Tale of Two Lymphomas: Peripheral T-Cell Lymphoma After Allogeneic Stem-Cell Transplantation for Marginal Zone Lymphoma

2012 ◽  
Vol 30 (31) ◽  
pp. e309-e311 ◽  
Author(s):  
Linda Lee ◽  
Jeffrey H. Lipton ◽  
Denis Bailey ◽  
Vishal Kukreti
Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4849-4849
Author(s):  
Ikuo Shimizu ◽  
Wataru Takeda ◽  
Takehiko Kirihara ◽  
Keijiro Sato ◽  
Yuko Fujikawa ◽  
...  

Abstract Abstract 4849 Background: Peripheral T-cell lymphoma (PTCL) is an intractable entity with limited response to CHOP-like regimens or more intensive regimens. Although some relapsed or refractory patients may benefit from allogeneic stem cell transplantation, management of elderly patients remains problematic. Sobuzoxane (MST-16) is an oral topoisomerase II inhibitor developed and approved in Japan (Narita T et al. Cancer Chemother Pharmacol 1990). Some anecdotal reports revealed its activity against refractory or relapsed PTCLs as a single-drug regimen or in combination regimens. Patients and Methods: We retrospectively reviewed consecutive cases of patients with angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) who were refractory to or relapsed after CHOP-like chemotherapy during the period spanning January 1990 to March 2012 at Nagano Red Cross Hospital (Nagano, Japan). Diagnosis was performed by certified pathologists based on biopsy samples and flow cytometry. We compared efficacy, safety, and survival time between patients who underwent MST-16-containing regimens and other salvage regimens, including autologous or allogeneic stem cell transplantation. Results: Among 40 patients with AITL or PTCL-NOS, 27 (median age, 65 years; range, 48–86) were administered salvage chemotherapy. The MST-16 group (n=13) received MST-16 alone (9), MST-16 and etoposide (3), or MTX-HOPE (methotrexate, hydrocortisone, vincristine, MST-16, and etoposide) (1). The median number of previous regimens was 3 (range 1–4). The non-MST-16 group (n=14) consisted of multiple regimens including EPOCH (2), ESHAP (2), CEPP (cyclophosphamide, etoposide, procarbazine, and prednisolone) (1), IVAM (2), DeVIC (1), DHAP (1), ABEP (doxorubicin, bleomycin, etoposide, and prednisolone) (1), or high dose therapy with autologous or allogeneic stem cell transplantation (3). Patients in the MST-16 group were of significantly higher age (p=0.027) and had less hepatosplenomegaly (p=0.028) compared to those in the non-MST-16 group. No significant difference was observed in patient performance status, B symptoms, LDH, immunoglobulin values, International Prognostic Index (IPI) scores, and Prognostic Index for T-cell lymphoma (PIT) scores between the two groups. Among MST-16 group, overall response rate was 62.1% (CR 31.0%, PR 31.0%). Notably, additional patients (14.3%) achieved durable SD by palliative MST-16 chemotherapy. With a median observation period of 25 months, median survival time was significantly longer in the MST-16 group compared to the non-MST-16 group (23 months vs. 4 months, respectively; p=0.027). Those with a longer remission period over 6 months due to a CHOP-like regimen tended to respond better to MST-16 salvage regimens (p=0.059). With respect to adverse events, two deaths occurred (one patient with pulmonary aspergillosis following ABEP, and one patient with pneumocystis pneumonia following MST-16). Conclusions: Although this study was of a small scale and retrospective, it supports the notion that MST-16-containing regimens may present a promising approach for relapsed/refractory AITL or PTCL-NOS patients, particularly for those who relapse following a long remission of over 6 months due to a CHOP-like regimen, those not indicated for SCT, and those for whom steroid use is difficult. Given the pleomorphic nature of these entities, there remains the possibility that selection bias may have accounted for the difference observed between the two arms. Further prospective studies with other approaches (e.g., biological or immunohistopathological) may lead to the identification of pathologies other than hepatosplenomegaly that benefit from MST-16. Disclosures: No relevant conflicts of interest to declare.


2007 ◽  
Vol 48 (3) ◽  
pp. 630-632 ◽  
Author(s):  
Takaaki Konuma ◽  
Jun Ooi ◽  
Satoshi Takahashi ◽  
Akira Tomonari ◽  
Nobuhiro Tsukada ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3042-3042
Author(s):  
Charalampia Kyriakou ◽  
C. Canals ◽  
G. Taghipour ◽  
J. Finke ◽  
H. Kolb ◽  
...  

Abstract AITL is a rare peripheral T-cell lymphoma characterised by an aggressive behaviour, which primarily affects the elderly. Chemotherapy regimens fail to alter the high relapse rate and overall survival hardly exceeds 25% at 5 years. To date, there is no information on the potential role of allogeneic stem cell transplantation (allo-SCT) in the management of AITL. We report the outcome of 39 patients with a median age of 47 years (24–68), who underwent an allo-SCT between 1995 and 2004 for AITL, and were reported to the EBMT registry. The median time from diagnosis to transplant was 10 months (4–72). Thirty-four patients (87%) had previously received two or more treatment lines, and 16 patients (41%) a previous autologous SCT. Fifteen patients (38%) had a primary refractory disease, 13 (33%) were transplanted in partial remission and the remaining patients were in complete remission (CR) (mostly in 2nd and 3rd CR). Twenty-four patients were transplanted from an HLA-identical sibling and 15 from a matched unrelated donor. A myeloablative conditioning regimen (MAC) was used in 21 patients (cyclophosphamide + total body irradiation in 14), while 18 patients received fludarabine-based reduced intensity conditionings (RIC). Peripheral blood was the source of stem cells in 35 patients (90%). Three patients failed to engraft (one patient in the RIC group). Twenty-one patients (54%) developed acute graft versus host disease (grade I-II, n=16; grade III-IV, n=5). Twenty-eight patients (72%) achieved a CR after the allogeneic procedure. Nine patients died from transplant related mortality (TRM) and 5 patients from disease progression. The cumulative incidence of TRM at 12 months was 19% for the MAC and 26% for the RIC group. After a median follow-up for the surviving patients of 20 months (6–74), 25 patients are alive. Relapse rates at 1 and 3 years were estimated at 10% and 18% for the MAC and 16 and 20% for the RIC patients. Progression free survival rates at 3 years were 67% and 50% and the overall survival at the same time 71% and 56% for the MAC and RIC group of patients, respectively. Although follow up is rather short, these data suggest that allo-SCT results in good overall response and is associated with a low relapse rate in this group of poor risk heavily pre-treated and rather elderly group of AITL patients. Allo-SCT could be considered a therapeutic option for eligible high-risk AITL patients. Nevertheless, the impact of this approach should be further explored in prospective collaborative studies.


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 ◽  
...  

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.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1660-1660 ◽  
Author(s):  
Michal Sieniawski ◽  
James Lennard ◽  
Christopher Millar ◽  
Simon Lyons ◽  
Philip Mounter ◽  
...  

Abstract Abstract 1660 Poster Board I-686 Background In the past two decades we have observed improvement in the outcome of patients diagnosed with some subtypes of lymphoma. However, the prognosis of patient with peripheral T-cell lymphoma (PTCL) still remains unsatisfactory. We prospectively evaluated aggressive chemotherapy and autologous stem cell transplantation (ASCT): IVE/MTX-ASCT in patients with de-novo PTCL. Patients and methods: The regimen was piloted from 1997 for new patients eligible for intensive treatment: first for pts with enteropathy associated T-cell lymphoma (EATL) and subsequently for other types of PTCL. This therapy delivers one cycle of CHOP, followed by 3 courses of IVE (ifosfamide, etoposide, epirubicin), alternating with intermediate dose methotrexate (MTX). Stem cells are harvested after IVE and complete remissions (CR) were consolidated with myeloablative ASCT. The patients were evaluated with an intent to treat analysis for feasibility, response, progression free survival (PFS) and overall survival (OS). Results 57 patients were treated with the aggessive regimen, 26 pts had EATL and 31 other types of PTCL: 17 peripheral T-cell lymphoma NOS, 6 anaplastic T-cell lymphoma ALK positive, 4 extranodal NK/T cell lymphoma nasal type, 3 anaplastic T-cell lymphoma ALK negative and 1 hepatosplenic gamma/delta T-cell lymphoma. The median age at diagnosis was 51 years (range 23 – 69), 36/57 (63%) pts were male and 27/55 (49%) presented with ECOG >1. Early stage disease was diagnosed in 22/57 (39%) pts and advanced disease in 35/57 (61%). Bone marrow was involved in 6/53 (11%) pts and LDH was elevated in 23/46 (50%). Among pts with primary nodal disease 14/26 (54%) had at least one extranodal site involved and 6/26 (23%) bulky disease. At present, 55 pts are available for response evaluation. Eight pts discontinued treatment prematurely; 4 due to toxicity (one severe sepsis and death, one severe encephalopathy, one bone marrow failure and one bleeding from the gastrointestinal tract), and four pts due to disease progression. Of the remaining 47 pts 33 went on to receive ASCT. ASCT was omitted due to: refractory disease in 5 pts, poor general condition in 4 pts, insufficient stem cell mobilisation in 4 pts and one pt declined further treatment. The most common severe toxicities were pancytopenia, infection, nausea/vomiting and obstruction/perforation. Complete remission was confirmed in 39/55 (71%) pts, partial remission in 3/55 (5%) pts and 13/55 (24%) pts failed the treatment. The remission rates were: CR-17/26 (65%) pts and PR-1/26 (4%) for EATL and 22/29 (76%) and 2/29 (7%), respectively for other PTCL. During the study time 17/57 (30%) pts died, 15 due to lymphoma. For all pts 3-years PFS was 59% and OS 67%. For pts with EATL the 3-years PFS and OS were 52% and 60% and for other types 65% and 72%, respectively. These results were unchanged after the exclusion of anaplastic T-cell lymphoma ALK positive: (61% and 72%, respectively). Conclusions For patients with PTCL, we propose that intensive chemotherapy and ASCT significantly improves outcome compared to CHOP-like regimens, and has acceptable toxicities. In conclusion, where feasible patients with PTCL should be considered for aggressive treatments, like IVE/MTX – ASCT as primary therapy. Disclosures No relevant conflicts of interest to declare.


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