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  • 1
    In: Internal Medicine, Japanese Society of Internal Medicine, Vol. 52, No. 11 ( 2013), p. 1217-1221
    Type of Medium: Online Resource
    ISSN: 0918-2918 , 1349-7235
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    Language: English
    Publisher: Japanese Society of Internal Medicine
    Publication Date: 2013
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  • 2
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3008-3008
    Abstract: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) has an indolent clinical course, with overall patient survival at 5 years after diagnosis of more than 85%. Although the cause of death in a significant proportion of MALT lymphoma patients is not the lymphoma itself, some patients experience early relapse or refractory disease. However, the risk factors capable of predicting aggressive disease in MALT lymphoma have not been clearly defined. Patients and Methods This is a retrospective pooled analysis of pathologically confirmed extranodal MALT lymphoma patients treated at our institute. Patients with nodal or splenic marginal zone lymphoma were excluded. The primary endpoint was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. Results From January 2000 to June 2013, 52 extranodal MALT lymphoma patients (26 females and 26 males) were referred to our institution. The median age of the patients was 68 years (range, 43–89 years). Thirty-three (63%) patients had limited stage disease (stage I/II) and 48 (92%) patients had an ECOG performance status of less than 2. The cumulative numbers of patients who were diagnosed with orbit, thyroid, salivary gland, stomach, lung, and intestine disease were 7 (13%), 5 (10%), 9 (17%), 16 (31%), 16 (31%), and 4 (8%), respectively. Fifteen (29%) patients had a prior history of autoimmune disease, and a serum electrophoresis study detected M-protein in 9 (17%) patients (5 patients had IgG, 3 patients had IgM, and 1 patient had IgA). There was no significant correlation between the presence of M-protein and prior history of autoimmune disease (Fisher's exact test, p=0.46). Of the 32 patients who underwent cytogenetic studies, 9 (28%) had cytogenetic aberrations involving MALT1. Histological transformation to diffuse large B-cell lymphoma (DLBCL) was confirmed in 3 patients. After a median follow-up time of 53 months (range, 1–142 months), 16 patients had relapsed (MALT lymphoma relapse or transformation to DLBCL), and 1 patient had died due to lymphoma. The 4-year PFS and overall survival rate were 76.3% (95% confidence interval (CI), 60.0–86.7%) and 98.0% (95% CI, 86.6–99.7%), respectively. Among the clinical variables measured at diagnosis, univariate analysis found that advanced stage, three or more extranodal sites, serum soluble IL-2 receptor concentration higher than 700 IU/L, lymphocyte count higher than 1x10^9/l, hemoglobin concentration lower than 12.5 g/dl, and the presence of M-protein adversely affected PFS (p 〈 0.05). In multivariate analysis including these six variables, only the presence of M-protein remained as a poor prognostic factor for PFS (hazard ratio (HR), 14.5; 95% CI, 1.47–142; p=0.021). The 4-year unadjusted PFS for patients with M-protein was 14.8% (95% CI, 7.36–47.6%), which was significantly poorer than that of patients without M-protein (90.9% [95% CI, 74.0–97.0%]; HR, 11.9; 95% CI, 3.46–41.1; log-rank, p 〈 0.001). Seven of the 9 patients who had M-protein received rituximab-containing combination chemotherapy (R-CHOP 5 and R-CVP 2), and 5 patients relapsed in a relatively short time (median, 10 months; range, 2–54 months). Conclusion Extranodal MALT lymphoma patients with M-protein had an increased risk of early disease progression. Patients with M-protein were more likely to had advanced stage disease (p=0.005) and more than three extranodal sites (p=0.02) compared to patients without M-protein. However, multivariate analysis showed that the prognostic impact of M-protein was better than that of advanced stage disease and the number of extranodal sites. Further studies are required to determine differences between the biological backgrounds of patients with and without M-protein, and a novel treatment strategy to obtain a durable disease control. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 3
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2962-2962
    Abstract: 〈 Introduction 〉 Diffuse large B-cell lymphoma (DLBCL) has an aggressive clinical course and, even in the R-CHOP era, about 10-20% of DLBCL patients (pts) show primary refractory disease. For pts with primary refractory disease, salvage chemotherapy with or without stem cell transplantation (SCT) is generally performed, but even with this treatment, less than half of the pts survive. To elucidate the pts population who require innovative therapy, we retrospectively analyzed the risk factors that lead to an unsuccessful outcome of primary refractory DLBCL. 〈 Patients and Methods 〉 DLBCL pts who received R-CHOP with curative intent were included. Pts with primary mediastinal large B-cell lymphoma, primary effusion lymphoma, intravascular large B-cell lymphoma and iatrogenic immunodeficiency-associated lymphoproliferative disorders were excluded. In this study, primary refractory disease was defined as disease progression during first-line immuno-chemotherapy or recurrence within 3 months after completion of the first-line therapy. The primary endpoint was overall survival (OS) after treatment failure, which was assessed using the Kaplan-Meier method. The log-rank test and Cox regression analysis were used to assess the prognostic values of each clinical variable. 〈 Results 〉 From January, 2004 to December, 2013, 440 DLBCL pts were referred to our institute. Among them, 60 pts (20 females and 40 males) were considered to have primary refractory disease (55 with progressive disease and 5 with early relapse). At the time of treatment failure, the median age was 72 (range, 31–90) and 44 pts (73%) showed advanced stage (stage IIIor more) disease. Nineteen (32%) had an ECOG performance status (PS) of 2 or more, and 23 (38%) had a high IPI score. In 31 pts, disease progression was observed at novel sites that had not been detected during the initial evaluation; patients with these sites were designated as "new lesion pts". The remaining 29 pts displayed regrowth of known lesions and were designated as "regrowth pts". Among new lesion pts, 29 displayed extranodal disease. After disease progression, 52 pts received salvage chemotherapy or radiotherapy, and 21 pts achieved a clinical response. Among the 24 patients less than 70 years old, 11 received autologous or allogeneic stem cell transplantation (SCT). After a median follow-up time of 17 months (range, 1–81 months), 39 pts had died of lymphoma. The 1-year OS rate (1y-OS) was 38.8% [95% confidence interval (CI), 25.5-51.8%].Univariate analysis using clinical variables at the time of treatment failure revealed that new lesion pts or patients with an IPI score 〉 3 had a poor 1y-OS rate (p 〈 0.05). The presence of CNS involvement or bulky disease at treatment failure had no effect on OS. In addition, progressive disease before the 4th course of R-CHOP or at a CHOP dose intensity less than half of that actually prescribed had no negative impact on OS. After adjusting for IPI score using multivariate analysis, new lesion pts had an independent, poor prognostic factor for OS (HR, 3.11; 95%CI, 1.34-7.23; p=0.008). The unadjusted 1y-OS of new lesion pts was 11.4% (95% CI, 2.9-26.3%), which was significantly lower than that of regrowth pts, who had a 1y-OS of 65.8% (95% CI, 43.9-80.8%) (HR, 4.4; 95% CI, 2.1-9.3; log-rank, p 〈 0.001). Of 31 new lesion pts, six achieved a clinical response after salvage chemotherapy, but the remission durations were short. Five patients who received SCT died of lymphoma. 〈 Conclusion 〉 Primary refractory DLBCL pts with new lesions, most of which were extranodal sites, have an extremely poor outcome. Disease progression at novel extranodal sites may indicate that the disease has chemotherapy-resistant characteristics. Routine approaches using platinum- or cytarabine-based salvage chemotherapy followed by SCT rarely overcome the progressive nature of the disease, and a novel treatment strategy is required. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 4
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5215-5215
    Abstract: Prospective clinical trials show that 5-Azicitidine (5-Aza) is superior to conventional care regimens in prolonging the survival of patients with high-risk myelodysplastic syndromes (MDS) (pts). To confirm the survival benefit of 5-Aza in daily clinical practice, we compared the survival of high-risk MDS patients who received parental treatment before 5-Aza approval to those who could be initially treated with 5-Aza. Methods In Japan, 5-Aza was approved in January 2011. We collected data of consecutive adult patients (pts) with high-risk MDS, namely refractory anemia with excess blasts-1 (RAEB-1), RAEB-2, and acute myeloid leukemia with MDS related features (AML/MRF), who received the first parental chemotherapy between January 2000 and April 2013. Survival was not calculated from the day on which the first chemotherapy was delivered, but from the day on which the diagnosis of high-risk MDS was established. Survival analysis was done by the Kaplan-Meier method. The Cox regression model was used for the analyses. A total of 107 pts with high-risk MDS were identified. They were divided into two groups (grps) on the basis of whether or not they could be initially treated with 5-Aza. In brief, pts who received the first parental treatment before January 2011 were categorized into the conventional care (CC) grp (N=75), and pts for whom treatment began after January 2011 were categorized in the 5-Aza grp (N=32). The following variables were also considered to affect survival in multivariate analysis: sex, age ( 〉 =65 years (yrs) old or 〈 65 yrs old), WHO classification, and IPSS at diagnosis of high-risk MDS. Results Median follow-up times of CC and 5-Aza grp were 43 and 11 months, respectively. As shown in Table 1, the distributions of sex, age, WHO classification and IPSS were nearly the same in both grps. As for initial treatment, pts in the CC group mainly received low-dose cytarabine (ld-AraC), whereas most pts in the 5-Aza grp were treated with 5-Aza. Unadjusted survival curves of the two grps are shown in Figure 1. The unadjusted 2-yr survival rate was 33% in the CC grp and 52% in 5-Aza era grp. Median survival times were 11 and 24 months in CC and 5-Aza grps, respectively. Uni-variate analysis of overall survival revealed a trend for improved survival in younger pts, but this was contradicted by the results of multi-variate analysis. In uni- and multi-variate analyses, the 5-Aza group showed an overall, and statistically significant higher survival benefit (Table 2). Removing the 26 patients allografted after parental treatment (10 in 5-Aza grp and 16 in CC grp) at the time of alloSCT from the analyses did not modify the survival advantage of the 5-Aza grp. Conclusion This retrospective analysis confirms that the introduction of 5-Aza has certainly improved the outcome of high-risk MDS in daily clinical practice. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
    In: Journal of Hematopoietic Cell Transplantation, The Japan Society for Hematopoietic Stem Cell Transplantation, Vol. 6, No. 1 ( 2017), p. 45-51
    Type of Medium: Online Resource
    ISSN: 2186-5612
    Language: English
    Publisher: The Japan Society for Hematopoietic Stem Cell Transplantation
    Publication Date: 2017
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  • 6
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3921-3921
    Abstract: Background About 70-80% of adult patients (pts) with acute myeloid leukemia (AML) achieve complete remission (CR); however, around a half of them experience a relapse. For the purpose of creating accurate decision-making process of post-consolidation strategy, stratification system using karyotype and recurrent gene mutations have been widely utilized. As is confirmed in childhood acute lymphocytic leukemia, however, the information of minimal residual disease (MRD) status would substantially improve the reliance of decision-making process of adult AML pts. Unfortunately, approximately a half of AML patients lack molecular targets suitable for MRD monitoring. The aims of this study are to evaluate the applicability of MRD detection using multiparametric flow cytometry (MPFC) and to estimate the impact of MRD measured with MPFC at the end of consolidation therapy in improving decision-making process. Patients and Methods We retrospectively studied 81 consecutive pts with newly diagnosed AML who received induction therapies and achieved CR in our institute between January 2007 and March 2013. Pts with acute promyelocytic leukemia were excluded. We routinely analyzed the bone marrow specimens with MPFC for the detection of leukemia-associated immunophenotypes (LAIPs) at diagnosis. Since April 2010, RT-PCR assay examined FLT3-ITD mutation in the same specimens. In pts who had traceable LAIPs, the relationships of the levels of MRD at the end of consolidation therapy with relapse free survival were analyzed. Positive MRD was defined as the detection of 0.2% and more LAIPs-positive cells with MPFC. We compared two patient groups: those with MRD at the end of consolidation (MRDp group) and those without (MRDn group). Relapse-free survival (RFS) was analyzed using the Kaplan-Meier method and the log-rank test was used for comparison between each group. A multivariate Cox regression analysis for RFS was fit to assess the effect of the followings: age at diagnosis (≥ vs. 〈 65 years old), the number of induction regimens required for achieving CR (≥ vs. 〈 2 times), cytogenetic risk groups of SWOG (unfavorable vs. favorable/intermediate). Results In 57 / 81 pts, MPFC could detect LAIPs in the bone marrow specimens at diagnosis (70.4% of all subjects; 15-82 years-old; follow-up time [median] 98-2211[517] days). FLT-ITD mutations were found in 13 pts, but not in 39 pts (the remaining 5 pts were not examined). The rate of detection of LAIPs with 6-color MPFC was significantly superior to 3-color MPFC (82.1% vs. 61.0%, p 〈 0.05). Induction chemotherapies the pts received were anthracyclin-containing regimens, such as idarubicin and cytarabin (3+7), in 52 pts (91.2%), low-dose cytarabin-based regimen in 4 pts (7.0%) and azacitidine in 1 pt. (1.8%). The MRDp and the MRDn groups were comprised of 20 and 37 pts (35.1% and 64.9%) , respectively. One-year RFS of the MRDp group was significantly inferior to the MRDn group (28.3% vs. 75.2%; log-rank p 〈 0.0005). In the multivariable analysis using the model above, MRD positivity at the end of consolidation remains a significant predictor (HR, 2.93, 95% CI 1.16-7.45, p 〈 0.05). In addition, the 1-year RFS in the MRDp group with FLT-ITD was significantly shorter than that in the MRDp group without FLT3-ITD (0% vs. 47.6% with positive and negative FLT3-ITD, log-rank p 〈 0.05). In the MRDn group, however, the negative impact of FLT3-ITD was not documented (85.7% vs. 69.3% with positive and negative FLT3-ITD, log-rank p=0.954). Conclusion Our retrospective study confirmed that LAIPs as MRD targets were applicable to the majority of pts with AML; MRD positivity measured with LAIPs was a promising predictor for early relapses at the end of consolidation, as was previously reported. When combined with FLT-ITD status, it might become a more sensitive prognostic factor. Disclosures: Takahashi: celgene: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2298-2298
    Abstract: Background: High-dose cytarabine (HD-AraC) is a promising therapy for acute myeloid leukemia (AML). However, it causes substantial toxicity, such as severe cytopenia and cytarabine-encephalopathy. The efficacy of HD-AraC for the treatment of core-binding-factor (CBF) AML has been well established; however, whether or not HD-AraC is suitable for the treatment of non-CBF AML is unclear. Moreover, it remains controversial whether HD-AraC is effective before allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of non-CBF AML. In this study, we investigated the efficacy of HD-AraC in terms of optimal numbers of HD-AraC cycles required to treat non-CBF AML patients who did and did not receive allo-HSCT. Methods: We retrospectively collected the data of consecutive AML patients who were aged 15-70 years, treated in our hospital and diagnosed between Jan. 2000 and Apr. 2014. Patients with acute promyelocytic leukemia (APL) and CBF AML were excluded. Only patients who achieved complete remission (CR) and received post-remission therapies with a curative intent were included; namely, only those who received allo-HSCT or completed more than one cycle of consolidation chemotherapy. Patients who exclusively received azacytidine-based or low-dose AraC-based therapies were excluded. HD-AraC therapy was defined as a chemotherapeutic regimen utilizing 12 g/m2/cycle or more of AraC. Patients who were not suitable for HD-AraC because of comorbidities were also excluded. Overall survival (OS) was separately analyzed in patients who underwent allo-HSCT in the 1st CR (group A) and in those who did not (group B). The unadjusted probabilities of OS were estimated using the Kaplan-Meier method, and univariate analysis was done using the log-rank test. Multivariate analysis was performed with Cox proportional hazard regression models, and 95% confidence intervals (CIs) were calculated. In multivariate analysis, the number of cycles of HD-AraC, age, cytogenetic data, and whether or not the patient achieved CR after the 1st cycle of chemotherapy were used as covariates. In group A, donor source and conditioning were also considered as covariates. Results: A total of 166 non-APL, non-CBF AML patients were identified. Seventy-one patients were excluded for the following reasons: 50 did not achieve CR, 13 underwent incomplete consolidation therapies because of complications or early relapse, 7 had missing data, and 1 had chronic renal disease. For HD-AraC, toxicity was not a consideration for the discontinuation of treatment, but the dose of AraC was reduced to an intermediate dose (AraC 〈 12g/m2/cycle) in some patients if severe toxicity was encountered. Among the 95 patients included in the study, the median age was 51 years. Twelve patients had unfavorable cytogenetics, and 50 patients received allo-HSCT in the 1st CR and were assigned to group A. As the treatment policy for consolidation therapy has undergone substantial changes in the last 15 years and the dose of AraC was switched from a high dose to an intermediate dose in some patients, the number of cycles of HD-AraC used for consolidation varied. The three-year OS (3y-OS) of patients who received 0, 1, 2, or 〉 2 cycles of HD-AraC were 50.6%, 85.7%, 75.0%, and 68.6% (n=22, 9, 8, 11) in group A, and 44.3%, 16.0%, 65.6%, and 50.0% (n=19, 10, 10, 6) in group B, respectively. Univariate analysis showed that patients in group A who received one or more cycles of HD-AraC had a longer 3y-OS (75.4% vs 50.6%, p=0.024) (figure 1), whereas patients in group B who received two or more cycles of HD-AraC had a longer 3y-OS (57.1% vs 36.2%, p=0.078) (figure 2). Multivariate analysis of patients in group A showed that one or more cycles of HD-AraC resulted in a survival benefit (Hazard ratio=0.26, 95%CI: 0.070-0.98, p=0.046), whereas multivariate analysis of patients in group B showed that two or more cycles of HD-AraC (Hazard ratio=0.36, 95%CI: 0.13-0.97, p=0.044) and intermediate-risk of cytogenetics resulted in a survival benefit. Conclusion: For consolidation chemotherapy, at least one cycle of HD-AraC is recommended for patients who plan to receive allo-HSCT, and at least two cycles is required for other patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 8
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 61, No. 13 ( 2020-11-09), p. 3128-3136
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2020
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  • 9
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1647-1647
    Abstract: 〈 Background 〉 The prognostic impact of interim positron emission tomography scans (I-PET) for patients with diffuse large B-cell lymphoma (DLBCL) is a matter of debate because its positive predictive value (20–80%) is low. Here, we aimed to improve the prognostic impact of I-PET by combining it with interim analysis of serum soluble interleukin-2 receptor (sIL2R) levels, the levels of which at the time of diagnosis are associated with the prognosis of DLBCL. 〈 Patients and Methods 〉 We retrospectively examined data from DLBCL patients diagnosed at our institution between January 2006 and October 2013. Patients were included in the analysis if they met all of the following criteria: six or more cycles of rituximab plus CHOP regimen (R-CHOP); I-PET performed after 2-4 cycles of chemotherapy; and sIL2R levels measured after each cycle. Patients with primary central nervous system lymphoma, primary mediastinal large B-cell lymphoma, or transformed DLBCL from indolent lymphoma were excluded. I-PET was assessed visually according to the International Harmonization Project criteria. The interim sIL2R (I-IL2) level was defined as the value measured just before the fourth R-CHOP cycle. I-IL2 levels 〉 800 U/ml, or 2000 U/ml if serum creatinine was 〉 2.0 mg/dl (sIL2R is influenced by renal function), were regarded as positive. The primary endpoint of the study was progression-free survival (PFS). The unadjusted probabilities of PFS were estimated using the Kaplan-Meier method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable. 〈 Results 〉 In total, 135 patients were enrolled. The median age was 66 years (range, 34–89) and 66 patients (48.9%) were male, 27 (20%) had an ECOG performance status 〉 1, 18 (13.3%) had bulky disease, 81 (60%) had advanced disease, and 61 (45.2%) had a high or high-intermediate International Prognostic Index (IPI) score. The median follow-up time was 25.6 months (range, 6.3–88.7) and the 2 year progression-free survival rate (2-y PFS) of the entire cohort was 72.9% (95% confidence interval (CI), 63.8–80). I-PET and I-IL2 were positive in 47 (34.8%) and 15 (11.1%) patients, respectively. Univariate analysis revealed that a high IPI score, a positive I-PET, and a positive I-IL2 had statistically significant poor prognostic effects on PFS, although gender and bulky disease did not. The three significant variables were entered into multivariate analysis, which identified positive I-PET and I-IL2 values (but not IPI) as independently associated with a poor prognosis. The 2-y PFS was 81.8% (95% CI, 70.4–89.1) for I-PET-negative and 56.3% (95% CI, 40.7–69.3; p 〈 0.001, log rank test) for I-PET positive, respectively. Although a negative I-PET was highly predictive of a favorable outcome, a positive I-PET was of limited clinical value. The 2-y PFS for the 13 patients (9.6%) that were both I-PET- and I-IL2-positive was significantly lower than that of the remaining patients (27.7% [95% CI, 7.1–53.6] and 77.7% [95% CI, 68.4–84.6] , respectively; p 〈 0.001). Patients that were positive for both I-PET and I-IL2, rather than patients that were positive for I-PET alone, had a poor outcome. 〈 Conclusion 〉 DLBCL patients that were both I-PET- and I-IL2-positive suffered a high rate of progression; therefore, such patients should be targeted by novel therapeutic approaches. Because the study was based on a retrospective analysis and a limited follow-up period, further studies are needed to confirm the prognostic impact of the combined use of I-PET and I-IL2. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 10
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3030-3030
    Abstract: Title Risk stratification of DLBCL patients according to NCCN-IPI in our hospital Background Recently, a robust prognostic tool termed enhanced International Prognostic Index (NCCN-IPI) for the rituximab era was reported. The aim of this study was to assess the usefulness of NCCN-IPI in risk discrimination and its suitability in clinical applications. Patients and Methods We retrospectively analyzed consecutive patients with de novo diffuse large B cell lymphoma (DLBCL) who were diagnosed and treated with R-CHOP or CHOP-like regimens between January 2004 and December 2013. Patients were required to be cancer-free for 5 years before diagnosis and had to have no prior documented history of indolent lymphoma. We stratified DLBCL patients using IPI and NCCN-IPI, and estimated overall survival (OS) in each risk group. The unadjusted probabilities of OS were estimated using the Kaplan-Meier(K-M) method. The log-lank test and multivariate Cox regression analysis were used to assess the prognostic values of each clinical variable. Results Three-hundred and seventy one patients were identified. The median age was 69 (20–93) years. The median follow-up time was 41 months. The numbers of patients with NCCN-IPI-defined low (L), low-intermediate (L-I), high-intermediate (H-I), and high (H) risk were 35 (9.4%), 125 (33%), 139 (37%), and 72(19%), respectively. The 3-year OS in each risk group was 93%, 89%, 70%, and 52%, respectively. NCCN-IPI was better for the discrimination of low- and high-risk groups (3-year OS, 93% vs 52%) than IPI (3-year OS, 87% vs 56%), and NCCN-IPI gave a better concordance index than IPI (c-Harrel = 0.678 vs 0.665). However, the discriminating power of NCCN-IPI was not as good as previously reported. In the multivariate analysis using the five independent variables of NCCN-IPI as covariates, age was not a significant factor in the 〈 40, 40-60, and 61-75 age groups, and LDH ratio was not a significant factor between≤1 and 〉 1-3 groups. Ann Arbor stage was not a significant factor either. Next, we examined extranodal involvement, which was a significant prognostic factor (HR, 2.3; p 〈 0.001). Multivariate analysis, using age, LDH, performance status, stage, and extranodal involvement in major organs as covariates, lung (HR, 3.5; p 〈 0.001) and bone marrow (HR, 1.8; p=0.048) involvement were significantly poor prognostic factors, and CNS (HR, 2.5; p=0.066) or GI tract (HR, 1.4; p=0.13) involvement adversely affected OS, although they were not significant factors. In contrast, liver involvement did not affect OS (HR, 0.87; p=0.70). We simplified the NCCN-IPI method by using a maximum of four scoring points for age ( 〉 75, 1pt), LDH ratio ( 〉 3, 1pt), extranodal disease (bone marrow, lung, CNS, or GI tract, but not liver, 1pt), and ECOG PS (≥2, 1pt) and not using Ann Arbor stage as a prognostic factor. Four distinct groups were formed based on K-M curves for OS: low (L, 0 pt), low-intermediate (L-I, 1pt), high-intermediate (H-I, 2pt), and high (H, 3-4 pt). Simplified NCCN-IPI better discriminated low- and high-risk groups (3-year OS, 93% vs 34%; c-Harrel = 0.705) than NCCN-IPI. When patient age was compared in each scoring system, high-risk patients were older in the NCCN-IPI (median age, 79 years old) and its simplified version (median age, 79 years old) than in IPI (median age, 72 years old). Conclusion NCCN-IPI showed better discrimination in our cohort than IPI. However, we found that the enhancement in predicting outcomes by including age and LDH was not as useful as previously reported, and stage and liver involvement was not an independent prognostic factor in our cohort. In the rituximab era, Ann Arbor stage is not a useful prognostic factor. Further validation and optimization of cut-off in each variable could improve the NCCN-IPI. The majority of the high risk patients evaluated by both NCCN-IPI and simplified NCCN-IPI were elderly, so innovative therapeutic approaches adjusted for age are required to improve the outcome of the high-risk group. To identify high-risk groups especially among younger patients, a refined scoring system including not only conventional clinical factors but also other factors such as biological markers will be required. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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