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  • American Society of Hematology  (6)
  • 1
    Online Resource
    Online Resource
    Absolute Monocyte Count in Follicular Lymphoma Patients Treated with Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1574-1574
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V120.21.1574.1574
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 2
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    Clinical Significance of Addition of Cytarabine or Thiotepa to TBI/CY Regimen.
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 3028-3028
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3028-3028
    Abstract: Abstract 3028 Introduction: We performed a multicenter retrospective study of the significance of the addition of cytarabine (CA) or thiotepa (TT) to the myeloablative standard regimen consisting of total body irradiation (TBI) and cyclophosphamide (CY). Methods: Among the patients who underwent allogeneic hematopoietic stem cell transplantation between 2,000 and 2,010 in the four institutions related to Yokohama City University Hematology Group, a total of 365 patients who used the TBI/CY-based regimen were included to the cohort. Conditioning regimens were distributed to three groups: TBI/CY group (TC, n=82), TBI/CY/CA group (TCC, n=90), and TBI/CY/TT group (TCT, n=193). A standard TBI and CY regimen consisted of 12 Gy of TBI with four fractions and 60 mg/kg of CY for two days. Two days of CA (2 g/m2/day) or TT (200 mg/m2/day) were added to the TBI/CY regimen. A minimum dose reduction was permitted according to an older age or poorer co-morbidity. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. Gray's test was employed for comparison of cumulative incidence curves for relapse and non-relapse mortality (NRM). NRM and relapse were competing events. Adjusted multivariate Cox regression models were employed for each disease stage. Results: The median age was 42 years old (16–62). Diagnoses were acute myeloid leukemia (AML, n=219), acute lymphoid leukemia (ALL, n=105), and myelodysplastic syndrome (MDS, n=41). Complete remission or refractory cytopenia with multilineage dysplasia was defined as the standard stage (n=211), while the others were advanced (n=154). The stem cell sources were related bone marrow (RBM, n=79), related peripheral blood (RPB, n=51), unrelated bone marrow (UBM, n=161), and unrelated cord blood (UCB, n=74). As for patient characteristics, there was a deviation in the transplant year (P 〈 0.001), disease stage (P=0.001), and stem cell source (P=0.022). Among the 195 patients with a previous transplant year (2000–2005), 187 patients (95.9%) received the TCT regimen, while only 6 patients with the TCT regimen were included in the recent transplant (2006–2010). Among 82 patients of the TC group, 62 patients (75.6%) were defined to be in the standard stage. The cumulative incidence of engraftment was 89.5% with a median of 17 days (8–48). Cumulative incidences of acute graft-versus-host disease (GVHD) (grade 2 to 4, at day 50) and chronic GVHD (at 1 year) were 47.0 and 42.3%, respectively, with no significant difference between the three conditioning regimens. The median follow up period among survivors was 61.4 months (12.4–144). Outcomes at 5 years in each group (TC/TCC/TCT) were as follows: OS rates were 51.2, 34.4, and 40.3 (P=0.107), respectively; DFS rate were 50.8, 31.5, and 38.5 (P=0.177), respectively; NRM rates were 23.8, 35.5, and 40.5 (P=0.045), respectively; relapse incidences (RI) were 21.4, 29.6, and 20.8 (P=0.193), respectively. In standard stage, hazard risks (HR) for each regimen (TC is referent) were as follows; OS (TCC, HR=1.19, 95%CI: 0.64–2.01, P=0.70; TCT, HR=1.08, 95%CI: 0.66–1.78, P=0.75), NRM (TCC, HR=1.32, 95%CI: 0.61–2.85, P=0.48; TCT, HR=1.55, 95%CI: 0.82–2.94, P=0.17), and RI (TCC, HR=0.78, 95%CI: 0.26–2.33, P=0.65; TCT, HR=0.69, 95%CI: 0.28–1.72, P=0.42). In advanced stage, HR for each regimen (TC is referent) were as follows; OS (TCC, HR=0.94, 95%CI: 0.48–1.81, P=0.85; TCT, HR=1.16, 95%CI: 0.62–2.17, P=0.64), NRM (TCC, HR=1.39, 95%CI: 0.51–3.77, P=0.52; TCT, HR=2.68, 95%CI: 1.06–6.78, P=0.04), and RI (TCC, HR=1.05, 95%CI: 0.44–2.50, P=0.92; TCT, HR=0.69, 95%CI: 0.30–1.57, P=0.37). In AML, the TC group showed superior OS and NRM compared with the TCT group (54.0 vs. 36.9%, P=0.034; 23.1 vs. 42.4%, P=0.023, respectively). In MDS, the TCT group showed a lower RI compared with the TCC group (0 vs. 34.5%, respectively, P=0.012). Conclusion: The benefit of the addition of CA or TT to the TC regimen was not demonstrated for each risk group. Especially in AML, TCT lead to inferior survival compared with TC. However, a bias in patient characteristics has to be considered, and a prospective study is needed in the future. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.3028.3028
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Retrospective Study of Standard R-CHOP Therapy in Localized DLBCL
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 1620-1620
    Details
    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
    URL: Article
    DOI: 10.1182/blood.V120.21.1620.1620
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 4
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    Incidence, Risk Factors and Outcomes of Bronchiolitis Obliterans after Allogeneic Stem Cell Transplantation.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3365-3365
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3365-3365
    Abstract: Background: Bronchiolitis obliterans (BO) after allogeneic stem cell transplantation (allo-SCT) is a late-onset, life-threatening respiratory complication which significantly reduces patients’ quality of life. Despite different therapeutic protocols, BO mortality remains high and most patients die of respiratory failure or infections. In recent practice, the source of stem cells and the conditioning regimen for allo-SCT have become more varied, but their influence on the incidence of BO is not established. Here, we retrospectively analyzed incidence of and risk factors for BO in allo-SCT protocols. Patients and methods: Between Jan 1994 and June 2005, 2692 patients underwent allo-SCT in 14 facilities of the Kanto Study Group for Cell Therapy (KSGCT) in Japan, and 2154 surviving at least 100 days after transplantation were evaluated in this study. Clinical diagnosis of BO was made by pulmonary function tests (PFT) revealing a forced expiratory volume for 1 second (FEV1) less than 70% and FEV1/forced vital capacity less than 80% of the predicted value, along with typical changes on high-resolution computed tomography. Results: BO developed in 57 patients with a cumulative incidence at 5 years post transplant of 2.6%. The Kaplan Meier estimate of median time interval from transplant to diagnosis of BO was 335 days (83–907). The cumulative incidence of BO at 5 years was 1.62% (12/691) in bone marrow transplants from related donors (R-BMT), 3.83% (16/424) in peripheral blood stem cell transplantation from related donors (R-PBSCT), 2.91% (24/808) in BMT from unrelated donors (UR-BMT), and 2.65% (5/199) in unrelated cord blood transplantation (CBT). The incidence of BO after R-PBSCT was significantly higher than after any other type of allo-SCT (p=0.02). At BO diagnosis, the mean value of FEV1% decreased to 52.1% from 82.2% pre-transplant. 94% of patients had already developed chronic GVHD before the onset of BO. Risk factors for BO by univariate analysis were R-PBSCT (p=0.019) and preceding chronic GVHD (p=0.000). Twenty eight patients died after developing BO, 21 of respiratory failure. Only one patient died of relapse of primary disease. Overall 5 yr-survival of patients with BO from the time of diagnosis was 46.5%, significantly less than for those without (76.2% from day 335, p=0.000) by semi-landmark analysis. Conclusions: The incidence of BO in CBT recipients was higher than R-BMT recipients and not significantly different with UR-BMT recipients. R-PBSCT recipients who have already developed chronic GVHD have a higher risk for developing BO and need extensive care and repeated PFT examinations.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.3365.3365
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 5
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    Proposal of Progressive Adult Onset EBV-Associated Lymphoproliferative Disorder (PAEBV) as a Rapid-Onset Neoplastic Disease.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2920-2920
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2920-2920
    Abstract: Abstract 2920 Poster Board II-896 [Background] Epstein-Barr virus (EBV) is currently recognized as a pathogen of several known human diseases ranging from transient infection, chronic lymphoproliferative disorder (LPD) to EBV-positive malignant lymphomas. Chronic active EBV infection (CAEBV) is typically an indolent but long-lasting EBV-LPD of childhood. Another well documented EBV-associated LPD is the post-transplant EBV-LPD, which also occurs in adults. Fulminant proliferation of EBV after primary infection or in the setting of CAEBV is an aggressive type of disease, which has recently been included in the 4th version of WHO classification as “systemic EBV-positive T-cell LPD of childhood”. Here, we present a previously unrecognized type of EBV-associated LPD mainly developed in adults who experienced progressive clinical course. [Patients] A total of 13 adult patients with progressive EBV-LPD was identified from patient files of collaborative institutions. The patient clinical records and data were investigated retrospectively. [Results] There were six males and seven females with an age ranging from 16 to 85 years (median: 27 years). All patients were previously healthy without history of opportunistic infections or administration of immunosuppressants. Patients presented with persistent fever, hepatosplenomegaly and cytopenia, and all showed increasing number of EBV-DNA copies in peripheral blood. Proliferation of T- or NK-cells was recognized. Four patients showed elevated VCA-IgM antibody, and fell in the category of fulminant EBV-positive T-cell LPD after primary EBV infection. However, the other nine showed EBV-antibodies of previous infection. The bone marrow, liver, and lymph nodes were common sites of involvement. Morphological atypia of lymphocytes were faint in peripheral blood or biopsied specimens. Therefore, pathological diagnosis of malignant condition was difficult at the initial presentation. Because of the deteriorating clinical conditions, chemotherapy was administered to 12 patients, but the disease was resistant in 10 patients. Four patients underwent allogeneic hematopoietic stem cell transplantation. In total, 3 patients are alive and 10 patients were dead. The causes of death were primary disease in 5 patients, bleeding in 2, infection in 2, but unknown in one. All but one patient without allogeneic transplantation died within a year. The median survival time was eight months. [Discussion] In contrast to CAEBV in childhood, these 13 adult patients pursued obviously different, more aggressive clinical courses. However, early diagnosis had been difficult because of the little morphological abnormalities and disease recognition. Prompt administration of cytotoxic chemotherapy and/or stem cell transplantation is possibly needed to conquer this aggressive disease. Therefore, for this purpose, we here propose a novel nomenclature of progressive adult-onset EBV-LPD (PAEBV). PAEBV is (1) the disease with increasing number of EBV-DNA in T or NK cells, (2) the malignant disease without or mild atypia in its early stage, and (3) associated with a poor prognosis. For adolescence or young adults, both classical CAEBV and PAEBV can be recognized. Further investigations for differential diagnosis are required, as well as those for appropriate therapeutic approaches against this rare and intractable disease. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2920.2920
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 6
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    Prognostic Impact of Programmed Cell Death-1-Positive Cells on Follicular Lymphoma Patients Might Diminish in the Rituximab Era
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 2645-2645
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2645-2645
    Abstract: Abstract 2645 Background Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T cell responses and promotion of T cell tolerance. PD-1 is known to negatively regulate T cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Carreas et al. (J Clin Oncol. 2009; 27: 1470–1476) examined 100 follicular lymphoma (FL) patients and reported better prognosis in the group that had high levels of PD-1-positive cells. In contrast, in the study performed by Richendollar et al. (Human Pathol. 2011; 42: 552–557), which involved 91 FL patients, high levels of PD-1-positive cells were found to have a poor prognostic impact. Although these studies have shown that high levels of PD-1-positive cells in FL patients influence their prognosis, both studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab-era (R-era) has not yet been elucidated. Materials and methods We retrospectively analyzed data for 91 FL patients uniformly treated by standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy in 5 institutions between 2001 and 2009. The median age of the entire cohort was 58 years (range, 34–85 years), and 46 (51%) of the patients were men. We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1-positive cells were counted using computer analysis at the Cancer Institute, Japanese Foundation for Cancer Research. Results The FL grade on diagnosis was grade 1 for 34 (37%) patients, grade 2 for 41 (45%) patients, and grade 3 for 16 (18%) patients. The median positivity for PD-1 staining was 16.0% (range, 0.01–51.9%) and was significantly higher in the high beta-2 microglobulin (B2M; at least 3) group (P = 0.009); the men had a high tendency for PD-1 positivity (P = 0.08). After a median follow-up of 29.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 61.1% and 88.6%, respectively. Stage 4 FL at diagnosis (P = 0.02) and bone marrow involvement (P = 0.05) resulted in worse PFS, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2–4 (P = 0.04), high Follicular Lymphoma International Prognostic Index (FLIPI; P = 0.02), B symptoms (P = 0.04), and high B2M levels (P = 0.005) worsened OS. Multivariate analysis showed that age over 60 years (P = 0.04) and high B2M levels (P = 0.07) were prognostic factors for PFS. PD-1 positivity was not found to be a prognostic factor with respect to both PFS and OS. Because the addition of rituximab to therapy regimens has altered the clinical course and prognosis of FL, some new prognostic factors have been proposed, and the impact of known prognostic factors has been changing. Rituximab might also have changed the prognosis of FL patients with high levels of PD-1-positive cells. Conclusion High levels of PD-1-positive cells were not found to be a prognostic factor in this study, indicating that the prognostic impact of PD-1 positivity might be eliminated in the R-era. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.2645.2645
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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