BEAM-Campath allogeneic stem cell transplant for patients with relapsed/refractory lymphoma - High incidence of long term mixed donor-recipient chimerism and the response to donor lymphocyte infusions

Lymphoma
06/09/2020

Biol Blood Marrow Transplant. 2020 Sep 2:S1083-8791(20)30543-7. doi: 10.1016/j.bbmt.2020.08.028. Online ahead of print.

ABSTRACT

BiCNU (carmustine), Etoposide, Ara-C, Melphalan (BEAM) and Campath conditioning was developed to reduce the high transplant-related mortality in patients with lymphoma, whilst delivering intensive anti-lymphoma immunotherapy, as well as to some extent a platform for allogeneic stem-cell engraftment. Significant numbers of patients appeared to have persistent recipient-derived haematopoiesis and therefore we retrospectively analysed patients with lymphoma undergoing BEAM-Campath conditioned


alloSCT at our centre (2003-2017) to characterise the patterns of chimerism and patient outcomes. Chimerism was analysed with short tandem repeat PCR. Mixed donor-recipient chimerism (MDRC) was defined as 5-94.9% donor. Fifty-two patients (n=30 male), with a median age of 45 years, were identified with histological diagnoses of Hodgkin lymphoma (n=13), DLBCL (n=7), low-grade NHL (n=16), mantle cell (n=10), and T-cell lymphoma (n=6). Pre-transplant, 93% achieved CR (52%) or PR (41%) with a median of 3 prior therapies (n=3 prior autoSCT). Donors were MSD (n=21), MUD (n=24), MMUD (n=6), syngeneic (n=1). Acute GvHD developed in 52% (81% grade I-II) and 12% chronic GvHD (83% extensive). MDRC of T cells (MDRCt) developed in 62% (n=32) and 29% (n=15) developed MDRC of myeloid cells (MDRCm), at a median onset of 100 days. DLI was given to 17 patients, median starting dose 1 × 106/kg. The first DLI was given at a median of 225 days post-transplant (range 99 days - 5.3 years). Of these, 9 developed acute post-DLI GvHD and 2 limited chronic GVHD. Conversion to full-donor occurred in 47% MDRCt, and 50% MDRCm. Multivariate analysis identified sibling donor type as associated with increased MDRCt (p=0.035, HR 0.17) and reduced TNC dose with increased MDRCm (p=0.021, HR 0.76). The median follow-up was 6 years and 2-year NRM cumulative incidence was 16% (95%CI 7-27%). Ten-year progression and extensive GvHD-free survival was 45% (95%CI 28-61%) and OS 66% (95%CI 50-78%). One year landmark analysis identified no increased GvHD or relapse risk with MDRCt or MDRCm, but reduced NRM risk with MDRCt (p=0.001). BEAM-Campath allografts for high risk lymphoma achieve long-term disease-free survival with low rates of GvHD and TRM. The frequent development of myeloid MDRC, demonstrates that BEAM-Campath is a non-myeloablative conditioning regimen in almost a third of patients. MDRCt is associated with reduced NRM, but neither MDRCtor MDRCm are associated with increased GvHD or relapse.