GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Society of Hematology  (9)
  • Hara, Takeshi  (9)
  • 1
    Online Resource
    Online Resource
    Management of Adverse Events Associated with Dasatinib during Early Periods of Therapy in the Treatment of Chronic Myeloid Leukemia -a Clinical Report of Daria-01 Study
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4537-4537
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4537-4537
    Abstract: Abstract Background: Dasatinib is a novel kinase inhibitor of BCR-ABL and SRC family kinases that has shown promising anti-leukemic activity against chronic myeloid leukemia (CML). However, some patients experience treatment-related toxicity shortly after initiating dasatinib administration and are managed by drug interruption and/or dose reduction (altered treatment) which can limit the potential benefits of treatment. Methods: To determine the factors that influence compliance and the efficacy of dasatinib therapy, we conducted a phase 2 study of mid-term compliance and the effectiveness of dasatinib therapy in patients with chronic phase CML (CML-CP) (DARIA-01 Study). Treatment was administered until disease progression or intolerable toxicity, as determined by the treating physician. Dasatinib at 100 mg once daily was initially administrated. Dose interruption or reduction to 50 mg once daily was allowed after grade 2 or worse nonhematologic toxicity or grade 3 or worse hematologic toxicity. Trough plasma concentrations of dasatinib (Cmin) at steady state were assessed at 28 days of therapy. Results: In April 2014, 32 CML-CP patients were enrolled in the study, which included at least 6 months of follow-up. The median age was 53 years (range, 20–86). Twenty-four (75.0%) were previously untreated patients with CML-CP, and the remaining eight (25.0%) were switched from other tyrosine kinase inhibitors (imatinib, five patients; nilotinib, three patients) because of intolerance or resistance to these drugs. During the initial 28 days, 28 patients continued with 100 mg/day treatment, and four received doses of 50 mg/day. The incidence of altered treatment was 25% during the initial 3 months and 34% during the initial 6 months from dasatinib administration. Four patients who experienced dose reduction during the initial 3 months continued with 50 mg/day treatment thereafter at their request. Except one who experienced gastro-intestinal bleeding, all patients could continue dasatinib therapy. Age ( 〉 60 years) and Cmin divided by the given dasatinib dose (Cmin/D) were significantly correlated with a higher incidence of altered treatment during the initial 3 months (p = 0.0095) (p = 0.0083). Twenty-five (78%) patients achieved complete cytogenetic response (CCyR), and 13 (40%) achieved major molecular response at 6 months. The incidence of pleural effusion during the initial 28 days was significantly correlated with Cmin/D (p = 0.032) but was not related to the molecular response rate at 6 months (40% vs. 41%, p = 0.98). Conclusion: Current data demonstrate that patients treated with dasatinib who displayed a high Cmin/D ( 〉 1.0) value at day 28 and/or who were aged 60 and over were at a high risk for altered treatment during the early periods of therapy. Patients who experienced pleural effusion could be well managed by dose reduction and/or temporal interruption of dasatinib and could still achieve the preferable molecular response rate. Individualizing therapy by incorporating a pharmacokinetic assay would improve compliance and the efficacy of dasatinib therapy, particularly for elderly patients. Disclosures Morita: Bristol: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.4537.4537
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    The Value of Combination of Serum L-Kynurenine Level and Expression of Indoleamine 2,3-Dioxygenase mRNA As a Prognostic Factor in Acute Myeloid Leukemia
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4947-4947
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4947-4947
    Abstract: Introduction: The intracellular enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step in the metabolism of the essential amino acid tryptophan along the L-kynurenine (KYN) pathway. Some metabolites derived from tryptophan via IDO catalysis such as KYN block antigen-driven specific T-cell proliferation and induce T-cell death. IDO activity might play an important role in regulating the immune response exerted by antigen presenting cells. Indeed, we have recently reported the utility of either serum KYN or the expression of IDO mRNA as prognostic factors for acute myeloid leukemia (AML) [Leuk Lymphoma: In press, Leuk Lymphoma 56:1398-405]. Here, we investigated the value of combination of serum KYN level and expression of IDO mRNA as a prognostic factor in AML patients. Patients and Methods: AML was diagnosed according to the WHO 2008 criteria based on standard cytological and histochemical assessments of smears of cryopreserved bone marrow cells from 29 consecutive adult patients between December 2005 and March 2014. All patients in this study had been enrolled in both our serum KYN study and expression of IDO mRNA study. All follow-up data were fixed on August 1, 2014. KYN concentrations in serum samples were measured by high-performance liquid chromatography. Bone marrow-derived mononuclear fractions were separated and IDO expression was analyzed by using extracted mRNA amplified by PCR. Results: We examined expression of IDO mRNA and serum L-kynurenine in a total of 29 patients (median age, 55 years; range, 18-74 years). Among them, 11, 14 and 4 patients were classified as having favorable, intermediate and unfavorable cytogenetic risk, respectively. Twenty seven patients underwent standard intensive chemotherapy, mainly consisting of cytosine arabinoside (Ara-C) and anthracycline. All patients with acute promyelocytic leukemia (n = 5) received induction therapy containing all-trans retinoic acid. Two patients received less intensive chemotherapy [J Cancer Res Clin Oncol. 133:547-53.], because of poor performance status. The median serum KYN level was 1.63 µM (range, 0.66-5.27 µM). We set the L-kynurenine cut-off value at 2.4 µM according to our previous report. The RT-PCR results showed that bone marrow from 12 (41%) patients were IDO-positive. No significant correlation was identified between serum KYN level and IDO expression. Complete remission (CR) rates were 57% and 86% for patients with KYN levels ≥2.4 and 〈 2.4 µM, respectively. CR with initial therapy was obtained by 67% of patients with positive IDO expression, compared to 88% with negative IDO expression, respectively. Three-year OS rates were 0% and 76% for patients with KYN ≥2.4 and 〈 2.4 µM, respectively (P 〈 0.0001), and 37% and 77% for patients with IDO-positive and IDO-negative AML, respectively (P=0.0511) (Figs. 1A, B). Three-year OS rates were 83%, 50% and 0% for patients with low KYN and IDO-negative, either high KYN or IDO-positive, and high KYN and IDO-positive, respectively (P 〈 0.005; Fig. 1C.). Discussion: In the present study, we assessed the significance of serum concentration of KYN, IDO mRNA expression, and the combination of these two factors in AML patients and demonstrated their prognostic value. High serum KYN concentration was associated with poor outcomes of AML. While, expression of IDO mRNA had a tendency with poor prognosis, it did not show significant difference on the survival of AML patients. These results were due to the small sample size in this study, and will have to be confirmed in future studies with larger numbers of patients.When we compare these two factors as prognostic value, serum concentration of KYN may be more useful because measurement of serum concentration of KYN is easier than IDO mRNA expression and identifies ultra-high risk patients. In contrast, serum concentration of KYN has poor separation capacity for many other patient, which can be further subdivided by adding measurement of IDO mRNA expression. Indeed, the combination of serum concentration of KYN and IDO mRNA expression was associated with poor outcomes of AML and was able to subdivide the AML patients to three different prognostic groups clearly. Conclusion: This study clearly showed the prognostic value of the combination of serum KYN concentration and IDOm RNA expression for AML patients. Figure 1. Overall survival according to serum L-kynurenine concentration and IDO expression. Figure 1. Overall survival according to serum L-kynurenine concentration and IDO expression. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.4947.4947
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    A Randomized Phase II/III Study of R-THP-Cop Vs R-CHOP for Patients Younger Than 70 Years with DLBCL
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 3078-3078
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3078-3078
    Abstract: Introduction: Since the introduction of rituximab (R), a prognosis of diffuse large B cell lymphoma (DLBCL) is markedly improved. The rituximab-CHOP (R-CHOP) regimen, consisting of R, cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisolone (PSL), has become the current standard treatment for patients with DLBCL. On the other hand, the cardiotoxic problem due to DXR still remains. Pirarubicin (tetrahydropyranyl adriamycin: THP), a derivative of DXR, was reportedly an anthracyclin with less cardiotoxicity than DXR. Before introduction of rituximab, we reported the equivalent result between CHOP and THP-COP using THP instead of DXR regimen in aggressive non-Hodgkin’s lymphomas (74% of enrolled patients were DLBCL) (Tsurumi H et al. J Cancer Res Clin Oncol. 2004). In addition, we reported the efficacy and safety of R-THP-COP regimen for DLBCL in phase II study (Hara T et al. J Cancer Res Clin Oncol. 2010). Here, we prospectively compared the efficacy and safety of R-THP-COP and R-CHOP regimens as a clinical trial in Gifu Hematology Study Group. Methods: In a prospective randomized phase II/III study, we assigned 80 patients (40 for R-CHOP or 40 for R-THP-COP) less than 70 years of age with previously untreated DLBCL, from July 2006 through September 2013. A diagnosis of DLBCL was histologically confirmed by 2 or 3 experts of pathology, according to the World Health Organization classification 2008. Patients who were infected with HIV or HTLV-1 were excluded. All patients provided written informed consent in accordance with the institutional guideline of Gifu University Graduate School of Medicine and the Declaration of Helsinki. The regimens consisted of R 375mg/m2 (day 1), DXR or THP 50 mg/m2 (day3), CPA 750 mg/m2 (day 3), VCR 1.4 mg/m2 (day 3) and PSL 100 mg/body for 5 days every 2 weeks for 6-8 cycles. The primary end point was the complete response rate, with the duration of overall survival (OS), safely and progression-free survival (PFS) as secondary end points. Results: No significant differences (N.S.) in known prognostic factors (elderly patients, advanced clinical stage, poor performance status, elevated LDH and number of extranodal sites 〉 1) were found between the both groups. At a median follow-up of 57 months (7 - 91 months), CR rate was 88.6% (87.2% for R-CHOP, 90.0% for R-THP-COP; P-value N.S.). The 2-year OS rates were 89.6% (87.1% for R-CHOP, and 92.1% for R-THP-COP; N.S.), respectively and 2-year PFS rates were 83.0% (79.0 % for R-CHOP, and 87.0 % for R-THP-COP; N.S.), respectively. In analyses of safety aspects, no cardiotoxicity of grade 3 or higher occurred in both groups. No serious adverse events were observed except for therapy-related acute myeloid leukemia in a patient with R-THP-COP group. The highest frequent adverse event was febrile neutropenia (32.5% in R-CHOP, 40% in R-THP-COP; N.S.). Therapy-related death was not observed. Conclusions: R-THP-COP regimen produced results equivalent to those of R-CHOP regarding efficacy and safety in DLBCL patients less than 70 years of age. This regimen might be an alternative therapy instead of R-CHOP for patients with DLBCL. Further large clinical study should be considered to confirm efficacy and safety of R-THP-COP compared with R-CHOP. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.3078.3078
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era
    American Society of Hematology ; 2016
    In:  Blood Vol. 128, No. 22 ( 2016-12-02), p. 4210-4210
    Details
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4210-4210
    Abstract: Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiotherapy (IFRT). The addition of rituximab has revolutionized the treatment of DLBCL. Rituximab combined with CHOP (R-CHOP) has been established as the standard treatment for patients with DLBCL. However, the role of consolidative radiotherapy (RT) in the treatment of limited stage DLBCL in the rituximab era is controversial. Patients and Methods: We retrospectively analyzed 108 patients with limited stage DLBCL who received R-CHOP or R-THP-COP (rituximab plus, cyclophosphamide, pirarubicin, vincristine and prednisone) regimen between June 2004 and August 2015. We compared overall survival (OS) and progression-free survival (PFS) according to the treatment. OS was calculated from the date of initiation of chemotherapy to the date of the last follow-up or death. PFS was calculated from the date of initiation of chemotherapy to the date of progression disease, death, or last contact, whichever occurred first. Survival was estimated from Kaplan-Meier curves and compared using the log-rank test. P 〈 0.05 was considered statistically significant. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for RT was used to account for differences in baseline characteristics. Results: Median age at diagnosis was 66 years (19-88 years), with 61 males and 47 females. Forty-three patients (40%) had stage I, and 65 patients (60%) received consolidative RT after chemotherapy. Patients who received consolidative RT were significantly younger (65 vs 72, P 〈 0.01) and were more likely to have stage I disease (51% vs 23%, P 〈 0.01). The median number of chemotherapy cycles was 4 (range 3-8) in patients who received RT, and 6 (range 3-8) in patients who did not. Median follow-up was 4.3 years (0.3-10.9 years), and the 5-year OS (92% vs 63%, P 〈 0.01) and PFS (87% vs 65%, P 〈 0.01) were significantly higher for patients who received RT than those who did not. Using IPW adjustment, RT remained predictive of OS (HR 0.30, CI 0.13-0.72, P 〈 0.01) and PFS (HR 0.47, CI 0.22-0.99, P 〈 0.05). Conclusion: Our results suggest that consolidative RT improves OS and PFS in patients with limited stage DLBCL in the rituximab era. Although consolidative RT seems to be gradually phased out by chemotherapy alone, it is still an important treatment strategy. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V128.22.4210.4210
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    The Pretreatment Controlling Nutritional Status (CONUT) Score Is an Independent Prognostic Factor in Elderly Patients with Diffuse Large B-Cell Lymphoma
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4210-4210
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 4210-4210
    Abstract: [Backgrounds] The controlling nutritional status (CONUT), one of the useful parameter of nutritional assessment tools, is a significant prognostic factor for various solid tumors. The CONUT score is an index calculated from the following factors; the serum albumin concentration (Alb), the total peripheral lymphocyte counts (Lymph) and total cholesterol concentration (Chol) (Table 1). Some predictive models specified the relationship between nutritional status and the prognostic value of malignant disease have been proposed. However, the role of the CONUT score in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. The aim of this study is to elucidate the impact of the pretreatment CONUT score on survival in patients with DLBCL who received rituximab (R) plus chemotherapy. [Patients and Methods] We retrospectively investigated 240 patients who were histologically diagnosed with DLBCL between June 2004 and November 2015. All patients received R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or R-THP-COP (cyclophosphamide, tetrahydropyranyl-adriamycin, vincristine, prednisone) regimen. We defined the best cutoff value of the CONUT score as 3 using a receiver operating characteristic curve. [Result] The mean and median of the CONUT score of all patients (median age 68, range 19 - 93, 140 male and 100 female) were 2.85 and 2 (range 0 - 12). The data of each parameter's median and range constituting CONUT (Alb, Lymph, Chol) was as follows: 4 (1.9 - 5.3), 1170 (105 - 13192), and 173 (49 - 287), respectively. Patients with High-CONUT score (≥3, n = 109) had significantly lower overall survival (OS) and progression-free survival (PFS) than those with Low-CONUT score (≤2, n = 131) (5-year OS, 63.0 vs. 83.6%, P = 0.006; 5-year PFS, 56.5 vs. 78.0%, P = 0.003). The conventional predictive factors such as International Prognostic Index (IPI; age, performance status, Ann Arbor stage, extra-nodal involvement sites and lactate dehydrogenase) were all significantly associated with a worse OS and PFS. A subsequent subgroup analysis based on age indicated that 70 years or elder patients (n = 108) with High-CONUT had a significantly worse 5-year OS and PFS as compared to Low-CONUT patients (OS, 50.0 vs. 77.2%, P = 0.008; PFS, 41.6 vs. 77.6%, P = 0.0004). In contrast, no significant differences were observed in the OS and PFS when High- and Low-CONUT patients less than 70-year-old were compared. The multivariate analysis of all of the significant parameters in patients older than 70 years indicated that High-CONUT was an independent prognostic factor for PFS (HR = 2.20, 95 % CI = 1.08-4.66, p = 0.03). [Discussion] The serum Alb concentration is a reliable indicator of nutritional status and systemic inflammation. Total peripheral Lymph, which play an important role in the immune response to the tumor, are known to indicate the immunological and nutritional status. It is also reported that Chol, an indicator of a patient's caloric reserves, increased the antigen-presenting function of monocytes. Organ function decreases with aging, and many elderly patients have comorbidities that compromise their capacity to tolerate standard dose chemotherapy. In addition, intensive chemotherapy is often complicated by deterioration of nutritional status as the elderly. Hence, elderly patients are an extremely heterogeneous population and optimal treatment strategy should be adapted in consid eration of comorbidities. On the other hand, DLBCL is a curable disease even in the elderly population. Therefor prognostic stratification in older population should be focused on the real biological age of patients and on primary variables that reflect tumor aggressiveness, immune interaction and nutritional status. In this respect, the pretreatment CONUT score is considered suitable for prognostic model of elderly patients. Previously, we have reported that sarcopenia is an independent poor prognostic factor for PFS in male patients with DLBCL (Ann Hematol, 2015). In this cohort, sarcopenia has no effect on PFS in elderly patients. [Conclusion] The pretreatment CONUT score is easily able to predict the prognosis of elderly patients with DLBCL. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-110055
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    The Incidence and the Risk Factors of Bowel Perforation Due to Chemotherapy in Gastrointestinal Diffuse Large B Cell Lymphoma
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 1515-1515
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1515-1515
    Abstract: BACKGROUND: Bowel perforation after chemotherapy is a serious life-threatening complication of diffuse large B cell lymphoma (DLBCL) involving gastrointestinal tract. R Vaidya et al reported that 9 % of patients with gastrointestinal lymphoma developed a perforation, of which 55% occurred after chemotherapy, and DLBCL was the most common lymphoma associated with perforation (R Vaidya et al Ann Oncol 2013). We assume that the dose reduction of chemotherapy may have advantages to reduce the risk of gastrointestinal perforation and shorten the duration of neutropenia. This study aimed to investigate the incidence of gastrointestinal perforation after chemotherapy, whether reduced dose intensity chemotherapy could reduce the risk of the bowel perforation and how therapeutic modalities influence on the prognosis. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 348 consecutive patients who were diagnosed as having DLBCL at the Gifu University Hospital between August 2004 and April 2015. Eighty-six patients (86/348, 24.7%) were identified to have gastrointestinal involvement of DLBCL by biopsy. The prognosis of DLBCL patients with GI involvement was retrospectively investigated regarding treatments. RESULTS: The involved sites were gastric (51 patients, 48.1%), duodenal (7 patients, 6.6%), colorectal (6 patients, 5.7%), small intestine (36 patients, 34.0%) with duplicate counts permitted. Fourteen patients (14/86, 16.3%) were provided surgical treatment prior to chemotherapy since many of them had already suffered from serious complications such as ileus, perforation and bleeding. Sixty-five patients (65/86, 75.5%) received R-CHOP or CHOP like regimen ± radiation therapy as a first-line chemotherapy. As for remaining patients, two patients received R-hyperCVAD regimen because their histology were Burkitt like, and another patients received Rituximab ± other low dose chemotherapy for their frailness. The 45 patients (45/65, 69.2%) of them received reduced dose intensity (RDI) chemotherapy at the first course because increased risk of gastrointestinal perforation with chemotherapy was concerned about by endoscopic findings. The reduction rates of chemotherapy determined by the attending physician were approximately from 10% to 50%. Six patients (6/65, 9.23%) developed gastrointestinal perforation after chemotherapy (stomach 1, duodenum 0, small intestine 5, colon 0). Three of them received full dose chemotherapy at the time of small intestinal perforation including 2 patients who developed grade 4 neutropenia after the perforation. One of them died of infection after the perforation. The perforation rate was 15.0% in full dose chemotherapy group and 6.67% in the RDI chemotherapy group (p=0.361). The median day of perforation after initiation of chemotherapy was 21 days (range; 5-63 days). The small intestine was the most common site of perforation and 4 patients (4/5, 80%) had the ulcerative type lesions in their perforation site. CONCLUSIONS: Prior to chemotherapy, risk of GI perforation should be evaluated. We consider that small intestinal ulcerative lesion is high risk of GI perforation. The RDI chemotherapy may be an optimal therapy for patients with primary GI DLBCL with high risk. Further and larger prospective study should be required to confirm this. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.1515.1515
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Sarcopenia and Adipopenia Are Independent Prognostic Factors in Patients with Acute Myeloid Leukemia
    American Society of Hematology ; 2015
    In:  Blood Vol. 126, No. 23 ( 2015-12-03), p. 4953-4953
    Details
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4953-4953
    Abstract: Background: The response to treatment and overall survival of patients with acute myeloid leukemia (AML) are heterogeneous. A number of prognostic factors related to patient and tumor characteristics have been described for AML, including age, performance status, and karyotype. The depletion of skeletal muscle (sarcopenia) and adipose tissue (adipopenia) are known to be associated with unfavorable prognosis in patients with some malignant diseases including lymphoma. Here, we studied the impact of sarcopenia and adipopenia on clinical outcomes of adult AML. Patients and Methods: We retrospectively analyzed 70 patients with adult AML (age ≥ 18 years) who received chemotherapy at Gifu University Hospital between December 2004 and September 2014. Skeletal muscle and adipose tissue were measured by the analysis of CT images at the L3 level before treatment. CT images were analyzed using SliceOMatic version 4.3 software (TomoVision, Montreal, QB, Canada), which enables specific tissue demarcation using previously reported Hounsfield unit (HU) thresholds. The CT HU thresholds were -29 to 150 for skeletal muscles and -190 to -30 and -50 to -150 for subcutaneous and visceral adipose tissue, respectively. These values were normalized for stature in order to calculate skeletal muscle index (SMI, cm2/m2) and adipose tissue index (ATI, cm2/m2). Results: Median age at diagnosis was 57 years (18-84 years), with 37 males and 33 females. SMI was significantly higher in male than female patients (P & lt; 0.001). ATI was significantly higher in patients aged 60 years and over than in those under 60 years (P & lt; 0.05). The sex-specific cut-offs for the SMI and ATI were determined by ROC curve analysis. Thirty-five (50%) and 31 (44%) patients were defined as sarcopenia and adipopenia, respectively. Sarcopenia and adipopenia did not significantly differ among various FAB subtypes or cytogenetic risk profiles. The rate of patients with poor performance status (ECOG ≥ 2) was significantly higher in the sarcopenic group (80% vs 45%, P & lt; 0.05), whereas not in the adipopenic group (40% vs 47%). With a median follow-up of 33.5 months, the 3-year overall survival (OS) in the sarcopeniac group was 34% compared with 74% in the non-sarcopenic group (P & lt; 0.001, Figure 1A) and 32% in the adipopenic group compared with 72% in the non-adipopenic group (P & lt; 0.005, Figure 1B). In a multivariate analysis, sarcopenia (HR = 2.84, CI = 1.08-8.08, P & lt; 0.05) and adipopenia (HR = 2.85, CI = 1.19-7.24, P & lt; 0.05) remained predictive of OS. Conclusion: Sarcopenia and adipopenia are independent prognostic factors in patients with AML. Evaluation of skeletal muscle and adipose tissue depletion by CT imaging is a useful objective tool to predict patient outcomes, but a larger prospective study is needed to confirm this effect. Figure 1. Overall survival according to sarcopenic (A) and adipopenic (B) status. Figure 1. Overall survival according to sarcopenic (A) and adipopenic (B) status. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V126.23.4953.4953
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Combination Of Indoleamine 2,3-Dioxygenase Inhibitor and Cytotoxic Agents Is a Novel Therapeutic Option For Non-Hodgkin Lymphoma
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 4408-4408
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4408-4408
    Abstract: Indoleamine 2,3-dioxygenase (IDO) catalyzes the rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. In tumors, increased IDO activity inhibits T cell and natural killer cell proliferation and induces apoptosis. We have previously reported that IDO expression in lymphoma cells and serum concentration of kynurenine in diffuse large B-cell lymphoma are useful prognostic factors. Preclinical studies in rodents have demonstrated that IDO inhibitors, such as 1-methyl-D-tryptophan (D-1MT), are therapeutically beneficial, especially when combined with different types of cytotoxic chemotherapeutic agents. We investigated the therapeutic potential of IDO inhibitor D-1MT with cyclophosphamide (CY) by using an IDO-positive B-cell lymphoma model mouse. Materials and Methods To establish tumors, 1x106 A20 cells (BALB/c B-cell lymphoma cell line) were subcutaneously injected into the lower back of naïve syngeneic BALB/c mice. Seven days later, 20 BALB/c mice were treated with D-1MT (Sigma-Aldrich, Saint Louis, MO, USA) and/or CY. The mice were fed with D-1MT-supplemented water (5mg/mL), which was replaced every two to three days. CY was administered at 80 mg/kg i.p. on day 10. To examine the effect of D-1MT on A20 tumors and tumor-draining lymph nodes (TDLNs), mice were sacrificed on day 28. Serum concentration of kynurenine and tryptophan were measured by high-performance liquid chromatography. CD4+CD25+Foxp3+ regulatory T cells (Tregs) were counted by flow cytometry with a FACSCantoII flow cytometer (BD Biosciences, San Jose, CA, USA), and data were analyzed with FACSDiva 6.1 software (BD Biosciences). Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed with specific primer/probe sets that amplify IDO1, Foxp3, IFN-γ, cyclooxygenase-2 (COX-2), and GAPDH genes (TaqMan Gene Expression Assays; Applied Biosystems, Foster City, CA). Results The mean body and spleen weights of the mice did not differ significantly among the groups. The mean drinking water intakes (mL/day/mouse) of the D-1MT, CY, and D-1MT+CY groups were significantly less than that of the control group (p 〈 0.05). All mice implanted with A20 cells developed tumors that became palpable after day 7. On day 28, the tumor volume in the D-1MT+CY group was significantly less than that in the control group (p 〈 0.05), and there were no significant differences among the other treatment groups (Figure 1). There were no significant differences in the serum kynurenine-to-tryptophan ratio and the IDO1 expression level in the tumors among any treatment groups. The expression levels of IFN-γ and COX-2 mRNA in TDLNs were found to be significantly up-regulated in the CY and D-1MT+CY groups. By quantitative RT-PCR, the expression levels of IFN-γ and COX-2 mRNA in TDLNs were found to be significantly up-regulated in the CY and D-1MT+CY groups. The Foxp3 expression level and number of Tregs in TDLNs in the CY and D-1MT+CY groups were significantly higher than in the control group on day 28. The number of Tregs in TDLNs in the D-1MT+CY group was significantly lower than those in CY groups on day 17 (p 〈 0.05) (Figure 2). Conclusion Our results suggest that D-1MT in combination with CY is an effective treatment for IDO-positive lymphoma in a model mouse by reducing Tregs and breaking tumor tolerance. This antitumor effect might be induced by the suppression of Tregs by D-1MT. Our findings suggest that inhibition of IDO might offer a promising treatment strategy for lymphoma. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.4408.4408
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    High Response Rate and Acceptable Toxicity of R-P-Imvp-16/CBDCA for Relapsed or Refractory Aggressive B-Cell Lymphoma
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4418-4418
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4418-4418
    Abstract: BACKGROUND: The optimal management of relapsed or refractory aggressive B-cell lymphoma is not standardized. We previously reported the salvage chemotherapy with P-IMVP-16/CBDCA consisting of methylprednisolone (mPSL), carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX) for patients (pts) with aggressive non-Hodgkin's lymphoma who had previously received CHOP consisting of cyclophosphamide (CPA), doxorubicin (DOX), Vincristine (VCR) and prednisolone (PSL) (Sawada M; Eur J Haematol 2002). The purpose of this study is to determine the efficacy and safety of salvage chemotherapy with rituximab (R) combined with P-IMVP-16/CBDCA (R-P-IMVP-16/CBDCA) for relapsed or refractory aggressive B-cell lymphoma. PATIENTS AND METHODS: We retrospectively analyzed 66 pts with relapsed or refractory aggressive B-cell lymphoma who had received R-P-IMVP-16/CBDCA (R: 375mg/m2 on day1, mPSL: 1000mg/body on days 2-4, IFM: 1000mg/m2 on days 2-6, MTX: 30mg/m2 on day 4 and 11, VP-16: 80mg/m2 on days 2-4, and CBDCA 300mg/m2 on day 2, with granulocyte colony-stimulating factor every 21 days in 5 institutes of Gifu Hematology Study Group between July 2004 and January 2014. The pts who had responded to R-P-IMVP-16/CBDCA underwent autologous transplantation or received 3 additional R-P-IMVP-16/CBDCA cycles. Pts aged 70 or older were given 75% or less of the standard dose. All patients received R-CHOP or R-THP-COP regimen as a first-line chemotherapy. THP (pirarubicin), a derivative of DOX, is an anthracyclin with less cardiotoxicity than DOX. THP-COP has an equivalent efficacy to CHOP (Turumi H; JCRCO 2004). RESULTS: Enrolled 66 pts had a median age of 64.5 years [range 25-83] and were 65% male. The pathology of underlying lymphoma comprised diffuse large-B cell lymphoma (n=51), follicular lymphoma grade 3 (n=11), intravascular large B-cell lymphoma (n=1), primary mediastinal B cell lymphoma (n=1) and mantle cell lymphoma (n=2). The response rate [complete response (CR/CRu) plus partial response (PR)] was 60.6% (40/66), including 28 (42.4%) CR/CRu and 12 (18.2%) PR. Another 5 pts had stable disease and 21 pts progressed. Median overall survival (OS) and progression-free survival (PFS) were 47.1 months and 9.2 months, respectively. The OS rate for the 66 pts was 65.1% at 1 yr and 57.3% at 2 yr. The PFS rate for the 66 pts was 45.6% at 1 yr and 31.2% at 2 yr. The survival rate for the 40 responders was 97.4% at 1 yr and 88.1% at 2 yr, and the survival rate for the 26 non-responders was 15.0% at 1 yr (P 〈 0.001). Common toxicity criteria grade ≥ 3 drug-related adverse events included: neutropenia, anemia, thrombocytopenia and febrile neutropenia. Although the major toxicities were neutropenia and febrile neutropenia, only one DLBCL pt with common variable immunodeficiency died of sepsis related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable. CONCLUSIONS: The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed or refractory aggressive B-cell lymphoma, with acceptable toxicity and should be considered a candidate for combination chemotherapy. Futher clinical studies should be required. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.4418.4418
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...