First Line Treatment of Aggressive Cutaneous NK/T Cell Lymphomas Based on High Dose Cytarabine and Stem Cell Transplantation Does Not Lead to Durable Remissions.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4669-4669
Author(s):  
C.J.M. Halkes ◽  
M.H. Vermeer ◽  
E.M. Noordijk ◽  
R. Willemze ◽  
Roelof Willemze
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Nk T Cell ◽  
First Line Treatment

Abstract Aggressive cutaneous NK/T-cell lymphomas are extremely rare with an estimated yearly incidence of less than 1 per 2,000,000 and a disease-specific 5 year survival of 0–16%. This dismal prognosis seems independent of the presence of extracutaneous localizations at diagnosis. Only a minority of patients respond to CHOP-like multiagent chemotherapy. Sustained complete remissions (CR) have been observed after stem cell transplantation of some heavily pre-treated patients. We hypothesized that stem cell transplantation may be the only treatment modality that may induce long term remissions in this very resistant disease. In order to get as many possible patients eligible for a stem cell transplantation we designed an intensive protocol in which patients with newly diagnosed aggressive cutaneous NK/T-cell lymphoma were treated with AML-like induction and consolidation courses followed by an allogeneic or an autologous stem cell transplantation. All patients with newly diagnosed aggressive cutaneous NK/T-cell lymphoma who were referred to our centre between 06-2003 and 06-2006 were screened for this study. Patients who were able to undergo this intensive therapy, were enrolled after informed consent. Induction treatment consisted of etoposide 120 mg/m2 and amsacrine 115 mg/m2 on days 1 and 7, methylprednisolone 60 mg/m2 on days 1–7, intrathecal methotrexate on day 1 and cytarabine on days 1–6: either 1000 mg/m2 twice daily (age <61) or 100 mg/m2 daily (age > 60). In case of partial remission (PR), induction treatment was repeated. In case of CR, consolidation treatment was given consisting of amsacrine and etoposide in similar doses as during induction, and cytarabin 3000 mg/m2 twice daily on days 1–4 or 300 mg/m2 twice daily on days 1–4 in older patients. In case of persisting CR after consolidation therapy, patients were eligible for allogeneic stem cell transplantation with total body irradiation (TBI) and high dose cyclophosphamide as conditioning regimen. In the absence of a HLA matched donor, autologous transplantation was planned. Six patients (3 males, 3 females) were treated for cutaneous peripheral T cell lymphoma not otherwise specified (n=3), cutaneous blastic NK cell lymphoma (n=2) or cutaneous NK-T cell lymphoma, nasal type (n=1). Mean age was 52 years (range 33–65). In two patients no extracutaneous localizations were found. After induction treatment two patients had progressive disease, and one patient showing PR died suddenly during leukopenic period after the second induction cycle. Three patients achieved the CR. One of them died due to an intracerebral hemorrhage just before transplantation. Two patients underwent stem cell transplantation (one autologous and one allogeneic) but both relapsed, 204 and 218 days after transplantation, respectively and died within weeks. Median overall survival was 214 days (range 30–382).First line treatment of aggressive cutaneous NK/T cell lymphoma using an intensive AML-like chemotherapy approach resulted in CR in 3 out of 6 patients. Only two of them reached a stem cell transplantation, but both patients died of relapsing disease. Based on these outcomes, first line treatment of aggressive cutaneous NK/T-cell lymphoma consisting of AML-like induction and consolidation therapy did not result in durable remissions, necessary to perform stem cell transplantation.

scholarly journals Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value

2003 ◽  
Vol 14 (11) ◽  
pp. 1673-1676 ◽  
Author(s):  
W.Y. Au ◽  
A.K.W. Lie ◽  
R. Liang ◽  
Y.-L. Kwong ◽  
C.-C. Yau ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
Progress Report ◽  
T Cell Lymphoma ◽  
Nk T Cell

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.

scholarly journals A Single-Center Retrospective Clinical Study of Chidamide in the Treatment of Adult Peripheral T-Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4551-4551
Author(s):  
Maogui Hu ◽  
Kaiyang Ding ◽  
Dongyao Wang ◽  
Xinchen Wang ◽  
Xiaoyu Zhu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Maintenance Treatment ◽  
Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
First Line Treatment

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive non-Hodgkin's lymphomas (NHL) with high heterogeneity. The first-line treatment commonly used for firstly-diagnosed PTCL is the CHOP-like regimen. However, in addition to ALK+ALCL, these regimens present poor long-term survival rate in other subtypes, mostly less than 30-40%. Even with the consolidation of autologous hematopoietic stem cell transplantation, studies have reported that the 5-year overall survival rate is barely about 50%. Therefore, for PTCL patients who have achieved remission and undergone autologous hematopoietic stem cell transplantation, there is an urgent need to explore a maintenance treatment strategy. Chidamide is an oral type of selective HDAC inhibitor with subtype specificity for HDAC 1, 2, 3, and 10. It has a regulatory effect on abnormal epigenetic functions of tumors and a novel induction and activation of cellular immune function. In China, it has been approved for relapsed or refractory PTCL at a dose of 30 mg/time, twice a week. The study of chidamide has proved its satisfactory efficacy and safety characteristics for PTCL again. This study preliminarily evaluates the near term effects of chidamide combined with chemotherapy in the first-line treatment and maintenance value of PTCL through retrospective analysis. Methods: We collect adult peripheral T-cell lymphomas inducing by CHOP-like regimen with chidamide or not. The complete response rate (CR), objective response rate (ORR), progression-free survival time (PFS) and overall survival time (OS) of patients in the combined chidamide group and non-combined group were separately analyzed and evaluated. Meanwhile, the OS in the chidamide-maintenance and non-chidamide maintenance of the PTCLs were also brought to study. Results: A total of 82 patients recruited, with a median age of 60 years (14-79 years), including 45 peripheral T-cell lymphoma (PTCL-NOS), 23 angioimmunoblastic lymphoma (AITL), 14 anaplastic large cell lymphoma (ALCL), and the follow-up time cutoff was April 30, 2021. Among 82 patients, 39 patients were treated with chidamide+CHOP-like as the first-line treatment, and 43 patients were treated with CHOP-like as the first-line treatment. The CR rate of the first-line combined chidamide group was 62%, and the ORR was 87%. The CR rate of the first-line non-combined chidamide group was 42% and the ORR was 74%. There was no significant difference in CR rate and ORR between the two groups, but the CR rate has potential clinical benefits. The median PFS of the combined chidamide group was longer than that of the non-combined group by 8 months (18.9m VS 10.9m), but there was no significant statistical difference (p=0.255). Among 82 patients, regardless of first-line treatment or salvage treatment, 42 patients in the maintenance treatment group of chidamide did not reach the median OS, and the median OS of 40 patients in the non-maintenance group was 18.9 months. The difference between the groups was statistically significant (p <0.001). There were totally 66 patients responding to the first-line treatment (CR+PR). 8 patients with sequential autologous stem cell transplantation (ASCT), 34 patients with chidamide maintenance treatment, and both groups didn't reach the median OS. The third group including 24 patients who did not undergo ASCT or chidamine maintenance presenting a median OS of 45.5 months. However, due to the limitation of follow-up time, the difference between the groups was not statistically significant, but the first two groups showed a trend of clinical benefit, which requires further follow-up. During the follow-up period, 48 patients had disease progression with first-line treatment, 23 patients had disease progression using combined chidamide as salvage treatment, and 25 patients in the non-combined chidamide group suffered disease progression. There was a statistically significant difference in OS between the groups (mOS: less than 11.8 months of VS, p =0.03). Subgroup analysis showed that chidamide maintenance treatment in the PTCL-NOS group provided a significant improvement in the prognosis (mOS: 21m VS 5.6m). Conclusion: It preliminarily suggested that chidamide maintenance therapy for PTCL provided an ideal survival benefit, especially In patients with PTCL-NOS subtypes. First-line treatment combined with chidamide and chidamide maintenance therapy may improve the poor survival prognosis. Disclosures No relevant conflicts of interest to declare.

Phase II/III randomized trial of CID-ATT with radiotherapy compared with CHOP with radiotherapy as first-line treatment for previously untreated early staging extranodal NK/T-cell lymphoma, nasal type (ENKL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
Tongyu Lin ◽  
He Huang ◽  
Chao Yong Liang ◽  
Chengcheng Guo ◽  
Ying Tian ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Chop Regimen ◽  
Nasal Type ◽  
Nk T Cell ◽  
First Line Treatment

8508 Background: Extranodal NK/T cell lymphoma, nasal type (ENKL) is more prevalent in Asia and has worse prognosis than B-NHL. No therapeutic strategy is currently identified for ENKL. This phase II/III study was undertaken to compare CHOP-B/IMVD/DHAP-Alternating Triple Therapy (CID-ATT) and standard CHOP regimen as first-line treatment prospectively. Methods:109 patients (pts) initially diagnosed as ENKL (16-70 ys old) with Ann Abor Stage I to II were randomized to receive CID-ATT or CHOP regimen from Jan 2006 to Jan 2012. CID-ATT alternated among CHOP-B, IMVD, and DHAP, given in alternating sequence for a total of 6 courses (2 circle). Involved field radiation was administered after 6 courses(2 circle) of CID-ATT regimen or 6 cycles of CHOP regimen. All pts received prophylactic granulocyte colony-stimulating factor, interleukin-11and thrombopoietin for each DHAP cycle. Results: 109 pts were evaluable (54CID-ATT; 55 CHOP). With a median follow-up of 40.3months,OS and PFS was significantly prolonged with CID-ATT compared with CHOP (1yOS :80.2% vs 78.6%, 3yOS:68.0% vs 42.3%, 5yOS: 64.2% vs 34.5%,P=0.023; 1yPFS: 74.9% vs 59.6%, 3yPFS:60.5% vs 32.0%, 5yPFS: 60.5% vs 32.0% ; P=0.016). Compared to CHOP group, CID-ATT group has a much higher complete remission rate (CID-ATT:47/54,87.0 % vs CHOP:29/55,52.7%, P<0.001). The survivals for pts who achieved CR after One circle (3 courses) were significantly better than those who were in non-CR group.(5yOS: CR group in ATT:75.3%, non-CR group in ATT:51.5%, CR group in CHOP:39.3%, non-CR group in CHOP:31.0%; P=0.003). No treatment related death was observed, although Grade III/IV neutropenia (30/54,55.6%) and thrombocytopenia (33/54,61.1%) were observed in CID-ATT regimen, especially in DHAP cycle. Conclusions: Our study has demonstrated that the CID-ATT regimen as an optimal first-line therapy achieved promising clinical activity with safe and tolerated toxicity under close monitoring and good supportive care of untreated early staging ENKL pts. CR of induce chemotherapy following radiotherapy is very important for ENKL survival. Clinical trial information: CSWOG0002.

A Restrospective Review of Peripheral T-Cell Lymphoma in a Single Institution Between 2000 and 2010

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1623-1623
Author(s):  
Florence Broussais ◽  
Diane Coso ◽  
Vadim Ivanov ◽  
Thérèse Aurran ◽  
Anne-Marie Stoppa ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Induction Treatment ◽  
Single Institution ◽  
First Line ◽  
Allogenic Stem Cell Transplantation

Abstract Abstract 1623 Background: Peripheral T-cell non-hodgkin lymphomas (NHL) comprise a heterogeneous group of malignancies, characterized by an aggressive disease course and a poor clinical outcome. T-cell lymphomas present in lymph nodes and they also frequently involve extra nodal sites. The first line treatment consists in CHOP-like regimen. Consolidation treatment in first line or in relapse is autologous stem cell transplantation (ASCT) or allogenic stem cell transplantation (SCT). Patients and methods: We retrospectively analysed the data of 189 adults who had received chemotherapy in our institution between 2000 and 2010. Results: Median age at time of presentation was 55 (range 17–89) years, 76% were <65 years. 50% had B symptoms and 50% serum elevated LDH. ECOG was 0–1 in 60% and 2–4 in 40%. According to the Ann Arbor classification, 15% were stage I-II and 85% were stage III-IV. 50% had low IPI (0-1-2) and 50% had elevated IPI (3-4-5). The histologic subtypes were 42% peripheral T-cell NHL unspecified (PTCL-U), anaplastic large cell lymphoma (ALCL), 8% had ALK+ and 10% had ALK-, 24% angioimmunoblastic lymphoma (AILT), 3% transformed mycosis fungoide, 2% instestinal T-cell lymphoma, 2% hepatosplenic γδ T-cell lymphoma and 1% adult T-cell lymphoma/leukemia. Primary extranodal lymphoma represented 17% and 8% were diagnosed with hemophagocytosis. Five-year overall survival (OS) was 28.3% (21.8–36.8%), and five-year progression free survival (PFS) was 18.4% (13.1–25.7%). On multivariate analysis, ALCL-ALK+ (p=0.008), AILT (p<0.001), extranodal involvement (p=0.01), PS>1 (p<0.001), LDH>N (p=0.003) were independent adverse factors for OS. Moreover B symptoms (p<0.01) was a significant factor for PFS. 86% received CHOP-like induction treatment. The median number of chemotherapy was 2 (1–7). 59% experienced a complete response during the therapeutic procedure, while 22% were primary refractory. 44% had ASCT and 14% allogenic SCT. Only 28% of patients referred for allogenic SCT received this treatment. Conclusions: This 10-year review of patients treated in a single institution with initial conventional chemotherapy followed by more intensive treatments confirms the poor OS and PFS in the case of T-cell lymphoma. Despite a low incidence, T-cell lymphoma could be a priority area of research for new treatments with a potential to improve OS and PFS. Disclosures: No relevant conflicts of interest to declare.

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