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  • 1
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1791-1791
    Abstract: [Introduction] Follicular lymphoma (FL) is an indolent neoplasm that is generally characterized by nodular proliferation of B cells arising from the follicular center of the lymph node.The typical chromosomal abnormality in FL is the translocation t(14;18)(q32;q21), which is found in more than 75% of cases. Several other chromosomal abnormalities, which might contribute to tumor progression, have been found. However, the prognostic significance of cytogenetic features of FL has not been clearly established in the Rituximab Era. The purpose of this study was to evaluate the pattern of chromosomal abnormalities in FL and to clarify the correlation between cytogenetic features and clinical outcome. [Patients and Methods] Cells from lymph nodes or other sites of disease at diagnosis from 201 patients with FL admitted to our hospital and affiliated hospitals between 2001 and 2013 were cytogenetically analyzed using standard methods of G-banding. Ninety nine (49.3%) men and 102 (50.7%) women with a median age of 59 years (range, 28 - 83 years) were included in the analysis. The median follow up period was 48.3 months. Forty three patients (21.4%) were Stage I or II; 156 patients (77.6%) were Stage III or IV; and 2 patients (1%) were unknown. Eighty patients (39.8%) were follicular lymphoma international prognostic index (FLIPI) low, 55 patients (27.4%) were intermediate, and 43 patients (21.4%) were high; and 23 patients (11.4%) were unknown. The distribution of FL pathological subgroups was as follows: FL Grade 1 - 2, 142 patients (70.6%); FL Grade 3a, 30 (15.0%); and unknown, 29 (14.4%). One hundred and fifty seven patients received Rituximab-containing chemotherapy as an initial treatment. [Results] t(14;18)(q32;q21) was the most common abnormality observed in 119 patients (59.2%); however, t(14;18) showed no correlation with clinical outcome. Other numerical or structural abnormalities that were identified in more than 5% of the patients were as follows: +X (17.9%), del(6)(q) / −6 (16.9%), +7 (14.4%), abnormality of 1q12-21 / 1q (12.9%), del(13)(q) / -13 (11.9%), abnormality of 3q27 (10.4%), abnormality of 10q22-24 (10.0%), +12 / dup(12)(q) (10.0%), abnormality of 1p21-22 / 1p(9.0%), +18 (9.0%), del(17)(p) / −17 (5.0%), and the number of cytogenetic aberrations higher than 3 (54.7%). Patients with +21 (p = 0.00171) or with 〉 3 cytogenetic aberrations (p = 0.00269) had a significantly shorter progression free survival (PFS) in univariate analysis. Patients with +21 (median OS 29.9 Mo vs. not reached, p 〈 0.001), with 3q27 abnormality (p 〈 0.001), with del(17)(p) / −17 (p = 0.00659), with +7 (p = 0.0369), and with 〉 3 cytogenetic aberrations (p = 0.0301) were associated with a shorter overall survival (OS). We also found an association between trisomy 21 or 3q27 abnormality and poor OS with and without t(14;18) (p 〈 0.001). Multivariate analysis identified +21 and 〉 3 cytogenetic aberrations as independent prognostic factors for PFS in this population. We also identified 3q27 abnormality and +21 as independent prognostic factors for OS in this population. When patients with or without +21 were compared, t(14;18) positivity was not significantly different between the two groups, but 3q27 positivity was significantly higher in the patients with +21 than in those without +21 (30.8% vs. 9.0%, p = 0.034). Patients with +21 were significantly older than patients without +21 (64.5 years vs. 58.4 years, p= 0.027). There were no differences between the groups in other characteristics such as stage, FLIPI, pathological grade, and laboratory data. [Conclusion] Both the presence of trisomy 21 and the presence of 3q27 abnormality were independent risk factors for overall survival in FL with and without t(14;18). Chromosomal analysis of FL at the time of diagnosis can provide important information about survival. 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: 2016
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5028-5028
    Abstract: Background: Analysis of prognostic factors and clinical trials of novel agents for Waldenstrӧm macroglobulinemia (WM) are ongoing in Western countries, but few studies of WM have been performed in Japan. As a step toward future investigations, we retrospectively analyzed clinical features and prognostic factors in Japanese patients with WM. Methods: We retrospectively analyzed clinical and laboratory characteristics, treatment and outcomes of 110 patients with WM, IgM-MGUS or lymphoplasmacytic lymphoma (LPL) diagnosed from January 2001 to March 2013 at 12 institutes. Overall survival (OS) was analyzed using Kaplan-Meier methods and survival was compared using log-rank testing. Several clinical characteristics at diagnosis were assessed by Cox regression for uni- and multivariate analysis for OS. Results: Median age at diagnosis was 69 (range, 41-96) years, 73.6% were male, 12.0% had an ECOG performance status 2-4 and 6.4% presented with B-symptoms. Hyperviscosity, peripheral neuropathy, amyloidosis, cryoglobulinemia and cold agglutinin disease were shown in 9.1%, 4.5%, 1.8%, 4.5% and 2.7%, respectively. In 94 patients with available CT findings at diagnosis, lymphadenopathy, hepatosplenomegaly, pleural effusion, lung involvement, bone involvement and skin involvement were shown in 41.5%, 14.9%, 8.5%, 4.3%, 4.3% and 6.4%, respectively. Median serum monoclonal protein level was 2.62 g/dl (range, 0.70-9.35 g/dl). Symptomatic WM was present in 76 patients, asymptomatic WM in 23 and IgM-MGUS in 2 according to criteria of the Second International Workshop on WM. Seven patients showed IgG- or IgA-secreting LPL and 2 showed LPL without bone marrow infiltration. In patients with symptomatic WM, international prognostic scoring system for WM (ISSWM) was low in 9.2%, intermediate in 34.2%, high in 39.5% and unknown in 17.1%. Among patients with asymptomatic and symptomatic WM, watchful waiting was performed in 91.3% and 40.0%, respectively, with 61.9% and 36.7% remaining untreated, respectively. Median time to treatment from diagnosis of asymptomatic or symptomatic WM was 240 days (range, 3-1238 days) and 31 days (range, 0-2011 days), respectively. Oral alkylating agents were administered to 34.7% of patients with WM, 19.4% were treated with CHOP or CHOP-like regimen with or without rituximab, 8.2% received fludarabine mono- or combination therapy and 6.1% received rituximab monotherapy. Rituximab-containing therapy was administered as the initial treatment in 33.8% of patients who received treatment. Overall response rate (ORR) (complete + partial response rate) was 48.6%, and patients treated with rituximab-containing therapy displayed higher ORR (64.0%) compared to those with non-rituximab therapy (40.8%). Plasmapheresis was performed in 3.7% of patients. Three patients (2.7%) showed transformation to diffuse large B-cell lymphoma, and 7 (6.4%) developed second primary malignancies. Median follow-up was 38 months, 5-year OS rate for all patients was 74.9% (95% confidence interval (CI) 62.5-83.7) and rates for those with symptomatic WM, asymptomatic WM and other LPL were 66.0% (95%CI 50.6-77.6), 100% and 88.9% (95%CI 43.3-98.4), respectively. Significant differences in survival between risk groups of ISSWM in patients with symptomatic WM were not seen (5-year OS: high, 62.4%; intermediate, 64.3%; low, 75.0%; p=0.86). Although no significant difference in OS was observed compared to initial treatment (p=0.265), patients treated with rituximab during the observation period showed significantly prolonged OS compared to those treated without rituximab (5-year OS rates: 78.9% vs. 45.6%, p=0.036). In univariate analysis, age, pleural effusion, serum albumin, C-reactive protein and serum IgM levels were poor prognostic factors for OS. In multivariate analysis, age 〉 65 years (hazard ratio (HR)=3.294; 95%CI 1.097-9.888, p=0.0336) and pleural effusion (HR=4.55; 95%CI 1.602-12.930, p=0.0045) were identified as significant prognostic factors for OS. Conclusion: Prognostic factors for WM in Western countries may not be applicable to Japanese patients. This study suggested presence of pleural effusion at diagnosis is associated with poor clinical outcomes. Further investigations including histopathological examinations and molecular analyses are required to elucidate prognostic factors in Japan. 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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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 5344-5344
    Abstract: Background:Although the addition of rituximab to CHOP regimen improved prognosis in DLBCL patients with more than 80% of a long-term survival rate, CNS relapse did not decrease and 5 to 10% of patients experienced CNS relapse after rituximab-containing chemotherapy. Risk factors for CNS relapse after standard chemotherapy have been aggressively investigated, and a risk model, CNS-international prognostic index (IPI), has been widely used. However, risk factors for CNS relapse after high-dose chemotherapy following ASCT, which is recognized as an important treatment option for high-risk DLBCL patients, have not been elucidated. So, we performed this retrospective analysis to address this unsolved issue. Patients and methods:This study analyzed 87 adult patients who underwent ASCT against chemo-sensitive DLBCL including intravascular large B-cell lymphoma (IVLBCL) between 1997 and 2015 at the four institutions in Gunma, Japan. There was no restriction on the type of conditioning regimens. CNS-directed regimens were defined as chemotherapy or conditioning regimens containing high dose cytarabin, high dose methotrexate, busulfan, ranimustine, or total body irradiation. Only the first relapse after ASCT was assessed in this study. Fisher's exact test was used to compare binary variables. Cumulative incidences (CIs) of CNS relapse were compared using the stratified Gray test, considering relapse without CNS lesions and death without the event as a competing risk. The Fine-Gray proportional hazard model was used for multivariate analysis of risk factors for CNS relapse. The potential risk factors evaluated in this analysis were age at transplant, gender, clinical stage, IPI (high-intermediate/high or not), and CNS-IPI (high or not) at diagnosis, CD5 positivity, CNS involvement prior to ASCT, CNS-directed chemotherapy prior to ASCT, and CNS-directed conditioning regimen. Values of p 〈 0.05 were considered significant. Results:Of the 87 patients assessed in this study, 48 were male and 39 were female, and the median age was 57 years (range: 23 to 66 years). CD5 was expressed in 19% of the patients, and 10% were diagnosed as IVLBCL. CNS-IPI at diagnosis was high in 53%, and rituximab and CNS-directed chemotherapy was administered prior to ASCT in 83% and 16%, respectively. CNS involvement was observed prior to ASCT and at the time of ASCT in 9% and 0%, respectively. Disease status at the time of transplant was first complete remission (CR) in 47%, advanced CR in 23%, and partial remission in 30%. CNS-directed conditioning regimens were used in 38%. With a median observation time of 21.9 months, seven patients experienced CNS relapse as the first relapse after ASCT. The 3-year CI of CNS relapse was 7.3% with 5.7 months of median duration from ASCT (range: 2.7 to 69.0 months). In univariate analysis, only CD5 positivity was identified as a significant risk factor for CNS relapse (3-year CIs in patients with and without CD5 expression: 27.0% vs. 2.2%, respectively; p 〈 0.01). In multivariate analysis, CD5 positivity, CNS-IPI at diagnosis, CNS-directed chemotherapy prior to ASCT, and CNS-directed conditioning regimen were evaluated, and only CD5 positivity was identified as an independent risk factor for CNS relapse (relative risk=20.1; p 〈 0.01). Of the seven patients with CNS relapse after ASCT, four expressed CD5 and five received CNS-directed chemotherapy prior to ASCT and/or conditioning regimens. All seven patients died from DLBCL within two years after CNS relapse. Conclusion:These results suggested that CNS relapse occurred in DLBCL patients even after ASCT with similar incidence to that after chemotherapy. Although prophylactic strategies for CNS relapse should be investigated especially in patients with CD5-positive patients, use of CNS-directed chemotherapy prior to ASCT and/or conditioning regimens did not affect the CIs of CNS relapse. A future study with a larger cohort is warranted to develop a risk model for CNS relapse after ASCT in DLBCL patients. Disclosures Handa: Ono: 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: 2019
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  • 4
    In: British Journal of Haematology, Wiley, Vol. 184, No. 4 ( 2019-02), p. 570-577
    Abstract: The chromosomal abnormalities associated with follicular lymphoma (FL) prognosis are not fully elucidated. Here, we evaluated the pattern of chromosomal abnormalities in FL, and clarified the correlations between the cytogenetic features and clinical outcome. Cytogenetic analysis was performed using standard methods of Giemsa‐banding at diagnosis for 201 FL patients admitted to our hospitals between 2001 and 2013. The identified chromosomal abnormalities were: t(14;18)(q32;q21) (59·2%), +X (17·9%), del(6)(q)/‐6 (16·9%), +7 (14·4%), abnormality of 1q12‐21/1q (12·9%), del(13)(q)/‐13 (11·9%), abnormality of 3q27 (10·4%), abnormality of 10q22‐24 (10·0%), +12/dup(12)(q) (10·0%), abnormality of 1p21‐22/1p (9·0%), +18 (9·0%), del(17)(p)/‐17 (5·0%), and a complex karyotype (54·7%). Patients with trisomy 21 had a significantly shorter progression‐free survival ( P  = 0·00171) and overall survival (OS) ( P   〈  0·001) than those without trisomy 21; additionally, patients with trisomy 21 in the rituximab‐treated cohort also had a significantly shorter OS ( P  = 0·000428). Multivariate analysis identified trisomy 21 as an independent risk factor in our cohorts with or without t(14;18) ( P  = 0·015). In conclusion, the presence of trisomy 21 was an independent risk factor for in FL. Chromosomal analysis of FL patients at diagnosis can provide useful information about their expected survival.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
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    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1475751-5
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  • 5
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1935-1935
    Abstract: Abstract 1935 Poster Board I-958 Introduction: Several reports have identified soluble-form IL-2 receptor á (sIL-2Rá) as a significant prognostic factor in patients with non-Hodgkin lymphoma treated using chemotherapy, particularly in rituximab-containing regimens. However, the clinical significance of sIL-2R is not fully understood, as only small populations have been studied to date. The rationale for increasing of serum level of sIL-2Rá in non-Hodgkin lymphoma is also unclear. Patients and Methods: We analyzed 409 patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2001 and July 2008. Treatment comprised CHOP-like regimen with (R-CHOP-like) or without rituximab. Levels of sIL-2R were evaluated with enzyme-linked immunosorbent assay at diagnosis. Overall survival (OS) and progression-free survival (PFS, death from any cause, relapse and refractory disease) were analyzed using Kaplan-Meier methods and survival was compared using log-rank tests. To estimate the survival impact of several factors, including sIL-2Rá level, PS, LDH, B symptoms, extranodal sites ≥2 and age, we performed multivariate analysis using Cox proportional hazards. In 166 of 409 patients, CD25 (IL-2Rá) expression on tumor cells was evaluated using a lymphoma sample from the lymph node, bone marrow, blood or other extranodal organ by flow cytometry. To estimate CD25 expression of tumor cell, CD45 bright cells (mature lymphocyte gate) were gated and considered positive if positivity was seen in 〉 20% of the population excluding CD4-positive cells) using three-color flow cytometry. Results: Median age was 68 years (range, 17-91 years), males/females 1.18, and 28.9% of patients were treated with CHOP-like regimen and 60.2% with R-CHOP-like regimen. Clinical stage was I in 24.4%, II in 24.2%, III in 13.1%, and IV in 38.8%. International Prognostic Index (IPI) was Low in 33.5%, LI in 23.5%, HI in 18.7% and H in 24.3%. Median follow-up for CHOP-like and R-CHOP-like groups was 924 days (range, 16-2878 days) and 799 days (range, 29-2688 days), respectively. Median sIL-2Rá value was 1360 U/L (range, 170-59,500 U/L). For the entire population, CR rate was 71.9%, 3-year OS was 67.6% and PFS was 58.8%. OS differed significantly between sIL-2R 〉 1000 U/L and ≤1000 U/L, between 〉 2000 U/L and ≤2000 U/L and between 〉 3500 U/L and ≤3500 U/L, (p 〈 0.001, 〈 0.001, 〈 0.001, respectively). PFS also differed at each sIL-2Rá point (p 〈 0.001, respectively). The sIL-2Rá value correlated moderately or well with other prognostic factors, such as LDH, PS ≥2, B symptoms, ≥2 extranodal lesions, age and clinical stage by Spearman correlation analysis (r=0.579, 0.258, 0.404, 0.474, respectively). Multivariate analysis showed sIL-2Rá as a significant prognostic factor, in addition to several factors. In a group treated with R-CHOP-like regimen, 3-year OS was 74.5% and PFS was 68.8%. OS again differed significantly between sIL-2Rá 〉 1000 U/L and ≤1000 U/L, between 〉 2000 U/L and ≤2000 U/L and, between 〉 3500 U/L and ≤3500 U/L (p 〈 0.001, respectively). PFS was also significant at each sIL-2Rá value. The higher the level of IL-2R, the worse the 3-year OS at each sIL-2R value (63.6%, 60.1%, 53.2%, respectively). However, we could not identify statistical significance of sIL-2 level by multivariate analysis. IL-2Rá usually functions as a cytokine receptor on cell surface, called CD25. To show the importance of CD25 expression in lymphoma cells on serum level of soluble form IL-2Rá, we compared sIL-2Rá levels in CD25-positive and -negative cases. CD25-positive cases showed significantly higher sIL-2Rá level than CD25-negative cases among the overall population. After defining two group according to clinical stage (I+II and III+IV), sIL-2Rá level was higher in the CD25-positive group than in the CD25-negative group for the stage III+IV group (p=0.001), but this difference was not seen for the stage I+II group (p=0.390). This trend was also seen in the case of IPI, L+LI (p=0.642) and HI+H (p=0.0016)). These results suggest that one rationale for increasing level of sIL-2Rá in DLBCL is removing from tumor cell like other cytokine receptor. Conclusion: In terms of survival and relapse, sIL-2R remains an important risk factor of DLBCL, not only in CHOP-like regimens, but also in the R-CHOP era. The survival rate of patients with sIL-2Rá 〉 3500 U/L is extremely poor even if treated with R-CHOP (53.2%). We showed that one rationale for increasing level of serum sIL-2Rá level in DLBCL is to remove from the tumor cell surface. 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: 2009
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  • 6
    In: International Journal of Hematology, Springer Science and Business Media LLC, Vol. 109, No. 1 ( 2019-1), p. 91-97
    Type of Medium: Online Resource
    ISSN: 0925-5710 , 1865-3774
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2028991-1
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  • 7
    In: Journal of Clinical and Experimental Hematopathology, Japanese Society for Lymphoreticular Tissue Research, Vol. 53, No. 3 ( 2013), p. 197-205
    Type of Medium: Online Resource
    ISSN: 1346-4280 , 1880-9952
    Language: English
    Publisher: Japanese Society for Lymphoreticular Tissue Research
    Publication Date: 2013
    detail.hit.zdb_id: 2395568-5
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  • 8
    In: Journal of Clinical and Experimental Hematopathology, Japanese Society for Lymphoreticular Tissue Research, Vol. 58, No. 1 ( 2018), p. 10-16
    Type of Medium: Online Resource
    ISSN: 1346-4280 , 1880-9952
    Language: English
    Publisher: Japanese Society for Lymphoreticular Tissue Research
    Publication Date: 2018
    detail.hit.zdb_id: 2395568-5
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  • 9
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3445-3445
    Abstract: Background: An increased risk of secondary myelodysplastic syndrome and acute myeloid leukemia (sMDS/AML) with a cumulative incidence of 4 to 18% has been described in adult patients with malignant lymphoma who undergo high-dose chemotherapy with autologous stem cell transplantation (ASCT). Although a high-dose VP-16 regimen has been reported to have greater stem cell mobilization potential than a high-dose cyclophosphamide regimen, this regimen was identified as a potential risk factor for sMDS/AML in several studies. Thus, this multi-center retrospective analysis of ASCT recipients with malignant lymphoma was performed to assess the safety of high-dose VP-16 as a stem cell mobilization regimen. Patients and methods: This study analyzed 153 adult patients who underwent ASCT against malignant lymphoma at four institutions in Gunma, Japan between 1997 and 2012. Patients with progressive disease were excluded. There was no restriction on the type of pathological diagnosis and conditioning regimens. The high-dose VP-16 regimen consisted of 350 mg/m2 of VP-16 (days 1 to 4) and 16 mg/body of dexamethasone (days 1 to 4). Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Fisher's exact test was used to compare binary variables. Cumulative incidences (CIs) of sMDS/AML were compared using the stratified Gray test, considering death without the event as a competing risk. The Fine-Gray proportional hazard model was used for multivariate analysis of risk factors for sMDS/AML. The potential risk factors evaluated in this analysis were age at transplant, sex, pathological diagnosis, prior malignancy, conditioning regimens (LEED or not), number of chemotherapy regimens before ASCT, prior radiation therapy, disease status, and cyclophosphamide equivalent dose (CED). Values of p 〈 0.05 were considered significant. Results: Of the 153 patients assessed in this study, 93 were male and 60 were female, and the median age was 56 years (range: 18 to 68 years). Underlying diseases were diffuse large B-cell lymphoma (including IVLBCL) in 87 patients, follicular lymphoma in 8, other B-cell lymphoma in 24, Hodgkin lymphoma in 16, and T-NK-cell lymphoma in 18, and 81 patients were conditioned with LEED regimens. Disease status at the time of transplant was first complete remission (CR) in 77, advanced CR in 34, and partial remission in 42. The high-dose VP-16 regimen was used to mobilize stem cells in 85 patients. Of the 68 patients not using the high-dose VP-16 regimen, stem cells were mobilized with (R-)CHOP in 17, CHASE(-R) in 28, and others in 23. There were no significant differences in patient characteristics, disease features, and transplant procedures between patients with and without the high-dose VP-16 regimen. With a median observation time of 55.2 months, eight patients developed sMDS/AML, and the 5-year cumulative incidence of sMDS/AML was 3.5%. Type of sMDS/AML was MDS in six, chronic myelomonocytic leukemia in one, and AML in one, and median duration from ASCT was 52.9 months (range: 31.2 to 104.4 months). On univariate analysis, only age over 50 years was identified as a significant risk factor for sMDS/AML (5-year CIs in age under and over 50 years: 0.0% vs. 5.3%, respectively; p = 0.043), but not stem cell mobilization with the high-dose VP-16 regimen (5-year CIs with and without high-dose VP-16 regimen: 1.5% vs. 6.6%, respectively; p = 0.528). On multivariate analysis, age, using high-dose VP-16, and CED were evaluated. Age over 50 years (hazard ratio [HR] = 44140; p 〈 0.001) was identified as an independent risk factor for sMDS/AML, but not the high-dose VP-16 regimen (HR = 0.58; p = 0.432). The 5-year OS rates were not significantly different between patients with and without the high-dose VP-16 regimen (56% vs. 54%, respectively; p = 0.845). Conclusion: These results suggest that stem cell mobilization with a high-dose VP-16 regimen was not associated with an increased risk of sMDS/AML and did not affect the long-term survival rate in adult patients who underwent ASCT against malignant lymphoma. Therefore, considering this regimen's greater potential to mobilize stem cells, a high-dose VP-16 regimen is considered a preferable stem cell mobilization regimen in these patients. Disclosures Matsumoto: Janssen Pharmaceutical: Honoraria; Celgene: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
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