Peripheral T/NK-cell lymphomas are uncommon disorders resulting from clonal proliferation of mature post-thymic lymphocytes and accounting for 5–10% of all non-Hodgkin’s lymphomas.1 Their optimal therapy remains to be established because of the lack of randomized trials. The disease is often diagnosed at advanced stages with unfavorable international prognostic index (IPI) scores. As a consequence, excluding ALK-positive anaplastic large cell lymphomas (ALCL) and indolent mycosis fungoides, most patients have a poor prognosis. The international peripheral T-cell and NK/T-cell lymphoma project reported 5-year OS of <35% in peripheral T-cell lymphomas not otherwise specified (PTCL-NOS) with IPI scores ⩾2 at diagnosis, and in ALK-negative ALCL with IPI scores ⩾3.2, 3, 4 As the median age of patients diagnosed with PTCL is 62 years,2 allogeneic SCT (allo-SCT) can be considered as a therapeutic option in some patients. The role of allo-SCT in patients with relapsed PTCL has been investigated with encouraging results in chemosensitive diseases where long-term survival ranged from 69% to 81%.5, 6, 7 However, no study has specifically addressed the role of early allo-SCT in first response. Thus, in an effort to explore this therapeutic option in younger patients, we undertook a retrospective analysis of patients treated at our center with allo-SCT in first response.
The records of all adult patients under 70 years of age diagnosed with T- or NK-cell lymphoma between January 2006 and December 2012 were reviewed. As shown in Figure 1, cutaneous T-cell lymphomas and ALK-positive ALCL were excluded. Patients with an IPI score of 0/1 at diagnosis were excluded as well as those who never reached at least a partial response according to the criteria reported by Cheson.8 During the study period, allo-SCT was always pursued in first response in patients with an IPI score ⩾2 at diagnosis. The absence of allo-SCT was explained by the absence of a suitable donor or by unfitness of the patient. All patients undergoing allo-SCT in first response were included. The objective of the study was to evaluate the outcome of allo-SCT in this high-risk and selected population of patients with a first response long enough to undergo allo-SCT. OS was calculated from the date of transplantation to either the date of death from any cause or last follow-up. Disease-free survival (DFS) was calculated from the date of transplantation to the date of relapse or progression, death from any cause or last follow-up. Survival estimates were determined using the Kaplan–Meier method. Cumulative incidence curves were used for acute and chronic GVHD in a competing risk setting with death as a competing event. Statistical analyses were performed with SPSS 19 (SPSS Inc., Chicago, IL, USA) and R 2.13.2 software packages (R Development Core Team, Vienna, Austria).
Sixteen patients were included in the study. The male/female ratio was 13/3. The median age at transplant was 54 years (21–67). The lymphoma subtypes were angioimmunoblastic (n=8), PTCL-NOS (n=4), ALK-negative ALCL (n=3), hepatosplenic γ/δ (n=1). The IPI scores at diagnosis were 2 (n=6), 3 (n=6), and 4 (n=4). The first-line chemotherapy regimens were CHOP or CHOP-like (n=15), and DHAP (n=1). The number of chemotherapy lines to reach the first response were 1 (n=9), 2 (n=3) or 3 (n=4). Two patients underwent an autologous SCT to reach the first response. The median time between diagnosis and allo-SCT was 6 months (3–23). The median time between first response and allo-SCT was 51 days (21–116). According to the criteria reported by Cheson,8 11 patients were in first complete response before allo-SCT while 5 were in first partial response. Donors were matched related (n=7), matched unrelated (n=6, HLA-A, B, C, DRB1, DQB1 at the allele level), mismatched unrelated (n=2, C and DQB1 mismatches, both at the Ag level). Prophylaxis of GVHD consisted of CsA alone (n=3), CsA+short course MTX (n=8), CsA+mycophenolate mofetil (n=5). Conditioning regimens were of reduced intensity, combining fludarabine with i.v. BU (n=12), or myeloablative, combining CY with either i.v. BU (n=3) or TBI 12 Gy (n=1). Rabbit antithymocyte globulin (Thymoglobuline 2.5 mg/kg/day at day −2 and day −1) was used in all reduced-intensity conditioning regimens. The sources of stem cells were peripheral blood (PB, n=12), BM (n=3) or cord blood (n=1). The median number of infused CD34-positive cells in PB+BM grafts was 6.3 × 106/kg (1.8–15.5). All patients achieved sustained engraftment. With a median follow-up of 38 months after allo-SCT (8–86), the 3-year OS and DFS were both 87±8% (Figure 2). Two patients relapsed at 1 and 2 months after transplant and died of disease progression at 1 and 5 months, respectively. There was no transplant-related death. The cumulative incidences of grade II–IV acute GVHD and chronic GVHD requiring systemic therapy were 37±12% and 20±10%, respectively.
The modest size of our study and its retrospective design preclude declaration of any firm conclusion. However, these preliminary data reported with a meaningful follow-up for aggressive lymphomas suggest that selected patients with high-risk PTCL (IPI⩾2) and a first response long enough to undergo allo-SCT might benefit from early transplantation in the course of their disease. These results are in line with previous studies reported in patients with relapsed but chemosensitive diseases, in whom long-term survival ranged from 69% to 81%.5, 6, 7 Collectively, these data suggest a potent graft-versus-lymphoma effect in patients with high-risk PTCL. Finally, it must be acknowledged that randomized studies are warranted to further delineate the optimal first line therapy in these patients. As a consequence, our center is currently participating in the ongoing ‘Auto versus Allo Transplantation in Peripheral T-Cell Lymphomas’ European study comparing both strategies in first response.
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Corradini P, Dodero A, Zallio F, Caracciolo D, Casini M, Bregni M et al. Graft-versus-lymphoma effect in relapsed peripheral T-cell non-Hodgkin’s lymphomas after reduced-intensity conditioning followed by allogeneic transplantation of hematopoietic cells. J Clin Oncol 2004; 22: 2172–2176.
Le Gouill S, Milpied N, Buzyn A, De Latour RP, Vernant JP, Mohty M et al. Graft-versus-lymphoma effect for aggressive T-cell lymphomas in adults: a study by the Société Francaise de Greffe de Moëlle et de Thérapie Cellulaire. Société Française de Greffe de Moëlle et de Thérapie Cellulaire. J Clin Oncol 2008; 26: 2264–2271.
Kyriakou C, Canals C, Finke J, Kobbe G, Harousseau JL, Kolb HJ et al. Allogeneic stem cell transplantation is able to induce long-term remissions in angioimmunoblastic T-cell lymphoma: a retrospective study from the lymphoma working party of the European group for blood and marrow transplantation. J Clin Oncol 2009; 27: 3951–3958.
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The authors declare no conflict of interest.
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