Cycles Of Dexamethasone Research Articles

Performance of Positron Emission Tomography at Diagnosis and Response Assessment in Low and Intermediate-Risk Nodular Lymphocyte Predominant Hodgkin Lymphoma

Background: Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) has different histology, clinical presentation, and outcomes than classical Hodgkin Lymphoma (cHL). Positron Emission Tomography (PET) plays an important role in staging and response assessment in cHL, but little is published about the use of PET to guide treatment in nLPHL. A better understanding of the clinical significance of PET response in nLPHL is critical for incorporating PET into prospective trials. Methods: Children's Oncology Group study AHOD03P1 (NCT00107198) enrolled patients with low-risk nLPHL and AHOD0031 (NCT00025259) enrolled patients with intermediate-risk cHL and nLPHL <22 years of age. AHOD03P1 patients with stage IA and >1 lymph node or stage IIA nLPHL were treated with 3 cycles of doxorubicin, vincristine, prednisone, and cyclophosphamide (AV-PC) chemotherapy, given every 21 days. Patients with a complete response (CR) based on anatomic response and qualitative reading (<mediastinal blood pool) of negative PET on central review did not receive radiation therapy while patients with <CR received 21-Gy involved field radiation therapy (IFRT). AHOD0031 patients with stages IB, IAE, IIB, IIAE, IIIA, IVA with or without bulk disease, and IA or IIA with bulk disease received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders were randomized to an additional 2 cycles of ABVE-PC with or without 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA) and all received IFRT. Rapid early responders (RERs) received 2 additional cycles of ABVE-PC. RERs with CR were randomized to IFRT or no further therapy. RER/non-CRs were non-randomly assigned to IFRT. PET scans from both trials available in the Imaging and Radiation Oncology Core (IROC) were retrospectively reviewed and assigned a score of 1-5 on the Deauville 5-point scale (5PS). Patients who did not have evaluable imaging due to either scans not performed, on CD-ROM and inaccessible, or poor quality, were excluded from this analysis. Three-year event-free survival (EFS) was analyzed by 5PS at end of therapy using the Kaplan Meier method. Results: AHOD03P1 enrolled 135 patients with low-risk nLPHL who received chemotherapy and AHOD0031 enrolled 96 patients with intermediate-risk nLPHL. PET imaging available for review at diagnosis in 99 low-risk patients, 92% 5PS=5, and 55 intermediate-risk patients, 98% 5PS=5. Median age 13.4 years (range 16.5), 84.9% male, 29.9% Stage I, 49.8% Stage II, 18.6% Stage III, and 1.7% Stage IV. After 3 cycles of chemotherapy, 106 low-risk patients had available PET scans, 5PS 1 n=50, 5PS 2 n=35, 5PS 3 n=11, 5PS 4 n=7, and 5PS 5 n=3. Three-year EFS for patients with end of chemotherapy 5PS was: 5PS 1 89.9% (95% CI 77.3-95.7%), 5PS 2 97.1% (95% CI 81.4-99.6%), 5PS 3 90.9% (95% CI 50.8-98.7%), 5PS 4 28.6% (95% CI 1.0-71.1%), 5PS 5 66.7% (95% CI 5.4-94.5%) p=0.0081. When categorized as PET negative (5PS 1-3) and PET positive (5PS 4-5), 3-year EFS was 92.6% (95% CI 85.2-96.4%) for PET negative and 45.0% (95% CI 10.6-75.3%) for PET positive patients, p=0.0036 (Figure 1A). Forty-nine intermediate-risk patients had available PET scans after 2 cycles of chemotherapy, 5PS 1 n=9, 5PS 2 n=26, 5PS 3 n=10, 5PS 4 n=3, and 5PS 5 n=1. Three-year EFS by interim response was: 5PS 1 88.9% (95% CI 43.3-98.4%), 5PS 2 96.0% (95% CI 74.8-99.4%), 5PS 3 100%, 5PS 4 100%, 5PS 5 0%, p<0.0001. Thirty-six patients had available PET scans after 4 cycles of chemotherapy, 5PS 1 n=20, 5PS 2 n=11, 5PS 3 n=3, 5PS 4 n=1, and 5PS 5 n=1. Three-year EFS by response after 4 cycles of chemotherapy: 5PS 1 95.0% (95% CI 69.5-99.3%), 5PS 2 100%, 5PS 3 100%, 5PS 4 100%, 5PS 5 0% p<0.0001. When divided into PET negative (5PS 1-3) and PET positive (5PS 4-5), 3-year EFS 97.0% (95% CI 80.4-99.6%) for PET negative and 50.0% (95% CI 0.6-91.0%) for PET positive patients after 4 cycles of chemotherapy, p=0.1449 (Figure 1B). Conclusions: At diagnosis, low and intermediate-risk nLPHL lesions are almost always PET avid with 5PS=5. PET response following 3 cycles of AV-PC chemotherapy is highly predictive of outcome in pediatric patients with low-risk nLPHL when considering 5PS=3 as PET negative. Intermediate-risk patients with negative PET following ABVE-PC achieved excellent outcomes. Whether PET maintains prognostic significance in patients with nLPHL treated with rituximab needs to be studied.

Correlation between Progression-Free Survival and Overall Survival in Patients with Relapsed Hodgkin Lymphoma: An Analysis of Individual Patient Data from Randomized GHSG Trials

Background: Progression-free survival (PFS) and overall survival (OS) are predominant measures of treatment efficacy in Hodgkin lymphoma (HL). Despite preference for OS from many regulatory authorities, PFS is most relevant to patients and frequently serves as primary endpoint in clinical trials. Recently we found a strong correlation between treatment effects on PFS and OS in the first-line setting (Bröckelmann PJ et al. EHA23/ICML23). However, their relationship in the relapsed setting remains unclear. We aimed to evaluate the correlation of PFS with OS after treatment of relapsed HL. Methods: We evaluated individual patient data of 375 patients with relapsed HL treated within the prospective randomized GHSG trials HDR1 (N= 141) and HDR2 (N= 234) between 02/1993 - 06/2007. Briefly, both trials included patients of 18 to 60 years of age with histologically confirmed relapsed HL after ≥1 prior line of treatment, who had not previously received high-dose chemotherapy and autologous stem-cell transplantation (ASCT). In HDR1 patients received two cycles of Dexa-BEAM (dexamethasone, carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and ASCT. In HDR2, patients were assigned to two cycles of dexamethasone, cytarabine, and cisplatin (DHAP), and thereafter randomly assigned to either BEAM followed by ASCT or sequential cyclophosphamide, methotrexate, and etoposide in high-doses before BEAM followed by ASCT. All patients who received at least one dose of salvage chemotherapy within the respective trial were included in the analysis. We correlated treatment effects and risk factor effects on PFS and OS with the Wei-Lin-Weissfeld (WLW) method and adjusted the analysis for age and sex. Additionally, we applied copula models to correlate the time-to-event variables PFS and OS themselves using their marginal distributions. Results: With a median follow-up of 4.5 years, at least one PFS event, defined as relapse or progression of relapsed HL or death for any reason, was recorded in 146 of 375 patients (38.9%). At least one OS event, defined as death for any reason, was documented in 111 of 375 patients (29.6%). The hazard ratios for treatment effects on PFS and OS were 0.61 (95% confidence interval, CI= 0.38-0.98) and 1.01 (95% CI= 0.63-1.63) for HDR1 and 1.1 (95% CI= 0.69-1.75) and 0.8 (95% CI= 0.44-1.47) for HDR2, respectively. The WLW analysis revealed high correlations of treatment effects on PFS and OS at patient level within the trials. Pearson correlation r of the treatment effects on PFS and OS were r= 0.72 (95% confidence interval CI= 0.66-0.76, P< 0.001) in all 375 patients analyzed, r= 0.72 (95% CI= 0.63-0.79, P<0.001) in the HDR1 trial and r= 0.74 (95% CI= 0.67-0.79, P< 0.001) in the HDR2 trial. The analysis with different risk factors and copula models revealed similarly high correlations, confirming a strong relation between PFS and OS in relapsed HL patients. Conclusions: PFS and OS as well as treatment effects and prognostic effects on PFS and OS are highly correlated in patients treated for relapsed HL. Confirming results in first-line treatment, PFS thereby constitutes a highly relevant endpoint also in the setting of relapsed HL.

A Dexamethasone Sparing-Regimen with Daratumumab and Lenalidomide in Frail Patients with Newly-Diagnosed Multiple Myeloma: Efficacy and Safety Analysis of the Phase 3 IFM2017-03 Trial

Background. Two-third of patients with newly diagnosed multiple myeloma (NDMM) are over the age of 65. Those patients have heterogeneous fitness and disparate tolerance to treatment. Frailty scoring systems have informed the stratification of elderly patients and treatment guidance. The use of long term dexamethasone is associated with multiple side effects specifically in elderly patients. Here we present the response rates and safety analysis of the randomized phase 3 IFM2017-03 trial, comparing daratumumab lenalidomide (DR) without long term dexamethasone to lenalidomide dexamethasone (Rd) in a frail population of patients with NDMM. Methods. Patients with NDMM over the age of 65 and with an ECOG proxy frailty score ≥ 2 were randomized 1:2 to receive 28-day cycles of lenalidomide (25mg/day, 21/28) and dexamethasone (20mg QW) or daratumumab (1800mg SC QW for 8 weeks, Q2W for 16 weeks and Q4W thereafter), lenalidomide (25mg/day, 21/28) and 2 cycles of dexamethasone (20mg QW for 8 weeks), until progression or unacceptable toxicity. Randomization was stratified on ISS and age. MRD by NGS at 10-5 was performed at 12 months for all patients. Interim analysis endpoints were overall response rate, VGPR or better rate, MRD rate and occurrence of grade 3 or more side effects. The present analysis was done at 12-months-therapy data cut. Results. In total, 295 patients were randomized (95 in Rd arm and 200 in DR arm). Median age was 81 years (68-92) with 84% of patients over the age of 75 years and 61% over the age of 80 years. Baseline demographics and disease characteristics were well balanced between arms. Overall response rates were 77% in Rd arm and 89% in DR arm (p=0.025). 12-months rates of VGPR or better were 42% and 58% in Rd and DR arms, respectively (p=0.013). Depth of response improved during treatment and the median time to reach VGPR was 11 months in Rd group and 5 months in DR group. Treatment benefit for DR was homogeneous across all subgroups defined by age, ECOG, Charlson, ISS, cytogenetics and creatinine clearance. Among patients with VGPR or better at 12 months, 63 were evaluable for MRD at 10-5 by NGS. MRD status at 12 months was negative in 18% of patients in Rd arm and 33% in DR arm (p=0.36). During the first year of treatment, at least one AE (grade ≥ 3) occurred in 64% and 76% of patients in Rd and DR arms, respectively (p=0.052). Patients in DR group had more grade ≥ 3 hematologic AE with neutropenia (Rd 15%, DR 44%, p<0.001) and anemia (Rd 2%, DR 11%, p=0.01) but similar grade ≥ 3 infections, with 17% in Rd and 13% in DR arms (p=0.38). Among patients with infections, 13 had COVID-19 (3 in Rd and 10 in DR). Discontinuations for AEs were similar in both arms (16% in Rd and 13% in DR, p=0.64). Conclusion. In this phase 3 trial dedicated for frail patients with NDMM, a dexamethasone-sparing regimen combining daratumumab and lenalidomide demonstrates deep and rapid responses and a favorable safety profile.

Effect of regular and irregular stimulation cycles of dexamethasone on circadian clock in NIH3T3 cells

ABSTRACT Animal studies have shown that irregular light-dark cycles cause circadian desynchronization, while few studies have addressed the effect of regular/irregular stimulation cycles of signaling hormones on the cellular clock in vitro. Here, we examined how cellular clocks respond to regular and irregular stimulation cycles of dexamethasone, using NIH3T3 cells transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Cyclic stimulation with dexamethasone at different time intervals (18–28 h, 3 times regularly) revealed that Bmal1-Luc bioluminescence rhythms can be entrained to 22 and 24 h cycles during the stimulation period, but not to other cycles. The rhythm entrained for 24 h cycles persisted for at least one day after the last stimulation. Irregular dexamethasone treatment (16, 24, and 16 h, sequentially; short-term jet lag protocol) resulted in an overall upregulation and phase shifts of the temporal expression of several clock genes and cell cycle genes, including c-Myc and p53. Regular dexamethasone stimulation three times with 24 h cycles also caused upregulation of Per1 and Per2 expression, but not c-Myc and p53 expression. In conclusion, our study identified the entrainable range of the circadian clock in NIH3T3 cells to the dexamethasone stimulation cycle and demonstrated that irregular dexamethasone treatment could disturb the expression of cell cycle genes.

A randomized phase 3 trial of autologous vs allogeneic transplantation as part of first-line therapy in poor-risk peripheral T-NHL

AbstractFirst-line therapy for younger patients with peripheral T-cell non-Hodgkin lymphoma (T-NHL) consists of 6 courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without etoposide (CHOEP), consolidated by high-dose therapy and autologous stem cell transplantation (auto-SCT). We hypothesized that allogeneic stem cell transplantation (allo-SCT) could improve outcomes. 104 patients with peripheral T-cell non-Hodgkin lymphoma, except ALK+ anaplastic large cell lymphoma, 18 to 60 years, all stages, and all age adjusted International Prognostic Index scores, except 0 and stage I, were randomized to 4 cycles of CHOEP and 1 cycle of dexamethasone, cytosine-arabinoside, and platinum (DHAP) followed by high-dose therapy and auto-SCT or myeloablative conditioning and allo-SCT. The primary end point was event-free survival (EFS) at 3 years. After a median follow-up of 42 months, the 3-year EFS after allo-SCT was 43%, as compared with 38% after auto-SCT. Overall survival at 3 years was 57% vs 70% after allo- or auto-SCT, without significant differences between treatment arms. None of the 21 responding patients proceeding to allo-SCT relapsed, as opposed to 13 of 36 patients (36%) proceeding to auto-SCT. Eight of 26 patients (31%) and none of 41 patients died of transplant-related toxicity after allo- and auto-SCT, respectively. The strong graft-versus-lymphoma effect after allo-SCT was counterbalanced by transplant-related mortality. This trial is registered at www.clinicaltrials.gov as #NCT00984412.

Early combination treatment of immune thrombocytopenia: Is this the way?

Early combination treatment of immune thrombocytopenia: Is this the way?

Long-term results of a phase-I/II study of sequential high-dose chemotherapy with autologous stem cell transplantation in the initial treatment of aggressive non-Hodgkin's lymphoma.

To improve the survival of patients with aggressive non-Hodgkin's lymphoma, we evaluated a risk-adapted therapeutic approach using high-dose (HD) or conventional-dose (CD) chemotherapy (CT) for poor-risk and good-risk patients, respectively. Twenty patients were treated in each group. In both groups, the first chemotherapy cycle consisted of dexamethasone, vincristine, ifosfamide, and etoposide. Thereafter, the CD or HD patients received 3 or 2 cycles of dexamethasone, vincristine, epirubicin, and cyclophosphamide, respectively, followed by 1 cycle of dexamethasone, carboplatin, and etoposide. In the HD group cyclophosphamide, epirubicin, carboplatin, and etoposide were dose-escalated by a factor of 6, 3, 3, and 3, respectively, as compared to the CD group, and autologous peripheral blood stem cells were administered after each HD-CT cycle. Grade III-IV toxicities were neutropenia and thrombocytopenia (100%), anemia (55%), and stomatitis (30%) in patients with HD-CT, and neutropenia (90%) in patients with CD-CT. One toxic death occurred in a patient with HD-CT. The overall response rate was 100% in HD-CT patients, including 70% complete remissions, and 80% in CD-CT patients, including 60% complete remissions. The 10-year overall survival was 55% for patients with HD-CT and 80% for patients with CD-CT. The risk-adapted treatment approach showed tolerable toxicities and was associated with encouraging results.

A case report of a young female with plasma cells leukemia

Plasma cell leukemia (PCL) is a rare and aggressive variant of plasma cell dyscrasias that can occur either de novo (primary) or as a leukemic transformation of end-stage multiple myeloma (MM). PCL is known with a poor prognosis and with a different biologic background, clinical, and laboratory features. Primary PCL presents more often with extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, elevated serum 2-microglobulin, and lactate dehydrogenase levels, in addition to impaired renal function in comparison with MM. Here, we report a case of a young female who was admitted with excessive thirst, polyuria, lower backache, fever, and weight loss over 2 months. Peripheral blood smear showed numerous atypical looking plasma cells, and immunophenotyping on bone marrow (BM) aspirate demonstrated the presence of clonal plasma cells. She was admitted to adult hematology ward in Hiwa Hemato-Oncology Hospital, Sulaimani, Kurdistan, Iraq and received four cycles of bortezomib, thalidomide, and dexamethasone chemotherapy, followed by two more cycles of dexamethasone, cyclophosphamide, etoposide, and cisplatin, and later, she proceeded to autologous BM transplantation. More details of the case are presented below.

Efficacy of Brentuximab-Vedotin (BV) in Peripheral T-Cell Lymphomas (PTCLs) Other Than Anaplastic Large Cell Lymphoma (ALCL)

Background. BV, an anti-CD30 antibody-drug conjugate, has been approved for the treatment of Hodgkin lymphoma (HL) and ALCL. Of interest, BV has shown activity in PTCLs other than ALCL that express low or even undetectable levels of CD30. In particular BV has been reported effective in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL-nos). Here, we report 4 cases with relapsed/resistant PTCLs (1 AITL, 1 NK-T nasal type, 1 PTCL with T-helper follicular phenotype-PTCL-TFH and 1 PTCL-nos) who responded to BV therapy.Results. On August 2014, a 53-y-old caucasian male was diagnosed with 5% CD30-positive AITL. The final stage was IIIA, because of a single left axillar node was documented at the PET-TC scan in addition to the excised inguinal lymphadenopathy. A complete metabolic PET remission (PET-CR) was documented after the 3th and confirmed after the 6th cycle of cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone (CHOEP). However, relapsing disease was documented 6 mths later. At that time, diffuse over and under-diaphragm nodal involvement was observed. A PET-CR was achieved after 2 cycles of dexamethasone, cytarabine, and cisplatin (DHAP), but disease progressed shortly after the 4th cycle before the planned autotransplantation (ASCT). A 3th line chemotherapy, consisting of mitoxantrone and high dose ARA-C (modified HAM), was performed and failed to control the disease. Furthermore HAM chemotherapy was associated with severe infectious complications (sepsis from MDR S. Epidermidis and pulmonary aspergillosis). On December 2015, BV was begun. A PET-CR was documented after the 4th and confirmed after the 8th cycle of therapy. The patients is still in CR, in continuous therapy (12th cycle), waiting for HLA matched unrelated donor.On July 2012 a 62-y-old caucasian man was diagnosed with extranodal NK/T-cell nasal type lymphoma. Both Epstein Barr virus (EBV) and CD30 molecule were not expressed by neoplastic cells. Weekly cisplatin and radiotherapy were concomitantly given followed by 3 cycles of etoposide, ifosfamide, cisplatin and dexamethasone. This treatment resulted in PET-CR. At the time of first relapse (Nov 2013), 3 cycles of methotrexate, L-asparaginase and dexamethasone, followed by ASCT (fotemustine, etoposide, cytarabine, melphalan), induced a 2nd PET-CR. However, two subsequent PET evaluations suggested the presence of active disease shortly after (December 2015) a biopsy proven relapse was documented. A PET-CR was observed after 2 and confirmed after 7 cycles of single agent BV. The patient is still undergoing treatment.On September 2015, a 49-y-old african man was diagnosed with PTCL-THF, showing AITL signs, with both EBV and CD30 positive (50-75%) Hodgkin/Reed-Sternberg cells. A progressive disease was documented after the 4th cycle of CHOEP. At that time, patient was not candidate to receive further chemotherapy, because of worsening of perfomance status (PS). BV, given as salvage therapy, resulted in a rapid control of all signs and symptoms after the 6th administration. Because of improved PS and a partial metabolic remission, the DHAP combination was begun on June 2016 and ASCT is now planned as consolidation.On November 2009, a 46-y-old caucasian man was diagnosed with classical HL. The final stage was IEA. The disease was refractory to doxorubicin, bleomycin, vinblastine, dacarbazine and radiotherapy. A PET-CR was achieved in response to ifosfamide, gemcitabine, vinorelbine and prednisone chemotherapy. After 3 yrs, a lymph node biopsy confirmed a relapsed HL. Four cycles of DHAP followed by ASCT resulted in a 2nd PET-CR. After 3 mths, a PTCL-NOS associated with blastic lymphoid B EBV positive cells was diagnosed on an excisional lymph node biopsy. On May 2014 BV as single-agent was started. A PET-CR lasted for 8 mths. Relapsing disease was documented on January 2015. The patient refused further chemotherapy and died because of disease progression on July 2015.Conclusion. In this experience BV, regardless of CD30 expression, has shown significant clinical activity in recurrent or refractory T-cell lymphomas and no significant toxicity, even in heavily pretreated patients. In consideration of the BV activity in PTCLs, combination studies with other molecules, such as romidepsine, are desirable. DisclosuresNo relevant conflicts of interest to declare.

Intermediate-Risk Lymphocyte-Predominant Hodgkin Lymphoma: AHOD0031: A Report from the Children's Oncology Group

Background: Children's Oncology Group (COG) AHOD0031 demonstrated that early response assessment in pediatric intermediate-risk Hodgkin lymphoma (HL) permits reduction or augmentation in therapy with maintenance of excellent event-free (EFS) and overall survival (OS). While the majority of patients on this trial had classical HL (cHL), patients with lymphocyte-predominant HL (LPHL) were included. Pediatric patients with LPHL typically present with localized disease and such low risk patients have excellent outcomes with surgical resection alone or minimal chemotherapy. However, management of patients with intermediate-risk LPHL is less clear due to their small number in most clinical trials. We report the outcomes of these patients on AHOD0031 and present directions for future therapeutic strategies.Methods: Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE-PC +/- 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA). All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of chemotherapy. RER patients received 2 additional cycles of ABVE-PC. RER with complete responder (CR) status (RER/CR) patients were randomized to involved field radiotherapy (IFRT) or no further therapy. RER/non-CR patients were non-randomly assigned to IFRT.Results: Ninety-seven (5.7%) of the 1712 eligible patients on AHOD0031 had LPHL, with the remainder cHL. Compared to patients with cHL, patients with LPHL were younger (p=0.0001), more often male (p<0.0001), and less likely to have B symptoms (p=0.0006), bulk (p<0.0001) or stage IV disease (p<0.0001). Five-year event-free survival (EFS) was marginally superior in patients with LPHL (91.2%) compared with cHL (83.2%) (p = 0.08) (Figure 1), without difference in overall survival (OS) (p = 0.21). LPHL patients treated with chemotherapy alone (N = 33) had a 5-year EFS of 93.4% and OS of 100%. Stage and presence of bulk disease, RER or SER status and use of IFRT did not impact EFS or OS in LPHL patients. The proportion of patients who were RER was higher in LPHL compared with cHL (93.7% vs. 81.0%). Furthermore, LPHL patients were more likely to achieve a CR compared to cHL patients (68% vs. 45%; p=0.00003). There was only one reported subsequent malignant neoplasm among the LPHL patients, a non-Hodgkin lymphoma one year after treatment in a patient who received IFRT.Discussion: Children and adolescents with intermediate-risk LPHL represent ideal candidates for response-adapted therapy based on their favorable outcomes as demonstrated in this analysis. The majority of patients treated with the ABVE-PC backbone achieve RER/CR status and can be successfully treated without radiation therapy. Future therapeutic strategies should focus on further reduction in cytotoxic therapy for these patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Subsequent Malignant Neoplasms Among Children and Adolescents with Hodgkin Lymphoma Treated with Response-Adapted Therapy: A Report from the Children's Oncology Group Study AHOD0031

▪Background:Survivors of childhood Hodgkin lymphoma (HL) have an increased risk of subsequent malignant neoplasms (SMN). Response-adapted treatment for HL may decrease the SMN risk by reducing therapy in patients who have a good initial response to treatment. The Children's Oncology Group Study AHOD0031, which enrolled patients from 2002 - 2009, evaluated the role of early treatment response in directing therapy for children and adolescents with intermediate-risk Hodgkin lymphoma. We report the incidence and risk factors for SMN among 1,711 eligible patients enrolled on AHOD0031.Methods:Eligible patients had clinical stage I-IIA with bulk, I-IIAE, I-II B, IIIA-IVA with or without bulk. Patients initially received 2 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (ABVE-PC), followed by a response evaluation of rapid early (RER) versus slow early responder (SER) status. All SER patients were randomized to an additional two cycles of ABVE-PC +/- 2 cycles of dexamethasone, etoposide, cisplatin and cytarabine (DECA). All SER patients received 21 Gy involved field radiotherapy (IFRT) following completion of chemotherapy. RER patients received 2 additional cycles of ABVE-PC. RER with complete responder (CR) status (RER/CR) patients were randomized to involved field radiotherapy (IFRT) or no further therapy. RER/non-CR patients were non-randomly assigned to IFRT. At a median follow-up of 6.2 years, an analysis of SMN was undertaken. The cumulative incidence of SMNs as a first event was calculated from the time of diagnosis adjusted for competing events due to relapse or death. Comparisons of the cumulative incidence among treatment groups were made using the K-sample test. A multivariable analysis using the Cox proportional hazard model assessed risk conferred by age, gender, race, disease stage, B symptoms, bulk disease, and IFRT.Results:Among 1,711 patients with a median follow up of 6.2 years, excluding non-melanoma skin cancer, 16 SMNs occurred, 13 as a first event. SMNs included seven hematologic malignancies and nine solid tumors. No subsequent breast cancer has been reported to date. Patients who experienced a SMN did not differ from those who did not with respect to age, gender, race, disease stage, B symptoms, or bulk disease. The median time to SMN as a first event was 4.1 years (range 1.1-9.5 years). The 5-year cumulative incidence of SMN as a first event was 0.53% (95% CI 0.16 to 0.90) (Figure 1A). A comparison of the cumulative incidence of SMN in patients who received IFRT and those who did not demonstrated an increased incidence of SMN in the IFRT group (p = 0.03) (Figure 1B). In fact, to date, all SMNs have occurred in patients who received IFRT. Therefore, a multivariate analysis was conducted among patients who received IFRT, which included age, gender, race, disease stage, B symptoms, and bulk disease. The presence of B symptoms was independently associated with increased risk for SMN with a hazard ratio of 15.24 (95% CI 1.73-134.04, p=0.01). Among the 13 patients with a SMN as first event, there were 4 deaths.Conclusions:With a median follow up of 6.2 years, the 5-year cumulative incidence of SMN in patients treated with response-adapted treatment on AHOD0031 is very low. It is likely that we have captured the cases of secondary leukemia related to etoposide exposure, as these generally occur within five years of treatment. Longer follow-up will be needed to assess the risk of solid tumors, which are generally known to have longer latencies without plateau in incidence over time. Evaluation of the location of secondary solid tumors relative to the IFRT fields is in progress. As AHOD0031 demonstrated no benefit in event-free or overall survival for RER/CR patients treated with IFRT, future intermediate risk patients treated according to this treatment strategy will be less likely to receive IFRT and can be expected to be at lower risk of SMN. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis

Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response. We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 109/L) and complete (platelets >100 × 109/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model. Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children. In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count. Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.

Gender and duration of disease differentiate responses to rituximab-dexamethasone therapy in adults with immune thrombocytopenia.

Adults often develop chronic immune thrombocytopenia (ITP) for which treatment order is uncertain. Rituximab and three cycles of dexamethasone (4R + 3Dex) improve treatment responses and short-term disease control but long-term outcome is not known. In adults with ITP treated with 4R + 3D, we sought long-term outcome and associated prognostic variables. Forty-nine adults treated at Weill-Cornell received 4R + 3Dex. Their clinical characteristics were reviewed. Duration was median time to treatment failure; Kaplan-Meier estimates were developed. Vbeta Tcell receptor (VBTCR) repertoire was obtained after treatment in 36 patients. Patients were adults with ITP 18-64 years old, median age 37. The 27 females were twice as likely to have an ongoing response to 4R + 3Dex (44.1%) as males (19.6%; P = 0.009). For ITP duration <12 months, 52.7% of patients had continuing responses to 4R + 3Dex compared to 15.3% of patients with diagnosis >12 months (P = 0.02). Females with ITP duration of <12 months had continuing responses in 78.6%, compared to males with <12 months duration of ITP (21.2%). For patients with disease duration <12 months, 67% of females had continuing responses, compared to 31% of males (P = 0.004). Post-treatment polyclonal VBTCR was seen in 9/10 continuing responders (six female, three male) but only 13/26 relapsers/nonresponders (P = 0.068). Durable remissions after treatment with 4R + 3Dex were more frequent in female patients with <12 months of ITP duration and those with polyclonal VBTCR after treatment, emphasizing the roles of duration of disease, gender and T cells in chronic ITP. Differences in pathophysiology of ITP by gender and by duration of ITP require further study. Am. J. Hematol. 91:907-911, 2016. © 2016 Wiley Periodicals, Inc.

Rituximab and three dexamethasone cycles provide responses similar to splenectomy in women and those with immune thrombocytopenia of less than two years duration.

Adults with newly diagnosed or persistent immunothrombocytopenia frequently relapse upon tapering steroids; adults and children with chronic disease have an even lower likelihood of lasting response. In adults with newly-diagnosed immunothrombocytopenia, two studies showed that dexamethasone 40 mg/day × four days and 4 rituximab infusions were superior to dexamethasone alone. Studies have also shown three cycles of dexamethasone are better than one and patients with persistent/chronic immunothrombocytopenia respond less well to either dexamethasone or rituximab. Therefore, 375 mg/m(2) × 4 rituximab was combined with three 4-day cycles of 28 mg/m(2) (max. 40 mg) dexamethasone at 2-week intervals and explored in 67 ITP patients. Best long-term response was assessed as complete (platelet count ≥ 100 × 10(9)/L) or partial (50-99 × 10(9)/L). Only 5 patients had not been previously treated. Fifty achieved complete (n=43, 64%) or partial (n=7, 10%) responses. Thirty-five of 50 responders maintained treatment-free platelet counts over 50 × 10(9)/L at a median 17 months (range 4-67) projecting 44% event-free survival. Duration of immunothrombocytopenia less than 24 months, achieving complete responses, and being female were associated with better long-term response (P<0.01). Adverse events were generally mild-moderate, but 3 patients developed serum sickness and 2 colitis; there were no sequelae. Dexamethasone could be difficult to tolerate. Fourteen patients became hypogammaglobulinemic and half had increased frequency of minor infections; 9 of 12 evaluable patients recovered their IgG levels. Rituximab combined with three cycles of dexamethasone provides apparently better results to reported findings with rituximab alone, dexamethasone alone, or the combination with one cycle of dexamethasone. The results suggest medical cure may be achievable in immunothrombocytopenia, especially in women and in patients within two years of diagnosis. (clinicaltrials.gov identifier:02050581).

First-LINE Treatment With High-Dose Dexamethasone Terapy For Adult Primary Inmune Thrombocytopenia

▪ IntroductionPrimary immune thrombocytopenia (ITP) is an acquired autoimmune disorder with a very variable outcome. Bleeding manifestations and platelets count are considered the main criteria to start treatment in these patients. The initial recommended therapy are corticosteroids and intravenous immunoglobulin (IgsIV). The aim of our study is the description of efficacy and safety of high-dose dexamethasone (Dx) used as frontline therapy in newly diagnosed ITP patients. MethodsA series of patients diagnosed in our centre from March 2009 to August 2012 has been studied. They have received first-line treatment with Dx (40 mg/d four consecutive days every 2 or 4 weeks) for 1 to 6 courses. Sex, age, cardiovascular risk factors, reasons to treat, response, courses of treatment, complications and relapse rate were recorded and analyzed. ResultsOur series of twenty-nine patients, 18 women (62%) and 11 men (38%), had a median age of 54 years (range 16-92 years). Twenty-five patients (86%) were treated after low platelet counts (30x 10e9 / L) with or without clinical bleeding, whereas the other four patients were treated as a surgery preparation. One patient received a reduced dose of Dx (20 mg/d x 4 days) because of comorbidities and high risk of infection. In thirteen patients, IgsIV were added to Dx in the first course (1g/kg/d x 2 days), because of high bleeding risk or more severe bleeding at diagnosis. Platelets count at baseline was 15x109/ L (range 1-29 x109/ L). Ninety-three percent of patients responded after the first course of Dx (69% complete response CR, 24% partial response PR), and 45% of the patients did not require additional Dx treatment. The median time to reach a response was 5 days since the first day of treatment (range 2-60).The sixteen patients who need more than one course received a median of 4 (range 2-10), all of them without IgsIV. After a median follow-up of 14 months (range 2-45), 69% of these patients maintained the response without further treatment. Therefore, the overall response of the series reaches 83%.After 6 courses of treatment, 5 subjects did not achieved response and were classify as corticosteroid dependent. Of these, one patient was splenectomized and at present he remains at CR after 30 months of follow up. Another patient is waiting for splenectomy, and other three received thrombopoietin analogs, remaining all them in CR under treatment.Thirteen patients received a combination of Igs and Dx in the first course due to high risk of bleeding (platelets less than 20 x 10e9/L and hemorrhagic manifestations). Eleven of them (81%) achieved response (4 PR, 7CR) at a median time of 4 days (range 2–60). After the first course of treatment, 61% (8 of 13) of patients receiving both IgsIV and Dx responded, vs 35% (5 of 16) of those treated only with Dx. This difference was not statistically significant, probably because of the small number of patients in our series. All patients treated with IgsIV and Dx in the first course got the best response after 4 cycles of dexamethasone, compared to 75% of subjects treated with Dx for 4 to 6 courses.Dx was usually well tolerated, since only 13% of the patients experienced side effects: one case of hypertension, another patient developed hyperglycemia associated to corticosteroids and other two presented mild transient steroid psychosis episodes. Infectious events were not observed. ConclusionsTreatment with high-dose dexamethasone as first-line treatment for ITP is a good alternative to prednisone because it shows a high efficacy and a good safety profile. In our experience, the association of IgsIV and Dx in the first course may improve the response rate and decrease the total dose of steroids needed to achieve a similar response. Disclosures:No relevant conflicts of interest to declare.

High-dose chemotherapy followed by autologous stem cell transplantation for patients with relapsed/refractory Hodgkin lymphoma.

Hodgkin lymphoma (HL) is one of the most common malignancies in young adults and has become curable for the majority of patients, even in advanced stage. After first-line therapy, 15% to 20% do not respond to treatment and relapse. For those patients, high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is a frequently used therapy option. To find the best available treatment with HDCT followed by ASCT for patients with relapsed or refractory HL after first-line treatment. We searched the Central Register of Controlled Trials (CENTRAL), MEDLINE, and relevant conference proceedings up to January 2013 for randomised controlled trials (RCTs). We also contacted experts for unpublished data. We included RCTs comparing HDCT followed by ASCT versus conventional chemotherapy without ASCT, or versus additional sequential HDCT (SHDCT) followed by ASCT. We also included RCTs with different HDCT regimens before ASCT in patients with relapsed or primary refractory HL after any first-line therapy. Two review authors (MR, NS) independently selected relevant studies, extracted data and assessed trial quality. We used hazard ratios (HR) for overall survival (OS) and progression-free survival (PFS), and we calculated risk ratios (RR) for the other outcomes. We presented all measures with 95% confidence intervals (CI).We assessed the quality of evidence using GRADE methods. Our search resulted in 1663 potentially relevant references, of which we included three trials with 14 publications, assessing 398 patients. Overall, we judged the quality of the trials as moderate. The trials were all reported as randomised controlled and open-label. We included two RCTs assessing the effect of HDCT followed by ASCT compared with conventional chemotherapy in a meta-analysis. The number of studies was very low, therefore, the quantification of heterogeneity was not reliable. We included one further RCT (one assessing additional SHDCT followed by ASCT versus HDCT followed by ASCT), which was not compatible with our meta-analysis. For this trial, we performed further analyses.Two trials showed a non-statistically significant trend that HDCT followed by ASCT compared to conventional chemotherapy increases OS (HR 0.67; 95% CI 0.41 to 1.07; P value = 0.10, 157 patients, moderate quality of evidence). However, the increase in PFS was statistically significant for people treated with HDCT followed by ASCT (HR 0.55; 95% CI 0.35 to 0.86; P value = 0.009, 157 patients, moderate quality of evidence). Adverse events were reported in one trial only and did not differ statistically significant between the treatment arms. We were not able to draw conclusions regarding treatment-related mortality (TRM) because of insufficient evidence (RR 0.61; 95% CI 0.16 to 2.22; P value = 0.45, 157 patients, moderate quality of evidence).For the second comparison, SHDCT plus HDCT followed by ASCT versus HDCT followed by ASCT there was no difference between the treatment arms regarding OS (HR 0.93; 95% CI 0.5 to 1.74; P value = 0.816, three-year OS: 80% SHDCT versus 87% HDCT, 241 patients), or PFS (HR 0.87; 95% CI 0.58 to 1.30; P value = 0.505, 241 patients). Seven patients died in the SHDCT arm and one in the HDCT arm due to increased toxicity of the treatment. Adverse events were increased with SHDCT plus HDCT followed by ASCT after two cycles of dexamethasone plus high-dose cytarabine plus cisplatin (DHAP) (88% SHDCT versus 45% HDCT, 223 patients, P value < 0.00001). Overall, more statistically significant World Health Organization (WHO) grade 3/4 infections occurred with SHDCT (48% SHDCT versus 33% HDCT; P value = 0.002, 223 patients). The currently available evidence suggests a PFS benefit for patients with relapsed or refractory HL after first-line therapy, who are treated with HDCT followed by ASCT compared to patients treated with conventional chemotherapy. In addition, data showes a positive trend regarding OS, but more trials are needed to detect a significant effect.Intensifying the HDCT regime before HDCT followed by ASCT did not show a difference as compared to HDCT followed by ASCT, but was associated with increased adverse events.

High response rate to low‐dose rituximab plus high‐dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia

Corticosteroids as initial therapy for primary immune thrombocytopenia achieve a low rate of sustained remission. We prospectively evaluated the efficacy, safety, and response duration of low-dose rituximab plus high-dose dexamethasone as frontline therapy in newly diagnosed primary immune thrombocytopenia patients. One cycle of dexamethasone, 40 mg/d/intravenously for four consecutive days, plus weekly intravenous rituximab, 100 mg for four doses, was delivered. Twenty-one consecutive adults were enrolled. The overall response at day +28 was 90.5%. Complete sustained response at 6 months and relapse rate were 76.2% and 15.8%, respectively, compared with 30% and 62.5% for a historical group who had received standard treatment with prednisone (P = 0.005 and P = 0.004). There was a 9.5% incidence of adverse effects. The combination of low-dose rituximab and high-dose dexamethasone as frontline therapy for adults with primary immune thrombocytopenia was effective and had a high overall response rate and a low incidence of relapse.

WS12-1 - Front-Line Concurrent Chemoradiotherapy (CCRT) Followed Consolidation Chemotherapy in Localized NASAL NK/T-Cell Lymphoma

ABSTRACT Background Extranodal, nature killer/T-cell lymphoma of nasal type, the nasal NKTCL, is known for its close association with EBV infection and poor clinical outcome after chemotherapy (C/T). The aims of the study are to evaluate the therapeutic efficacy of front-line concomitant chemoradiotherapy (CCRT) plus consolidation C/T and the impact of EBV viral status on the clinical outcomes in patients with localized nasal NKTCL. Methods Patients with newly diagnosed, measurable stage I/II nasal NKTCL were eligible. The CCRT was comprised of two cycles of dexamethasone and etoposide D1-3, plus cisplatin D1, the DEP regimen, q 4 weeks with concurrent 5040 cGy radiation in 28 fractions/5 weeks. Tumor assessment was carried out 4 weeks after completion of CCRT. Patients without disease progression after CCRT were subjected for two cycles of consolidation C/T consisted of dexamethasone, etoposide, ifosphamide, mesna and cisplatin D1-4, the DVIP regimen, q 4 weeks. Serial blood samples were collected for EBV viral titer and IFN-γ determination. Results A total of 33 patients were enrolled. The best tumor response was complete response (CR) in 23, partial response (PR) in 5, with an overall response rate and CR rate of 84.8% and 69.7%, respectively. The 2- and 5-year progression-free survival (PFS) rate of intent-to-treat population was 63.1% (95% CI, 46.5–79.7%) and 56.1% (95% CI, 36.5–75.7%), respectively; while the corresponding overall survival (OS) rate was 72.0% (95% CI, 56.5–87.65%) and 61.7% (95% CI, 42.7–80.8%), respectively. The most common treatment-related grade 3/4 toxic effects were leucopenia (84.9%), febrile neutropenia (39.4%), nausea/vomiting (33.4%), anemia (30.3%) and mucositis (30.3%). Detectable baseline plasma EBV DNA level was an adversely prognostic factor for both PFS (log-rank test, P = 0.04) and OS (log-rank test, P = 0.01) of CR/PR patients. Conclusions Front-line CCRT plus consolidation chemotherapy is feasible and active in localized nasal NKTCL.

Standard Dose Rituximab Plus 2–4 Cycles of Pulse Dexamethasone Is Effective and Tolerable in Treatment of Immune Thrombocytopenia (ITP)

Abstract 1166▪▪This icon denotes a clinically relevant abstract Background:70–80% of patients with ITP respond to initial corticosteroid-based treatment, but almost all experience recurrent thrombocytopenia requiring further therapy. Rituximab is effective in inducing responses in about 50% of patients with ITP, but most do not experience sustained remission. Strategies to improve the efficacy of rituximab would be of value. Cheng and colleagues have shown that a single 4 day course of dexamethasone is effective in newly diagnosed ITP, and GIMEMA demonstrated that multiple courses are even more efficacious. Zaja and colleagues reported that the combination of rituximab with a single course of dexamethasone is superior to dexamethasone alone in previously untreated patients. Given the activity of these two drugs, patients at Weill Cornell Medical College (WCMC) with ITP have been treated with a combination of standard rituximab and 2–4 cycles of pulse dexamethasone (R+Dex) given at 2 week intervals. We preliminarily reported results of 14 patients treated with this combination; we have expanded this cohort to 34 patients to obtain a broader evaluation of efficacy and safety of this therapeutic approach in ITP. Methods:Patients who had received rituximab concurrently with multiple courses of pulse dexamethasone were retrospectively identified. Response was initially assessed at 8 weeks after initiation of therapy. Complete remission (CR) was defined as platelet count greater than or equal to 100×109/L, and partial remission (PR) as platelet count of 50–100×109/L. Variables were compared either by chi-square or fisher exact test including duration of ITP at greater or less than one year, age of patients, prior therapy, and lymphocyte subsets. The study was approved by the WCMC Institutional Review Board. Results:Thirty-four ITP patients received concurrent rituximab and pulse dexamethasone. All patients were treated for platelet count less than 30 or inability to discontinue chronic therapy such as corticosteroids or thrombopoietin receptor agonist. Median age was 21 years (range 2–63 years), and median time since diagnosis of ITP was 12 months (range 1–180 months). All patients but one had previously been treated, with median of 2 prior therapies (range 0–7). Thirty-two of 34 patients received 4 infusions of standard dose rituximab (the other 2 received 2 and 3 infusions). All patients received between one and 4 cycles of dexamethasone, with most (22/34) receiving 3 cycles. Twenty-four patients responded at 8 weeks from start of therapy or later (71% ORR). Best response was CR in 20 patients (59%) and PR in 4 (12%). Two responding patients relapsed to no response at 3 and 6 months, and 3 additional patients relapsed from CR but maintained PR at last follow up. At median follow up of 8 months, 22 patients (65%) remain in response: CR in 47% and PR in 18%. None of the variables tested was predictive of response; there was a trend toward increased response rate in adults (p=0.13). Adverse events related to R+Dex were mostly mild, with most common toxicities including fatigue, headache, infusion-related events, and gastrointestinal upset. Dexamethasone was often poorly tolerated. One patient experienced colitis requiring hospitalization. That patient and one other interrupted therapy for AE’s. Conclusion:Rituximab plus multiple courses of dexamethasone is active with manageable toxicity in patients with ITP. This regimen merits further exploration in a prospective trial. Disclosures:Elstrom:Genentech: Speakers Bureau. Off Label Use: Rituximab is approved for use in NHL, CLL and RA. Bussel:Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding.

Concurrent Radiotherapy and Dexamethasone, Etoposide, Ifosfamide, and Carboplatin (DeVIC) for Patients with Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Single Institution Analysis in Japan

Abstract 1611 Background:Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a recognized a rare distinct entity strongly associated EBV infection, accounting for 3% to 10% of malignant lymphomas in East Asia. Recent studies suggest that concurrent chemoradiotherapy was effective as first-line therapy for patients with localized ENKL, nasal type. We assess treatment results with concurrent chemoradiotherapy for ENKLs. Patients and methods:From December 2007 to July 2010, newly diagnosed localized ENKL, nasal type, and treated with concurrent radiotherapy (median 50 Gy; range 46–56 Gy) and 3 cycles of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) at the Cancer Institute Hospital, Tokyo, Japan were analyzed retrospectively. All the histopathological samples were reviewed according to the WHO classification by expert hematopathologists. Results:Total of sixteen patients was identified. Baseline patients. characteristics included a median age of 56.5 years (range; 30–76 years), eleven men and five women, thirteen patients (81%) with stage IE and three (19%) with stage IIE. For IPI, patients with low and low-intermediate risks were thirteen patients (81%) and three (19%), respectively. For NKIPI, patients with group 1, 2, and 3 were six patients (37%), seven (44%), and three (19%), respectively. All patients received concurrent chemoradiotherapy, and eleven patients (69%) achieved complete remission, with 2 partial remissions. The overall response rate was 81%. At a median follow-up of 17 months (range; 2–44), the 2-year progression-free survival and overall survival rates were 54.7% and 61.1%, respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. Grade 3/4 adverse events were leukopenia (100%), neutropenia (100%), anemia (19%), mucositis (63%), anorexia (81%), and febrile neutropenia (25%), respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. No treatment-related deaths were observed. Conclusions:Concurrent radiotherapy and DeVIC for patients with localized ENKL, nasal type, demonstrated favorable outcomes. We are now investigating what factors indicate good or poor prognosis in this regimen.Progression free survival of concurrent radiotherapy and DeVIC regimen [Display omitted] [Display omitted] Disclosures:Yokoyama:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy. Mishima:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy.