Dismal outcome of t-cell lymphoma patients failing first-line treatment: results of a population-based study from the Modena Cancer Registry

2014 ◽  
Vol 33 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Irene Biasoli ◽  
Marina Cesaretti ◽  
Monica Bellei ◽  
Antonino Maiorana ◽  
Goretta Bonacorsi ◽  
...  
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1611-1611 ◽  
Author(s):  
Irene Biasoli ◽  
Marina Cesaretti ◽  
Stefano Luminari ◽  
Monica Bellei ◽  
Alessandra Dondi ◽  
...  

Abstract Abstract 1611 Introduction: For many T-cell lymphoma (TCL) patients (pts), current treatment strategies are largely ineffective. In particular, pts failing first line therapy are expected to have a dismal outcome but little is known about them. The purpose of this population-based study was to establish the outcome of TCL pts following relapse/progression. Material and methods: All TCL pts diagnosed in the province of Modena, Italy between January 1, 1997 and December 31, 2010 were identified from the archives of the Modena Cancer Registry that covers a population of approximately 600.000 people. Additional data on disease characteristics, treatment modalities, together with response assessments and outcome were actively retrieved and collected. Results: A total of 146 TCL pts were initially identified, and 18 excluded because of missing data; therefore 128 were available for the present analysis. The most common subtypes were Peripheral T-cell lymphoma not otherwise specified in 46 pts (36%), Anaplastic large T-cell lymphoma in 46 patients (36%) Angioimmunoblastic T-cell lymphoma in 15 (12%), and other subtypes in 21 (16%). The male to female ratio (M/F) for the entire population was 1.7 and the median age was 64 years (16–90). A total of 100 (78%) pts received initial treatment within 3 months of their diagnosis: 74 received combination chemotherapy (CT), 9 received radiation therapy (RT) only, 10 underwent surgery and 7 were addressed to high dose therapy and autologous stem cell transplant (ASCT) as part of initial therapy. Among the remaining 28 patients, 24 (19%) died within 3 months of their diagnosis and 4 (3%) received only palliative therapy because of their comorbidities. The majority of pts received anthracyclines (ADM) containing regimens as part of their initial therapy (71/74, 96%). At the end of first line treatment, 59 (59%) pts achieved complete remission (CR), 13 pts partial remission (PR), 8 pts stable disease (SD) and 20 cases had disease progression (PD). Overall, 59 pts presented relapse/progression; 23 (39%) of them died before receiving any salvage treatment, 14 pts received DHAP (7 of whom were subsequently addressed to ASCT), 8 received gemcitabine-containing regimens, 6 received ADM containing regimes and 8 other CT regimens; 2 patients were treated with RT. At a median follow-up for living patients after relapse/progression of 28 months (range 9–111 months), 49 patients died, and the cause of death was found to be lymphoma progression in all of them. The median overall survival (OS) following relapse/progression was 1.9 months. Among the 36 pts that received salvage treatment median OS was not reached for those who received ASCT and was 4.5 months for those who received conventional dose salvage treatment (p=0.003). A Cox regression analysis was performed in order to identify prognostic factors among these 59 pts: age at relapse (≥60 years, HR=2.35, CI95% 1.04–5.28, P=0.038) and advanced stage (HR=3.24, 1.31–7.98) were associated with a higher risk of death and salvage treatment ASCT was associated with a better survival (HR=0.04, IC95% 0.006–0.36). No other clinical characteristic (gender, histology, LDH and performance status) at diagnosis was associated with higher risk of death among relapsing/progressing patients. Conclusion: In the general population, outside clinical trials, the outcome of TCL pts is dramatically poor. First, about 20% of the whole cohort is not able to receive any kind of therapy mainly due to early death; second, the rate of pts failing first line therapy that could not receive any salvage therapy rose to 39%. As a result, progression during initial therapy or relapse after first line treatment entails a very dismal prognosis with less than 2 months of median survival. Only a few patients that could receive ASCT after relapse had promising chances of long lasting remission. Based on the results of this population based study, it is evident that there is urgent need for novel agents to be offered to TCL pts requiring second line treatment. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 16 (1) ◽  
pp. 108-113 ◽  
Author(s):  
P. M. Brown ◽  
S. Tzannes ◽  
S. Nguyen ◽  
J. White ◽  
V. Langova

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4669-4669
Author(s):  
C.J.M. Halkes ◽  
M.H. Vermeer ◽  
E.M. Noordijk ◽  
R. Willemze ◽  
Roelof Willemze

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.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3005-3005
Author(s):  
Umberto Falcone ◽  
Melania Pintilie ◽  
Ri Wang ◽  
Vishal Kukreti ◽  
John G. Kuruvilla ◽  
...  

Abstract Introduction: T-cell lymphomas (T-NHL) represent rarer entities compared to B-NHL, accounting for 5% -10% of NHL in Western countries and 15%-20% in Asia. They are divided into clinico-pathologic subtypes based on etiology, morphology, and clinical behavior. Because of the rarity and the lack of specific histologic features for the different subtypes, the diagnosis is difficult and clinical picture is usually very helpful to establish the diagnosis. We conducted a retrospective analysis of patients (pts) with T-NHL treated at our Centre, with the purpose of studying overall outcome and possible prognostic factors, including histologic subtypes, from our database. Patients and methods: Consecutive T-NHL pts (excluding Adult T-cell leukemia/lymphoma, NK/T NHL, and primary cutaneous T-NHL), receiving primary treatment at the Princess Margaret Cancer Centre (PMCC) between 2001-2014 were included. Data were extracted from a prospective patient database and the medical record regarding baseline characteristics, treatment, response and outcome. Response assessment was with CT imaging as per 1999 Working Group criteria. Results: Of a total of 2155 pts with aggressive histology NHL treated at PMCC between 2001-2014, 2031 pts had B-NHL and 124 (5.7%) T-NHL. Median age was 56 years (18-90), male/female ratio: 2.4; 63% presented with advanced stage (III-IV) disease, 22% had bone marrow involvement; 63% had elevated LDH and 44% had B symptoms. Observed subtypes were: Peripheral T-cell lymphoma, NOS 58 pts (PTCL NOS, 47%), Anaplastic large cell lymphoma, ALK-negative 16 pts (ALCL-ALK-, 13%), ALCL, ALK-positive 22 pts (ALCL-ALK+, 18%), Angioimmunoblastic T-cell lymphoma 13 pts (AITL, 10.5%), Enteropathy-associated T-cell lymphoma 7 pts (EATL, 5.6%), Hepatosplenic T-cell lymphoma 8 pts (HSTCL, 6%). 105/124 pts (85%) received induction chemotherapy; CHOP-like regimens were used in 94 pts (90%), and involved field radiation therapy (RT) was included in primary treatment in 24 pts (19%). Nineteen pts were treated palliatively, 5 pts with RT alone, 14 pts received palliative chemotherapy or supportive care only. Complete response (CR) was obtained in 63/105 pts (60%; Table 2), PR in 2 pts (1.9%) and 40 pts had no response or progressive disease (SD and PD; 38%). Considering together the most common subtypes (ALCL-ALK+/-, AITL, PTCL NOS), CR rate was 84% in limited stage vs 52% in advanced stage disease. Among patients with CR, 24 relapsed (38%). Fourteen pts received autologous stem cell transplant (8 at relapse, 6 for PD); 7/14 (50%) were alive at last follow-up. At a median follow-up of 5.3 years, 57/124 (46%) pts are alive. Cause of death was T-NHL in 50/124 (40%) pts. Two pts died of second malignancy (1.6%). Median overall survival (OS) and progression-free survival (PFS) were 4.57 years (95%CI: 2.23-9.53; 5yOS: 48%) and 1.5 years (0.87-3.17; 5yPFS: 37%), respectively (Table 2). For pts with limited stage disease median PFS was 4.57 years (5yPFS: 49%) and median OS 10.0 years (5yOS: 62%), while for pts with stage III/IV, median PFS was 0.82 years (5yPFS: 31%) and OS 1.81 years (5yOS: 38%). Median OS for pts who did not experience relapse (39/63; 62%) was 13.38 years (95%CI: 9.53-NA; 5yOS: 93%) vs 3.12 years (95%CI: 1.69-4.07 years; 5yOS: 25%) in pts who had relapse after CR1 (p<0.001). Pts failing to achieve CR (PR, SD, PD) had a very poor outcome with median OS 1.15 years (95%CI: 0.62-1.32 years; 5yOS: 17%). For PTCL NOS pts, outcomes were poor while those with ALCL had more favorable results regardless of ALK status (Table 2). Conclusions: Failure to achieve CR with first-line treatment was the main cause of treatment failure in patients with T-NHL treated with anthracycline-based chemotherapy. Patients with limited stage lymphoma and with ALCL ALK+/- subtypes have more favorable outcomes. For PTCL NOS, the most common subtype, and less common entities (HSTCL, EATL), results are poor and new induction strategies are needed. Disclosures Kukreti: Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2938-2938
Author(s):  
Raul Cordoba ◽  
María Socorro Rodriguez-Pinilla ◽  
Narvaez Javier ◽  
Fina Climent ◽  
Joaquin Sanchez ◽  
...  

Abstract Purpose The objective of this study was to investigate clinicopathologic features and prognostic factors of patients diagnosed with PTCL in 13 sites across Spain. Patients and Methods A multicenter, retrospective study was carried out between September 2015-November 2017.Medical charts of patients diagnosed with PTCLs between January 2008 and December 2013 that have signed the approved informed consent form were reviewed. PTCLs were then classified according to the 2016 revision of the WHO classification of lymphoid neoplasms. Clinical characteristics,history, standard immunohistochemistry (IHC) data, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (TCL) (PIT) were also assessed. Medians (range), mean (standard deviation) and frequency as the number of patients (n) and percentages (%) with confidence intervals at 95% (CI95%) were calculated. Overall Survival (OS) and Progression Free Survival (PFS) were analyzed using the Kaplan Meier method. Results 175 (88.4%) patients were successfully analyzed, the male/female ratio was 1.7:1.0, and the median age was 67.2 years (range: 24.8 years -95.8 years). ECOG performance status >1 was reported for 31.9% patients. Ann Arbor stages were III and IV 27.4% and 45.7%, respectively, and LDH levels were elevated to 92 patients (52.6%). Those with B symptoms accounted for 39.4%, while soft tissue was the most frequent location (23,7%) among the 76 patient with extranodal disease; bone marrow infiltration was confirmed in 18.3% patients. Relevant clinical antecedents related to immunological aspects were also frequently reported, including previous neoplasia (18.9%), autoimmune disease (16%), immunosuppressive treatments (7.3%) and previous viral diseases (HIV, HBV or HCV, 5.7%, 4.6% and 7.4%, respectively). Most patients presented with angioimmunoblastic TCL (31.4%); similar proportions of patients were observed among nodal PTCL with TFH phenotype (13.1%, PTCL not otherwise specified (12.0%) and extranodal NK/TCL nasal type (11.4%). CD30 expression and staining pattern (ranged 1-4) allowed the stratification of patients according CD30 intensity (n= 121; weak: 35, moderate: 57, and intense: 29); Patients were also classified based on CD30 expression considering the median value of quantitative CD30 in our sample (15%) the cut-off point: n=132; Negative <15%: 64; Positive, ≥15%: 68). First-line treatment with a CHOP/CHOP-like regimen was the most common finding (69.7%). Best response was observed after a median of 4 months since the start of first-line treatment (range 0.0 months - 65.2 months). Overall response rate after first-line treatment was 66.9%, with 61/151 patients reaching complete response (CR). Median PFS (n=157) and OS (n=175) of this series were 7.87 months (CI95%: 4.98 months-10.75months) and 15.77 months (CI95%: 10.23 months -21.30 months), respectively. Overall, IPI and PIT scores influenced the PFS and OS (p<0.001). A higher number of adverse factors was associated with a shorter survival. Reaching a CR was associated with a better PFS (CR: 62.6m; CI95%: 20.2 months -105.1 months) than the rest of patients (3.97m: CI95%: 3.08 months -4.85m; p<0.001). Response was also associated with OS; patients with CR showed an average OS of 67.01 months (CI95%: 58.2 months -75.9 months) that were significantly longer than that of patients with No-CR (median: 7.34 months; CI95%: 5.85 months -8.83 months; p<0.001). Conclusion This is the largest series of T cell Lymphoma reported in Spain and has allowed the description of distribution of PTCL subtypes, analyzed through central hematopathologists reanalysis and reclassification of samples from 175 PTCL patients, according to the WHO 2016 classification of lymphoid neoplasms. Our data confirm the poor prognosis of these patients, as well as the impact of prognostic indexes and the response to first line treatment on their outcome. Disclosures Rodriguez-Pinilla: Takeda: Honoraria. Piris:Takeda: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Kura: Honoraria. Ruiz-Zorrilla:Takeda: Employment. Montoto:Takeda: Employment.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
Tongyu Lin ◽  
He Huang ◽  
Chao Yong Liang ◽  
Chengcheng Guo ◽  
Ying Tian ◽  
...  

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.


2019 ◽  
Vol 24 (5) ◽  
Author(s):  
Nicholas C. Richardson ◽  
Yvette L. Kasamon ◽  
Haiyan Chen ◽  
R. Angelo de Claro ◽  
Jingjing Ye ◽  
...  

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