Reduced-intensity allogeneic stem cell transplantation (RIC-AlloSCT) is being increasingly considered for patients with aggressive lymphoma, but limited evidence exists in mantle cell lymphoma (MCL). We report a retrospective study of transplant outcomes of RIC-AlloSCT for MCL in 70 patients (median age, 48 years, range: 30-67 years), with 57 patients receiving an Alemtuzumab-containing regimen. Thirty-four percent of patients had received a prior autologous stem cell transplant. The 1- and 5-year nonrelapse mortality (NRM) was 18% (95% confidence interval [CI] 10-27) and 21% (95% CI 12-31), respectively. The incidence of severe (grade III and IV) acute graft-versus-host disease (aGVHD) was 10%, and the 5-year incidence of chronic GVHD (cGVHD) was 61%. The cumulative relapse risk was 65% (95% CI 48-77) at 5 years, significantly affected by disease status at transplant (P = .0495), specifically the presence of chemosensitive disease (P = .0364). Fifteen of 18 relapsed patients received donor lymphocyte infustion (DLI) (n = 14) or a second RIC-AlloSCT (n = 1), with 11 of 15 currently in CR. The 5-year overall survival (OS) and progression-free survival (PFS) were 37% (95% CI 25%-56%) and 14% (95% CI 6%-34%), respectively. Age at transplantation and having <2 prior lines of therapy influenced the OS, whereas having <2 prior lines of therapy was the only factor to influence PFS. The use of Alemtuzumab in the conditioning was associated with an improved OS at 3 years (P = .0271). RIC-AlloSCT is a potential treatment modality for aggressive MCL. For patients relapsing post-AlloSCT, the disease is salvageable with DLI. The timing of RIC-AlloSCT should be explored in prospective studies to establish the optimal role in the management of this aggressive lymphoma.
Autologous stem cell transplant as primary (first ASCT) therapy in multiple myeloma (MM) is standard practice. The role of a second ASCT as management of relapsed disease remains uncertain. We conducted a retrospective case-matched control analysis on patients (n = 106) who underwent a second ASCT compared with conventional chemotherapy (CCT) as for relapsed MM. The median age was 53 years (range: 26-75) and median follow-up 48 months (range: 8, 136). The cumulative incidence of 1 and 5 years nonrelapse mortality (NRM) was 7% (95% confidence interval [CI] 3%-13%) and 12% (95% CI 7%-19%), with a second ASCT inducing a greater partial remission (PR) rate of 63%. The 4-year overall survival (OS) rate was 33% (95% CI 24%-45%). Factors associated with improved OS and progression-free survival (PFS) included younger age (<55 years), β(2)MG <2.5 mg/L at diagnosis, a remission duration of >9 months from first ASCT, and a greater PR in response to their first ASCT. In a matched-cohort analysis with patients receiving conventional chemotherapy (CCT), the same factors were associated with improved OS, with the exception of a longer remission duration (>18 months) from first ASCT. Second ASCT in relapsed MM is associated with superior OS and PFS compared with CCT, offering a potential consolidative option for selected patients.
Fifty-one patients with primary myelofibrosis (PMF) received allogeneic haematopoietic stem cell transplants from related (n ¼ 33) or unrelated (n ¼ 18) donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative regimens including CY plus BU (n ¼ 4) or TBI (n ¼ 23). Twenty-four patients, 40-64 years old, received reduced-intensity conditioning (RIC) regimens. All RIC regimens contained fludarabine, combined with melphalan (n ¼ 19) or BU (n ¼ 5), and alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n ¼ 19). Four patients (17%) in the RIC group had primary graft failure. Previous splenectomy reduced time to engraftment in the RIC group (13 versus 20 days; P ¼ 0.008). For MA and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31% (P ¼ 0.67), progressionfree survival 44 and 24% (P ¼ 0.87), and actuarial relapse rates 15 and 46% (P ¼ 0.06). Non-relapse mortality at 3 years was 41% for the myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of patients in the myeloablative and RIC groups, respectively. Extensive chronic GVHD developed in 30 and 35% of evaluable patients, respectively.
This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P ¼ 0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P ¼ 0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P ¼ 0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P ¼ 0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients. Keywords: aplastic anemia; alemtuzumab; ATG; SCT INTRODUCTION Long-term OS of patients transplanted for acquired aplastic anemia (SAA) using matched sibling donors (MSD) is excellent but is age dependent. For children, survival approaches 90% but for patients aged 450 years, survival is 45-50%.1,2 Graft rejection occurs in 5-10% of patients. Standard conditioning for patients aged o30-40 years uses CY 200 mg/kg with antithymocyte globulin (ATG) and CsA with MTX as post-graft immune suppression. [3][4][5][6][7][8][9] Outcomes following matched unrelated donor (MUD) hematopoietic SCT (HSCT) for SAA show survival in excess of 75%, and for some subgroups 480%, and a graft rejection rate of 15-17%. [10][11][12][13][14][15][16][17] Fludarabine in combination with lower-dose CY and ATG, and low-dose TBI (2-3 Gy) for adults, is now most commonly used as conditioning regimen for MUD HSCT.12 This regimen is also considered for older MSD HSCT.
57 58Improving haematopoietic cell transplantation outcomes by selection of an HLA 59 matched unrelated donor is best practice, however donor selection by secondary 60 characteristics is controversial. We studied 1271 recipients with haematological 61 malignancies who underwent T cell depleted allografts and who had complete 62 data on HLA matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and 63 clinical outcome data. 5-year overall survival was 40.6%. HLA mismatching (at 64 HLA-A, -B, -C, -DRB1, -DQB1) (Relative Risk (RR) 1.22, 95% CI 1.2-1.5, p=0.033 for 65 1 mismatch and RR 1.46, 95% CI 1.1-1.9, p=0.009 for >1 mismatch) and CMV 66 mismatching (RR 1.37, 95% CI 1.2-1.6, p<0.001) were significantly associated 67 with inferior survival. Donors under 30 years were associated with a trend 68 towards better survival (RR 1.17, 95% CI 0.99-1.4, p=0.069). In a multivariate 69 model for mortality combining CMV and HLA match status, we found a RR of 1.36 70 (95% CI 1.1-1.7, p=0.003) for HLA matched/CMV mismatched, a RR of 1.
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