scholarly journals Peripheral Blood Involvement By Flow Cytometry As a Prognostic Factor in Aggressive T Cell Lymphomas Following Autologous Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4055-4055
Author(s):  
Namrata S Chandhok ◽  
Scott F. Huntington ◽  
Iris Isufi ◽  
Lohith Gowda ◽  
Mina L Xu ◽  
...  

Introduction: Aggressive T cell lymphomas (TCL) are a heterogenous group of lymphomas that are frequently associated with poor outcomes. Autologous stem cell transplantation (ASCT) is recommended according to the NCCN guidelines and by practice standards for most subtypes as a consolidation for patients in first remission. A large prospective study of up-front ASCT by the Nordic Lymphoma group identified age, ECOG performance status <2, and bone marrow involvement as important prognostic factors. We have identified peripheral blood involvement by flow cytometry at diagnosis in up to one third of patients with aggressive TCL and analyzed whether this was a prognostic factor for outcomes after ASCT. Methods: We retrospectively analyzed data from consecutively treated patients (pts) with aggressive T-cell lymphomas who underwent ASCT at our institution from July 2009 to February 2019. Patient and disease characteristics were summarized using descriptive statistics. Kaplan-Meier analysis was used to estimate progression free survival (PFS) that was defined as the time from SCT to the first evidence of recurrence, and overall survival (OS) that was defined as the time from SCT to death or last institutional follow up with a hematologist. We collected data on age, co-morbidities, disease subtype, stage, response to therapy and treatment both pre and post SCT. Flow cytometry was obtained at diagnosis and phenotype of atypical circulating cells was compared with immunophenotype from tumor biopsy specimens. Results: 50 pts with TCL who received ASCT were identified for this analysis. Of this population, 41 (80%) of pts had peripheral blood flow available at the time of initial diagnosis. T-cell lymphoma types included peripheral T cell lymphoma not otherwise specified (PTCL NOS, 17 pts), angioimmunoblastic T cell lymphoma (AITCL, 15pts), ALK negative anaplastic large cell lymphoma (ALCL, 1pt), enteropathy-type T-cell lymphoma (EATL, 2pts), extranodal natural killer T-cell lymphoma (NKTCL, 2pts) and panniculitis like T cell lymphoma (2 pts) (Table 1). Median age of the cohort was 62 years (range 20-75 years) and all patients included had an ECOG PS 0-1 at the time of diagnosis. The majority had stage 4 disease (36/41, 87.8%), but analysis included a small number of patients with stage 2 (1/41, 2.4%) and stage 3 (4/41,9.7%) disease. Bone marrow involvement by morphologic criteria was noted on bone marrow biopsy in 8/41 (19.5%) pts; bone marrow was negative in 28/41 or 61% pts and not evaluated in 8/41 or 19.5% pts. Flow cytometry of peripheral blood performed as part of initial staging was positive for circulating malignant cells in 13/41 pts (31.7%) at the time of diagnosis. All patients underwent ASCT in first remission. The median PFS and OS were 15.2 and 29.9 months respectively in the flow positive group, while neither median PFS nor OS were reached in the flow negative group (Figures 1 and 2). Flow cytometry results from time of diagnosis was not strongly associated with PFS (log rank, p = 0.39), however, it was associated with overall survival (log rank, p = 0.012). There were 11 deaths in the cohort- 4 in the flow negative group and 7 in the flow positive group. Further, when bone marrow involvement was evaluated, 7 of 13 pts with positive flow cytometry (53.8%) and 5 of 28 (17.8%) pts with negative flow cytometry had BM involvement, suggesting a correlation between positive bone marrow and detection of lymphoma cells in the peripheral blood at the time of diagnosis. Conclusions: We demonstrate in our cohort of patients that detection of circulating lymphoma cells at diagnosis by flow cytometry was associated with a worse outcome in patients with aggressive T cell lymphomas undergoing ASCT as a consolidation in first remission. Larger cohorts will be needed to validate these findings, but these results suggest peripheral blood involvement by sensitive flow cytometry may identify patients with worse outcomes who might benefit from a more aggressive strategy such as allogeneic stem cell transplantation or alternative consolidation strategies. Disclosures Huntington: Bayer: Consultancy, Honoraria; Pharmacyclics: Honoraria; Celgene: Consultancy, Research Funding; DTRM Biopharm: Research Funding; Genentech: Consultancy; AbbVie: Consultancy. Isufi:Celgene: Consultancy; Novartis: Consultancy; Astra Zeneca: Consultancy. Foss:Seattle Genetics: Consultancy, Other: fees for non-CME/CE services ; Mallinckrodt: Consultancy; miRagen: Consultancy; Spectrum: Other: fees for non-CME/CE services ; Eisai: Consultancy; Acrotech: Consultancy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4652-4652
Author(s):  
Hongyan Tong ◽  
Feng Xiao ◽  
Tieying Dai ◽  
Jie Jin ◽  
Haitao Meng ◽  
...  

Abstract T-cell lymphoma is the special malignant type of non-Hodgkin’s lymphoma. The diagnosis and the treatment were usually troublesome for physician in clinical practice. We retrospectively reviewed 63 cases of T-cell lymphomas from 360 cases of lymphomas in our hospital during the period from January 2000 to July 2006. This study is to determine the clinicopathological characteristics of T cell lymphomas. The patients were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. The median follow-up duration was 5 months (range 21days to 36 months). There were slightly more males than females (36 versus 27), and the median age at the onset were 40 years (range 13 to 77 years). The major subtype was peripheral T-cell lymphoma, which accounted for 78% (49/63). Besides, there were 5 cases of anaplastic T large cell lymphoma, 3 lymphoblastic lymphoma, 2 T/NK-cell lymphoma, 2 angioimmunoblastic lymphoma, 1 mycosis fungoides and 1 pre-T cell lymphoma. The most common manifestation was fever, which accounted for 60% (38/63). 27% (17/63) patients presented with obvious enlargement of lymphonodes. Other manifestation included skin rash or phymata, pruritus, jaundice, abdominal pain, rhinorrhagia, puffiness, diarrhea, hoarseness and ulcus. Interestingly, we found that only 32% obvious enlarged lymphonodes could be confirmed by physical examination, hepatomegaly 33% and Splenomegaly 44% respectively. Besides, there were several significant laboratory findings: 40% cases had cytopenia of at least 2 cell lines, 68% had high level of LDH, 70% had elevated β2-microglobulin and 68% were detected T-cell receptor (TCR) and immunoglobulin heavy chain (IgH) gene rearrangement. Furthermore, 53% (33/63) patients had bone marrow involvement at the onset and 27% were diagnosed only by bone marrow biopsy. We also observed 20 cases of lymphoma associated hemophagocytic syndromes (LAHS). The median age for this disease was 37 year. The median life span was 39 days (range 21days to 10 months). The initial manifestations included fever (19/20), splenohepatomegaly (18/20), and cytopenias in all patients. Only 15% patients had enlargement of lymphonodes, which was suggested to be infrequent in LAHS. Immatural T-cell infiltration in bone marrow was detected in 75% (15/20) cases. Chromosome disorder of [der(21)(p11), −22] was detected in 3 cases. We also found that 2 cases which underwent plasmapheresis got much better after chemotherapy. 19 cases were under our follow-up. 17 patients could not survival longer than 6 months. The 6-month overall survival (OS) for LAHS was merely 2 of all 20. Furthermore, nobody survived more than 1 year, which indicated the poor prognosis of LAHS. There were 11 out of 63 cases had received trial chemotherapy including liposomal Doxorubicin, L-asparaginase, velcade, autologous bone marrow transplantation, or plasmapheresis before chemotherapy. The median survival time prolonged obviously from 2 months up to 8 months, which suggested the encouraging efficiency of these methods.


2015 ◽  
Vol 143 (2) ◽  
pp. 265-273 ◽  
Author(s):  
Noah A. Brown ◽  
Charles W. Ross ◽  
Johann E. Gudjonsson ◽  
Daniel Wale ◽  
Attaphol Pawarode ◽  
...  

Skin Cancer ◽  
2011 ◽  
Vol 26 (2) ◽  
pp. 134-138
Author(s):  
Norihiro SUZUKI ◽  
Daisuke SUZUKI ◽  
Atsushi FUJITA ◽  
Chiyo NOMURA ◽  
Kazuyasu FUJII ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss

Abstract Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of malignanices that represent 10–15% of non-Hodgkin lymphoma (NHL). This group has a worse prognosis with conventional chemotherapy compared to B-cell lymphomas. Both autologous (AutoSCT) and allogeneic stem cell transplantation (AlloSCT) have been used as consolidation in first remission and at relapse, but the role of transplantation has not been clearly defined. We report a retrospective analysis of 42 patients with PTCL who underwent AutoSCT (24) or AlloSCT (18) between 8/1997 and 12/2007. The AlloSCT group consisted of 4 PTCL unspecified (PTCLu), 3 angioimmunoblastic T-cell lymphomas (AITL), 2 panniculitic T-cell lymphomas, 2 cutaneous T-cell lymphomas (CTCL) with large cell transformation, 2 NK-cell lymphomas, 2 anaplastic large cell lymphomas (ALCL, 1 Alk+, 1 Alk unknown), 1 hepatosplenic T-cell lymphoma, 1 enteropathic T-cell lymphoma, and 1 refractory CTCL. The AutoSCT group consisted of 6 PTCLu, 12 ALCL (5 Alk+, 5 Alk−, 2 Alk unknown), 4 AITL, 1 CTCL with transformation, and 1 T-lymphoblastic lymphoma. The median age of the AlloSCT and AutoSCT groups was 51 (range 29–72) and 52 years (range 19–67), respectively. The median number of prior treatments of the AlloSCT and AutoSCT groups were 3 (range 1 to 5) and 1 (range 1 to 5), respectively. Within the AlloSCT group there were 14 matched-related donor transplants, and 4 matched-unrelated donor transplants; 7 were ablative and 11 were reduced-intensity transplants; the AlloSCT conditioning regimens varied. The AutoSCT group predominantly received BEAM as their conditioning regimen. Median time from diagnosis to AlloSCT or AutoSCT was 18.4 (range 6.9 to 109) and 7.5 (range 3.9 to 25) months, respectively. Median follow-up times for the AlloSCT and AutoSCT groups were 28.6 and 23.5 months, respectively. The day 100 transplant-related mortality rates in the AlloSCT and AutoSCT groups were 11% and 0%, respectively. Within the AlloSCT group the relapse and non-relapse mortalities were 11% and 33%, respectively. In the AutoSCT group, the relapse mortality was 33%. The 1- and 2-year overall survival (OS) rates were similar within the AlloSCT and AutoSCT groups (78% vs 74%, and 67% vs 60%, respectively). The 1- and 2-year progression-free survival (PFS) rates for the AlloSCT vs AutoSCT groups were 68% vs 52%, and 53% vs 45%, respectively (p = 0.28). Within the AutoSCT group, 14 patients (58%) were transplanted in first complete remission (CR1), and 10 (42%) in second complete remission (CR2), beyond CR2, or partial remission (PR). Patients in CR1 had significantly better PFS (57 vs 17 months, p=0.007) and OS (76 vs 29 months, p=0.004) than those in CR2, PR2, or beyond. Within the AlloSCT group, there was a trend toward poorer OS in 6 patients (33%) who had prior AutoSCT (32 vs 60 months, p=0.15). One patient (6%) was transplanted in CR1, and is still alive. We conclude that outcomes for AutoSCT are best in CR1. For patients with resistant or relapsed disease, AlloSCT should be strongly considered rather than AutoSCT. Prior AutoSCT may affect the outcome of AlloSCT. These results suggest that a prospective randomized trial comparing AutoSCT and AlloSCT for aggressive PTCL in first remission is warranted.


2014 ◽  
Vol 94 (6) ◽  
pp. 963-967 ◽  
Author(s):  
Zhiyuan Zhou ◽  
Changying Chen ◽  
Xiang Li ◽  
Zhaoming Li ◽  
Xudong Zhang ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (18) ◽  
pp. 2274-2274
Author(s):  
Hiromichi Matsushita ◽  
Dai Maruyama

Haematologica ◽  
2007 ◽  
Vol 92 (2) ◽  
pp. e24-e25 ◽  
Author(s):  
R.P. Falcao ◽  
E.G. Rizzatti ◽  
F.P. Saggioro ◽  
A.B. Garcia ◽  
A.F. Marinato ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1675-1675
Author(s):  
Brady E Beltran ◽  
Denisse Castro ◽  
Julio C Chavez ◽  
Eduardo M. Sotomayor ◽  
Jorge J. Castillo

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are rare hematologic malignancies with a poor prognosis when treated with current standard therapies. Several factors have been developed to prognosticate survival in PTCL patients; however, more refined, easy to use and reliable prognostic tools are needed. The neutrophil to lymphocyte ratio (NLR) has been reported prognostic in patients with diffuse large B-cell lymphoma (Troppan et al. BJC 2014). We have investigated the prognostic value of the NLR in the overall survival (OS) of patients with untreated PTCL. Methods: We included patients with a pathological diagnosis of PTCL who were diagnosed and treated at our institution between 2001-2013. We excluded cases with primary cutaneous PTCL, CNS involvement, and patients with >50% incomplete data. IRB approval was obtained prior to research. Pathological samples were reviewed by expert hematopathologists to confirm a diagnosis of PTCL. Pertinent clinicopathological data such as age, sex, performance status, LDH levels, stage, bone marrow involvement, extranodal sites of disease, PTCL subtype, and absolute neutrophil and lymphocyte countswere collected through chart review, and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the lymphocyte count, and dichotomized in NLR>=4 and NLR<4. The Prognostic Index for PTCL (PIT) was estimated using the clinical data above. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using Cox proportional-hazard regression models. Results: A total of 209 patients were included in our analysis from which 93 (44.5%) were PTCL, not otherwise specified (NOS), 83 (40%) were adult T-cell leukemia/lymphoma (ATLL), 22 (10.5%) were anaplastic large cell lymphoma (ALCL), 7 (3%) were extranodal NK/T-cell lymphoma (NKTCL), and 4 (2%) angioimmunoblastic T-cell lymphoma (AITL). The median age was 57 years (range 3-87 years) with equal distribution among men (52%) and women (48%). Poor performance status (ECOG >1) was seen in 85 (49%), elevated LDH levels in 116 (64%), >1 extranodal site in 31 (19%), bone marrow involvement in 64 (31%), and advanced stage (stage 3 and 4) in 151 (74%) of patients. Based on the NLR, 91 patients (59%) had NLR<4 and 62 (n=41%) had NLR>=4. Patients with NLR >=4 were more likely men (67% vs. 44%, p=0.005), and tended to present with elevated LDH (73% vs. 47%, p=0.002), advanced stage (87% vs. 61%, p=0.001) but lower bone marrow involvement (19% vs. 37%, p=0.02). There were no differences in age, performance status and number of extranodal sites. NLR>=4 was associated with a worse OS (HR 2.27, 95% CI 1.40-3.69; p=0.001). Specifically, NLR>=4 was associated with a worse OS in patients with non-ATLL PTCL (HR 2.99, 95% CI 1.67-5.37; p<0.001) but not in patients with ATLL (HR 1.16, 0.48-2.81; p=0.75). In the multivariate analysis, NLR>=4 was independently associated with worse OS when adjusting for the PIT score in non-ATLL PTCL patients (HR 2.12, 95% CI 1.06-4.26; p=0.03). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS in patients with untreated non-ATLL PTCL, independent of the PIT score. The NLR did not seem to be prognostic in ATLL patients. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with PTCL. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 91 (7) ◽  
pp. 63-69
Author(s):  
N G Chernova ◽  
Y V Sidorova ◽  
S Y Smirnova ◽  
N V Ryzhikova ◽  
E E Nikulina ◽  
...  

Aim: to determine molecular diagnostics routine for different tissue samples in angioimmunoblastic T-cell lymphoma. Materials and methods. Molecular studies were performed for 84 primary AITL patients. The median age was 61 year (29-81); the male to female ratio was 48/36. T-cell and B-cell clonality was assessed by GeneScan analysis of rearranged T-cell receptor (TCRG, TCRB) and immunoglobulin heavy chain genes. For the quantitative determination of cells with RHOA G17V mutation real - time polymerase chain reaction (PCR) with allele - specific LNA modified primers was used. Results. In lymph nodes rearrangements of T-cell receptor genes were determined in 76 (90.5%) of 84 patients and were absent in 8 (9.5%) cases. Identification of the same clonal products of the TCRG and TCRB genes in the lymph node and in peripheral blood and/or bone marrow indicated the prevalence of the tumor process and was observed in 64.7% of patients. Clonal products in peripheral blood and/or bone marrow different from those in the lymph node indicated reactive cytotoxic lymphocyte population and were noted in 58.8% of AITL cases. Simultaneous detection of T- and B-cell clonality in the lymph node was observed in 20 (24.7%) of 81 patients. Cells with RHOA G17V mutation were detected in lymph node in 45 (54.9%) of 82 patients. The use of allele - specific PCR with LNA modified primers revealed presence of the tumor cells in peripheral blood in 100% and in bone marrow in 93.9% of patients with G17V RHOA mutation in the lymph nodes. Conclusion. The validity of different molecular assays performed on certain tissue samples for the diagnosis of angioimmunoblastic T-cell lymphoma has been evaluated. Quantitative allele - specific PCR assay for RHOA G17V mutation based on LNA modified primers possesses sufficient sensitivity for tumor process prevalence evaluation and minimal residual disease monitoring.


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