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  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1620-1620
    Abstract: Abstract 1620 Few randomized prospective studies have been conducted on patients with localized DLBCL in the rituximab era. The SWOG 0014 study examined DLBCL patients treated with 3 cycles of R-CHOP followed by involved-field radiotherapy. Each of the patients had at least 1 of the 4 risk factors (nonbulky stage II, over 60 years of age, WHO performance status [PS] of 2, or elevated LDH), but showed 4-year progression-free survival (PFS) and 4-year overall survival (OS) rates of 88% and 92%, respectively. However, long-term observations showed that the PFS and OS curves did not plateau (Persky DO, et al. J Clin Oncol 2008). We retrospectively analyzed a series of patients with localized DLBCL treated with R-CHOP therapy alone. This study included 190 consecutive, untreated patients with localized DLBCL seen between 2003 and 2009 in 1 of the 7 participating hospitals. All the patients were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP in 1 of the hospitals. Patients who required a dose reduction of more than 20% were excluded from the study, as were patients with special forms of DLBCL, such as intravascular lymphoma, primary mediastinal large B-cell lymphoma, and T-cell-rich B-cell lymphoma. Patients who achieved partial remission (PR) after the 4 initial cycles underwent a total of 8 R-CHOP cycles. Patients who did not achieve PR after the 4 initial cycles or those with disease progression at any time during the study underwent salvage therapy, and that time point was designated as the point at which the disease progression began. Additional local irradiation was allowed in patients with PR. Patients who received additional radiotherapy following CR in the decision of attending physicians were excluded from this study. Patients who achieved CR but who were initially at risk of central nervous system (CNS) involvement received 4 intrathecal doses of methotrexate (15 mg) and hydrocortisone (25 mg) for CNS prophylaxis. Central pathological reviews were not performed; only the individual institutional diagnoses were used. The study included 111 men and 79 women, with a median age at diagnosis of 63 years (range, 18–80 years). According to the IPI, 133 patients were classified as L; 49, as LI; 5, as HI; and 3, as H. Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. CNS prophylaxis was performed in 15 patients who had an initial CNS risk and achieved CR. The median observation period for the living patients was 52 months. The responses to therapy were 180 CR, 8 PR, and 2 progression of disease (PD). The 5-year PFS and 5-year OS rates were 84% and 90%, respectively, and both plateaued (Figure 1). None of the patients experienced PD after 4 years of observation. Multivariate analysis revealed that the presence of bulky mass, which was evident in 18 patients, was an independent risk factor for PFS (P = 0.007, relative risk [RR] 3.5) and OS (P = 0.003, RR 5.8), along with poor performance status. During the observation period, 29 patients experienced PD. The progression sites included the primary sites in 15 patients, outside the primary sites in 10, and undetermined in 4. There were 16 deaths, 14 of which were due to the lymphoma. In 149 patients with at least one of the 4 risk factors used in the SWOG 0014 study, the 5-year PFS and 5-year OS rates were 86% and 94%, respectively. Six cycles of R-CHOP therapy alone were observed to be highly effective in attaining good survival results with plateaus. These results suggest that the “standard” strategy of 3 cycles of R-CHOP followed by involved-field radiotherapy for localized DLBCL should be replaced by R-CHOP alone. 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: 2012
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  • 2
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1630-1630
    Abstract: Abstract 1630 Background: In almost all cases, follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are CD20 positive. Since the introduction of rituximab (R), the outcome of the patients with FL or DLBCL has improved perceptively. Since 2001 and 2003, the Yokohama City University Hematology Group in Japan has uniformly treated FL and DLBCL patients, respectively, with 6 cycles of standard (21 days) R-CHOP therapy with curative intent, except in the case of stage 1 FL. Here, we report our experience. Patients and Methods: Five hundred and twenty-six untreated consecutive patients (158, FL; 368, DLBCL) between 2001 and 2009 were the subjects of this study. All the patients were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP in our 7 hospitals. Patients who had partial remission (PR) after the 4 initial cycles were administered a total of 8 R-CHOP cycles. Patients who did not achieve PR after the 4 initial R-CHOP cycles or those with disease progression at any given time received salvage therapy, and that time point was designated as the point at which the disease had started progressing. Patients who required more than 20% dose reduction were excluded from the study. Those with special forms of DLBCL, such as intravascular lymphoma, primary mediastinal large B-cell lymphoma, and T-cell-rich B-cell lymphoma, were also excluded. Additional local irradiation was performed in patients with PR or complete remission (CR) if deemed necessary by the attending physician. No patients received maintenance therapy with R. DLBCL patients who achieved CR but were initially at risk of central nervous system (CNS) involvement received methotrexate (15 mg) and hydrocortisone (25 mg) 4 times intrrathecally for CNS prophylaxis. Central pathological reviews were not performed; only the individual institutional diagnoses were used. Results: In the cases of FL, the pathological grading was grade 1 for 65 patients, grade 2 for 61 patients, grade 3a for 20 patients, and grade 3b for 12 patients. There were 81 men and 77 women, and the median age at diagnosis was 57 years (range, 25–76). In accordance with the International Prognostic Index (IPI), 60 patients were at low risk (L); 60, at low-intermediate risk (LI); 26, at high-intermediate risk (HI); and 12, at high risk (H). According to the Follicular Lymphoma IPI, 43 patients were classified as L; 49, as being at intermediate risk; and 59, as H. For 7 patients, the risk was undetermined. Ten patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. None received CNS prophylaxis. Twelve deaths were observed among the FL patients, 10 of which were due to the lymphoma. In the DLBCL group, there were 209 men and 159 women, and the median age at diagnosis was 64 years (range, 18–80). According to the IPI, 158 patients were classified as L; 93, as LI; 57, as HI; and 60, as H. Thirty-seven patients received additional local irradiation in PR/CR at the end of the R-CHOP therapy. CNS prophylaxis was performed in 42 patients who had an initial CNS risk and achieved CR. In the observaton period, there were 58 deaths among the DLBCL patients, 50 of which were due to the lymphoma. The median observation period for the living patients with FL and DLBCL was 45 months and 43 months, respectively. For the FL group, the CR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) rates were 86%, 50%, and 92%, respectively. Between patients with grade 1–2 FL, and grade 3 FL, the PFS (P = 0.16) and OS (P = 0.17) were not significantly different. This was found to also be true when the PFS (P = 0.19) and OS (P = 0.32) of grade 1–3a and grade 3b FL patients were compared. For the DLBCL group, the CR, 5year PFS, and 5-year OS rates were 89%, 72%, and 80%, respectively. The PFS rate was significantly higher in the DLBCL group compared to the FL group (Fig 1(A), P = 0.001), but the OS was significantly greater in the FL group (Fig 1(B), P = 0.006). Conclusion: Standard R-CHOP therapy is effective for patients with FL and DLBCL, with the 5-year OS rate exceeding 80% for both. However, in the FL group, the PFS did not show a plateau, suggesting the incurability of this lymphoma with R-CHOP therapy. The good OS indicated the effectiveness of salvage therapy for FL patients. Since the OS and PFS in patients with grade 3 FL were similar to those in patients with grade 1–2 FL, all grades of FL should probably be categorized simply as “FL” with regard to R-CHOP therapy. 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: 2011
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  • 3
    In: British Journal of Haematology, Wiley, Vol. 161, No. 3 ( 2013-05), p. 383-388
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2013
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  • 4
    In: Journal of Clinical and Experimental Hematopathology, Japanese Society for Lymphoreticular Tissue Research, Vol. 53, No. 2 ( 2013), p. 121-125
    Type of Medium: Online Resource
    ISSN: 1346-4280 , 1880-9952
    Language: English
    Publisher: Japanese Society for Lymphoreticular Tissue Research
    Publication Date: 2013
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  • 5
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 1574-1574
    Abstract: Abstract 1574 Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma (NHL), with a highly variable natural history ranging from an indolent disease to a rapidly progressive one such as its transformation to aggressive NHL. We have used the Follicular Lymphoma International Prognostic Index (FLIPI) that uses patient- or tumor-specific characteristics for the risk-stratification of patients with FL at the time of diagnosis. The tumor microenvironment, including variable monocyte-derived cell infiltration, has recently shown to play an important role in the clinical course of FL patients. Wilcox et al. showed that an elevated absolute monocyte count (AMC) is associated with inferior overall survival of FL patients receiving varying treatment strategies (Wilcox RA, et al. Leuk Lymphoma 2012). We retrospectively evaluated the prognostic changes in AMC at diagnosis in FL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy alone. This study included 157 consecutive FL patients treated with the R-CHOP therapy at 1 of the 7 participating hospitals between 2001 and 2009. Since 2001, the Yokohama City University Hematology Group in Japan uniformly and curatively treated patients with FL, except for those with stage 1 FL; the patients were treated with 6 cycles of standard R-CHOP therapy for 21 days. Patients who showed partial response (PR) after the initial 4 cycles were administered a total of 8 R-CHOP cycles, and those who did not show PR after the initial 4 cycles or patients in whom the disease progressed at any given time received salvage therapy. Patients who had bulky masses at diagnosis received involved field radiation following 6—8 cycles of R-CHOP therapy. Patients for whom the doses had to be reduced by more than 20% were excluded from the study. The study included 80 men and 77 women, with a median age of 63 years at diagnosis (range, 18—80 years). The FL of the 157 patients were classified as grade 1 (n = 65), grade 2 (n = 60), grade 3a (n = 20), and grade 3b (n = 12) according to the World Health Organization (WHO) scheme. The median AMC at diagnosis was 349 cells/μL (range, 10—1110 cells/μL). The median observation period for surviving patients was 45 months. The 5-year progression-free survival (PFS) estimated for the entire cohort was at 71.3%. The differences in the PFS when patients were stratified according to their AMCs were not significant. The effect of the following variables on PFS were assessed: (1) AMC 〉 390 cells/μL; (2) age 〉 60 years; (3) hemoglobin level 〈 120 g/L; (4) elevation of serum lactate dehydrogenase levels; (5) nodal areas 〉 4; and (6) advancement of clinical stage. In the univariate analysis, the presence of more than 4 nodal areas (hazard ratio [HR] = 2.65, 95% CI, 1.58—4.47, P 〈 0.001) and advanced clinical stage (HR = 2.75, 95% CI, 1.26—6.03, P= 0.01) were associated with inferior PFS. However, in the multivariate analysis, the association between the presence of more than 4 nodal areas and survival was found to be significant (HR = 2.33, 95% CI, 1.28—4.24, P = 0.006). Therefore, both univariate and multivariate analyses indicate that AMC was not a prognostic factor for PFS. There was no statistically significant correlation between AMC and FL patients' clinical outcome. AMC is not a prognostic factor in FL patients treated by R-CHOP. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 6
    In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 17, No. 9 ( 2011-09), p. 1389-1394
    Type of Medium: Online Resource
    ISSN: 1083-8791
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2011
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    detail.hit.zdb_id: 2057605-5
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  • 7
    In: Leukemia Research, Elsevier BV, Vol. 37, No. 10 ( 2013-10), p. 1208-1212
    Type of Medium: Online Resource
    ISSN: 0145-2126
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
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  • 8
    In: Artificial Organs, Wiley, Vol. 37, No. 10 ( 2013-10), p. 932-936
    Abstract: Sinusoidal obstruction syndrome ( SOS ) is one of the severe complications of hematopoietic stem cell transplantation ( HSCT ). Systemic management including respiratory and circulatory support is necessary. In addition, abdominal paracentesis is often needed for pain relief and to reduce the pressure of tense ascites. Concentrated ascites reinfusion therapy ( CART ) involves the filtration, concentration, and reinfusion of drained ascites, which contributes to reuse of autologous proteins. CART has been reported as supportive therapy for patients with liver cirrhosis and cancer. We retrospectively reviewed the efficacy and safety of CART in three patients (two with acute myelogenous leukemia and one with chronic myeloid leukemia) who developed SOS after allo‐ HSCT . They all had symptomatic, tense, and diuretic‐refractory ascites with right costal pain and marked weight gain. Two patients showed immediate improvement after CART . However, one patient experienced four CARTs with slow recovery. All patients are now alive and are being monitored as outpatients over 2 years with remission. No severe adverse event was observed related to CART , and 25.2–98.0 (median 30.2) grams of albumin was collected and reinfused. CART after paracentesis reduces protein loss in ascites by reinfusion of autologous protein instead of exogenous albumin preparations. Although transient fever is reported as a frequent adverse event, no events like severe bleeding or infection were observed. While its safety has not been fully established in patients with hematological disease after HSCT , CART may be a considerable supportive therapy for SOS with tense ascites.
    Type of Medium: Online Resource
    ISSN: 0160-564X , 1525-1594
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2003825-2
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  • 9
    In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 92, No. 3 ( 2010-10), p. 463-467
    Type of Medium: Online Resource
    ISSN: 0925-5710 , 1865-3774
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2028991-1
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  • 10
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4883-4883
    Abstract: Background: Approximately 80% of patients with diffuse large B-cell lymphoma (DLBCL) achieve a complete response (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy (R-CHOP) as first-line treatment but approximately 25% of patients with CR experience relapse. Disease recurrence generally occurs in the first 2 years following the first CR, but some patients relapse in the 5 years following the first CR. The optimal follow-up strategy for patients with non-Hodgkin's lymphoma has been under consideration. There are limitations to surveillance imaging, including risk of increase in healthcare costs, and increased anxiety due to the possibility of recurrence. To assess the role of surveillance imaging in the rituximab era, we retrospectively analyzed DLBCL patients, treated with a uniform treatment regimen, who relapsed after achieving the first CR. Patients and Methods : Between 2004 and 2009, DLBCL patients were newly diagnosed and were treated with 6 to 8 cycles of full-dose R-CHOP therapy (50 mg/m2 doxorubicin, 750 mg/m2 cyclophosphamide and 1.4 mg/m2 [maximum 2.0 mg/body] vincristine on day 1, 100 mg/body per day of prednisolone on days 1 to 5, and 375 mg/m2 rituximab per treatment cycle; treatment cycles were repeated every 3 weeks) at the 8 institutions of the Yokohama City University Hematology Group. Physical examinations were performed every 1 to 3 months, and periodical CT was generally performed every 6 months for 5 years after achieving CR. The relapses were categorized into 2 groups based on the modality of detection. One group consisted of the relapses that were detected by surveillance imaging (SI) in the absence of symptoms. The other group was composed of relapses that were detected by clinical symptoms, abnormal laboratory data, or SI in the presence of symptoms. Overall survival (OS) was measured from the start of the initial treatment until the time of the last follow-up or death. Using Kaplan-Meier survival analysis and the log-rank test, we assessed OS based on the modality of relapse detection. Result s: In total, 315 patients with DLBCL were diagnosed and treated with R-CHOP therapy. Further, 289 patients achieved the first CR. We identified 52 patients who relapsed after the first CR. The patients who relapsed were at a more progressed clinical stage and had a higher International Prognostic Index (IPI) score than the patients in CR, although there were no significant differences in the age, gender, or median duration of follow-up between the patients with or without CR. Of the 52 relapsed patients, 19 relapses (37%) were detected by routine SI in the absence of clinical symptoms. The remaining 33 relapses (63%) were detected by SI in the presence of clinical symptoms (CS) or were detected following unscheduled imaging due to the presence of clinical symptoms or abnormal laboratory findings. The most frequently observed clinical symptom in the CS group was lymphadenopathy (n = 13, 39%). Median observation period after the first relapse in the 24 survivors (10 in SI group and 14 in CS group) was 62 months. There were no significant differences in age, gender, clinical stage, IPI, or median relapse-free duration between the SI and CS groups. The OS curve is shown in Figure below. There was no significant difference (P = 0.23) in the 5-year OS rates in the SI and the CS groups. Conclusion: Periodic surveillance imaging does not prolong the OS in relapsed patients. There are more to be discussed about the follow up strategy for DLBCL. 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: 2015
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    detail.hit.zdb_id: 80069-7
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