e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identif... more e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identification of biologically rational targets, which may translate into effective and non-toxic treatment strategies, is a high priority. The pro-survival BCL-2 family members BCL-2, BCL-XL (BCL2L1), BCL-W (BCL2L2), BCL2A1 and MCL-1 contribute to tumor maintenance, progression, and chemo-resistance across a range of cancers, but their contributions in PTCL, NOS are poorly understood. Methods: Patients with PTCL, NOS treated between 09/2000 and 09/2019 and with available tissue biopsy were included in the study. Diagnosis was retrospectively confirmed by two expert hematopathologists. BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 expression was assessed by immunohistochemistry (IHC), and the percentage of positive tumor cells assessed by standard microscopy. The 2014 Lugano Classification was used to define response to therapy. Progression-free survival (PFS) and overall survival (OS) were estimated ...
Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than th... more Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than the general population; however, bidirectional risks of developing B- and T-cell lymphomas (BCL; TCL) specifically are less well understood. We used population-based cancer registry data to estimate the subtype-specific risks of second primary lymphoma among patients with first BCL (n=288,478) or TCL (n=23,747). We observed nearly five-fold increased bidirectional risk between BCL and TCL overall (TCL following BCL: standardized incidence ratio [SIR]=4.7, 95% confidence interval [CI]=4.2-5.2; BCL following TCL: SIR=4.7, 95%CI=4.1-5.2), but the risk varied substantially by lymphoma subtype. The highest SIRs were observed between Hodgkin lymphoma (HL) and peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (PTCL-NOS following HL: SIR=27.5, 95%CI=18.4-39.4; HL following PTCL-NOS: SIR=31.6, 95%CI=17.3-53.0). Strikingly elevated risks also were notable for angioimmunoblastic T-cell ly...
BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type, (ENKTCL) is a rare and aggress... more BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type, (ENKTCL) is a rare and aggressive peripheral T-cell lymphoma associated with Epstein-Barr virus infection of neoplastic cells. The current standard-of-care for patients (pts) with localized disease is combined modality with radiation and systemic chemotherapy, while advanced disease is treated with asparaginase-based combination chemotherapy or chemoradiation. To date, there is limited real-world data regarding the clinico-pathological markers, survival patterns, and long-term outcomes ENKTCL in the United States. METHODS: We conducted a retrospective study of pts with ENKTCL. We reviewed clinical variables, pathological characteristics, treatment patterns and outcomes. Patients who were treated/referred to our instituition from 2009-2020 were included in the analysis. We excluded cases with missing treatment and/or no follow up information. Fisher's exact test or Chi-square test was used to evaluate the associat...
The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase b... more The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase but the data regarding autologous stem cell transplantation (ASCT) for elderly patients are limited. We analyzed 484 patients, ages 60 years or over, diagnosed with relapsed/refractory DLBCL who received ASCT from 1993 to 2010 in the Japan Society for Hematopoietic Cell Transplantation database. Median age was 64 years (range, 60 to 78). To evaluate the impact of age at ASCT, patients were classified into 3 groups: those between the ages of 60 to 64, 65 to 69, and 70 years or over. Overall nonrelapse mortality (NRM) at day 100, 1 year, and 2 years was 4.1%, 5.9% and 7.7%, respectively. NRM did not significantly differ among age groups (P = .60). Two-year progression-free survival (PFS) and overall survival (OS) were 48% and 58%, respectively. PFS and OS were significantly longer in patients 60 to 64 years old; however, the survival rate was acceptable even in those 70 or over, with a 2-ye...
Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concur... more Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concurrent with cladribine (CDAR) improves response rate, but long-term outcomes are unknown. We report final results of a phase II study of CDAR for patients with HCLv. Twenty patients with 0-1 prior courses of cladribine and/or rituximab, including 8 previously untreated, received cladribine 0.15 mg/kg days 1-5 with 8 weekly rituximab doses 375 mg/m2. Patients received a 2nd rituximab course ≥6 months after cladribine, if/when minimal residual disease (MRD) was detected in blood. The complete remission (CR) rate from CDAR was 95%, 95% confidence interval (95%CI) 75-100%. Sixteen of 20 patients (80%, 95% CI: 56-94%) became MRD-negative by bone marrow at 6 months. The median duration of MRD-negative CR was 70.1 months and 7 of 16 are still MRD-negative up to 120 months. With median follow-up of 69.7 months, 11 patients received delayed rituximab and the 5-year progression-free survival (PFS) a...
Background: Obesity is increasing worldwide, with the highest prevalence in the United States. Hi... more Background: Obesity is increasing worldwide, with the highest prevalence in the United States. High or low body mass index (BMI) is a well-established risk factor for increased all-cause mortality and also has been associated with cancer-specific mortality. However, the impact of BMI on survival following diagnosis with lymphoma currently remains controversial. We leveraged a prospective cohort of lymphoma patients to assess the relationship of BMI two years prior to diagnosis (BMI-2), at diagnosis (BMI-dx), and three-years post-diagnosis (BMI+3) with lymphoma-specific survival (LSS) as the primary endpoint and with event-free survival (EFS) and overall survival (OS) as secondary endpoints. Patient and Method: Patients were prospectively enrolled at lymphoma diagnosis to the SPORE Molecular Epidemiology Resource (MER) cohort at Mayo Clinic and University of Iowa from 2002-2015. BMI-2 and BMI+3 were self-reported in patient questionnaires, while BMI-dx was extracted from the medical ...
FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse over... more FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.3...
Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for pa... more Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for patients who do not benefit from purine analogues. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown. Therefore, we conducted a multisite phase 2 study (NCT01841723) of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate at 32 weeks with response at 48 weeks and best response during treatment also assessed. Key secondary objectives were characterization of toxicity and determination of progression-free and overall survival. Thirty-seven patients were enrolled (24 at 420mg, 13 at 840mg). The median duration of follow-up was 3.5 years (range 0-5.9). The overall response rate at 32 weeks was 24% which increased to 36% at 48 weeks. The best overall response rate was 54%. The e...
Introduction The outcome and the role of allogeneic hematopoietic cell transplantation (Allo-HCT)... more Introduction The outcome and the role of allogeneic hematopoietic cell transplantation (Allo-HCT) with reduced-intensity conditioning (RIC) in patients with nodal peripheral T-cell lymphomas (PTCLs) remain unclear. Patients and Methods To address this issue, we retrospectively analyzed the outcome of Allo-HCT for patients with nodal PTCLs using the transplant registry data from the Japan Society for Hematopoietic Cell Transplantation (JSHCT). Patients who fulfilled the following criteria were included in this study: aged 16-69 years, diagnosed with PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or anaplastic large cell lymphoma (ALCL), and received the first Allo-HCT in Japan between January 1, 2001 and December 31, 2011. In this analysis, conditioning regimen intensity was the main variable of interest. The conditioning regimen was classified as myeloablative conditioning (MAC) if it included total body irradiation (TBI) > 8 Gy, oral busulfan...
Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature nat... more Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature natural killer cell neoplasms that is closely associated with Epstein-Barr virus. ANKL presents a fulminant clinical course, resulting in a poor prognosis with a median overall survival of approximately 2 months. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment, but the long-term outcomes after allo-HSCT remain unclear. Methods Using the national Japanese transplant registry database, the outcomes of 59 ANKL patients who underwent first allo-HSCT between 1997 and 2016 were analyzed. Correlation between groups was examined by the c2 test, Mann-Whitney U test, and Kruskal-Wallis test. Patient survival data were analyzed using the Kaplan-Meier method and compared by the log-lank test. The cumulative incidence of relapse and non-relapse mortality were calculated considering competing risks. Results The median patient age was 37 years (range...
Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients ... more Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n = 111) or allogeneic (n = 51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P = 0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were > 60 years of age at HCT (P = 0.017), higher score of HCT-specific comorbidity index at HCT (P = 0.033), and receiving MCEC (ranimustine + carboplatin + etoposide + cyclophosphamide) regimen (P = 0.017), while higher performance status at HCT (P = 0.011) and longer interval from diagnosis to HCT (P = 0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.
Background: CNS relapse is a rare but fatal complication of patients with peripheral T-cell lymph... more Background: CNS relapse is a rare but fatal complication of patients with peripheral T-cell lymphoma (PTCL). Several large studies have identified risk factors for CNS relapse in PTCL, such as elevated serum lactate dehydrogenase (LDH),…
[Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the ov... more [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive neoplasm derived from CD4+ T-cells with HT... more Adult T-cell leukemia/lymphoma (ATLL) is an aggressive neoplasm derived from CD4+ T-cells with HTLV-I infection, and its mechanisms of tumorigenesis still remain to be elucidated. The fact that tumor cells rarely proliferate in vitro is one of the most important problems to be solved. The establishment of cell line from ATLL patient samples has been difficult even in the presence of interleukins. Previously we established one cell line (HU-ATTAK) from acute or lymphoma types of 10 ATLL cases which did not proliferate in the presence of IL-2 and/or IL-4. HU-ATTAK is critically dependent on IL-2 and human umbilical cord vein endothelial cells (HUVEC) as feeder cells. In HU-ATTAK, adding anti-OX40 ligand antibody into the culture system completely inhibited its proliferation. So, OX40 ligand as well as L-2 and/or IL-4 is suggested be necessary for the proliferation of ATLL cells, and feeder cells may also confer the favorable environment. As the substitute of HUVEC, follicular dendriti...
Background: Despite recent approval of 4 new drugs for relapsed PTCL, an unmet need remains for n... more Background: Despite recent approval of 4 new drugs for relapsed PTCL, an unmet need remains for new therapies. Survival of relapsed/refractory PTCL patients is improved by stem cell transplant particularly if patients are in CR prior to transplant (Smith 2013). ICE (ifosfamide, carboplatin and etoposide) is commonly used salvage regimen which produces CR rates ranging from 7% to 23% in patients with PTCL (Zelenetz 2003, Mikesch 2013). Romidepsin is a HDAC inhibitor which showed overall response rate of 25% with CR rate of 15% in a large phase II trial for relapsed/refractory PTCL (Coiffier 2012). To further improve outcomes particularly in CR rates pre-transplant, we conducted a phase I study of romidepsin in combination with standard ICE in patients with relapsed/refractory PTCL. Methods: The primary objective of this trial is to determine the toxicity profile and to identify the maximum tolerated dose of the romidepsin in combination with standard ICE. A statistical design of modi...
Background: CNS relapse is uncommon but challenging complication in patients with mantle cell lym... more Background: CNS relapse is uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor that identification of high risk population is therefore critical in whom prophylactic chemotherapy may play a role. Patients and Methods: A total of 405 patients (median age, 66 years; range 22-85) with MCL newly diagnosed between 1994 and 2012 at 48 institutions in Japan were analyzed.Pathological specimens were centrally reviewed in all patients. We evaluated risk factors for CNS relapse in patients with MCL using competing risk regression analysis. Patients were excluded if they had evidences of CNS involvement at initial diagnosis. Overall, 81% of the patients received rituximab containing regimen with 222 patients received CHOP, 133 patients received high-dose cytarabine containing regimen and 50 patients received other regimen such as fludarabine. At a median follow up duration of 40.4 months, 25 patients (6.2%) experienced...
Introduction Marginal zone lymphoma (MZL) is an indolent lymphoma, which includes extra-nodal MZL... more Introduction Marginal zone lymphoma (MZL) is an indolent lymphoma, which includes extra-nodal MZL of mucosa-associated lymphoid lymphoma (MALToma), nodal MZL (NMZL), and splenic MZL (SMZL). There are currently several treatment options for patients with relapsed or refractory (R/R) MZL, including high-dose chemotherapy with autologous hematopoietic cell transplantation (HCT). Allogeneic HCT is considered to be an optional therapy for R/R MZL patients, but there is no specific data to support allogeneic HCT for R/R MZL. Objectives We retrospectively analyzed the outcomes among R/R MZL patients treated with autologous or allogeneic HCT to identify the potential clinical efficacy of allogeneic HCT. Methods Patient information was derived from the Transplant Registry Unified Management Program database, collected by the Japanese Data Center for Hematopoietic Cell Transplantation, and sponsored by the Japanese Society for Hematopoietic Cell Transplantation. The 70 patients with R/R MZL (25 MALToma, 31 NMZL, and 14 SMZL) were receiving either autologous HCT (n=56, 19 MALToma, 27 NMZL and 10 SMZL) or allogeneic HCT (n=14, 6 MALToma, 4 NMZL and 4 SMZL). Results No patients with MALToma died because of non-relapse mortality (NRM) following autologous HCT and no patients developed relapse with MALToma and NMZL at allogeneic HCT. Progression-free survival (PFS) and overall survival (OS) of R/R SMZL patients who underwent allogeneic HCT were significantly lower compared with the autologous HCT group (median PFS, 65.6% and 25.0% at 1 year after autologous and allogeneic HCT, P=0.014; median OS, 78.7% and 25.0% at 1 year after autologous and allogeneic HCT, P=0.0030). There were no significant differences in the PFS and OS of R/R MALToma and NMZL patients who underwent autologous HCT compared with allogeneic HCT. The main findings of this study indicated that both autologous and allogeneic HCT may be acceptable for patients with chemo-sensitive MALToma and NMZL, but the results of allogeneic HCT for chemo-resistant MALToma and SMZL were inconclusive. Conclusion The parameters for choosing between autologous and allogeneic HCT for R/R MZL have not been defined, and strategies aimed at improving the selection of R/R MZL patients for autologous HCT and excluding R/R chemo-resistant MALToma patients, may allow us to identify individual R/R MZL patients who are at high risk of death after both autologous and allogeneic HCT. Selecting suitable R/R SMZL patients for allogeneic HCT might reduce NRM. The introduction of novel therapies before and after receiving allogeneic HCT could improve outcomes among R/R SMZL patients.
Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate that is highly effective in pati... more Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate that is highly effective in patients with relapsed/refractory anaplastic large cell lymphoma (ALCL). However, survival outcomes following suboptimal response or subsequent relapse are not well known. We conducted a multicenter study analyzing outcomes of patients with relapsed/refractory ALCL who have received BV with a secondary focus on survival after progression following BV. A total of 56 patients were treated with BV for relapsed or refractory ALCL. The overall response rate to BV was 73% with complete response (CR) rate of 46%. The median failure‐free survival and overall survival (OS) after BV were 15.5 month and not reached, respectively. The median duration of response was 27.6 months in patients who achieved CR by BV, while the median OS of those who did not achieve CR by BV was 9.5 months. There was no significant difference in OS between those who underwent stem cell transplant (SCT) and those who did not in patients who achieved CR after BV. However, if patients were in PR after BV, SCT was associated with significantly longer OS. Thirty patients experienced progressive disease on BV or required a subsequent treatment. The median OS after BV failure was 2.9 months with 2‐year OS of 27.1%. There were seven long‐term survivors (≥12 months) following failure. After an adequate response to subsequent salvage therapy, five patients underwent subsequent SCT (three allogeneic and two autologous), four of which were long‐term survivors (17+, 25+, 32+, and 50+ months). In conclusion, BV failure is associated with a poor outcome in patients with ALCL, which defines a small but important group with unmet need. SCT may have benefit in patients with relapsed/refractory ALCL who failed BV.
e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identif... more e19531 Background: The outcome of patients with PTCL, NOS is generally very poor, and the identification of biologically rational targets, which may translate into effective and non-toxic treatment strategies, is a high priority. The pro-survival BCL-2 family members BCL-2, BCL-XL (BCL2L1), BCL-W (BCL2L2), BCL2A1 and MCL-1 contribute to tumor maintenance, progression, and chemo-resistance across a range of cancers, but their contributions in PTCL, NOS are poorly understood. Methods: Patients with PTCL, NOS treated between 09/2000 and 09/2019 and with available tissue biopsy were included in the study. Diagnosis was retrospectively confirmed by two expert hematopathologists. BCL-2, BCL-XL, BCL-W, BCL2A1 and MCL-1 expression was assessed by immunohistochemistry (IHC), and the percentage of positive tumor cells assessed by standard microscopy. The 2014 Lugano Classification was used to define response to therapy. Progression-free survival (PFS) and overall survival (OS) were estimated ...
Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than th... more Lymphoma survivors have a significantly higher risk of developing second primary lymphoma than the general population; however, bidirectional risks of developing B- and T-cell lymphomas (BCL; TCL) specifically are less well understood. We used population-based cancer registry data to estimate the subtype-specific risks of second primary lymphoma among patients with first BCL (n=288,478) or TCL (n=23,747). We observed nearly five-fold increased bidirectional risk between BCL and TCL overall (TCL following BCL: standardized incidence ratio [SIR]=4.7, 95% confidence interval [CI]=4.2-5.2; BCL following TCL: SIR=4.7, 95%CI=4.1-5.2), but the risk varied substantially by lymphoma subtype. The highest SIRs were observed between Hodgkin lymphoma (HL) and peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (PTCL-NOS following HL: SIR=27.5, 95%CI=18.4-39.4; HL following PTCL-NOS: SIR=31.6, 95%CI=17.3-53.0). Strikingly elevated risks also were notable for angioimmunoblastic T-cell ly...
BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type, (ENKTCL) is a rare and aggress... more BACKGROUND: Extranodal natural killer/T-cell lymphoma, nasal type, (ENKTCL) is a rare and aggressive peripheral T-cell lymphoma associated with Epstein-Barr virus infection of neoplastic cells. The current standard-of-care for patients (pts) with localized disease is combined modality with radiation and systemic chemotherapy, while advanced disease is treated with asparaginase-based combination chemotherapy or chemoradiation. To date, there is limited real-world data regarding the clinico-pathological markers, survival patterns, and long-term outcomes ENKTCL in the United States. METHODS: We conducted a retrospective study of pts with ENKTCL. We reviewed clinical variables, pathological characteristics, treatment patterns and outcomes. Patients who were treated/referred to our instituition from 2009-2020 were included in the analysis. We excluded cases with missing treatment and/or no follow up information. Fisher's exact test or Chi-square test was used to evaluate the associat...
The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase b... more The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase but the data regarding autologous stem cell transplantation (ASCT) for elderly patients are limited. We analyzed 484 patients, ages 60 years or over, diagnosed with relapsed/refractory DLBCL who received ASCT from 1993 to 2010 in the Japan Society for Hematopoietic Cell Transplantation database. Median age was 64 years (range, 60 to 78). To evaluate the impact of age at ASCT, patients were classified into 3 groups: those between the ages of 60 to 64, 65 to 69, and 70 years or over. Overall nonrelapse mortality (NRM) at day 100, 1 year, and 2 years was 4.1%, 5.9% and 7.7%, respectively. NRM did not significantly differ among age groups (P = .60). Two-year progression-free survival (PFS) and overall survival (OS) were 48% and 58%, respectively. PFS and OS were significantly longer in patients 60 to 64 years old; however, the survival rate was acceptable even in those 70 or over, with a 2-ye...
Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concur... more Hairy cell leukemia variant (HCLv) responds poorly to purine analog monotherapy. Rituximab concurrent with cladribine (CDAR) improves response rate, but long-term outcomes are unknown. We report final results of a phase II study of CDAR for patients with HCLv. Twenty patients with 0-1 prior courses of cladribine and/or rituximab, including 8 previously untreated, received cladribine 0.15 mg/kg days 1-5 with 8 weekly rituximab doses 375 mg/m2. Patients received a 2nd rituximab course ≥6 months after cladribine, if/when minimal residual disease (MRD) was detected in blood. The complete remission (CR) rate from CDAR was 95%, 95% confidence interval (95%CI) 75-100%. Sixteen of 20 patients (80%, 95% CI: 56-94%) became MRD-negative by bone marrow at 6 months. The median duration of MRD-negative CR was 70.1 months and 7 of 16 are still MRD-negative up to 120 months. With median follow-up of 69.7 months, 11 patients received delayed rituximab and the 5-year progression-free survival (PFS) a...
Background: Obesity is increasing worldwide, with the highest prevalence in the United States. Hi... more Background: Obesity is increasing worldwide, with the highest prevalence in the United States. High or low body mass index (BMI) is a well-established risk factor for increased all-cause mortality and also has been associated with cancer-specific mortality. However, the impact of BMI on survival following diagnosis with lymphoma currently remains controversial. We leveraged a prospective cohort of lymphoma patients to assess the relationship of BMI two years prior to diagnosis (BMI-2), at diagnosis (BMI-dx), and three-years post-diagnosis (BMI+3) with lymphoma-specific survival (LSS) as the primary endpoint and with event-free survival (EFS) and overall survival (OS) as secondary endpoints. Patient and Method: Patients were prospectively enrolled at lymphoma diagnosis to the SPORE Molecular Epidemiology Resource (MER) cohort at Mayo Clinic and University of Iowa from 2002-2015. BMI-2 and BMI+3 were self-reported in patient questionnaires, while BMI-dx was extracted from the medical ...
FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse over... more FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.3...
Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for pa... more Hairy cell leukemia is a rare B-cell malignancy where there is a need for novel treatments for patients who do not benefit from purine analogues. Ibrutinib, an oral agent targeting Bruton tyrosine kinase in the B-cell receptor signaling pathway, is highly effective in several malignancies. Its activity in HCL was unknown. Therefore, we conducted a multisite phase 2 study (NCT01841723) of oral ibrutinib in patients with either relapsed classic or variant hairy cell leukemia. The primary outcome measure was the overall response rate at 32 weeks with response at 48 weeks and best response during treatment also assessed. Key secondary objectives were characterization of toxicity and determination of progression-free and overall survival. Thirty-seven patients were enrolled (24 at 420mg, 13 at 840mg). The median duration of follow-up was 3.5 years (range 0-5.9). The overall response rate at 32 weeks was 24% which increased to 36% at 48 weeks. The best overall response rate was 54%. The e...
Introduction The outcome and the role of allogeneic hematopoietic cell transplantation (Allo-HCT)... more Introduction The outcome and the role of allogeneic hematopoietic cell transplantation (Allo-HCT) with reduced-intensity conditioning (RIC) in patients with nodal peripheral T-cell lymphomas (PTCLs) remain unclear. Patients and Methods To address this issue, we retrospectively analyzed the outcome of Allo-HCT for patients with nodal PTCLs using the transplant registry data from the Japan Society for Hematopoietic Cell Transplantation (JSHCT). Patients who fulfilled the following criteria were included in this study: aged 16-69 years, diagnosed with PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or anaplastic large cell lymphoma (ALCL), and received the first Allo-HCT in Japan between January 1, 2001 and December 31, 2011. In this analysis, conditioning regimen intensity was the main variable of interest. The conditioning regimen was classified as myeloablative conditioning (MAC) if it included total body irradiation (TBI) > 8 Gy, oral busulfan...
Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature nat... more Introduction Aggressive natural killer cell leukemia (ANKL) is a rare leukemic form of mature natural killer cell neoplasms that is closely associated with Epstein-Barr virus. ANKL presents a fulminant clinical course, resulting in a poor prognosis with a median overall survival of approximately 2 months. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment, but the long-term outcomes after allo-HSCT remain unclear. Methods Using the national Japanese transplant registry database, the outcomes of 59 ANKL patients who underwent first allo-HSCT between 1997 and 2016 were analyzed. Correlation between groups was examined by the c2 test, Mann-Whitney U test, and Kruskal-Wallis test. Patient survival data were analyzed using the Kaplan-Meier method and compared by the log-lank test. The cumulative incidence of relapse and non-relapse mortality were calculated considering competing risks. Results The median patient age was 37 years (range...
Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients ... more Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n = 111) or allogeneic (n = 51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P = 0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were > 60 years of age at HCT (P = 0.017), higher score of HCT-specific comorbidity index at HCT (P = 0.033), and receiving MCEC (ranimustine + carboplatin + etoposide + cyclophosphamide) regimen (P = 0.017), while higher performance status at HCT (P = 0.011) and longer interval from diagnosis to HCT (P = 0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.
Background: CNS relapse is a rare but fatal complication of patients with peripheral T-cell lymph... more Background: CNS relapse is a rare but fatal complication of patients with peripheral T-cell lymphoma (PTCL). Several large studies have identified risk factors for CNS relapse in PTCL, such as elevated serum lactate dehydrogenase (LDH),…
[Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the ov... more [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive neoplasm derived from CD4+ T-cells with HT... more Adult T-cell leukemia/lymphoma (ATLL) is an aggressive neoplasm derived from CD4+ T-cells with HTLV-I infection, and its mechanisms of tumorigenesis still remain to be elucidated. The fact that tumor cells rarely proliferate in vitro is one of the most important problems to be solved. The establishment of cell line from ATLL patient samples has been difficult even in the presence of interleukins. Previously we established one cell line (HU-ATTAK) from acute or lymphoma types of 10 ATLL cases which did not proliferate in the presence of IL-2 and/or IL-4. HU-ATTAK is critically dependent on IL-2 and human umbilical cord vein endothelial cells (HUVEC) as feeder cells. In HU-ATTAK, adding anti-OX40 ligand antibody into the culture system completely inhibited its proliferation. So, OX40 ligand as well as L-2 and/or IL-4 is suggested be necessary for the proliferation of ATLL cells, and feeder cells may also confer the favorable environment. As the substitute of HUVEC, follicular dendriti...
Background: Despite recent approval of 4 new drugs for relapsed PTCL, an unmet need remains for n... more Background: Despite recent approval of 4 new drugs for relapsed PTCL, an unmet need remains for new therapies. Survival of relapsed/refractory PTCL patients is improved by stem cell transplant particularly if patients are in CR prior to transplant (Smith 2013). ICE (ifosfamide, carboplatin and etoposide) is commonly used salvage regimen which produces CR rates ranging from 7% to 23% in patients with PTCL (Zelenetz 2003, Mikesch 2013). Romidepsin is a HDAC inhibitor which showed overall response rate of 25% with CR rate of 15% in a large phase II trial for relapsed/refractory PTCL (Coiffier 2012). To further improve outcomes particularly in CR rates pre-transplant, we conducted a phase I study of romidepsin in combination with standard ICE in patients with relapsed/refractory PTCL. Methods: The primary objective of this trial is to determine the toxicity profile and to identify the maximum tolerated dose of the romidepsin in combination with standard ICE. A statistical design of modi...
Background: CNS relapse is uncommon but challenging complication in patients with mantle cell lym... more Background: CNS relapse is uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor that identification of high risk population is therefore critical in whom prophylactic chemotherapy may play a role. Patients and Methods: A total of 405 patients (median age, 66 years; range 22-85) with MCL newly diagnosed between 1994 and 2012 at 48 institutions in Japan were analyzed.Pathological specimens were centrally reviewed in all patients. We evaluated risk factors for CNS relapse in patients with MCL using competing risk regression analysis. Patients were excluded if they had evidences of CNS involvement at initial diagnosis. Overall, 81% of the patients received rituximab containing regimen with 222 patients received CHOP, 133 patients received high-dose cytarabine containing regimen and 50 patients received other regimen such as fludarabine. At a median follow up duration of 40.4 months, 25 patients (6.2%) experienced...
Introduction Marginal zone lymphoma (MZL) is an indolent lymphoma, which includes extra-nodal MZL... more Introduction Marginal zone lymphoma (MZL) is an indolent lymphoma, which includes extra-nodal MZL of mucosa-associated lymphoid lymphoma (MALToma), nodal MZL (NMZL), and splenic MZL (SMZL). There are currently several treatment options for patients with relapsed or refractory (R/R) MZL, including high-dose chemotherapy with autologous hematopoietic cell transplantation (HCT). Allogeneic HCT is considered to be an optional therapy for R/R MZL patients, but there is no specific data to support allogeneic HCT for R/R MZL. Objectives We retrospectively analyzed the outcomes among R/R MZL patients treated with autologous or allogeneic HCT to identify the potential clinical efficacy of allogeneic HCT. Methods Patient information was derived from the Transplant Registry Unified Management Program database, collected by the Japanese Data Center for Hematopoietic Cell Transplantation, and sponsored by the Japanese Society for Hematopoietic Cell Transplantation. The 70 patients with R/R MZL (25 MALToma, 31 NMZL, and 14 SMZL) were receiving either autologous HCT (n=56, 19 MALToma, 27 NMZL and 10 SMZL) or allogeneic HCT (n=14, 6 MALToma, 4 NMZL and 4 SMZL). Results No patients with MALToma died because of non-relapse mortality (NRM) following autologous HCT and no patients developed relapse with MALToma and NMZL at allogeneic HCT. Progression-free survival (PFS) and overall survival (OS) of R/R SMZL patients who underwent allogeneic HCT were significantly lower compared with the autologous HCT group (median PFS, 65.6% and 25.0% at 1 year after autologous and allogeneic HCT, P=0.014; median OS, 78.7% and 25.0% at 1 year after autologous and allogeneic HCT, P=0.0030). There were no significant differences in the PFS and OS of R/R MALToma and NMZL patients who underwent autologous HCT compared with allogeneic HCT. The main findings of this study indicated that both autologous and allogeneic HCT may be acceptable for patients with chemo-sensitive MALToma and NMZL, but the results of allogeneic HCT for chemo-resistant MALToma and SMZL were inconclusive. Conclusion The parameters for choosing between autologous and allogeneic HCT for R/R MZL have not been defined, and strategies aimed at improving the selection of R/R MZL patients for autologous HCT and excluding R/R chemo-resistant MALToma patients, may allow us to identify individual R/R MZL patients who are at high risk of death after both autologous and allogeneic HCT. Selecting suitable R/R SMZL patients for allogeneic HCT might reduce NRM. The introduction of novel therapies before and after receiving allogeneic HCT could improve outcomes among R/R SMZL patients.
Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate that is highly effective in pati... more Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate that is highly effective in patients with relapsed/refractory anaplastic large cell lymphoma (ALCL). However, survival outcomes following suboptimal response or subsequent relapse are not well known. We conducted a multicenter study analyzing outcomes of patients with relapsed/refractory ALCL who have received BV with a secondary focus on survival after progression following BV. A total of 56 patients were treated with BV for relapsed or refractory ALCL. The overall response rate to BV was 73% with complete response (CR) rate of 46%. The median failure‐free survival and overall survival (OS) after BV were 15.5 month and not reached, respectively. The median duration of response was 27.6 months in patients who achieved CR by BV, while the median OS of those who did not achieve CR by BV was 9.5 months. There was no significant difference in OS between those who underwent stem cell transplant (SCT) and those who did not in patients who achieved CR after BV. However, if patients were in PR after BV, SCT was associated with significantly longer OS. Thirty patients experienced progressive disease on BV or required a subsequent treatment. The median OS after BV failure was 2.9 months with 2‐year OS of 27.1%. There were seven long‐term survivors (≥12 months) following failure. After an adequate response to subsequent salvage therapy, five patients underwent subsequent SCT (three allogeneic and two autologous), four of which were long‐term survivors (17+, 25+, 32+, and 50+ months). In conclusion, BV failure is associated with a poor outcome in patients with ALCL, which defines a small but important group with unmet need. SCT may have benefit in patients with relapsed/refractory ALCL who failed BV.
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