Rituximab-Supplemented High-Dose Sequential (HDS) Chemotherapy with Autograft Is Highly Effective in High-Risk (aaIPI 2–3) Diffuse Large B-Cell Lymphoma: Results of a Prospective Multicenter Study on 91 Consecutive Patients Treated at Diagnosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 891-891 ◽  
Author(s):  
Manuela Zanni ◽  
Massimo Di Nicola ◽  
Caterina Patti ◽  
Claudia Castellino ◽  
Alessandra Pescarollo ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Jc Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Sequential Administration ◽  
Large B Cell

Abstract Recent trials have shown that anti-CD20 monoclonal antibody Rituximab may be effectively employed in association with high-dose (hd) chemotherapy and peripheral blood progenitor cell (PBPC) autograft in the management of high-risk B-cell lymphoma. Addition of Rituximab has a dual effect: increased tumour cytoreduction and in vivo purging prior to PBPC harvesting. We here report the results of a prospective, multicenter trial evaluating Rituximab-supplemented hd-sequential chemotherapy (R-HDS) as frontline treatment in patients with high-risk Diffuse Large B-Cell Lymphoma (DLBCL). So far, 6 Italian Centres associated to GITIL have participated to the study. Eligibility criteria included: i. biopsy-proven DLBCL, with CD20+ phenotype; ii. no previous cytotoxic treatments; iii. age between 16–60 yrs.; iv. advanced stage disease with 2–3 aaIPI score. The R-HDS regimen includes an initial debulkying (3 APO courses) and then the sequential administration, at 15–20 day intervals, of: i. cyclophosphamide (CY) 7gr/sqm (day 1) + Rituximab 375mg/sqm (day +2 and +10), followed by PBPC harvest; ii. Ara-C 2gr/sqm b.i.d. for 6 days, reinfusion of 1–3x106 autologous CD34+ve cells/kg (day 7) and then Rituximab 375mg/sqm (day +8 and day +18); iii. etoposide 2.4gr/sqm day +1 + Cisplatin 100mg/sqm day +2; iv. a final myeloablative regimen (Mitoxantrone 60mg/sqm + L-Pam 180mg/sqm), with PBPC autograft (≥5x106 CD34+ve cells/kg) + Rituximab 375 mg/sqm (day +30 and +37); v. involved-field radiotherapy on areas of previous bulky lesions or residual lesions, within 2–3 mos. following autograft. Presently, 91 patients (median age: 48 yrs.) have been enrolled and are evaluable. They all had 2 (58) or 3 (33) aaIPI score; in addition, 63 (69%) presented with disease-related symptoms, 52 (57%) had extranodal disease, and 27 (30%) had BM involvement. There were 4 early toxic deaths (three due to sepsis following CY, Ara-C and autograft, respectively, and one due to leucoencephalopathy from JC-virus infection 2 mos. after autograft); one more toxic death due to pneumonia occurred at 10 mos. after R-HDS, for an overall TRM of 5.5%. In addition, 21 patients had CMV or VZV reactivation that resolved after antiviral therapy. Overall 73 patients (80 %) reached CR. So far, at a median follow-up of 24 mos., 76 patients (83.5%) are alive and 68 (75%) are in continuous CR (CCR), with 4.3-yr OS and and EFS projections of 80% and 74%, respectively. There was a trend towards a better outcome in aaIPI 2 vs. 3, although the difference was not statistically significative. Among 27 patients with BM+, 17 (63%) are presently in CCR, at a median follow-up of 25 mos. In conclusion, R-HDS was feasible at the multicenter level although the occurrence of severe infectious complications should not be underestimated. Nevertheless, both CR rate and survival curve projections compare favorably with the poor outcome usually observed in aaIPI 2–3 patients managed with conventional chemotherapy. The results here presented urge a comparative analysis between conventional vs. intensified Rituximab-supplemented chemoimmunotherapy in younger patients with high-risk DLBCL.

Front-Line Autologous Stem Cell Transplantation (ASCT) in Primary Mediastinal Large B-Cell Lymphoma: The GEL-TAMO Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3056-3056 ◽  
Author(s):  
Jose Rodriguez ◽  
Eulogio Conde ◽  
Antonio Gutierrez ◽  
Juan Carlos Garcia-Ruiz ◽  
Juan Jose Lahuerta ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Front Line ◽  
Large B Cell Lymphoma ◽  
Peripheral Stem Cells ◽  
Large B Cell

Abstract From 1985 to 2006, 71 patients with primary mediastinal large B-cell lymphoma receiving induction doxorubicine-based chemotherapy followed by ASCT as front-line therapy were registered in the GEL-TAMO (Spanish Group for Lymphoma and Autologous Transplantation). Median age was 28 years, 56% of patients were female, 40% presented with an ECOG ≥ 2; B-symptoms at diagnosis were present in 25% of the patients. Most patients presented with high-risk clinical features: bulky tumours defined as ≥10 cms of diameter were observed in most patients (87%), high LDH in 72% and, as previously reported (Rodriguez et al, Ann Oncol, 1994), β2m was elevated only in 7% of the cases. Forty-seven percent of patients presented 2–3 risk factors of the a-IPI. At transplant, thirty-five patients (49%) in first complete remission (CR), 23 (33%) in partial response and 13 patients (18%) failing the first induction therapy were transplanted, respectively. Conditioning regimens were BEAM or BEAC in 90% of the patients. 39 patients received Radiotherapy: 19 prior and 20 after the transplant. Most patients (91%) received peripheral stem cells. Only a patient failed to engraft after the transplant. After the transplant 73% of the patients achieved a CR and 17 patients were refractory. With a median follow-up from transplantation of 46,5 months the OS, PFS and DFS are 68%, 59% and 81% respectively. Progression of the disease was the main cause of death (78%). A patient died of a second neoplasia and 3 patients died of sepsis. There were no deaths related to transplant toxicity. By multivariate survival analysis both status of the disease at transplant (CR vs PR vs failure) and the Tumor score (Rodriguez et al, Ann Oncol,1992 ) were the only independent variables associated with the OS and PFS, respectively. In conclusion our experience, with a prolonged follow-up, shows that patients with primary mediastinal large B-cell lymphoma presenting at diagnosis with high-risk features have an encouraging survival and PFS with front-line ASCT. However, patients who received the transplant having failed the induction regimen have a very poor prognosis and should be tested with another innovative approach.

Addition of R-HMA to R-DA-EPOCH Favourably Changes the Outcome in Patients with Untreated High-Grade Diffuse Large B-Cell Lymphoma: The First Results of Russian Prospective Multicenter Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2708-2708
Author(s):  
Olga A. Gavrilina ◽  
Eugene E. Zvonkov ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Nelly G. Gabeeva ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Approximately 50% of diffuse large B-cell lymphomas (DLBCL) are defined as high-grade by IPI. They are characterized by aggressive course and poor response to standard chemotherapy (CT): 5-years overall survival (OS) rate of less than 30%. R-DA-EPOCH has demonstrated very optimistic results (overall and progression-free survival (PFS) were 90%), but high-risk patients (IPI 3-4) showed only 43% of OS and PFS [1]. The addition of high-dose AraC (12 g/m2) to the upfront therapy of high-risk DLBCL has significantly improved the outcome on Hyper-CVAD/HMA and mNHL-BFM-90 protocols [2, 3]. But high toxicity of these protocols restricts their application. We suggested that addition of courses R-HMA in rotation with R-DA-EPOCH could improve the treatment outcome and decrease toxicity. Aim: To evaluate the efficacy and toxicity of R-DA-EPOCH/R-HMA protocol in patients with untreated high-grade diffuse large B-cell lymphoma. Patients and Methods: 33 untreated DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2015; stage II-IV; ECOG 0-3; median age 55 years (27-76); age ≥60y/<60y 50%/50%; M/F 60%/40%; IPI: 48% high-intermediate and 52% high risk; 15% with bone marrow involvement. All patients underwent 4-8 courses (2-4 cycles) of chemotherapy: R-DA-EPOCH (standard dose and scheme), R-HMA (R 375 mg/m2 d1, MTX 1000 mg/m2 24 hours d 2, AraC 3000 mg/m2 q 12 hrs d 3-4). For patients older than 60 year dose of R-HMA was reduced (R 375 mg/m2 d1, MTX 500 mg/m2 24 hours d 2, AraC 1000 mg/m2 q 12 hrs d 3-4). In 4 cases of DLBCL with bone marrow involvement BEAM conditioning and autologous stem cell transplantation were applied. Results: The median follow-up is 12 months (4-24). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 29 (88%) patients. In 2 patients we observed progression of the disease after first cycle of chemotherapy, in another 2 cases - partial remission after 2-3 cycles and following progression of disease. In patients older than 60 years with doses reduction in R-HMA failures were absent, except one later relapse after 13 month CR. With a median follow 12 months overall and disease-free survival of 33 patients constituted 90,5% and 74% , respectively. In a group of patients older than 60 years results of therapy seemed to be better than in young patients: OS were 100% vs 85,6% (p=0,1), DFS were 80% vs 74,9% (p=0,2), respectively. So the combination of R-DA-EPOCH/R-HMA may be considered as optimal intensive approach in the older patients. Conclusions: TheR-DA-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in patients with high-grade DLBCL. This protocol has shown optimistic results in the elderly patients and it could be recommended for further investigation in that group. Ññûëêè: 1. Salit RB, Fowler DH, Wilson WH, et al. Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies.J Clin Oncol. 2012. 10;30(8):830-6. 2. Oki Y, Westin JR, Vega F, et al. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol 2013; 163(5):611-20. 3. Magomedova AU, Kravchenko SK, Kremenetskaia AM, et al. Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma. Ter Arkh. 2011;83(7):5-10. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Long Term Follow up of SWOG S0313: Ibritumomab Tiuxetan Consolidation after 3 Cycles of CHOP Plus Radiotherapy for High Risk Limited Stage Aggressive B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4414-4414
Author(s):  
Daniel O Persky ◽  
Thomas P. Miller ◽  
Joseph M Unger ◽  
Catherine M. Spier ◽  
Soham D. Puvvada ◽  
...  
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: Patients with limited stage aggressive B-cell non-Hodgkin lymphoma (LS-NHL) and at least one stage-modified adverse risk factor have an excessive relapse rate leading to a 5-year overall survival (OS) of 50-77% and 10-year OS of 0-50%. In SWOG S0014 we have shown that the addition of rituximab to 3 cycles of CHOP plus involved field radiation therapy (IFRT) resulted in an improved estimated 4-year progression-free survival (PFS) of 88% and OS of 92%. Relapses were largely systemic (5 of 6 evaluable) and continued to be seen with longer follow-up. Ibritumomab tiuxetan (Zevalin ®) is a radiolabeled anti-CD20 antibody that has excellent single agent activity in diffuse large B-cell lymphoma and could prevent systemic relapse of disease. We now report long term results of SWOG S0313, a phase II study of ibritumomab tiuxetan consolidation after 3 cycles of CHOP plus IFRT in patients with LS-NHL. Methods: Patients with LS-NHL and at least one stage-modified adverse risk factor (non-bulky stage II, age > 60 years, elevated LDH, or WHO performance status of 2) were treated with CHOP on days 1, 22, and 43, followed 3 weeks later by 40-50 Gy of IFRT. Ibritumomab tiuxetan regimen was initiated 3 – 6 weeks following IFRT. Results: Forty-six patients were registered and eligible, with median follow-up of 7.3 years. Median age was 61, 37% of patients had elevated LDH, and 20% had systemic symptoms. Grade 4 adverse events occurring more than once included neutropenia (8 patients), leukopenia (5), and lymphopenia (2). Febrile neutropenia was observed in 4 patients. No cases of treatment-related myeloid neoplasms were noted. Eleven patients progressed and 8 patients died. The PFS estimate is 89% at 2 years, 82% at 5 years, and 75% at 7 years. OS estimate is 91% at 2 years, 87% at 5 years, and 82% at 7 years. These outcomes compare favorably to matched cohorts on prior SWOG trials, with 7-year PFS estimate of 68% on S0014 and 65% on S8736 (original pre-Rituximab trial); and 7-year OS estimate of 80% on S0014 and 73% on S8736 cohorts. Conclusions: Patients with high-risk LS-NHL treated with 3 cycles of CHOP plus IFRT followed by ibritumomab tiuxetan consolidation had outcomes that compare favorably to our historical experience. A US cooperative group study of R-CHOP and response-adapted IFRT followed by consolidative ibritumomab tiuxetan is ongoing. Disclosures Off Label Use: ibritumomab tiuxetan in diffuse large B-cell lymphoma.

scholarly journals Numbers of early CD34+ progenitors of bone marrow hematopoiesis in patients with diffuse large B-cell lymphoma

2017 ◽  
Vol 89 (1) ◽  
pp. 43-48
Author(s):  
E I Dorokhina ◽  
A U Magomedova ◽  
I V Galtseva ◽  
V N Dvirnyk ◽  
S A Glinkina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Late Period ◽  
Large B Cell Lymphoma ◽  
Relationship Of ◽  
Large B Cell

Aim. To estimate the number of early progenitors of bone marrow (BM) hematopoiesis in patients with diffuse large B-cell lymphoma (DLBCL) in the late period after high-dose chemotherapy (HDCT) according to the mNHL-BFM-90 program. Subjects and methods. The investigators analyzed the results of BM immunophenotypic and histological studies in 40 patients (median age, 57 years) with DLBCL who received HDCT according to the mNHL-BFM-90 program at the Hematology Research Center (HRC), Ministry of Health of the Russian Federation (MHRF), in the period 2002 to 2009. A comparison group consisted of 19 patients (median age, 70 years) treated according to the CHOP/R-CHOP program at HRC, MHRF, in the same period. The median follow-up period was 6 years. The results of BM examination were analyzed before and 5—10 years after the end of HDCT. Immunophenotypic study determined the number of early CD34+ hematopoietic progenitors. BM cellularity, the size of erythroid, granulocytic and megakaryocytic lineages, their ratio, the presence of dysplasia signs, and secondary stromal changes were histologically determined. The BM toxic injury signs found for the first time were evaluated as manifestations of late myelotoxicity. Results. At 5-to-10-year follow-ups after the end of HDCT according to the mNHL-BFM-90 program, the patients showed a smaller number of early CD34+ progenitors of BM hematopoiesis in 31 (78%) cases than those treated according to the CHOP/R-CHOP-21 program (n=8 (2%)) (p=0.005). Myelopoiesis with decreased CD34+ cell count was characterized by hypocellularity in 8 (26%) patients (p=0.07), the narrowing of megakaryocytic lineage in 14 (45%) (p=0.006), erythroid one in 7 (23%) (p=0.01), and granulocytic one in 8 (26%) (p=0.92), pronounced secondary stromal changes in 15 (48%) (p=0.03), and grade 1 thrombocytopenia in 13 (42%); p=0.02). Conclusion. There is evidence that the number of early CD34+ progenitors of BM hematopoiesis decreased in patients with DLBCL in the late period after HDCT. The investigation shows the relationship of the reduction in the number of early CD34+ progenitors of BM hematopoiesis in the late follow-up period to the presence of pronounced secondary changes in the BM stroma (p=0.02). There was no statistically significant relationship of the decreased number of CD34+ cells to the age younger or older than 60 years, to the period after the end of chemotherapy, to gender or presence of specific BM injury.

Efficacy and Safety of Liposomal Cytarabine as Intrathecal Prophylaxis in Patients with Diffuse Large B Cell Lymphoma at High Risk of CNS Involvement: A Multicentric Study Including 80 Patients in Spain.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1663-1663
Author(s):  
Adolfo de la Fuente ◽  
Antonio Salar ◽  
Carlos Panizo ◽  
Belen Navarro ◽  
Teresa Olave ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Retrospective Study ◽  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Liposomal Cytarabine ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1663 Poster Board I-689 Introduction Lymphomatous meningitis (LM) in patients with Diffuse Large B Cell Lymphoma (DLBCL) is usually an early complication and with poor prognosis. Risk factors have been previously identified for this complication. DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial. Purpose and Methods A retrospective study was carried out in 24 Spanish sites including patients diagnosed of DLBCL and at risk of LM – defined by the presence of at least one of the following: retroperitoneal mass ≥ 10 cm; Waldeyer ring, sinus, vertebral or bone, and testicular involvement; LDH more than twice the upper normal limit; bone marrow involvement > 30% and serology VIH+. All patients had received LC as IT prophylaxis for LM in the period April 2005 – June 2009. Main endpoints were effectiveness (leptomeningeal involvement rate) and safety of the IT prophylaxis. Results Data from 80 patients were analyzed. Baseline characteristics were: Mean age 55 ± 16 years (range: 18-80 years). Males 74%; Ann Arbor stage IV 54%. All patients received alkylating based regimens, being R-CHOP as the most frequent one (88%). LC was administered as intrathecal prophylactic treatment for LM in all patients. 64 patients completed the IT prophylaxis treatment with a mean of 2,8 ± 0,83 administrations and a median follow up of 17 months (range: 3-40 months) (8 patient still on treatment and 8 patients died before finish prophylaxis). Just one patient (1,6%) had leptomeningeal spread: 76 years old man with primary testicular DLBCL, treated with R-CHOP regime, who did not reach complete response and died after 8 months of follow up due to respiratory failure. Twenty four patients out of eighty (30%) showed adverse events, being headache the most frequent side effect (27%), and 14% grade IV. Headache was reversible in all cases. Chemical arachnoiditis prophylaxis was given to 70 patients. Conclusions This retrospective study has shown that in DLBCL patients and high risk of LM, prophylaxis with LC was feasible and well tolerated. With a median follow up of 17 months (range: 3-40 months) the incidence of LM was 1,6 %. Prospective, randomized comparative studies versus conventional prophylaxis regimes are needed. Disclosures Off Label Use: DepoCyte is an extended released liposomal cytarabine formulation (LC) which has demonstrated better efficacy compared to standard cytarabine for the treatment of LM in one randomized clinical trial. Prphylaxis effectiveness..

Use of exon-based transcriptome profiling to identify novel signaling pathways and survival-associated genes in diffuse large B-cell lymphoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8074-8074
Author(s):  
Sirpa Leppa ◽  
Minna Taskinen ◽  
Satu Koivula ◽  
Ping Chen ◽  
Riku Louhimo ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Transcriptome Profiling ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Large B Cell

8074 Background: Identification of biological prognostic factors that could be used to define poor risk diffuse large B-cell lymphoma (DLBCL) patients is a main concern. Methods: Study population consisted of 38 de novo high risk DLBCL patients less than 65 years old. The patients were treated in the Nordic phase II protocol with six courses of R-CHOEP14 followed by systemic central nervous system prophylaxis with one course of high dose methotrexate and one course of high dose cytarabine. Exon array-based profiling was used to screen signaling pathways and differentially expressed genes between the clinically high risk patients, who had relapsed or remained in remission in response to dose dense chemoimmunotherapy. At the time of the analysis, median follow up was 34 months, progression free survival (PFS) 78% and overall survival (OS) 78%. Results: The screen between relapsed patients and the patients in remission using criteria of p ≤ 0.05 and fold change ≥ 1.6 revealed 566 differentially expressed genes (131 protein coding), of which 24 were likely to be involved in conventional signaling pathways, including those regulating antigen processing and presentation (CIITA, HLA-DQA2, HLA-DQB1, RFXAP), Jak-STAT signaling (SOCS3), Notch signaling (NOTCH1) and Toll-like receptor signalling (IRF5). In cox univariate analysis, 12 of 24 genes were found to associate with PFS (p<0.05). Of these, high expression of CIITA, DLL4, HLA-DQA2, HLA-DQB1, IRF5, NOTCH1, PER1, RFXAP, SEMA4D and ZFP36 had a favorable impact on PFS, whereas high levels of ENPP3 and PRKAR2B were associated with adverse outcome. Differential expression of four genes was confirmed by quantitative PCR, and prognostic value of six genes validated using Lymphoma/Leukemia Molecular Profiling Project microarray data set. Immunohistochemical validation of the findings in a larger patient cohort is ongoing. Germinal centre B-cell signature did not predict survival in this cohort. Conclusions: The results provide evidence that exon-based transcriptome profiling can identify biologically relevant signaling pathways and genes that discriminate the outcome of homogenously treated young high risk DLBCL patients.

Rituximab Improves the Efficacy of High-Dose Chemotherapy With Autograft for High-Risk Follicular and Diffuse Large B-Cell Lymphoma: A Multicenter Gruppo Italiano Terapie Innnovative nei Linfomi Survey

2008 ◽  
Vol 26 (19) ◽  
pp. 3166-3175 ◽  
Author(s):  
Corrado Tarella ◽  
Manuela Zanni ◽  
Michele Magni ◽  
Fabio Benedetti ◽  
Caterina Patti ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Late Relapse ◽  
High Dose ◽  
Refractory Disease ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Purpose To investigate the impact of adding rituximab to intensive chemotherapy with peripheral-blood progenitor cell (PBPC) autograft for high-risk diffuse large B-cell lymphoma (DLB-CL) and follicular lymphoma (FL). Patients and Methods Data were collected from 10 centers associated with Gruppo Italiano Terapie Innnovative nei Linfomi for 522 patients with DLB-CL and 223 patients with FL (median age, 47 years) who received the original or a modified high-dose sequential (HDS) chemotherapy regimen. HDS was delivered to 396 patients without (R−) and to 349 patients with (R+) rituximab; 154 (39%) and 178 patients (51%) in the R− and R+ subsets, respectively, underwent HDS for relapsed/refractory disease. Results A total of 355 R− (90%) and 309 R+ patients (88%) completed the final PBPC autograft. Early treatment-related mortality was 3.3% for R− and 2.8% for R+ (P = not significant). Two parameters significantly influenced the outcome: disease status at HDS, with 5-year overall survival (OS) projections of 69% versus 57% for diagnosis versus refractory/relapsed status, respectively, and rituximab addition, with 5-year OS of 69% versus 60% in the R+ versus R− groups, respectively. In the multivariate analysis, these two variables maintained an independent prognostic value. The marked benefit of rituximab was evident in patients receiving HDS as salvage treatment: the 5-year OS projections for R+ versus R− were, respectively, 64% versus 38%, for patients with refractory disease or early relapse and 71% versus 57%, for patients with late relapse, partial response, or second/third relapse. Conclusion The results of this large series indicate that rituximab should be included in the current practice of PBPC autograft for DLB-CL and FL.

scholarly journals Radiation Exposure As a Link to Primary Ocular Diffuse Large B Cell Lymphoma (PODLBCL) - a Possible Cluster Related to the Chernobyl Explosion

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5381-5381
Author(s):  
Sanford Kempin ◽  
Paul Finger ◽  
John Rescigno ◽  
Jeffrey Rubin ◽  
Walter Choi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Lymphoid Cells ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
The Mean ◽  
Large B Cell

Abstract Background: PODLBCL, a rare form of diffuse large B cell lymphoma (DLBCL), arises primarily from the retina and urea. It is estimated to occur in 100 patients/3 years in the United States. Its etiology is unknown although chronic inflammation is thought to play a significant role. It is observed most commonly in immunocompetent patients. EB virus has not been associated with the form of lymphoma. The disease is frequently bilateral (80%) and 56-85% of patients will develop intracerebral metastases. There is a slight male predominance. The peak of incidence is between the fifth and seventh decade. Methods: We have recently had an opportunity to evaluate six patients at the MS/BICCC from 2010-2013. All received initial therapy at MS/BICC. We have analyzed disease presentation, various demographic factors, possible exposure information, treatment and outcome. In addition, epidemiologic studies of the Chernobyl (Ukraine) nuclear power plant explosion (April 26, 1986) were reviewed. The most contaminated regions included Belarus and the Ukraine, with volatile fission products traveling at greater distances (Bard D, Verger P, Hubert P. Chernobyl, 10 Years After: Health Consequences Epidemiologic Reviews 1997:19 (2):187-201). The main health effect continues to be that of thyroid cancers. With respect to ocular findings, liquidators were found to develop senile cataracts, premature myopia and arteriosclerosis of the fundic vessels. The ten-year follow-up demonstrated a slight increase in subcapsular lens changes in children. At the 20 year follow-up (Cardis E, Howe G, Ron E, et al.) Cancer Consequences of the Chernobyl Accident: 20 Years On. J. Radiol Prot 2006; 26:127-140) there has been no conclusive reported increase in childhood or adult leukemia of lymphoma. In the most recent update (Pflugbeil S, Claussen A, Schmitz-Feuerhake. Health Effects of Chernobyl 25 Years After the Reactor Catastrophe. 2011: Gesellschaft fur Strahlenschutz) there is still no definitive evidence of an increase in lymphoma. Results: In our series the most common complaint was cloudiness of vision and the most common findings were anterior chamber inflammation, sheets of cells within the vitreous, uveitis and subretinal and retinal infiltrates. The presentation was bilateral in all patients. The mean age at presentation was 76 years (62-84), including five women and one man (the female predominance is unusual). At the time of exposure, four of the patients were living in the Ukraine; one in Moldova and one is southern Poland. The mean time possible exposure to appearance of PODLBCL was 26 years. The diagnosis was made by vitreous FNA (2), vitreous biopsy (4), clinical presentation (1). Initial treatments included chemotherapy (high dose methotrexate) in two patients, and radiation therapy in four patients. Of the six there was one synchronous presentation with brain lymphoma. Two patients developed spread to the brain, one of whom expired and one of whom is considered NED after whole brain irradiation and temazolomide. Five patients remain NED, but at short follow-up. Conclusions: Conceptionally, lymphomas are thought to develop because of an inherent sensitivity of lymphoid cells to genetic instability, immune stimulation, inherited genetic disorders, toxins, infections agents as well as radiation injury. For almost all etiologies it is accepted that a long prodromal period between exposure and subsequent appearance of neoplasia occurs and these case reports may be an illustration of this phenomena. It is estimated that several million Europeans were exposed to radiation as a result of this explosion. As the ocular globe would appear to be one of the most exposed organs, more patients with this unusual malignancy may be seen and an appreciation of this possibility would seem warranted. Disclosures No relevant conflicts of interest to declare.

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