Hematological Oncology Hematol Oncol 2015; 33: 164–165 Published online 10 June 2014 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hon.2145
Letter to the Editor
Role of autologous stem cell transplantation in T-cell lymphoma patients: a single institution retrospective analysis To the Editor T-cell lymphomas (TCLs) are a rare and heterogeneous group of malignancies as recognized by the 2008 World Health Organization classification, with a 5-year overall survival rate of about 20–30% across most studies [1,2]. To date, high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT), the best salvage therapy for aggressive B-cell lymphomas, has shown promising results with TCL, too [3]. After obtaining approval from our institutional review board, a computer-based search into our electronic registry was performed to retrospectively review our TCL patients who underwent HDC/ASCT as frontline approach or at disease relapse: cases were consecutively considered to avoid selection bias. Written informed consent was obtained. Final sample was composed by 34 patients (22 men, 12 women) with a median age of 40.7 years at time of ASCT treated between 1986 and 2010. Full study patients’ characteristics are reported in Table 1. Twenty eight patients presented with stage IV disease (eight with bone marrow involvement) and B symptoms occurred in 17 cases. Induction therapy was BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in 21 patients and BAVC (carmustine, amsa, m-amsacrine, etoposide, cytarabine) regimen in the remaining 13. Patients underwent consolidative ASCT after a median number of two previous lines of therapy (range 1–11). Fourteen patients were transplanted in complete response (CR), 4 in partial response (PR) and 16 with progressive disease. After transplantation, 24 patients achieved a CR (13 improving their response), 4 were in PR, 1 had stable disease and 5 progressed. Overall response rate (ORR) was 82.4%, with a CR rate of 70.6%. To date, a CR was maintained in 10 (29.41%) cases: five anaplastic large-cell lymphoma, four T-NOS and one nasal type with a median number of two previous lines of therapy (range 1–3) and starting from a CR (n = 8), PR (n = 1) and a progressive disease (n = 1) status, respectively. The other 24 patients underwent subsequent treatments: in particular, two received further allogeneic bone marrow transplantation and one underwent a tandem ASCT-allogeneic transplant achieving response.
Copyright © 2014 John Wiley & Sons, Ltd.
At a median follow-up of 5.3 years (range 1.9–15.0), 16 patients are still alive, 14 in CR (10 since ASCT and 4 after further therapies) with a median duration of response of 40 months (range 1.6–101.3), 2 in PR and 1 in stable disease. Seventeen patients died, mainly of disease progression (82.4%). A 10-year overall survival from ASCT is 31.9% for the whole sample (median of 4.9 years) and 50.0% for the subgroup of patients who underwent ASCT just after first line. Toxicity profile was quite acceptable because we had only two patients who died of infectious complications related to transplantation, namely because of Pseudomonas and Aspergillus infections. Few data are available on HDC/ASCT in the salvage or frontline setting in TCL lymphoma patients. In particular, two prospective studies investigated peripheral TCL (PTCL) treated with ASCT as first-line therapy: Reimer et al. showed an ORR of 66% (CR 56%) and a 3-year OS of 48% [4], d’Amore et al. reported a 78% of CR rate with a 5-year OS of 51% [5]. Recently, Ahn et al. investigated the clinical outcomes of HDT/ASCT as an intensifying frontline treatment in 31 patients with newly diagnosed PTCL. With a median follow-up of 32.4 months, the 3-year probability of overall survival and progression-free survival was 64.5 ± 8.6% [6]. The policy of our institute is to start the transplant programme in all patients with TCL, regardless of histological subtype, except for the cases in which there are contraindications (e.g. age, presence of significant comorbidities or other life-threatening conditions). Unlike the majority of reported series, our study included different subtypes of TCL. After ASCT, we had an ORR of 82% and a CRR of 70.5%. Albeit the retrospective nature of the research, our data suggest a key role of ASCT in the management and therapeutic approach of TCL patients regardless of the histological subtype. Twenty (59%) patients underwent ASCT as consolidation and 14 at relapse: No difference in baseline characteristics between these two groups was found. Further data are needed to better define the role of ASCT in PTCL in the perspective of a tailored patient programme.
Letter to the Editor
165
Table 1. Study sample characteristics Gender (male/female), n Age at diagnosis, median (range) Histology, n PTCL-NOS ALCL (ALK-) C-ALCL, CD30+, ALKAITL Lymphoblastic Mycosis fungoides T/NK-nasal type Pleomorphic lymphoma Stage, n I II III IV B symptoms, n Bone marrow involvement, n Bulky Therapies prior to ASCT, median (range) Status pre-ASCT, n CR PR SD PD Response to ASCT, n CR PR SD PD Improvement of response after ASCT, n PR to CR PD to CR PD to PR Rate of response improvement, n (%) ORR CRR Current status, n CR PR SD PD Dead
Conflict of interest 22/12 40.7 (20.1–60.2) 14 6 (2) 2 3 6 1 1 1 1 5 0 28 17 8 5 2 (1–11) 14 4 0 16 24 4 1 5 2 8 3 13/34 (38.2) 28/34 (82.4) 24/34 (70.6) 14 (10 since ASCT) 2 1 0 17
PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; ALCL, anaplastic large-cell lymphoma; ALK-, anaplastic lymphoma kinase negative; C-ALCL, cutaneous ALCL; AITL, angioimmunoblastic T-cell lymphoma; NK, natural killer; ASCT, autologous stem cell transplantation; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, overall response rate; CRR, complete response rate.
Copyright © 2014 John Wiley & Sons, Ltd.
The authors report no conflicts of interest.
Acknowledgement The Italian Association for Leukemias, Lymphomas, and Myeloma (AIL, Bologna, Italy) has partially funded the study. The funding source had no role in the study design, collection, analysis or interpretation of the data, or in writing this report.
References 1. Lopez-Guillermo A, Cid J, Salar A, et al. Peripheral T-cell lymphomas: initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. classification. Ann Oncol 1998; 9: 849–855. 2. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Swerdlow SH, Campo E, Harris NL, et al. (eds). IARC: Lyon, 2008. 3. Rodríguez J, Caballero MD, Gutiérrez A, et al. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol 2003; 14: 1768–1775. 4. Reimer P, Rüdiger T, Geissinger E, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 2009; 27: 106–113. 5. d’Amore F, Relander T, Lauritzsen GF, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T01. J Clin Oncol 2012; 30: 3093–3099. 6. Ahn JS, Yang DH, Jung SH, et al. Autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide as an intensifying frontline treatment in patients with peripheral T cell lymphomas: a multicenter retrospective trial. Ann Hematol 2013; 92: 789–797.
Vittorio Stefoni Alessandro Broccoli Lisa Argnani Roberto Maglie Cinzia Pellegrini Letizia Gandolfi Pier Luigi Zinzani Institute of Hematology ‘L. e A. Seràgnoli’, University of Bologna, Bologna, Italy *[email protected]
Hematol Oncol 2015; 33: 164–165 DOI: 10.1002/hon
Letter to the Editor
Role of autologous stem cell transplantation in T-cell lymphoma patients: a single institution retrospective analysis To the Editor T-cell lymphomas (TCLs) are a rare and heterogeneous group of malignancies as recognized by the 2008 World Health Organization classification, with a 5-year overall survival rate of about 20–30% across most studies [1,2]. To date, high-dose chemotherapy with autologous stem cell transplantation (HDC/ASCT), the best salvage therapy for aggressive B-cell lymphomas, has shown promising results with TCL, too [3]. After obtaining approval from our institutional review board, a computer-based search into our electronic registry was performed to retrospectively review our TCL patients who underwent HDC/ASCT as frontline approach or at disease relapse: cases were consecutively considered to avoid selection bias. Written informed consent was obtained. Final sample was composed by 34 patients (22 men, 12 women) with a median age of 40.7 years at time of ASCT treated between 1986 and 2010. Full study patients’ characteristics are reported in Table 1. Twenty eight patients presented with stage IV disease (eight with bone marrow involvement) and B symptoms occurred in 17 cases. Induction therapy was BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in 21 patients and BAVC (carmustine, amsa, m-amsacrine, etoposide, cytarabine) regimen in the remaining 13. Patients underwent consolidative ASCT after a median number of two previous lines of therapy (range 1–11). Fourteen patients were transplanted in complete response (CR), 4 in partial response (PR) and 16 with progressive disease. After transplantation, 24 patients achieved a CR (13 improving their response), 4 were in PR, 1 had stable disease and 5 progressed. Overall response rate (ORR) was 82.4%, with a CR rate of 70.6%. To date, a CR was maintained in 10 (29.41%) cases: five anaplastic large-cell lymphoma, four T-NOS and one nasal type with a median number of two previous lines of therapy (range 1–3) and starting from a CR (n = 8), PR (n = 1) and a progressive disease (n = 1) status, respectively. The other 24 patients underwent subsequent treatments: in particular, two received further allogeneic bone marrow transplantation and one underwent a tandem ASCT-allogeneic transplant achieving response.
Copyright © 2014 John Wiley & Sons, Ltd.
At a median follow-up of 5.3 years (range 1.9–15.0), 16 patients are still alive, 14 in CR (10 since ASCT and 4 after further therapies) with a median duration of response of 40 months (range 1.6–101.3), 2 in PR and 1 in stable disease. Seventeen patients died, mainly of disease progression (82.4%). A 10-year overall survival from ASCT is 31.9% for the whole sample (median of 4.9 years) and 50.0% for the subgroup of patients who underwent ASCT just after first line. Toxicity profile was quite acceptable because we had only two patients who died of infectious complications related to transplantation, namely because of Pseudomonas and Aspergillus infections. Few data are available on HDC/ASCT in the salvage or frontline setting in TCL lymphoma patients. In particular, two prospective studies investigated peripheral TCL (PTCL) treated with ASCT as first-line therapy: Reimer et al. showed an ORR of 66% (CR 56%) and a 3-year OS of 48% [4], d’Amore et al. reported a 78% of CR rate with a 5-year OS of 51% [5]. Recently, Ahn et al. investigated the clinical outcomes of HDT/ASCT as an intensifying frontline treatment in 31 patients with newly diagnosed PTCL. With a median follow-up of 32.4 months, the 3-year probability of overall survival and progression-free survival was 64.5 ± 8.6% [6]. The policy of our institute is to start the transplant programme in all patients with TCL, regardless of histological subtype, except for the cases in which there are contraindications (e.g. age, presence of significant comorbidities or other life-threatening conditions). Unlike the majority of reported series, our study included different subtypes of TCL. After ASCT, we had an ORR of 82% and a CRR of 70.5%. Albeit the retrospective nature of the research, our data suggest a key role of ASCT in the management and therapeutic approach of TCL patients regardless of the histological subtype. Twenty (59%) patients underwent ASCT as consolidation and 14 at relapse: No difference in baseline characteristics between these two groups was found. Further data are needed to better define the role of ASCT in PTCL in the perspective of a tailored patient programme.
Letter to the Editor
165
Table 1. Study sample characteristics Gender (male/female), n Age at diagnosis, median (range) Histology, n PTCL-NOS ALCL (ALK-) C-ALCL, CD30+, ALKAITL Lymphoblastic Mycosis fungoides T/NK-nasal type Pleomorphic lymphoma Stage, n I II III IV B symptoms, n Bone marrow involvement, n Bulky Therapies prior to ASCT, median (range) Status pre-ASCT, n CR PR SD PD Response to ASCT, n CR PR SD PD Improvement of response after ASCT, n PR to CR PD to CR PD to PR Rate of response improvement, n (%) ORR CRR Current status, n CR PR SD PD Dead
Conflict of interest 22/12 40.7 (20.1–60.2) 14 6 (2) 2 3 6 1 1 1 1 5 0 28 17 8 5 2 (1–11) 14 4 0 16 24 4 1 5 2 8 3 13/34 (38.2) 28/34 (82.4) 24/34 (70.6) 14 (10 since ASCT) 2 1 0 17
PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; ALCL, anaplastic large-cell lymphoma; ALK-, anaplastic lymphoma kinase negative; C-ALCL, cutaneous ALCL; AITL, angioimmunoblastic T-cell lymphoma; NK, natural killer; ASCT, autologous stem cell transplantation; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; ORR, overall response rate; CRR, complete response rate.
Copyright © 2014 John Wiley & Sons, Ltd.
The authors report no conflicts of interest.
Acknowledgement The Italian Association for Leukemias, Lymphomas, and Myeloma (AIL, Bologna, Italy) has partially funded the study. The funding source had no role in the study design, collection, analysis or interpretation of the data, or in writing this report.
References 1. Lopez-Guillermo A, Cid J, Salar A, et al. Peripheral T-cell lymphomas: initial features, natural history, and prognostic factors in a series of 174 patients diagnosed according to the R.E.A.L. classification. Ann Oncol 1998; 9: 849–855. 2. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Swerdlow SH, Campo E, Harris NL, et al. (eds). IARC: Lyon, 2008. 3. Rodríguez J, Caballero MD, Gutiérrez A, et al. High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience. Ann Oncol 2003; 14: 1768–1775. 4. Reimer P, Rüdiger T, Geissinger E, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol 2009; 27: 106–113. 5. d’Amore F, Relander T, Lauritzsen GF, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T01. J Clin Oncol 2012; 30: 3093–3099. 6. Ahn JS, Yang DH, Jung SH, et al. Autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide as an intensifying frontline treatment in patients with peripheral T cell lymphomas: a multicenter retrospective trial. Ann Hematol 2013; 92: 789–797.
Vittorio Stefoni Alessandro Broccoli Lisa Argnani Roberto Maglie Cinzia Pellegrini Letizia Gandolfi Pier Luigi Zinzani Institute of Hematology ‘L. e A. Seràgnoli’, University of Bologna, Bologna, Italy *[email protected]
Hematol Oncol 2015; 33: 164–165 DOI: 10.1002/hon
