1662 Objectives: Repeated trials of radioimmunotherapy (RIT) with high-dose anti-CD20 I-131 rituximab could be an approach that is useful to raise therapy efficacy in the treatment of non-Hodgkin’s lymphoma (NHL). In this study, we evaluate the absorbed dose of whole-body and red marrow in repeated RIT studies with administration of high-dose I-131 rituximab, using high-dose gamma imaging. Methods: Total 15 RIT studies with therapeutic dose of I-131 rituximab (7536 ± 1211 MBq) were performed on 6 patients with NHL. The number of repeated administration was 2 for 5 patients and 5 for one patient. The interval between repeated administrations was 13.9 ± 6.8 weeks. Whole-body planar images were acquired sequentially for 5 days using a gamma camera (Scintron, MiE, Germany) with high-energy collimator. Serial venous blood samples were obtained at the same points of imaging time. During the emission scan, several standard sources were placed beside patient in the field of view. All anterior and posterior images were converted to geometric-mean images with corrections of dead-time, physical-decay and attenuation, and used in further analysis for dosimetry. The time-activity curves (TACs) of whole-body and blood were used to estimate residence time and absorbed dose of whole-body and red marrow, respectively. Results: The shape of TACs was not different between repeated studies. The residence time of whole-body and blood were 25.7 ± 5.0 hr and 0.8 ± 0.4 hr, respectively. The values of absorbed dose were 29.8 ± 8.2 cGy for whole-body and 44.0 ± 19.6 cGy for red marrow, respectively, and showed the linear relationship with the amount of administered I-131 rituximab (r2 = 0.5971 for whole-body, r2 = 0.7423 for red marrow). Conclusions: The bio-kinetics of I-131 rituximab in repeated RIT was similar between studies. This dosimetry strategy in repeated RIT study with high-dose I-131 rituximab would be useful in monitoring and planning of treatment for NHL, with improved efficacy and safety.
Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas.Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS).Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively.131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.
1785 Objectives: Radioimmunotherapy (RIT) using I-131 anti-CD20 rituximab is one of the promising therapeutic model for treatment of patient with non-Hodgkin’s Lymphoma (NHL). Although dosimetric approaches of low-dose I-131 rituximab imaging have been reported, there is no study of dosimetry with high-dose imaging in patient with NHL yet. In this study, we investigated the kinetic behavior and absorbed dose to bone marrow and whole body in RIT study with high-dose strategy using I-131 rituximab for NHL. Methods: I-131 rituximab with high-dose (5032 ~ 7400 MBq) was administrated to patients (n = 4) with NHL. Both anterior and posterior planar images of whole body were acquired simultaneously using a gamma camera (Scintron, MiE, Germany) with high-energy collimator at 5 min, 5hr, 24hr, 48hr, 72hr and 1 or 2 weeks post administration. Sampling venous blood was performed at the same points of imaging time. Prior to the administration, blank and transmission images were acquired using Co-57 sheet source, for attenuation correction, respectively. During the emission acquisition, several small vials filled with known activities of I-131 were placed beside patient, for correction of deadtime due to high-activity of I-131. The acquired anterior and posterior images were converted to geometric mean image for further analysis. Using the time-activity curves (TACs) of blood and whole body, the values of effect half-life of the blood and whole body time activity curves were calculated, and mean absorbed doses to bone marrow and whole body were estimated, respectively. Results: Deadtime on gamma images induced underestimation (~64%) of area under the TAC of whole body radioactivity. The radioactivity in blood and whole body decreased rapidly with time, and the residence time of blood and whole body were 27.5 ± 6.7 hr and 32.4 ± 7.8 hr, respectively. The values of mean absorbed dose were range from 0.26 to 0.93 Gy for bone marrow and from 0.12 to 0.39 Gy for whole body, respectively. The dominant contribution of dose was from bone marrow self dose (> 60%). Conclusions: Using the RIT protocol with high-dose I-131 rituxmab, quantitative estimation of absorbed dose to bone marrow and whole body was possible. This RIT strategy of I-131 rituxmab would be useful in monitoring treatment for NHL.
Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal.We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation.Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529).In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.
Chronic infection with Epstein-Barr virus (EBV) without previous immunodeficiency or immuno-suppressive therapy is relatively rare. Severe chronic active EBV (SCAEBV) infection was reported for the first time in 1984 as 'chronic mononucleosis syndrome', and diagnostic criteria were proposed. It is characterized by clinical features including fever, severe hepatosplenomegaly, lymphadenopathy, hematologic features such as anemia and thrombocytopenia, and elevated antibody titers to EBV. We experienced a 21-year-old woman who initially presented with fever and chronic fatigue; however, no definite diagnosis could be made at the time of admission. Three months after the initial admission, there was evidence of only splenomegaly and the patient had persistent, multiple, paraaortic lymphadenopathies in abdominal CT. Diagnostic splenectomy was performed, and SCAEBV infection with T-cell lymphoproliferative disorder was ultimately diagnosed.
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