Outcomes Following Allogeneic Stem Cell Transplantation (AlloSCT) in Patients with Primary Mediastinal (PMBL), Germinal Center B (GCB) and Non-GCB Cell-like Diffuse Large B Cell Lymphomas (DLBCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2563-2563 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M Saliba ◽  
Zijun Y. Xu-Monette ◽  
Martin Korbling ◽  
Gabriela Rondon ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Stem Cell Source ◽  
The Impact

Abstract Background: Primary mediastinal (PMBL), GCB and non-GCB B-cell lymphoma are three major subtypes of DLBCL with distinct clinical outcomes. PMBL and DLBCL of GCB immunophenotype have a higher chance of cure than patients with non-GCB DLBCL when treated with conventional chemotherapy. In the relapsed/refractory setting, there is paucity of data regarding the impact of histological classification of DLBCL on survival following alloSCT in patients who were not eligible for or who have failed a prior autologous SCT (ASCT). Herein, we compare outcomes of alloSCT in these patients. Methods and Patients: We identified 101 de novo DLBCL patients who were treated at our center from January 1, 1998 to December 31, 2011. Seventeen (17%) tumors were PMBL. We determined the cell-of-origin in the remaining patients, based upon the Visco/Young and Choi immunohistochemical algorithms, and classified 62 (61%) as GCB and 22 (22%) as non-GCB tumors. GCB patients were older than non-GCB [median (range): 54 (21-70) vs 48(24-58) years, p=0.003)] and PMBL [26(19-48), P <0.001)]. Patients with PMBL, however, were more likely to have bulky disease at study entry (SE) than other subtypes [24% (PMBL) vs 5% (GCB) and 5% (non-GCB); P= 0.04]. Stage III-IV at SE in GCB, non-GCB and PMBL was present in 42%, 45% (P=0.8) and 35% (P=0.6), respectively; the number of prior chemotherapies received was 4 in both GCB and non-GCB and 5 in PMBL (P=0.3). The proportion of patients who have failed a prior ASCT was comparable in all three groups (32%, 32% and 47%, P=0.2). Refractory disease was present in 35% of GCB and PMBL patients at SE compared to 14% in non-GCB patients (P=0.03). Distribution of IPI, LDH, and proportion of PET+ patients (47%, 45% and 47%) were not statistically different in all 3 groups. A larger proportion of GCB patients (44%, reference) received non-myeloablative conditioning than non-GCB (23%, P=0.07), or PMBL (12%, P=0.3); the remaining patients received reduced-intensity conditioning (RIC). The proportion of patients who received a matched sibling donor in GCB, non-GCB and PML were 69% (reference), 64% (P=0.6) and 41% (P=0.03), respectively. The remaining patients received matched unrelated donors. More GCB patients received peripheral blood as stem cell source than non-GCB (89% vs 73%, P=0.08) or PMBL (47%, P=0.001) patients. Median year of transplant was 2006 in both GCB and non-GCB and 2004 in PMBL. Results: Median (range) follow-up months in surviving GCB, non-GCB and PML patients were 63 (5-157), 29 (7-117) and 52 (10-133) months respectively. The 3-year cumulative OS were 52% (reference), 18% (P=0.09) and 46% (P=0.6). The 3-year cumulative PFS were 39%, 12% (P=0.1) and 41% (P=0.9) (Figure). When we restricted the comparison to patients who had chemosensitive disease and received RIC, the 3-year OS rates for GCB, non-GCB and PMBL were 47%, 25% (HR=0.6, P=0.3) and 44% (HR=0.9, P=0.9), respectively. The 3-year PFS rates were 37%, 10% (HR=0.6, P=0.2) and 44% (HR=0.7, P=0.8). Non-relapse mortality at 3-years was 29% (reference), 47% (P=0.1), and 35% (P=0.6). The incidence of acute II-IV GVHD was 24%, 27% and 29%. The incidence of extensive chronic GVHD was 34%, 54% (P=0.07) and 41% (P=0.5). The major cause of death in all 3 subgroups was disease progression (38%, 38%, and 33%), followed by acute GVHD 14%, 13%, and 33%. Conclusions: Our results suggest a tendency for inferior survival after alloSCT in non-GCB when compared to GCB and PMBL subtypes of DLBCL. This occurred despite the younger age in the non-GCB versus GCB group. Innovative approaches are needed to improve outcomes in non-GCB patients after alloSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Cell of Origin in Richter's Transformation of CLL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4574-4574
Author(s):  
Nadia Khan ◽  
Ami Chitalia ◽  
Metin Ozdemirli ◽  
Gregory Ray ◽  
Edmund Gehan ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
B Cell Lymphoma ◽  
Small Sample ◽  
Investigational Drug ◽  
Cell Of Origin ◽  
Richter’S Transformation ◽  
Richter's Transformation ◽  
Tissue Specimens

Abstract Abstract 4574 Richter's transformation (RT) from chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL) occurs in about 5% of pts and confers significant morbidity and mortality. In de novo DLBCL the cell of origin (COO), either activated B-cell like (ABC) or germinal center B-cell like (GCB), is prognostic. The ABC group has been shown to have both a less favorable response to chemoimmunotherapy and a shorter overall survival than the GCB group. However, COO has not been previously described for pts with RT. The aim of our study was to determine the pattern of COO in RT and to determine if prognostic correlates exist. Clinical information on 30 pts with CLL and pathologically-confirmed RT were obtained from the CLL cohort treated at our institution from 1980 to July, 2012, and, of these, 13 pts had sufficient data for inclusion in the analysis. Paraffin-embedded DLBCL tissue specimens were subjected to antigen retrieval and antibody staining via commercially manufactured products. CD10, BCL-6, and MUM-1 were the antigens identifiable by staining and used in the Hans method for COO determination. Immunoglobulin heavy chain VDJ-PCR was performed on CLL and RT tissue specimens and compared in order to establish clonality on some tissue specimens. Kappa and lambda immunophenotyping was compared between CLL samples and RT tissue samples for clonal assessment as well. Of the 13 pts evaluated, 10 were ABC-type and 3 were GCB-type. Median age was 59 yrs, 7 male, 6 female, 3 ZAP 70 +, 6 IgVH mutated. EBER staining was positive in 2/13 RT pts. For the ABC-type, median time to transformation (TTT) was 25 mos (0–288 mos) for the GCB- type median TTT was 48 mos (48–100 mos). The one-year OS for pts after RT was 38%; 40% for ABC-type and 33% for GCB-type. For the ABC-type, survival after transformation (SAT) was a median of 10.5 mos (1–96 mos), for the GCB-type median survival was 3 mos (9 days-14+ mos). The pts with the longest TTT (98 and 288 mos), had an IPI of 2. Those with shortest TTT (0, concurrent diagnosis of RT and CLL) had IPIs of 5. Of the pts with ABC-type: 5 were previously treated with chemotherapy for CLL; 4/5 fludarabine-based regimens, and 2 with rituximab monotherapy. Available treatment information for RT in ABC-type: 1 with HyperCVAD, 4 with RCHOP, 1 with HyperCVAD followed by REPOCH. One pt went on to BMT, and one required IT chemotherapy for CNS involvement. For the 3 pts with GCB-type, 2 received prior treatment for CLL with FR, the other pt was previously untreated. Treatment for RT in the GCB-type included: R-CHOP, DCDT-2980S (an investigational drug–antibody conjugate), and ongoing treatment on a clinical trial with ibrutinib in one pt who remains alive, radiation therapy for another who died 3 mos after RT, and one pt who died 9 days after RT and was not treated for transformed disease. Five of the 11 evaluable samples were found to be of a different clone from the original CLL and 6/11 were the same clone based on VDJ-PCR and immunophenotype. Longer TTT (48 mos or more) correlated with the finding of a different clone in the RT. The 2 pts who had synchronous diagnoses of RT and CLL were from the same clone. A higher prevalence of ABC-type DLBCL was noted in this series of RT pts. Among 10 ABC-type RT pts, there was a shorter median TTT compared with GCB–type RT pts. In the ABC-type RT pts there was a correlation between longer TTT and longer survival, which may be reflective of the underlying biology of the lymphoma within the ABC-type. This correlation was not seen in the GCB group. An association between the type of chemotherapy used in the CLL setting and the COO was not identified. In the ABC-group, survival was not impacted by type of chemotherapy used in RT. In contrast to de novo DLBCL, there was a suggestion of a more favorable outcome with the RT ABC-type. In those cases of longer TTT (4 yrs +), the RT clone appeared different than the original CLL based on PCR or immunophenotype. This difference may represent a CLL clone that escaped chemotherapeutic destruction and then developed into RT, or the possibility of a newer clone that emerged independent of the original lymphoma and confirms what has been previously described, that all RT are not clonally evolved but a de novo event in some cases. Though a small sample size, the results of this series of pts is hypothesis-generating. Improved prognostic accuracy and risk-directed therapeutic strategies may become possible with an improved classification of COO of RT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes

2019 ◽  
Vol 53 (4) ◽  
pp. 473-479 ◽  
Author(s):  
Chrishanthi Rajasooriyar ◽  
Jeremy Tey ◽  
Lea Choung Wong ◽  
Michelle Poon ◽  
Rao Nandini ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Background Patients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT. Patients and methods Patients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed. Results Seventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS. Conclusions The outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

Primary Mediastinal B Cell Lymphoma Treated with CHOP-Like Chemotherapy with or without Rituximab: 5-Year Results of the Mabthera International Trial Group (MInT) Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1612-1612 ◽  
Author(s):  
Mathias Witzens-Harig ◽  
Anthony D Ho ◽  
Evelyn Kuhnt ◽  
Marek Trneny ◽  
Michael Rieger ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Long Term Outcome ◽  
Free Survival ◽  
The Impact

Abstract Abstract 1612 Purpose The aim of this subgroup analysis of the MInT study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B cell lymphoma (PMBCL) in comparison to other diffuse large B-cell lymphoma (DLBCL). Extended follow-up was needed to establish long-term effects. Patients and Methods Eligible for the randomized open-label MInT study were patients aged 18–60 years with DLBCL who had 0–1 risk factors according to age-adjusted International Prognostic Index (aaIPI), stage II-IV disease, or stage I disease with bulk. Patients were randomly assigned to six cycles of CHOP-like regimens with or without rituximab. Consolidating radiotherapy was given to sites of primary bulky disease. Results Of 824 patients enrolled, 87 had PMBCL and 627 other types of DLBCL. Rituximab increased the rates of complete remission (unconfirmed) in both PMBCL (from 54% to 80%; p =.015) and DLBCL (from 72% to 87%; p<.001). In PMBCL rituximab virtually eliminated progressive disease (PD) (2.5% vs 24%; p =.006), whereas without rituximab PD was more frequent in PMBCL than in DLBCL (24% vs 10%; p =.023). With a median observation time of 62 months for PMBCL and 73 months for DLBCL, the 5-year event-free survival was improved by rituximab for PMBCL (79.1% vs 47.3%; p =.011) and for DLBCL (76.9% vs 59.7%; p <.001). Furthermore, 5-year progression-free survival was improved by rituximab for PMBCL (89.8% vs 60.1%; p=.006) and DLBCL (81.1% vs. 67.8%; p <.001). Overall survival benefit was similar for DLBCL (92.0% vs 80.9%; p <.001) and PMBCL (90.2% vs 78.3%; p =.234). Conclusion Addition of rituximab to 6 cycles of CHOP-like chemotherapy improved long-term outcome for young patients with PMBCL and aaIPI 0–1 and eliminated differences in outcome between PMBCL and DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India

2021 ◽  
Vol 11 ◽  
Author(s):  
Ajay Gogia ◽  
Sukesh Nair ◽  
Shalabh Arora ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
...  
Keyword(s):  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Ecog Performance Status ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Impact

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p &lt; 0.001), age &gt;60 years (p = 0.001), bulky disease (p &lt; 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p &lt; 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

VEGFA and VEGFR2 Genetic Polymorphisms and Survival In Patients with Diffuse Large B Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 994-994
Author(s):  
Min Kyoung Kim ◽  
Cheolwon Suh ◽  
Hyun Sook Chi ◽  
Hee Soon Cho ◽  
Kyung Hee Lee ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Vegf Receptor ◽  
Curative Intent ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 994 Background: Angiogenesis and angiogenic factors are increased in most lymphomas and it has been associated with adverse outcome or more aggressive behavior of malignant lymphomas in previous studies. There is substantial inherited genetic variability within VEGF and one of its receptors, VEGF receptor 2 (VEGFR2), including multiple single nucleotide polymorphisms (SNPs). The level of VEGF expression has been found to vary depending on the presence of a genetic polymorphism. Moreover, VEGFR2 gene polymorphisms affect the binding efficacy of VEGF to VEGFR2. We therefore assessed the association between VEGFA and VEGFR2 polymorphisms and survival outcomes in patients with diffuse large B cell lymphoma (DLBCL). Patients and Methods: This study included 494 patients with de novo DLBCL treated at 5 hospitals throughout Korea from August 2001 through August 2009. Patients were included if they were (1) ethnic Koreans; (2) had blood samples taken at diagnosis; (3) had been treated with R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisolone) with curative intent; and (4) were available for follow-up at the treating institution. Genes and polymorphisms known to modulate angiogenesis were selected. Criteria included: (1) SNPs involved in the VEGF pathway; (2) potentially functional SNPs predicting alterations in protein function; (3) SNPs relevant to outcomes in other settings; (4) and SNPs with a minor allele frequency >5% in the study population. We selected a total of five genotypes, three in the VEGFA gene (rs699947, rs833061, and rs3025039) and two in the VEGFR2 gene (rs1870377 and rs2305948). Results: There was a trend towards greater proportions of patients > 60 years (P=0.078) patients with bulky disease (P=0.072) and patients who did not achieved complete response (P=0.068) among the VEGF2R rs1870377 TT type than the TA+AA genotype patients. Of the five polymorphisms, VEGF2R rs1870377T>A was significantly associated with both OS and PFS; in the dominant model, the TT genotype had worse OS (P=0.002) and PFS (P=0.004) than the AA+TA genotype. Among patients with low IPI scores (0 to 2), those with the VEGFR2 rs1870377 AA+TA genotype had significantly better OS (P=0.035); a similar difference for this genotype was observed among patients with high IPI scores (3 to 5) (P=0.043). Patients in the moderate (P=0.031) and high (P=0.043) risk subgroups, according to revised IPI scores, with the VEGFR2 rs1870377 AA+TA genotype also had better outcomes than those with the TT genotype. Multivariate analysis showed that the rs1870377 genotype was an independent prognostic factor for OS (HR for TT vs AA+AT, 1.71; 95% CI, 1.21 to 2.43; P=0.002) and PFS (HR for TT vs AA+AT, 1.57; 1.13 to 2.17; P=0.007). Age > 60 years (P=0.0001 for OS; P=0.0001 for PFS), LDH level > normal (P=0.005 for OS; P=0.003 for PFS), extranodal disease > 1 (P=0.013 for OS; P=0.017 for PFS) and presence of B symptom (P=0.0001 for OS; P=0.0001 for PFS) were also independent prognostic factors for the survival of patients with DLBCL. Conclusion: The VEGFR2 rs1870377 polymorphism may affect survival in patients with DLBCL. These findings suggest that increased angiogenic activity may be related to tumor progression in patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

Addition of Rituximab (R) to CHOP Improves Survival in the Non-GCB Subtype of Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 816-816 ◽  
Author(s):  
Pedro Farinha ◽  
Laurie Sehn ◽  
Brian Skinnider ◽  
Joseph M. Connors ◽  
Randy D. Gascoyne
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Chop Chemotherapy ◽  
Entire Study ◽  
Survival Difference

Abstract Background: The cell of origin (COO) distinction provides a prognostic and biologically relevant subclassification of DLBCL. Germinal center B cell (GCB) and non-GCB subtypes were originally characterized by gene expression studies and subsequently validated at the protein level by Hans et al., Blood 193: 275–82 (2004). The addition of R to CHOP chemotherapy has been shown to improve the outcome of patients with DLBCL. The underlying mechanism(s) responsible for this effect is largely unknown. However, it is known that R may preferentially prevent chemotherapy failure in DLBCLs that express Bcl-2 protein or fail to express Bcl-6 (Mounier et al., Blood101: 4279–84 2003, Winter et al., Blood107: 4207–13 2006). Bcl-2 over-expression and absence of Bcl-6 is more common in the non-GCB subtype. Thus, R may benefit mostly non-GCB lymphomas. To test this hypothesis we assessed the clinical impact of CHOP-R vs CHOP in DLBCL distinguished by COO subtypes. Method: We identified 163 patients with DLBCL treated with either CHOP or CHOP-R with available paraffin blocks and interpretable immuno-staining. All were de novo DLBCL cases diagnosed between 1999 and 2002 at the BCCA. The two treatment cohorts represent consecutive eras of therapy (Sehn et al., JCO2005; 23: 5027–33), and thus the median follow-up of living patients was 5.1 and 4.0 y for CHOP and CHOP-R, respectively. HIV+ patients or those with active secondary malignancies were excluded. Tissue microarrays (TMA) were built using duplicate 0.6mm cores from paraffin embedded formalin fixed (FFPE) tissues and stained with antibodies against CD10, Bcl-6, MUM1, and Bcl-2. The COO distinction was determined using the method of Hans. Results: Patients were treated with either CHOP (81) or CHOP-R (82). Their clinical characteristics, including the IPI, were evenly matched. The median follow-up of living patients was 4.4 y. The IPI was predictive of overall survival (OS) (p&lt;0.0001) for the entire study population. Six cases had uninterpretable immunostains resulting in 74 cases with a GCB phenotype and 83 with a non-GCB phenotype (n = 157). Overall, 71% and 75% of the cases over-expressed Bcl-2 and Bcl-6, respectively. Bcl-2 protein was expressed in 70% GCB cases and 73% non-GCB (p= 0.72). Bcl-6 was expressed in 96% GCB cases and 63% non-GCB cases (p&lt;0.0001). In univariate analysis, the addition of R was associated with a better prognosis in the non-GCB cases (p=0.02), but not in the GCB cases (p=0.3). This survival difference was not solely explained by either Bcl-2 or Bcl-6 expression. The addition of R to CHOP chemotherapy and IPI were independent predictors of OS in non-GCB DLBCL (p=0.02; p=0.016, respectively). The addition of R was also of prognostic importance in the lymphomas over-expressing Bcl-2 (p=0.0081). Conclusion: Immuno-chemotherapy using CHOP-R is associated with better OS in DLBCL, due largely to its effect on the non-GCB subgroup. Although Bcl-2 expression does not contribute to the determination of COO distinctions, the OS of Bcl-2-positive DLBCL patients is significantly improved by the addition of R. These results provide insight into the possible mechanisms by which R exerts its beneficial therapeutic effect. Overall Survival for 157 DLBCL Based on Cell of Origin Overall Survival for 157 DLBCL Based on Cell of Origin

Efficacy of High-Dose Sequential Chemotherapy and Autograft for Transformed Non Hodgkin’s B Cell Lymphoma: Results of a Retrospective Analysis from GITIL (Gruppo Italiano Terapie Innovative nei Linfomi).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3440-3440
Author(s):  
Massimo Di Nicola ◽  
Liliana Devizzi ◽  
Alessandro Rambaldi ◽  
Manuela Zanni ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Bulky Disease ◽  
Number Of Patients ◽  
Sequential Administration ◽  
Histological Transformation ◽  
The Impact

Abstract Background - Follicular lymphoma (FL) transforms in a more aggressive lymphoma in 25–60% of patients representing the outgrowth of a more malignant subclone. Transformation is usually associated to a rapidly progressive clinical course, refractoriness to treatment, and short survival. To define the impact of high dose sequential (HDS) therapy and peripheral blood stem cell (PBSC) autograft on outcome of transformed FL (TFL), we analyzed a consecutive series of 66 pts with a confirmed diagnosis of TFL registered at the GITIL centers from March 1988 to September 2004 and treated with the HDS regimen. Methods - Biopsy-proven histological transformation (HT) in diffuse large B cell lymphoma (DLBCL) was observed at diagnosis (n=24; 36%) or at relapse after a treatment for FL (n= 42; 64%). Main patient characteristics were as follows: male/female 36/30; median age 51 yrs (range 33–66), stage I-II/III-IV 8/58, IPI score 0–1/≥2 28/38. HDS regimen included: i. 3 APO or 3 DHAP courses (for patients relapsed after anthracycline-containing regimens); ii. sequential administration of hd-CTX (7g/mq), hd-Ara-C, (2g/mq q12h for 6 days) hd-Etoposide (2.4 g/mq), with PBSC harvests following hd-CY and hd-Ara-C; iii. myeloablative regimen with hd-Mitoxantrone/L-Pam (n=28) or BEAM (n=28 pts who could not receive additional anthracycline), or TBI-PAM (n=3); iv. PBSC autograft; v. consolidation radiotherapy on bulky disease. From January 1999, hd-CTX and hd-Ara-C has been supplemented with Rituximab (RHDS; n=34) with in-vivo purging intent. Results - Overall 59 patients achieved a complete remission (CR; 89%), 1 patient responded partially and underwent allogeniec bone marrow transplantation, 6 patients died for progressive disease while on therapy (PD; 9%). With a median follow-up of 67 months (range 23–170), 42 patients are alive (63.6%), 24 patients relapsed and died for progressive disease (n= 23) or toxicity (n= 1). Five-year event free survival (EFS) and overall survival (OS) are 53.0% and 63.6%, respectively. No significant differences in OS and EFS were observed between patients with HT at diagnosis or at relapse, with IPI O-1 vs IPI >2. Of note, pts treated with R-HDS showed an improved clinical outcome (OS: 76% vs. 50%; EFS: 67.6 vs. 37.5 respectively), with a large difference that did not reach statistical significance because of the limited number of patients. Conclusion - Our data strongly suggest that HDS regimen, in particular when supplemented with rituximab (R-HDS), is a very effective regimen in transformed B cell lymphoma.

Autologous Stem Cell Transplantation (ASCT) for Elderly Patients (≥ 60 Years) with Non-Hodgkin’s Lymphoma (NHL): An Analysis Based on EBMT Registry.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1888-1888
Author(s):  
Esa Jantunen ◽  
Carmen Canals ◽  
Didier Blaise ◽  
Alessandro Rambaldi ◽  
Herve Tilly ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Performance Status ◽  
Poor Performance ◽  
B Cell Lymphoma ◽  
Poor Performance Status ◽  
Significant Prognostic Factor ◽  
Bulky Disease ◽  
Stem Cell Source ◽  
Mantle Cell

Abstract Limited data is available on feasibility and efficacy of ASCT in elderly patients with NHL. Patients: In 2000–2005 15869 NHL patients with ASCT were reported to EBMT database, 3133 (20%) were ≥ 60 years. Only patients with MED-B dataset and those with either diffuse large B-cell lymphoma (DLBCL), mantle cell (MCL) or follicular lymphoma (FL) were subjected to more detailed analysis. This group included 906 elderly NHL patients (median age 63 years, range 60–75) (DLBCL, n = 463; MCL, n = 208; FL, n = 235) who were compared with 3661 patients &lt; 60 years (DLBCL, n = 2149; MCL, n = 435; FL, n = 1077) regarding outcome. Bulky disease was more common in younger patients (26% vs. 15%, p &lt; 0.001) as well as B-symptoms at diagnosis (42% vs. 36%, p = 0.02). Elderly patients had received more often at least two treatment lines before ASCT (70% vs. 59%, p&lt;0.001). The median follow-up for the surviving patients was 14 months. Results: Non-relapse mortality (NRM) was higher in patients ≥ 60 years of age: 3.8% vs.2.3% at 100 days, 6.9% vs. 3.9% at 1 year and 9.4% vs. 5.8% at 3 years (p&lt;0.001). No differences in NRM were observed between patients aged 60–64 years (n = 633) and those aged 65–69 (n = 240). A higher NRM was observed in DLBCL and MCL patients compared to FL patients (p=0.001and p=0.002, respectively). Other variables associated with a higher NRM were an elevated LDH at diagnosis (p=0.04), ≥ 2 treatment lines before ASCT (p&lt;0.001); a poor performance status at ASCT (p&lt;0.001); not being in CR1 at ASCT (chemosensitive disease vs. CR1, p=0.02; chemorefractory disease vs. CR1, p&lt;0.001) and BM as stem cell source (p=0.02). In multivariate analysis, elderly patients showed a higher NRM [RR = 1.6 (CI 1.2–2.1), p=0.001]. In patients with DLBCL, age ≥ 60 years at ASCT was associated with a trend to a higher risk of relapse or progression (p =0.07) and a worse PFS (p=0.008). PFS at 2 years was 69% vs. 79% for patients in CR1 and 52% vs. 60% for patients with sensitive disease at ASCT, respectively. In MCL, elderly patients had worse PFS (p=0.008). PFS at 2 years was 78 vs. 81% for MCL patients in CR1 and 52% vs. 67%, respectively for those patients autografted with sensitive disease. Older age was not a significant prognostic factor either for relapse rate or for PFS in patients with FL. PFS at 2 years was 69% and 81% for FL patients in CR1, and 69% and 69% for FL patients with sensitive disease, respectively. Conclusions: ASCT is feasible in selected NHL patients aged 60–69 years. The outcome is promising taking into account the generally poorer prognosis of lymphomas in elderly population.

Outcome and Prognostic Index for Reduced-Intensity Allogeneic Stem Cell Transplantation (RIST) for Elderly Patients with De Novo Acute Myeloid Leukemia (AML): A Study From the AML Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1918-1918
Author(s):  
Heiwa Kanamori ◽  
Takahiro Fukuda ◽  
Shuichi Taniguchi ◽  
Masashi Sawa ◽  
Tadakazu Kondo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
De Novo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Prognostic Index ◽  
Risk Groups ◽  
Stem Cell Source ◽  
Reduced Intensity

Abstract Abstract 1918 Background: Reduced-intensity allogeneic stem cell transplantation (RIST) has become more common in elderly patients with acute myeloid leukemia (AML). To clarify the clinical significance of RIST from an HLA-identical donor in elderly patients and identify prognostic factors, we retrospectively surveyed AML patients receiving RIST who were registered in the JSHCT database. Patients and Methods: This study included de novo AML patients aged ≥50 years who received fludarabine-based RIST as the first transplantation between 2000 and 2009. The conditioning regimen was classified as fludarabine-based reduced intensity conditioning if it included non-myeloablative chemotherapy (total dose of busulfan ≤ 8 mg/kg or melphalan ≤ 140 mg/m2) with or without total body irradiation (TBI) ≤ 6 Gy. Results: There were a total of 396 patients, including 146 in first complete remission (CR1), 111 in ≥CR2, and 139 in non CR. Their median age was 58 years (range: 50–73 years), with 255 males and 141 females. Conditioning regimens contained fludarabine combined with melphalan (FM, n=171) or busulfan (FB, n=225, including oral busulfan [n=115] and intravenous busulfan [n=110]). TBI was used in 178 patients. Bone marrow from related donors was transplanted in 59 patients, as well as peripheral blood stem cell from related donors in 134 and bone marrow from unrelated donors in 203. Primary graft failure occurred in two patients and death before engraftment was observed in 14 patients. Granulocyte engraftment was confirmed after a median of 16 day. The incidence of grade II-IV and grade III-IV acute GVHD was 38% and 12%, respectively. After a median follow-up of 19 months (range: 1–113 months), 5-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) was 45%, 41%, 37%, and 22%, respectively. There were no differences in OS according to stem cell source or conditioning regimen. On univariate analysis for all patients, pre-transplant factors associated with worse 5-year OS included age (≥60 years old) at transplantation (vs 50–59 years old: 36% vs 51%, p=0.003), non CR (vs CR: 20% vs 59%, p<0.001), and unfavorable karyotype (SWOG/ECOG) (vs others: 36% vs 49%, p=0.005). Non CR (vs CR: 59% vs 25%, p<0.001), FB (vs FM: 42% vs 32%, p=0.040), and unfavorable karyotype (vs others: 64% vs 51%, 0.006) were significantly correlated with higher 5-year CIR. Adverse factor for NRM was not detected in the pre-transplant variables. Furthermore, according to multivariate analyses for outcomes, recipient age (≥60 years old), disease status at transplantation (non CR), and karyotype (unfavorable) were each assigned a score. The sum total was tested as a prognostic index based on four risk groups: low (score=0), intermediate (score=1), high (score=2), and very high (score=3). The 5-year OS of the low- (n=143), intermediate- (n=153), high- (n=63), and very high- (n=19) risk groups was 66%, 41%, 26%, and 14%, respectively (p<0.001). The 5-year CIR of each groups was 22%, 37%, 52%, and 75% (p<0.001), but there were no differences in NRM. The prognostic index was also useful for subgroups classified with stem cell source or conditioning regimen. Moreover, chronic GVHD was an important post-transplant event for OS and CIR. Patients with chronic GVHD (n=150) showed better outcomes compared with those without chronic GVHD (n=173) in 5-year OS (57% vs 50%, p=0.017) and CIR (25% vs 42%, p<0.001). Conclusions: This retrospective survey suggested that fludarabine-based RIST from HLA-identical donors is a promising strategy for elderly patients with AML and graft-versus-leukemia effects due to chronic GVHD contribute to long-term outcomes. The prognostic index including age and disease risk for RIST may be helpful to stratify patients for clinical research, although studies in other cohorts are necessary for validation. Disclosures: No relevant conflicts of interest to declare.

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