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dc.contributor.authorThomson, Kirsty J
dc.contributor.authorMorris, Emma C
dc.contributor.authorMilligan, Donald W
dc.contributor.authorParker, Anne
dc.contributor.authorHunter, Ann
dc.contributor.authorCook, Gordon
dc.contributor.authorBloor, Adrian
dc.contributor.authorClark, Fiona
dc.contributor.authorKazmi, Majid
dc.contributor.authorLinch, David C
dc.contributor.authorChakraverty, Ronjon
dc.contributor.authorPeggs, Karl S
dc.contributor.authorMackinnon, Stephen
dc.date.accessioned2010-10-12T14:38:15Z
dc.date.available2010-10-12T14:38:15Z
dc.date.issued2010-08-10
dc.identifier.citationT-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma. 2010, 28 (23):3695-700 J Clin Oncolen
dc.identifier.issn1527-7755
dc.identifier.pmid20606089
dc.identifier.doi10.1200/JCO.2009.26.9100
dc.identifier.urihttp://hdl.handle.net/10541/112842
dc.description.abstractPURPOSE: 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.
dc.language.isoenen
dc.subjectAnticancerous Agentsen
dc.subjectGraft vs Tumour Effecten
dc.subjectHaematopietic Stem Cell Transplantationen
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntineoplastic Agents
dc.subject.meshGraft vs Tumor Effect
dc.subject.meshHematopoietic Stem Cell Transplantation
dc.subject.meshHumans
dc.subject.meshLymphocyte Depletion
dc.subject.meshLymphocyte Transfusion
dc.subject.meshLymphoma, Follicular
dc.subject.meshMiddle Aged
dc.subject.meshProspective Studies
dc.subject.meshRecurrence
dc.subject.meshSurvival Analysis
dc.subject.meshT-Lymphocytes
dc.subject.meshTransplantation Conditioning
dc.subject.meshTreatment Outcome
dc.titleT-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, University College Hospital, London, UK. Kirsty.thomson@uclh.nhs.uken
dc.identifier.journalJournal of Clinical Oncologyen
html.description.abstractPURPOSE: 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.


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