PURPOSE: Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored. PATIENTS AND METHODS: This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors. RESULTS: With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors). CONCLUSION: The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
PURPOSE:Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored. PATIENTS AND METHODS: This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors. RESULTS: With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors). CONCLUSION: The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.
Authors: A-K Zoellner; S Fritsch; D Prevalsek; N Engel; M Hubmann; R Reibke; C T Rieger; J C Hellmuth; M Haas; F Mumm; T Herold; G Ledderose; W Hiddemann; M Dreyling; A Hausmann; J Tischer Journal: Bone Marrow Transplant Date: 2015-02-02 Impact factor: 5.483
Authors: S Yano; T Mori; Y Kanda; J Kato; C Nakaseko; S Fujisawa; N Tomita; R Sakai; K Shono; T Saitoh; N Aotsuka; N Kobayashi; T Saito; S Takahashi; H Kanamori; S Okamoto Journal: Bone Marrow Transplant Date: 2015-07-13 Impact factor: 5.483
Authors: Silvia Montoto; Janet Matthews; Paul Greaves; Debra Lillington; Deborah Anderson; John G Gribben; T Andrew Lister Journal: Haematologica Date: 2012-11-09 Impact factor: 9.941
Authors: Craig S Sauter; Joanne F Chou; Esperanza B Papadopoulos; Miguel-Angel Perales; Ann A Jakubowski; James W Young; Michael Scordo; Sergio Giralt; Hugo Castro-Malaspina Journal: Leuk Lymphoma Date: 2014-03-20
Authors: S R Solomon; C A Sizemore; X Zhang; S Brown; H K Holland; L E Morris; A Bashey Journal: Bone Marrow Transplant Date: 2014-05 Impact factor: 5.483
Authors: Evgeny Klyuchnikov; Ulrike Bacher; Nicolaus M Kröger; Parameswaran N Hari; Kwang Woo Ahn; Jeanette Carreras; Veronika Bachanova; Asad Bashey; Jonathon B Cohen; Anita D'Souza; César O Freytes; Robert Peter Gale; Siddhartha Ganguly; Mark S Hertzberg; Leona A Holmberg; Mohamed A Kharfan-Dabaja; Andreas Klein; Grace H Ku; Ginna G Laport; Hillard M Lazarus; Alan M Miller; Alberto Mussetti; Richard F Olsson; Shimon Slavin; Saad Z Usmani; Ravi Vij; William A Wood; David G Maloney; Anna M Sureda; Sonali M Smith; Mehdi Hamadani Journal: Biol Blood Marrow Transplant Date: 2015-08-04 Impact factor: 5.742