Long‐term follow‐up of reduced‐intensity allogeneic hematopoietic stem cell transplantation for refractory or relapsed follicular lymphoma

Abstract

Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative treatment for refractory or relapsed follicular lymphoma (FL), transplant-related mortality (TRM) greatly interferes with the success. A variety of reduced-intensity conditionings (RICs) have been used to reduce TRM, but an optimal conditioning for FL has not been fully established. We retrospectively evaluated the outcome of allogeneic HSCT for FL with RIC consisting of fludarabine and melphalan. Nineteen adult patients with relapsed or refractory FL were conditioned with fludarabine (125 mg/m 2 ) and melphalan (140 mg/m 2 ), and received grafts from an HLA-identical sibling (n 5 6) or an unrelated donor (n 5 13). For the prophylaxis of graft-versus-host disease (GVHD), cyclosporine A or tacrolimus with short-term methotrexate was given. There were no early deaths before engraftment, and all patients achieved engraftment. Three patients died of extensive-type chronic GVHD (n 5 2) or bacterial infection (n 5 1) without disease progression. With a median follow-up period of 75.2 months (range: 33.3-111.9 months), 16 patients were alive without disease progression. Both the 5-year overall and progression-free survival rates were 84.2% (95% CI: 67.7-100%). These results strongly suggest that allogeneic HSCT with RIC using fludarabine and melphalan could be a promising treatment choice for refractory or relapsed FL. Current chemotherapies, such as rituximab-containing regimens, have improved the prognosis of follicular lymphoma (FL). However, FL is generally considered incurable with these conventional treatments, and the disease relapses in most patients [1]. High-dose chemotherapy with autologous or allogeneic hematopoietic stem cell transplantation (HSCT) has been shown to improve the survival rates of relapsed or refractory FL [2,3]. When compared with autologous HSCT, a significant reduction in relapse rate has been observed after allogeneic HSCT with myeloablative conditioning [4][5][6]. The suggested mechanism of the reduced relapse rate is the graft-versus-lymphoma (GVL) effect provided by transplanted donor cells. However, this favorable effect is often offset by the high transplantrelated mortality (TRM) of allogeneic HSCT following myeloablative conditioning. To reduce TRM, most of the recent studies have focused on the use of reduced-intensity conditioning (RIC). The outcomes are promising and the practice of allogeneic HSCT has shifted in favor of RIC, although registry data showed an increased risk of late disease progression after RIC regimens [7,8]. The definition of RIC included a variety of regimens which varied significantly in their intensity and immunosuppressive effects. Thus, the optimal RIC regimens of allogeneic HSCT for FL have yet to be established, and long-term follow-up is also lacking in most of the earlier studies. Therefore, we retrospectively evaluated the long-term outcome of allogeneic HSCT with RIC consisting of fludarabine and melphalan for relapsed or refractory FL.Nineteen patien...

Clinical outcomes of allogeneic stem cell transplantation for relapsed or refractory follicular lymphoma: a retrospective analysis by the Fukuoka Blood and Marrow Transplantation Group

“…Although the availability of rituximab has improved both the outcome and survival of FL [22,23], patients with relapsed or refractory FL are advised to undergo allo-HSCT before they receive excessive chemotherapies and their physical condition is exacerbated by the adverse effects. The previous reports of allo-SCT for relapsed and refractory FL are summarized in Table3 [8,[24][25][26][27][28][29][30][31][32]. PFS and OS rates among the patients who received allo-SCT with RIC varied between approximately 40% and 80%, which was almost equivalent to those of our result.…”

“…A comparative retrospective study revealed a significantly lower relapse rate in patients with relapsed FL who underwent allo-SCT compared with those who underwent autologous SCT (auto-SCT) or salvage chemotherapy [5,6]. Therefore, allo-SCT has become the treatment of choice for patients with relapsed or refractory FL [7,8]. However, the potential survival benefits of allo-SCT compared with that of auto-SCT is often offset by the high treatment-related mortality (TRM) rate, due to direct toxicity and high incidence of severe graft-versus-host disease (GVHD).…”

“…Because of these advances, allo-SCT is rapidly being adopted for patients with FL requiring allo-SCT. However, only few reports have described the efficacy of allo-SCT for FL in the Japanese population [8][9][10].…”

Hematopoietic Stem Cell Transplantation for Follicular Lymphoma : Optimal Timing and Indication

“…By contrast, in 2 retrospective studies of allo-SCT for relapsed or refractory FL from Japan, using FM (Flu and Mel)-based or FB (Flu and Bu)-based RIC in a majority of cases, 49,50 the percentages of patients who had chemoresistant disease at allo-SCT were notably higher (63%-68%) than from other series from North America or Europe (Table 2). Nevertheless, the 5-year PFS and OS in those studies were 70%-84% and 77%-84%, respectively, with low NRM (16% for each study).…”

Favorable survival after allogeneic stem cell transplantation with reduced-intensity conditioning regimens for relapsed/refractory follicular lymphoma

“…There were 46 patients identified as being eligible for the study, and 19 of them have been reported previously. 15…”