diagnostic significance.

Adult↗

PubMed2004

Allogeneic myeloablative transplantation for patients aged 50 years and over.

Allogeneic hematopoietic stem cell transplantation (HSCT) has been performed mainly for young patients due to concern about the high incidence of treatment-related mortality (TRM). Recent advances to reduce TRM by using peripheral blood stem cells or nonmyeloablative conditioning regimens have increased the age limit for this procedure, and correctly identifying the indication for transplant is essential for older patients. In this study, we analyzed data from 398 patients aged 50 or over selected from 5147 patients, who received conventional allogeneic HSCT (c-HSCT). Patients aged 50 or older showed inferior outcomes for TRM and overall survival (OS). Mulitivariate analyses confirmed that an age of 50 or over was an independent risk factor for TRM (P<0.0001) and OS (P<0.0001). Among patients aged 50 or older, increasing age remained an adverse factor for OS (P=0.0213). Regimens including total-body irradiation (TBI) correlated with a higher risk of TRM and a lower OS for older patients (P=0.0095 and 0.0303, respectively). These findings indicate that allogeneic c-HSCT should be offered to patients over 50 years only if the increased risk of TRM is acceptable, and that a non-TBI regimen is preferable when the transplant is performed.

Adolescent↗

PubMed2004

Recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation.

Human Valpha24+ natural killer T (NKT) cells have an invariant T-cell receptor-alpha chain and are activated in a CD1d-restricted manner. Valpha24+ NKT cells are thought to regulate immune responses and to play important roles in the induction of allograft tolerance. In this report, we analyzed the recovery of Valpha24+ NKT cells after hematopoietic stem cell transplantation and its correlation with graft-versus-host disease (GVHD). Patients who received a dose-reduced conditioning regimen, antithymocyte globulin- or CAMPATH-1H-containing conditioning regimen were excluded. NKT cells were reconstituted within 1 month after transplantation in peripheral blood stem cell transplantation recipients, while their numbers remained low for more than 1 year in bone marrow transplantation (BMT) recipients. The number of Valpha24+ NKT cells in BMT recipients with acute GVHD was lower than that in patients without acute GVHD, and both the CD4+ and CD4- Valpha24+ NKT subsets were significantly reduced. With regard to chronic GVHD, BMT recipients with extensive GVHD had significantly fewer Valpha24+ NKT cells than other patients. Furthermore, the number of CD4+ Valpha24+ NKT cells was also significantly reduced in patients with chronic extensive GVHD. Our results raise the possibility that the number of Valpha24+ NKT cells could be related to the development of GVHD.

Adolescent↗

PubMed2004

Tacrolimus instead of cyclosporine used for prophylaxis against graft-versus-host disease improves outcome after hematopoietic stem cell transplantation from unrelated donors, but not from HLA-identical sibling donors: a nationwide survey conducted in Japan.

Despite recent advances, graft-versus-host disease (GVHD) remains the main cause of treatment failure for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Tacrolimus (FK506) has been increasingly used in place of cyclosporine (CSP), and several studies have shown that FK506 reduces the incidence of acute GVHD more effectively than does CSP. However, no survival benefits have been demonstrated, and no established consensus exists on the choice of these immunosuppressive agents. To compare a CSP-based and an FK506-based regimen, we performed a large-scale retrospective study by using the data of 1935 patients who underwent HSCT from HLA-identical sibling donors (SIB-HSCT) and 777 patients who underwent HSCT from unrelated donors (UD-HSCT). For patients undergoing UD-HSCT, FK506 significantly reduced the risk of acute GVHD and treatment-related mortality (TRM) without an increase in relapse, thus improving overall survival (OS) (hazard ratio (HR): 2.20, 95% confidence interval (CI): 1.60-3.04, P<0.0001 for grade II-IV acute GVHD; HR: 1.81, 95% CI: 1.32-2.48, P=0.0003 for TRM; HR: 1.62, 95% CI: 1.23-2.14, P=0.0007 for OS). This superiority of FK506 was not observed in SIB-HSCT cases. These findings indicate that the use of FK506 instead of CSP for GVHD prophylaxis is beneficial for patients undergoing UD-HSCT.

Acute Disease↗

PubMed2004

Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.

Adult↗

PubMed2004

Interleukin-1beta increases RANTES gene expression and production in synovial fibroblasts from human temporomandibular joint.

BACKGROUND: Synovial fibroblasts of temporomandibular joint (TMJ) are poorly characterized, although they have important roles in progression of temporomandibular disorders (TMD). In this study, we investigated responses of synovial fibroblasts to interleukin (IL)-1beta. METHODS: We examined gene expression profiles of synovial fibroblasts in response to IL-1beta, using Affymetrix GeneChip. Regulated upon activation normal T-cell expressed and secreted (RANTES) gene expression was confirmed by polymerase chain reaction (PCR) and real-time PCR. RANTES protein levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The RANTES was preferentially up-regulated in synovial fibroblasts by IL-1beta. The increase in RANTES gene expression in response to IL-1beta was confirmed by PCR and real-time PCR. Protein level of RANTES in synovial fibroblasts was also increased by IL-1beta. CONCLUSIONS: The RANTES, a cc-type chemokine, has chemotactic effects on lymphocytes and monocytes. Increased gene expression and protein production of RANTES in synovial fibroblasts, in response to IL-1beta, may play an important role in recruitment of inflammatory cells into synovium and progression of synovitis in TMD.

Adolescent↗

PubMed2003

Regression of an unresectable pancreatic tumor following nonmyeloablative allogeneic peripheral-blood stem-cell transplantation.

A 59-year-old female with an unresectable, large pancreatic tumor (10.0 x 8.0 cm(2) on CT scan) underwent nonmyeloablative allogeneic peripheral-blood stem-cell transplantation from her HLA-identical sibling. Pronounced tumor regression and relief from pain without acute graft-versus-host disease (GVHD) were observed following transplantation. The patient is surviving (more than 300 days) after transplantation, with extensive chronic GVHD, and has tumor regression with an 80% reduction in tumor size. The observed clinical course may suggest a graft-versus-tumor effect on the pancreatic tumor following allogeneic stem-cell transplantation.

Adenocarcinoma↗

PubMed2003

Clinical features and treatment of hematopoietic stem cell transplantation-associated gastric antral vascular ectasia.

Gastric antral vascular ectasia (GAVE) may occur after hematopoietic stem cell transplantation (HSCT) and cause severe and prolonged gastric bleeding. The underlying pathology of transplant-associated GAVE (HSCT-GAVE) is poorly understood and an effective therapeutic strategy has not been established yet. We retrospectively reviewed the medical records of 230 consecutive allogeneic transplant recipients in our institution between January 1997 and June 2002. We identified five patients who developed HSCT-GAVE (2.2%). Four patients had bleeding from HSCT-GAVE and one patient had HSCT-GAVE discovered incidentally. The clinical features of these patients were similar in that they all received conditioning treatment with busulfan and had history of thrombotic microangiopathy. Furthermore, treatment with a beta-blocker apparently improved the outcome of HSCT-GAVE in three patients.

Adolescent↗

PubMed2003

Acute effects of ethanol on feeding behavior and leptin-induced STAT3 phosphorylation in rat hypothalamus.

OBJECTIVE: Drinking ethanol stimulates the appetite, producing a positive energy balance. The mechanism by which ethanol regulates the appetite in the central nervous system, however, has not been fully understood. The aim of this study is to investigate the interaction of ethanol with the satiety effect of leptin, a hormone which suppresses the appetite in the hypothalamic region. DESIGN: : Leptin (7.5 micro g) or the same dose of phosphate buffer saline (PBS) was administered into the third ventricle (i.c.v.), 30 min after an intraperitoneal injection (i.p.) of ethanol (0.5 g/kg body weight) or the same dose of PBS. MATERIALS: Adult male Sprague-Dawley rats weighing 290-320 g were used. MEASUREMENTS: Food intake was measured 2, 12 and 24 h after leptin i.c.v. infusion. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was analyzed by Western blotting. RESULTS: The cumulative food intakes in the saline/leptin group (saline i.p.+leptin i.c.v.) were markedly reduced to about 45% of the saline/PBS group (saline i.p.+PBS i.c.v.) at 2, 12 and 24 h time points (P<0.05, 0.001, and 0.005, respectively). As compared with the saline/leptin group, those of the ethanol/leptin group (ethanol i.p.+leptin i.c.v.) were significantly increased to the level seen in the saline/PBS group at 12 and 24 h time points (P<0.05, and P<0.005 vs the saline/leptin group, respectively). Ethanol administration resulted in about a 50% reduction of the leptin-induced STAT3 tyrosine phosphorylation seen in the hypothalamic protein as compared to that of the saline/leptin group. CONCLUSION: These findings suggest that ethanol-induced enhancement of the appetite may, in part, result from leptin resistance transiently caused by ethanol to attenuate the leptin signal transduction.

Animals↗

PubMed2003

Nonmyeloablative stem cell transplantation with fludarabine and cyclophosphamide for patients with hematologic malignancies.

We conducted a multi-center phase I/II trial of nonmyeloablative stem cell transplantation for patients with hematologic malignancies. The aim of this trial was to assess the safety and feasibility of this treatment modality for older or younger patients with significant organ dysfunction, who could not be treated with conventional high dose chemoradiotherapy. Twelve patients were treated with a conditioning regimen consisting of fludarabine and cyclophosphamide, followed by peripheral blood stem cell transplantation from human leukocyte antigen (HLA) identical siblings. Nonhematologic toxicities were mild. Median time to absolute neutrophils above 0.5 x 10(9)/l, 1.0 x 10(9)/l and platelets above 50 x 10(9)/l were 8, 10 and 12 days, respectively. Donor dominant hematopoiesis was achieved in all patients, with or without donor leukocyte infusion. The cumulative incidence of acute and chronic graft-versus-host disease (GVHD) was 75 and 56%, respectively. Only one patient experienced early death within 100 days, caused by acute GVHD complicated by fungal infection. All patients except one achieved complete remission. With a median follow-up of 330 days, expected progression-free survival is 75%. Overall survival is 76%. Our study confirms that nonmyeloablative stem cell transplantation with cyclophosphamide and fludarabine conditioning is a safe and promising treatment for elderly patients with hematologic malignancies. A further study in large-scale setting is warranted.

Age Factors↗

PubMed2001

Use of real-time PCR on blood samples for diagnosis of invasive aspergillosis.

We developed a new quantitative system for diagnosis of invasive pulmonary aspergillosis (IPA) using real-time automated polymerase chain reaction (PCR). Intra-assay and interassay precision rates for in vitro examination were 2.53% and 2.20%, respectively, and the linearity of this assay was obtained when there were >20 copies/well. We examined 323 samples taken from 122 patients with hematological malignancies, including 33 patients with IPA and 89 control patients. Blood samples were subjected to PCR antigen detection methods, using enzyme-linked immunosorbent assay (ELISA) and determination of plasma (1-->3)-beta-D-glucan (BDG) concentration. The sensitivities of PCR, ELISA, and BDG measurement for diagnosis of IPA were 79%, 58%, and 67%, respectively; the specificities were 92%, 97%, and 84%. Positive findings on PCR preceded those of computed tomography by -0.3+/-6.6 days, those of BDG measurement by 6.5+/-4.9 days, and those of ELISA by 2.8+/-4.1 days. Real-time PCR was sensitive for IPA diagnosis, and quantitation was accurate.

Adolescent↗

PubMed2001

Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation.

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

Adenovirus Infections, Human↗

PubMed2001

Second allogeneic peripheral blood stem cell transplantation with fludarabine-based low-intensity conditioning regimen for relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation.

We describe the case of a 51-year-old patient with relapsed myelodysplastic syndrome after allogeneic bone marrow transplantation (BMT), who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) after conditioning with a novel regimen consisting of fludarabine, busulfan, and antithymocyte globulin. The second PBSCT was performed early, at 3 months after the initial allogeneic BMT, but it was well tolerated and complete hematologic remission was documented. The patient did not experience any early transplantation-related organ toxicity but died from opportunistic infection 6 months after the second transplantation. Our experience suggests that this novel regimen may induce remission and could be offered to patients relapsing after the first transplantation; however, the fludarabine-containing regimen might be accompanied by profound immunosuppression.

Antineoplastic Agents↗

PubMed2001

Acquired storage-pool disorders occurring late after allogeneic bone marrow transplantation: partial activation of platelets in asymptomatic patients.

Bone marrow transplantation (BMT) may be complicated by coagulation abnormalities. The present study evaluated whether platelets might be activated in patients who had undergone BMT without significant coagulopathy. The patients selected had received allogeneic BMTs a median of 39 months before the study (range, 11-124 months) and had not received cyclosporine, FK506 (tacrolimus), or other medication affecting cyclo-oxygenase for at least 3 months prior to the collection of blood samples. Furthermore, patients had platelet counts greater than 100 x 10(9) cells/L and normal serum creatinine levels. Twenty-five healthy volunteers acted as controls. Platelet aggregation studies and a mepacrine assay of platelets showed abnormal aggregation and decreased staining in some patients. The platelet storage-pool adenosine 5'-triphosphate (ATP) level in 15 patients after BMT was 0.45+/-0.24 micromol per 10(11) platelets, whereas the level in 18 controls was 1.03+/-0.36 micromol per 10(11) platelets (P = .00078). The total ATP levels of platelets in patients and controls were 4.33+/-1.14 and 5.63+/-1.51 micromol per 10(11) platelets, respectively (P = .016). With the exception of 1 patient, plasma levels of thrombomodulin and von Willebrand factor were all within the normal range. The average plasma level of 11-dehydrothromboxane B2 was significantly increased in 15 patients after BMT compared with controls, 20.6+/-8.2 and 10.3+/-1.2 pg/mL, respectively (P = .0004). These findings suggest a long-term process of platelet activation in patients after BMT and, following the cessation of cyclosporine, development of acquired storage-pool disorder of platelets.

Adenosine Triphosphate↗

PubMed2001

Hepatitis B virus reactivation in a patient with chronic GVHD after allogeneic peripheral blood stem cell transplantation.

We report a patient with fatal hepatitis B virus (HBV) reactivation after treatment for chronic graft-versus-host disease (GVHD) following allogeneic peripheral blood stem cell transplantation to treat chronic myelogenous leukemia. The presence of antibodies to hepatitis B surface antigen (HBsAb) prior to transplantation indicated previous HBV infection. Liver damage first developed 8 months after transplantation with the disappearance of HBsAb. Hepatitis B antigen was first noted during an examination of liver damage that occurred 22 months after transplantation. Retrospective examination of serum by real-time detection polymerase chain reaction (RTD-PCR) revealed HBV in both the first and second episodes of liver damage (89 copies/mL and 2 x 10(6) copies/mL, respectively). HBV may have been reactivated, leading to fatal liver damage in this HBsAb-positive patient. We propose that RTD-PCR-based analysis should be performed to diagnose liver dysfunction after hematopoietic stem cell transplantation.

Antibodies, Viral↗