Extended Follow-Up of Reduced Intensity Transplantation with an Alemtuzumab-Containing Regimen for Follicular Lymphoma

Autor: Anne Parker, Adrian Bloor, Gordon Cook, Emma C. Morris, Donald Milligan, Ann Hunter, Kirsty Thomson, Charles Craddock, Ronjon Chakraverty, Karl S. Peggs, Stephen Mackinnon, Lynny Yung
Rok vydání: 2007
Předmět:
Zdroj: Blood. 110:1666-1666
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v110.11.1666.1666
Popis: Allogeneic transplant with reduced intensity conditioning (RIC) is currently being investigated as potential curative therapy for patients with lymphoma. We report 64 consecutive patients with follicular lymphoma (FL) transplanted at 9 centres with a RIC regimen containing fludarabine 150mg/m2, melphalan 140mg/m2 and alemtuzumab (20–100mg). Cyclosporin A was given at 3mg/kg. Donors were HLA-matched siblings in 34 (53%), and unrelated in 30 (47%), of whom 9 (14%) were HLA-mismatched at up to 2/10 loci. Median age was 44 yrs (26–65), median lines of previous therapy was 3 (1–8) and 17 (27%) had failed a prior autograft. Fifty-five patients (86%) had chemosensitive disease pre-RIC (complete remission 11, partial remission 44), 8 (12%) were chemorefractory and 1 had untreated relapse. Median follow-up was 39 months (1–98). Non-relapse mortality (NRM) at 5 yrs was 12%, with 9% at 5 yrs for sibling donors and 15% for unrelated (p=0.41). There was no significant impact of prior autograft on NRM. Acute graft-versus-host disease (GVHD) grade II occurred in 11 (17%) with no grade III-IV, and extensive chronic GVHD occurred in 9 (16%). Relapse rate (RR) was 18% at 1 year and 32% at 5 years. Those who had failed a prior autograft had an increased RR (53% at 5 yrs) compared to those with no prior autograft (22% at 5 yrs; p=0.01). Median time to relapse from RIC was 8 months (1–43) with 15/17 events occurring within the 1st 2 years. Donor lymphocyte infusions (DLI) were given to 13 patients, at a starting dose of 1–10×106 CD3+/kg. Nine patients remitted, of whom 6 had no GVHD and 7 had received prior rituximab. Median follow-up from last DLI dose was 34 months (3–72). Overall survival (OS) for the whole cohort was 80% at 1 yr and 76% at 5 yrs. On univariate analysis, those with sibling donors had significantly improved OS (88% at 5 yrs), compared to unrelated donors (61% at 5 yrs; p=0.016), as did those with chemosensitive disease pre-RIC (80% at 5 yrs) compared to chemorefractory disease (50% at 5 yrs; p=0.028), and those who had not undergone a prior autograft (86% at 5 yrs) compared to those who had (47% at 5 yrs; p=0.001). Similarly, current progression-free survival (cPFS) for the whole cohort was 79% at 1 yr and 77% at 5 yrs, with significantly superior outcome in those with sibling donors (88% at 5 yrs) compared to unrelated donors (63% at 5 yrs; p=0.018), those with chemosensitive disease (81% at 5 yrs) compared to those with chemorefractory disease (50% at 5 yrs; p=0.0198), and those who had not failed a prior autograft (86% at 5 yrs) compared to those who had (50% at 5 yrs; p=0.001). No factor remained significant for OS or cPFS on multivariate analysis. In conclusion, RIC for FL using an alemtuzumab-containing regimen can be undertaken with relatively low rates of significant acute and chronic GVHD, and low NRM for both HLA-matched and mismatched related and unrelated donors. Responses to DLI occur, often in the absence of clinical GVHD, and appear durable so far, although further follow-up is required.
Databáze: OpenAIRE
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