Allogeneic Stem Cell Transplantation (Allo-SCT) for Relapsed/Refractory T Cell Lymphomas in Adults: A Survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3020-3020
Author(s):  
Steven Le Gouill ◽  
Jean-noël Milpied ◽  
Jean-paul Vernant ◽  
Norbert Ifrah ◽  
Françoise Mechinaud ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Disease Status ◽  
T Cell Lymphoma ◽  
Myeloablative Conditioning ◽  
Prognosis Factors ◽  
T Cell Lymphomas

Abstract Background: Adult mature T-cell and NK-cell neoplasms include several lymphomas entities. Taken together, T- and NK- cell lymphomas represent 10–15 % of non-Hodgkin’s lymphoma in adults, presenting with aggressive behaviour and poor outcome (except for ALCL ALK positif lymphomas). Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Therefore, allo-SCT is an attractive second-line strategy. We retrospectively analyzed T-cell lymphomas patients (lymphoblastic lymphomas were systematically excluded) reported to the SFGM-TC registry and transplanted from an HLA identical sibling donor with or without myeloablative conditioning regimen. Results: In the present intermediate report, we analysed 24 patients. Because of misdiagnosis, we excluded two cases. Among the 22 remaining patients, there were peripheral T-cell lymphoma NOS (PTCL) in 5 cases, angioimmunoblastic T-cell lymphoma (AITL) in 3 cases, anaplastic large cell lymphoma (ALCL) in 10 cases (ALK positif in 3 cases; negative in 2 cases and unknown in 5 cases; respectively), hepatosplenic g/d lymphoma (HSL) in 2 cases, T-cell granular lymphocytic leukemia (GLL) in 1 case and localized nasal NK/T cell lymphoma (NK/L) in one case. There were 15 males and 7 females. Median age was 38.5 years (15.5–54). All patients have been considered eligible for allo-SCT because of poor prognosis factors: HSL diagnosis in 2 cases, relapsed/refractory disease in 16 cases (including all ALCL cases) and/or failure to reach CR in 8 cases. Disease status at the time of transplantation was CR in 9 cases, PR in 7 cases and PD/refractory in 3 cases; respectively. All patients but 2 underwent myeloablative conditioning regimen prior to transplantation (TBI/EDX in 70%). The majority of patients (86%) received BMSC graft from related HLA-matched sibling donor. Median overall survival (OS) was 70 months for the all cohort. Median OS was not reached in the ALCL subgroup compared to 20 months for the non-ALCL subgroup. According to disease status, 7 out of 9 patients in CR at the time of transplantation are alive and in CR at the time of the analysis compared to 6 out of 13 in non-CR patients. Cause of death was AGVH in 2 cases, bacterial or fatal infections in 4 cases and relapse in 2 cases, respectively. Conclusion: these preliminary results show that allo-SCT is a treatment of choice for refractory/relapsed T-cell lymphomas. Results are very encouraging in relapsed/refractory ALCL patients and highlight the role of graft versus T-cell lymphoma effect. Further analysis are required to identify prognosis factors and additional cases will be analyzed at the time of the meeting.

Allogeneic stem cell transplantation (allo-SCT) in T-cell lymphomas: A French national survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8095-8095 ◽  
Author(s):  
S. le Gouill ◽  
N. Milpied ◽  
A. Buzyn ◽  
G. Socié ◽  
M. Mothy ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
T Cell Lymphoma ◽  
Myeloablative Conditioning ◽  
T Cell Lymphomas

8095 Background: T- and NK-cell lymphomas represent 10–15% of non-Hodgkin's lymphoma in adults.Despite intensive chemotherapy including or not autologous stem cell transplantation upfront, a majority of patients experience relapse. Methods: We retrospectively analyzed T-cell lymphomas patients transplanted from a related or unrelated HLA identical sibling donor with myeloablative or non-myeloablative conditioning regimen. Patients younger than 15 years at the time of transplantation, HIV positive patients or lymphoblastic lymphomas were excluded. We present the results of this study based on the SFGM-TC data-base. At the present time, we analyzed 57 cases from 10 french centers. Results: Diagnosis was PTCL (n=19) , AITL (n=8), anaplastic large cell lymphoma (ALCL) (n=20), hepatosplenic γ/d lymphoma (n=2), T-cell granular lymphocytic leukemia (n=1) and localized nasal NK/T cell lymphoma (n=3), NK/T cell lymphoma (n=1), HTLV1 cell lymphoma (n=2) and enteropathy-associated T-cell lymphoma (n=1). There were 38 males and 19 females. Median age at diagnosis was 38 years (13 - 61 y). At diagnosis, 51 patients had IPI score > or = 3. Median time from diagnosis to transplantation was 12 months (4.6–17). All patients but 15 underwent myeloablative conditioning regimen. Source of stem cells was BMSC (n=38), peripheral stem cells (n=18) or cord blood (n=1). Transplantation was performed from a related HLA-matched sibling donor in 53 cases. Disease status at the time of transplantation was CR in 25 cases, PR in 19 cases and SD/PD/refractory in 13 cases. Eleven patients presented acute GVH grade 3/4. After transplantation, 91% of patients were in CR compared to 43 % before. Six patients experienced relapse and eighteen patients died because toxicity related mortality. Conclusions: Preliminary results show that allo-SCT is an attractive option in aggressive T-cell lymphomas and confirm the role of a graft versus T-cell lymphoma effect. Ongoing analysis will identify prognostic factors and be presented at the time of the meeting. The present study will provide usefull tools for clinicians to evaluate the role of allo-SCT in the specific field of adult T- cell lymphomas. No significant financial relationships to disclose.

Efficacy of Allogeneic Stem-Cell Transplantation for T/NK-Cell Lymphomas in Adults.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3038-3038
Author(s):  
Steven Le Gouill ◽  
Noel-Jean Milpied ◽  
Agnes Buzyn ◽  
Regis Peffault de la Tour ◽  
Jean-Paul Vernant ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
T Cell Lymphoma ◽  
Nk T Cell

Abstract Mature peripheral T/Natural killer (NK)-cell neoplasms represent 10–15% of non-Hodgkin’s lymphoma (NHL) in adults. T/NK-NHL have a worst prognosis compared with B-cell lymphomas. Allogeneic stem cell transplantation (allo-SCT) is an attractive option for these patients. On behalf of the SFGM-TC group, we conducted a retrospective analysis and included seventy-seven T/NK-cell lymphoma patients. Diagnosis were: ALCL (n=27), Peripheral T-cell Lymphoma Not-Otherwise Specified (PTCL-NOS) (n=27), Angioimmunoblastic T-cell Lymphoma (AITL) (n= 11), Hepatosplenic g/d lymphoma (HSL) (n=3), T-cell granular lymphocytic leukemia (T-GLL) (n=1), nasal NK/T-cell lymphoma (nasal-NK/L) (n=3) case or non-nasal NK/T-cell lymphoma (non nasal-NK/L) (n=2), enteropathy-Type T-cell (n=1) and HTLV-1 lymphoma (n=2). Fifty-seven patients received myeloablative conditioning regimen prior allo-SCT. Donors were HLA-matched in 70 cases and related in 60 cases. Patients status at the time of allo-SCT was CR in 31 cases, PR in 26 cases and SD/PD in other cases. Five-year toxicity-related mortality (TRM) rate was 34%. Major cause of death was infection. Five-year OS and EFS rates were 57% and 53.3%, respectively. In a multivariate analysis, chemoresistance disease (SD, refractory or progressing disease at the time of allo-SCT and aGVHD grade III/IV were the only adverse prognostic factors for OS (p= 0.027 and p=0.033, respectively). Disease status at transplantation influenced EFS (p= 0.0032) and a HLA-mismatched donor increased TRM (p= 0.0386). A plateau was reached after one and a half year after allo-SCT. Only 5 out of 59 patients in CR after allo-SCT experienced a relapse. The 5-year OS rate for chemo-resistant patients was also encouraging. These patients were not curable with conventional approaches and near of one third have taken advantage of allo-SCT. Furthermore, two patients received DLI at relapse and they both reached a second durable CR. Taken together, this suggests that there is a graft versus T-/NK-lymphoma effect which may play a role in the curative potential of allo-SCT. we conclude that randomized clinical trials comparing allo-SCT versus conventional chemotherapy upfront for PTCL, aggressive AITL or histopathological subtypes (HSL, HTLV-1 lymphomas) have to be encouraged.

A Retrospective Comparison of Autologous Vs. Allogeneic Transplantation for Peripheral T-Cell Lymphoma: A Single Institution Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4392-4392
Author(s):  
Frederick Lansigan ◽  
Stuart Seropian ◽  
Dennis Cooper ◽  
Francine Foss
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Unrelated Donor ◽  
T Cell Lymphomas ◽  
First Remission

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.

Frontline Autologous Stem Cell Transplantation As Intensive Consolidation in Patients with Peripheral T Cell Lymphomas: Multicenter Phase II Trial in Korea

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4477-4477 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Yee Soo Chae ◽  
Sang Kyun Sohn ◽  
Jae-Yong Kwak ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Large Cell Lymphoma ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 4477 Peripheral T cell lymphomas (PTCLs) are an aggressive subtype of non-Hodgkins lymphoma and they have shown the shorter survival compared with B cell lymphoma. High-dose chemotherapy (HDT) followed by autologous stem cell transplantation (HDT/ASCT) for PTCLs has a potential meaning of consolidating remission for PTCLs. However, the effectiveness of ASCT on distinct conditioning regimens, the optimal transplant timing in the frontline or relapsed are still unclear. We investigated the clinical outcomes of HDT/ASCT as frontline intensification in 46 patients with newly diagnosed PTCLs except ALK(+) anaplastic large cell lymphoma. Patients underwent ASCT with a uniform conditioning regimen (busulfex, cyclophosphamide and etoposide). The median age was 47 years (17–65). The histological subtypes were 47.9% PTCL-NOS (n=23), 18.8% anaplastic large cell lymphoma (n=9), 4.2% angioimmunoblastic T cell lymphoma (n=2), 25% extranodal NK/T cell, nasal type (n=12), 2.1% hepatosplenic T cell lymphoma (n=1) and 2.1% enteropathy-associated T cell lymphoma. Thirty patients (62.6%) presented with advanced stage disease (III/IV) and 16 (33.3%) had B symptoms. At diagnosis, 21 patients (43.8%) were classified as high-intermediate/high risk by the age-adjusted IPI (aaIPI) and 10 (20.9%) were classified as high-risk (more than 2 factors) by the prognostic index for PTCL (PIT). Thirty-one patients (67%) could undergo HDT/HSCT and disease status at pretransplant consisted of 23 patients (50 %) with CR and 8 patients (17.4%) with PR. 6 out of 8 patients with PR at pretransplantation improved the response to CR after HDT/ASCT. There was no significant difference of the response rate between CHOP alone or CHOP-like chemotherapy and non-anthracycline-based chemotherapeutic regimen. At a median follow-up of 32.9 months, 23 patients (50%) are alive. The 5-year probability of overall and progression-free survival (PFS) was 48.2 ± 8.1 % and 47.4 ± 8.1%, respectively. However, the 5-year OS and PFS rate in transplanted patients was 57.3± 10.2 % and 55.3 ± 11.3 %, respectively. Conclusion: Frontline HDT/ASCT in patients with PTCL could be performed with a high response rates and a substantial impact on improving outcome for PFS. Our findings also indicate that busulfex, cyclophosphamide and etoposide is a feasible conditioning regimen in ASCT for PTCLs. Disclosures: No relevant conflicts of interest to declare.

Treatment of Enteropathy Associated T Cell Lymphoma with Combination Chemotherapy Followed by Autologous Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5424-5424
Author(s):  
Mark J. Bishton ◽  
Andrew P. Haynes ◽  
Jenny L. Byrne ◽  
Nigel H. Russell
Keyword(s):  
Weight Loss ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Coeliac Disease ◽  
Autologous Stem Cell Transplantation ◽  
Combination Chemotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas

Abstract Background: Enteropathy associated T cell lymphoma (EATL) accounts for less than 1% of all Non-Hodgkins lymphomas and ~5% of gastro-intestinal lymphomas, and is strongly associated with Coeliac disease. Treatment has traditionally involved Doxorubicin based combination chemotherapy such as CHOP although there is no consensus on guidelines for treatment. Patients are often emaciated due to malabsorbtion at diagnosis and often tolerate treatment poorly with death occurring due to perforation and gastro-intestinal bleeding. There appears to be a high relapse rate in those who complete treatment, and overall survival rates are agreed to be around 20% at 5 years. Methods: Consecutive patients with biopsy proven Enteropathy associated T cell lymphomas were treated in a single institution. All patients were made nil by mouth, and given intra-venous fluids with oral ciprofloxacin and metronidazole as gut prophylaxis 48 hours prior to chemotherapy. When the risk of perforation was considered to be over continuous NJ feeding was instituted with regular dietetic support. 2 cycles of a combination of Ifosphamide, Etoposide and Epirubicin (IVE) were given 4 weeks apart. Patients had peripheral blood stem cells mobilised with G-CSF support following the second cycle. After stem cell harvest 2 cycles of high dose methotrexate (3g/m2) with folinic acid rescue were given. Following this, patients were admitted for consolidation with autologous stem cell transplantation with BEAM conditioning. Results: The median age of the patients was 56 years (40–59). 5 were diagnosed following laporotomy and small bowel resection and one by lymph node biopsy. All but 1 patient had stage 1E disease. 3 were known to have coeliac disease previously while 3 were diagnosed post-operatively. All 6 patients were able to tolerate the planned treatment with no deviation from protocol and there was no transplant related mortality. There were no episodes of perforation or GI bleeding. One patient was unable to be harvested due to sepsis and was mobilised with G-CSF alone prior to methotrexate being given. All patients suffered with severe diarrhoea and weight loss ranging from 5–11 kilograms during their autograft, despite continuous parenteral feeding. Standard CT restaging showed five patients achieved a complete remission (CR) and one other a very good partial response (VGPR). Of the 6 patients, 2 had florid relapse at 0.21 and 1.71 years post PBSCT and subsequently rapidly died due to intestinal perforation. The other 4 remain alive and in CR at 1.83, 3.35, 3.67 and 4.32 years following transplant respectively. Conclusion: EATL is a rare extra-nodal T cell lymphoma with a very poor prognosis with standard treatment, and large case series take many years to build. EATL is also often added to series of other high-grade T cell lymphomas or GI non Hodgkin’s lymphomas, making it difficult to determine optimal management. In our series of patients there were no serious complications following gut sterilisation and induction and consolidation chemotherapy, and despite marked weight loss all were able to tolerate PBSCT. 4 out of 6 patients (66.7%) remain alive and in a sustained CR, while 2 suffered an early relapse and rapidly died. We conclude that this regimen appears to be extremely efficacious in the treatment of EATL.

scholarly journals Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Harinder Gill ◽  
Raymond H. S. Liang ◽  
Eric Tse
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Nasal Type

The World Health Organization (WHO) classification recognizes 2 main categories of natural killer (NK) cell-derived neoplasms, namely, extranodal NK/T-cell lymphoma, nasal type, and aggressive NK-cell leukaemia. Extranodal nasal NK/T-cell lymphoma is more frequent in the Far East and Latin America. Histopathological and immunophenotypical hallmarks include angiocentricity, angiodestruction, expression of cytoplasmic CD3 epsilon (ε), CD56, and cytotoxic molecules and evidence of Epstein-Barr virus (EBV) infection. Early stage disease, in particular for localized lesion in the nasal region, is treated with chemotherapy and involved-field radiotherapy. On the other hand, multiagent chemotherapy is the mainstay of treatment for advanced or disseminated disease. L-asparaginase-containing regimens have shown promise in treating this condition. The role of autologous hematopoietic stem cell transplantation is yet to be clearly defined. Allogeneic hematopoietic stem cell transplantation, with the putative graft-versus-lymphoma effect, offers a potentially curative option in patients with advanced disease.

Autologous stem cell transplant in peripheral T cell lymphomas: Single institution 10-year retrospective analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19538-e19538
Author(s):  
C. E. Vigil ◽  
E. Ayala ◽  
L. Sokol
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Retrospective Analysis ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Disease Status ◽  
Autologous Stem Cell Transplant ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma

e19538 Background: Peripheral T-cell lymphoma is a rare entitydisease, compromising 10% of non-Hodgkin's lymphoma worldwide and 5% of all lymphoid neoplasms in the United States. The long-term survival of conventional therapies has led the exploration of alternatives. High-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, has been explored in recent years with little experiences. We are reporting our single-institute data in this population. Methods: A retrospective analysis on patients with diagnosis of peripheral T-cell lymphoma receiving autologous stem cell transplant was conducted (January 1997 to July 2008). The patients were stratified according to their International Prognostic Index (IPI), disease status at the time of transplant and histology type. Results: Twenty-nine subjects were identified, with a median age of 51; 13 patients had Anaplastic T cell, 18 patient had PTCL-nos, and 6 patients with angioimmunoblastic T cell lymphoma. Seventeen patients (58.62%) presented with an aa IPI score greater than 2.4 patients were in complete remission, 15 at first relapse, 4 in greater than 1 episode, and 6 with refractory disease at the time of transplantion.Kaplan Meier overall survival (OS) 72 and relapse free survival (RFS) was 62 at 1 year respectively. A multivariate analysis and new risk stratification based on the IPI score system and disease status at time of transplant were employed. We found that the lower risk category demonstrated a higher likelihood of longer survival HR 3.4. However, such outcome was not statistically significant (p = 0.1360). Conclusions: The status at time of transplant with new methods for evaluation of minimal residual disease may help in assessing outcome. Larger prospective studies investigating innovative regimens is warranted. No significant financial relationships to disclose.

Assessment of FDG-PET Imaging in T-Cell and NK-Cell Lymphomas

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5305-5305
Author(s):  
Juan Chalapud-Revelo ◽  
Pedro Sobrevilla-Calvo ◽  
Cadena-Eumaña Carlos ◽  
Rivas-Vera Silvia ◽  
Lopez-Navarro Omar ◽  
...  
Keyword(s):  
T Cell ◽  
Fdg Pet ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Histological Subtypes ◽  
Cutaneous Lesions ◽  
Nasal Type ◽  
T Cell Lymphomas ◽  
Nasal Region

Abstract BACKGROUND: Malignant T-cell lymphomas are a heterogeneous group of disorders that frequently involve extranodal regions. Treatment and prognosis depend on accurate staging and histological evaluation. PET is widely used in staging and response evaluation of B-cell lymphomas, however, the use of FDG-PET have not been well studied for T-cell and natural killer cell lymphomas, and there is controversy if PET can detect accurately extranodal tumor activity. PATIENTS AND METHODS: We retrospectively evaluated FDG-PET in 38 patients with active T-cells, and T/NK-cells lymphoma diagnosed according to the World Health Organization (WHO) classification, from May 2007 to May 2008. We also evaluated the Standard Uptake values (SUV) according the different subtypes and the accuracy of PET in detecting tumor activity in the skin and nasal region. RESULTS: Histological subtypes included were extranodal NK/T-cell lymphoma nasal type (ENKL, n=12); Anaplastic T-cell lymphoma (ATCL, n=11); peripheral T-cell lymphoma (PTL, n=7); mycosis fungoides and Sezary syndrome (MF/SS, n=5), angioimmunoblastic (An=3). FDG-PET detected a lymphoma lesion in at least one site in 35 out of 38 patients (91%). The positivity rate was high in all histological subtypes ENKL 92%, ATCL 100%, PTL 86%, MF/SS 80%, A 100%. Among 13 patients who had cutaneous lesions only 7 had FDG-avid skin lesions (sensitivity =53.8% and specificity=100%) and among 11 patients with nasal region lesions, 91% had FDG-avid cutaneous lesions (sensibility = 91%, specificity=100%). The SUV Value in the different subtypes is shown in the table and there was not statistical differences between the groups (p= 0.067) Lymphoma N Mean SD(+/−) Range An 3 4.1 1.7 2.7–6 MF/SS 5 4.2 3.0 1.9–8.6 ATCL 11 8.3 5.3 1.6–20.8 PTL 7 3.5 1.6 2.2–6.0 ENKL 12 7.2 4.1 2.2–13.8 Total 38 6.35 4.3 1.6–20.8 CONCLUSIONS: Most of the T and T/NK cell lymphomas were detected by FDGPET. All cases, except one, of ENKL nasal type were FDG-avid, but only half of cutaneous lesions were detected by PET. In the whole T-Cell lymphomas group the mean SUV was 6.35, ATCL had the highest SUV, and we did not find any statistically differences between the groups. We conclude that PET has a high sensitivity for detection of active ENNK nasal type lymphomas and this information should be the basis for designing further studies to assess its value in staging, tumor response and as a prognostic factor.

Superior Survival with Allogeneic Compared to Autologous Stem Cell Transplantation in Patients with Aggressive T Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 680-680
Author(s):  
Sivesh Kathir Kathir Kamarajah ◽  
Behrad Barmayehvar ◽  
Ali Z Gondal ◽  
Ram Malladi ◽  
Sridhar Chaganti
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Free Survival ◽  
T Cell Lymphomas

Abstract Introduction: Aggressive T-cell lymphomas often carry poor prognosis. With the exception of ALK+ anaplastic large cell lymphoma (ALCL), median survival for most entities is < 3 years from diagnosis. Whilst stem cell transplant (SCT) consolidation is sometimes used in an attempt to improve survival, its role remains controversial. Encouraging results have been reported with both autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) but it is unclear if one is better than the other. To inform this debate, we set out to examine outcomes of patients receiving SCT consolidation for aggressive T-cell lymphomas at our institute over a 10-year period (between 2005 Ð 2015), comparing results of ASCT versus allo-SCT. Methods: Review of our transplant database identified 59 patients receiving SCT for T-cell lymphomas between the years 2005 - 2015. We excluded 4 patients with low grade T cell lymphomas (mycosisfungoides/sezarysyndrome) from analysis. A further 4 patients were excluded as they had 2 SCT procedures (ASCT followed by an allo-SCT). Thus, 51 patients were eligible for analysis; all having received a single SCT procedure (either ASCT or allo-SCT) for treatment of aggressive T-cell lymphoma. Results: Median age of the entire cohort at the time of transplant was 54 years (range 18-72 years) with 39 male and 12 female patients. The most frequent histologies were: ALCL (n=13), angioimmunoblastic T cell lymphoma (n=10) and high grade T-NHL/ peripheral T-cell lymphoma (PTCL) not further classified (n=16).Thirty sevenof 51 patients had advanced (stage 3 or 4) disease. Median overall survival (OS) and progression free survival (PFS) for the entire cohort were 67 and 23 months respectively. All 30 patients receiving ASCT were conditioned with the BEAM regimen. Of the 21 patients receiving an allo-SCT, sixteen patients had reduced intensity conditioning and 5 myeloablative conditioning with cyclophosphamide and total body radiotherapy. Stem cell source was sibling donor in 11 and unrelated donor in 10patients.Nineteenpatients received a T-cell depleted graft (17 within vivo campath and 2 with ATG). The ASCT and allo-SCT groups were comparable for several baseline variables including tumour stage, LDH, performance status and presence of B symptoms. The allo-SCT cohort was younger with only 24% being over the age of 60 compared to nearly 47% in the ASCT group (median age 45 vs 56.5 years). The allo-SCT cohort had a higher risk disease with only 14 of the 21 patients (68%) being in 1st / 2nd remission at the time of transplant compared with 27 of 30 (90%) in the ASCT group. Furthermore, 16/21 (76%) patients in the allo-SCT cohort received >2 lines of treatment prior to transplant compared to only 2 (7%) in the ASCT cohort. Three patients in the allo-SCT (14%) and 2 in the ASCT (7%) groups were not in remission at the time of SCT. The 5-year OS for the allo-SCT cohort (68%) was significantly superior to the ASCT cohort (36%) (p=0.01). Median OS was significantly superior for the allo-SCT compared to the ASCT cohort (NR vs 21 months, respectively; p=0.03). The 5-year PFS for the allo-SCT cohort (62%) was significantly superior to that of the ASCT (34%) cohort (p= 0.03). The median PFS for the allo-SCT cohort was superior compared to the ASCT cohort (79 vs 17 months, p=0.083). On Cox regression multivariate analysis, disease status at the time of transplant (1st remission vs 2nd remission vs beyond 2nd remission vs not in remission) was significant for predicting both OS and PFS. Prognosis was dismal for those not in remission at the time of transplant with survival of <12 months. Transplant type (Allo vs auto) was significant for OS (HR 0.087, p=0.001) but not for PFS. Conclusion: Our data suggests allo-SCT may confer a survival benefit compared with ASCT for patients with aggressive T-cell lymphomas. This novel observation has not been reported previously and if validated in a larger cohort will be practice changing. Figure 1 Cumulative overall survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 1. Cumulative overall survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 2 Progression free survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Figure 2. Progression free survival for the autologous (ASCT) and allogeneic stem cell transplant (allo-SCT) cohorts. Disclosures No relevant conflicts of interest to declare.

scholarly journals Histone Deacetylase Inhibitors Downregulate CCR4 Expression and Decrease Mogamulizumab Efficacy in CCR4-Positive Mature T-Cell Lymphomas

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 720-720
Author(s):  
Akihiro Kitadate ◽  
Sho Ikeda ◽  
Fumito Abe ◽  
Naoto Takahashi ◽  
Norio Shimizu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Research Funding ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Selective Inhibitor ◽  
T Cell Lymphoma ◽  
Lymphoma Cell ◽  
Class I ◽  
T Cell Lymphomas

Abstract Background: Histone deacetylase inhibitors (HDACis) are promising agents for various T-cell lymphomas, including cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL), and adult T-cell lymphoma/leukemia (ATLL). CCR4 is an important therapeutic target molecule because mogamulizumab, an anti-CCR4 antibody, has shown promising efficacy against CTCL, PTCL, and ATLL. However, their combined effects and interactions have not been examined thus far. We previously showed that CCR6, a chemokine receptor, is overexpressed in cutaneous T-cell lymphomas (Ito et al., 2014 Blood). Moreover, we recently demonstrated that HDACis downregulate CCR6 expression in advanced cutaneous T-cell lymphomas (Abe et al., 2017 Oncotarget). These reports lead us to hypothesize that HDACis might also downregulate CCR4 in various T-cell lymphomas. In this study, we clarify the effect of the combined use of mogamulizumab and HDACis on various T-cell and NK-cell lymphomas. Based on our findings, we discuss what benefits or adverse effects might be assumed for patients if these molecular targeting agents are used in clinical practice. Methods: We evaluated changes in CCR4 expression and antibody-dependent cell-mediated cytotoxicity (ADCC) activities against mogamulizumab- and HDACi-treated T-cell and NK-cell lymphoma lines and primary cases. To determine which HDAC mainly regulated CCR4 expression, we used isoform-specific HDACis and induced knockdown of respective HDACs for T-cell lymphoma cell lines. To examine the effect of CCR4 downregulation by HDACis in clinical cases, we examined the CCR4 expression of CTCL skin samples, which were obtained from the same patients before and after HDACi treatment (n = 6). Results: We first examined the expression of CCR4 for 15 T-cell and NK-cell lymphoma cell lines and a peripheral blood mononuclear cell (PBMC) sample derived from healthy donors to investigate the effect of vorinostat, a pan-HDACi, on CCR4 expression. The expression of CCR4 was mostly expressed in the (11 out of 15) cell lines: ATLL (MT-1, MT-2, MT-4, and TL-Su), CTCL (My-La, HH, and MJ), and NK/T-cell lymphoma cell lines (Kai3, SNK6, HANK1, and SNK10). We found that vorinostat decreases mRNA expression and surface expression of CCR4 except for the cell lines without CCR4 expression. Next, we used isoform-specific HDACis to examine which isoform of HDAC is involved in the regulation of CCR4. We used the following class-specific HDACis: romidepsin as a class I selective HDACi, CI-994 as an HDAC1/HDAC2-selective inhibitor, RGFP966 as an HDAC3-selective inhibitor, ricolinostat as an HDAC6-selective inhibitor, and PCI-34051 as an HDAC8-selective inhibitor. When these drugs were exposed to T-cell lymphoma cells, romidepsin and CI-994 strongly suppressed CCR4 expression. These results suggest that class I HDACs might controls CCR4 expression. We further performed knockdown experiments using siRNAs against HDAC1, HDAC2, and HDAC3. When we compared the expression change of CCR4 in HDAC-knockdown cells, HDAC2 knockdown cells showed the most significantly decreased expression of CCR4. These results suggest that class I HDACs, especially HDAC2, might be deeply involved in CCR4 expression regulation. When we examined the CCR4 expression in skin samples from primary CTCL, obtained from the same patients before and after vorinostat treatment, we found that CCR4 expression was greatly reduced after vorinostat treatment. Finally, when we conducted an ADCC assay with mogamulizumab by using various lymphoma cell lines and primary T-cell lymphoma samples, we found that the efficacy of mogamulizumab was significantly reduced by pre-treatment with vorinostat. Conclusion: Our results suggest that the primary use of HDACis before treatment of mogamulizumab might not be suitable to obtain synergistic effects. Moreover, these results provide potential implications for optimal therapeutic sequences in various CCR4 positive T-cell and NK-cell lymphomas. Disclosures Kitadate: Kyowa Kirin: Research Funding; Fujimoto: Research Funding; Eisai: Research Funding; Otsuka: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Asahi Kasei: Research Funding; Chugai: Research Funding; Toyama kagaku: Research Funding. Abe: Kyowa Kirin: Research Funding; Fujimoto: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Otsuka: Research Funding; Toyama Kagaku: Research Funding; Chugai: Research Funding; Asahi Kasei: Research Funding; Eisai: Research Funding. Tagawa: TaNeDS (Daiichi Sankyo): Research Funding.

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