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    ABSTRACT: To further define the relative impact of immunotherapy and subsequent development of graft-versus-host disease (GVHD) on survival in patients with relapsed acute leukaemia postallogeneic hematopoietic stem cell transplant (SCT), we performed a single-centre retrospective analysis of 32 actively treated patients between 2003 and 2011. A total of 13 patients were identified who were treated actively with cessation of immunosuppression ± Fludarabine, Cytarabine, G-CSF (FLAG) induction, but no donor leucocyte infusion (DLI) (non-DLI group) and 19 patients received the same step-wise therapy plus G-CSF mobilized DLI (G-DLI group). Groups were not statistically different with regards to baseline characteristics; however, the G-DLI group contained more sibling donors as opposed to unrelated donors than the non-DLI group. With a median follow-up of 47 months, the median overall survival (OS) of the non-DLI and G-DLI groups was not statistically different (8 months vs. 9 months, respectively, P = 0.5). Survival at 3 years was <10% in both groups. Univariate analysis identified response to FLAG, and new onset chronic GVHD as the only factors associated with improved OS. Second donor stem cell infusions are unwarranted in the treatment of relapse after allogeneic SCT and therapeutic strategies should focus on cytoreduction followed by immune modulation with the aim of invoking chronic GVHD.
    International journal of laboratory hematology 09/2013; · 1.30 Impact Factor
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    ABSTRACT: Patients with leukemia relapsing after allogeneic hematopoietic SCT have a dismal prognosis. A second SCT offers a further opportunity for cure, but has a high rate of treatment failure. To determine the utility of this option, we analyzed 59 consecutive patients relapsing after a myeloablative HLA-matched sibling T cell-depleted (TCD) SCT. Twenty-five patients (13 relapsing within 6 months and 12 relapsing between 6 and 170 months after the first SCT) received a T-replete second SCT. Thirty-eight patients relapsing early had a shorter survival than the 21 patients relapsing later (median 96 vs 298 days, P=0.0002). In patients relapsing early, the second SCT did not improve OS compared with patients receiving non-SCT treatments (median survival 109 vs 80 days, P=0.41). In patients relapsing late, despite an early trend in favor of second SCT, survival was comparable for patients receiving a second SCT compared with non retransplanted patients (median survival 363.5 vs 162 days, P=0.49). Disappointingly, our results do not demonstrate an important survival benefit for a second T-replete allogeneic SCT to treat relapse following a TCD SCT.Bone Marrow Transplantation advance online publication, 25 March 2013; doi:10.1038/bmt.2013.39.
    Bone marrow transplantation 03/2013; · 3.00 Impact Factor
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    ABSTRACT: Abstract We retrospectively studied patients who relapsed after allogeneic stem cell transplantation (SCT) to identify factors influencing outcomes. Of the 296 patients (196 with AML and 100 with ALL), 102 (34%) experienced relapse at a median of 222 days (range: 30-2,748 days) after SCT. Treatment after relapse included supportive care (n = 13), re-induction chemotherapy (n = 37), donor lymphocyte infusion with/without prior chemotherapy (n = 22), and second SCT (n = 30). The 2-year post-relapse survival (PRS) was 14% for all relapsed patients. Multivariable analysis showed that high disease risk (hazard risk [HR]: 1.95; 95% confidence interval [CI]: 1.17-3.24; p = 0.010), unrelated donor (HR: 1.76; 95% CI: 1.10-2.80; p = 0.018), and interval of <180 days from SCT to relapse (HR: 2.10; 95% CI: 1.26-3.51; p = 0.004) were independent factors of 2-year PRS. These factors were each assigned a score and the sum was used as a prognostic index for PRS. The 2-year PRS in patients of score 0, score 1, score 2, and score 3 was 38%, 19%, 3%, and 0%, respectively (p < 0.001). Our new prognostic index may be helpful for selecting the treatment strategy including investigational salvage therapy for relapsed patients after SCT.
    Leukemia & lymphoma 02/2014; · 2.61 Impact Factor

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May 20, 2014