Allogeneic transplantation following a reduced-intensity conditioning regimen in relapsed/refractory peripheral T-cell lymphomas: long-term remissions and response to donor lymphocyte infusions support the role of a graft-versus-lymphoma effect

Abstract

Rescue chemotherapy or autologous stem cell transplantation (autoSCT) gives disappointing results in relapsed peripheral T-cell lymphomas (PTCLs). We have retrospectively evaluated the long-term outcome of 52 patients receiving allogeneic SCT for relapsed disease. Histologies were PTCL-not-otherwise specified (n ¼ 23), anaplastic large-cell lymphoma (n ¼ 11), angioimmunoblastic T-cell lymphomas (n ¼ 9) and rare subtypes (n ¼ 9). Patients were allografted from related siblings (n ¼ 33, 64%) or alternative donors (n ¼ 13 (25%) from unrelated and 6 (11%) from haploidentical family donors), following reducedintensity conditioning (RIC) regimens including thiotepa, fludarabine and cyclophosphamide. Most of the patients had chemosensitive disease (n ¼ 39, 75%) and 27 (52%) failed a previous autoSCT. At a median follow-up of 67 months, 27 of 52 patients were found to be alive (52%) and 25 (48%) were dead (n ¼ 19 disease progression, n ¼ 6 non-relapse mortality (NRM)). The cumulative incidence (CI) of NRM was 12% at 5 years. Extensive chronic graft-versus-host disease increased the risk of NRM (33% versus 8%, P ¼ 0.04). The CI of relapse was 49% at 5 years, influenced by disease status at the time of allografting (P ¼ 0.0009) and treatment lines (P ¼ 0.007). Five-year overall survival and progression-free survival (PFS) were 50% (95% CI, 36 -63%) and 40% (95% CI, 27 -53%), respectively. The current PFS was 44% (95% CI, 30-57%). In all, 8 out of 12 patients (66%) who received donor-lymphocytes infusions for disease progression had a response. At multivariable analysis, refractory disease and age over 45 years were independent adverse prognostic factors. RIC allogeneic SCT is an effective salvage treatment with a better outcome for younger patients with chemosensitive disease.

Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

“…In the largest series of patients treated with DLI for cutaneous T-cell lymphoma, preceded by chemotherapy or radiotherapy for 5 of 12 patients, a response was observed in 8 patients. 5 A response to DLI has also been reported in a small number of patients with non cutaneous TCL. [4][5][6]8 Itonaga et al 13 recently reported results for 35 patients who relapsed after allo-SCT for adult T-cell leukemia/lymphoma.…”

“…However, some data suggest a beneficial allogeneic effect against PTCL. In a study by Dodero et al, 5 52 patients received second-line allografts with RIC. The OS rate among patients with chemoresistant disease before the graft was 29% at 5 years, suggesting a persistent GvL effect.…”

“…2 Allogenic SCT (allo-SCT) is increasingly used as an alternative strategy, based on a potent graft-versus-lymphoma effect (GvL). However, data from retrospective [3][4][5][6][7][8][9][10][11] and prospective non-randomized studies 12 are insufficient to recommend allo-SCT as first-line treatment. The European Bone Marrow Transplantation Society currently considers allo-SCT to be an option for selected patients with chemosensitive disease in first or second complete response (CR), if a sibling or unrelated HLA-matched donor is available (grade 2 recommendations).…”

“…In an Italian series, 76% of 25 patients who relapsed after transplantation died, within a median of 8 months. 5 Some responses have been reported after immunomodulation based on tapering of immunosuppressive drugs and/or on donor lymphocyte infusion (DLI). [4][5][6][7][8]13,14 To better assess the possible GvL effect in PTCL, we studied 63 patients who relapsed after allo-SCT, focusing on the impact of immunomodulation based on tapering of immunosuppressive drugs and/or DLI on subsequent outcome.…”

“…4 Third, chronic GvHD has been linked to a lower risk of relapse. 5 Finally, a negative impact on survival, due to a high relapse rate (70%), has been reported with T-cell-depleted grafts in primitive cutaneous T-cell lymphoma (TCL). 7 Few data are available on treatment options after PTCL relapse.…”