Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience

Abstract

Key Points• ATL patients who relapsed after allogeneic HSCT have a very high mortality rate and present a serious therapeutic challenge.• No large study exists that assesses the role of salvage therapies for relapsed ATL after HSCT; this is the first report summarizing the outcome.Adult T-cell leukemia/lymphoma (ATL) relapse is a serious therapeutic challenge after allogeneic hematopoietic stem cell transplantation (allo-SCT). In the present study, we retrospectively analyzed 35 patients who experienced progression of or relapsed persistent ATL after a first allo-SCT at 3 institutions in Nagasaki prefecture (Japan) between 1997 and 2010. Twenty-nine patients were treated by the withdrawal of immune suppressants as the initial intervention, which resulted in complete remission (CR) in 2 patients. As the second intervention, 9 patients went on to receive a combination of donor lymphocyte infusion and cytoreductive therapy and CR was achieved in 4 patients. Of 6 patients who had already had their immune suppressants discontinued before the relapse, 3 patients with local recurrence received local cytoreductive therapy as the initial treatment, which resulted in CR for more than 19 months. Donor lymphocyte infusion-induced remissions of ATL were durable, with 3 cases of long-term remission of more than 3 years and, interestingly, the emergence or progression of chronic GVHD was observed in all of these cases. For all 35 patients, overall survival after relapse was 19.3% at 3 years. The results of the present study suggest that induction of a graft-versus-ATL effect may be crucial to obtaining durable remission for ATL patients with relapse or progression after allo-SCT. (Blood. 2013;121(1):219-225)

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)

“…Three similar cases of CR from PTCL after withdrawal of immunosuppressive drugs have been reported. 13,18,19 Patients in relapse Figure 1. Treatments at post-transplant relapse and disease response to treatment in DLI and non-DLI group.…”

“…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. Immunosuppressive drugs were tapered in 29 patients, resulting in two CRs.…”

“…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.…”

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia–lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group

“…In the allo-SCT group, relapse with skin involvement was more likely to develop in the absence of GVHD. We previously reported that recurrent ATL with skin involvement represented a good target for DLI; 22 therefore, skin involvement needs to be accurately diagnosed. Although it is often difficult to distinguish a cutaneous lesion of ATL from other causes (including GVHD and viral infection), 38 southern blotting analysis or high-throughput DNA sequencing may be a promising tool for an accurate diagnosis by showing the clonal proliferation of HTLV-1-infected cells.…”

“…non-aggressive disease) could benefit from DLI. 21,22 These findings implied that an intervention for the residual disease at the early phase may improve the outcomes of ATL patients; however, a standard method to monitor the residual disease after remission has not yet been established. Moreover, very few studies have examined the clinical manifestation of relapsed ATL by carefully analyzing an adequate number of cases.…”