Poster Board III-196
The use of lineage-specific chimerism studies following allotransplantation has shown that low levels of donor T-cell chimerism can be seen following some preparative regimens despite good engraftment of donor myeloid-origin cells. Furthermore, low levels of early T-cell chimerism have been associated with eventual graft rejection, malignant relapse and poorer event-free survival [Maris et al Blood 102: 2021-2030 (2003); Saito et al Biol Blood Marrow Transplant 14: 1148-1155 (2008)]. There is no consensus regarding the management of such differential engraftment. Withdrawal of immunosuppression, DLI, and second transplant with repeat conditioning have all been used. We utilized a strategy of low dose DLI (initial dose 0.1-1 × 10e7 CD3+ cells/kg) without additional conditioning or withdrawal of immunosuppression in patients with donor T-cell chimerism < 50% following allotransplant who had no evidence of relapse/progression of malignancy. Nineteen consecutive patients treated this way between Nov 2005 and April 2009 were included in this analysis - median age 59 (range 36-63);15M, 4F; NHL 5, AML 5, MDS 3, CLL2, CML 2, MPS 2; donor =MRD 3, MUD 16; Preparative regimen for transplant- reduced intensity 18, myeloablative 1, and consisted of fludarabine/busulfan (11), fludarabine/cyclophosphamide (6), other (2). Alemtuzumab was used in the preparative regimen in 15 and rabbit antithymocyte globulin in 2. The first DLI was administered a median of 66 days post BMT (range 36-237). Median CD3+ and CD34+ cell dose was 1.0 ×10e7/kg (range 0.1-1) and 0.24 × 10e6 (0.02-0.74) respectively. Cryopreserved G-CSF mobilized cells collected at the time of BMT were used for the DLI in all patients. Median (range) donor chimerism in blood CD3+ cells and CD33+ cells prior to DLI was 14% (0-34%) and 100% (10-100%) respectively. Pre and post DLI donor T-cell chimerism is shown in the Figure below. Full donor CD3 chimerism (FDC) (>90% donor-derived CD3+ cells) was achieved after one DLI in 9 evaluable patients (50%) at a median 90 d post infusion (range 30-180 d). Eight patients received additional DLI (median 1 range 1-3) at a CD3+ cell dose up to 4 × 10e7/kg and 7 of these patients achieved FDC in CD3+ cells [total success rate in achieving FDC = 89%]. FDC was durable in all cases. Acute GVHD (none > gd 2 overall) developed in three evaluable patients following DLI (17% - median 43d [35-57d]) and chronic GVHD (extensive mild 1, moderate 8, severe 1) developed in ten patients (55% -median 119d [53-166d]). One patient died of chronic GVHD. With a median follow-up of 728d (135-1240d) estimated 2yr survival from DLI is 74%.
This strategy is highly effective at correcting poor donor T-cell chimerism without inducing severe GVHD.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.