Impact of graft‐versus‐lymphoma effect on outcomes after reduced intensity conditioned‐alemtuzumab allogeneic haematopoietic stem cell transplantation for patients with mature lymphoid malignancies

Abstract

Summary Allogeneic haematopoietic stem cell transplant (allo‐HSCT) offers potentially curative therapy for patients with relapsed/refractory lymphoid malignancies. Reduced‐intensity conditioning (RIC) with Alemtuzumab reduces transplant‐related mortality and graft‐versus‐host disease (GvHD), but may be associated with increased risk of relapse. With the aim of studying the effect of GVHD and donor lymphocyte infusions (DLI) on relapse, we performed a retrospective study of 288 patients (57% non‐Hodgkin lymphoma, 24% Hodgkin lymphoma and 19% chronic lymphocytic leukaemia; 58% were relapsed/refractory) who underwent RIC‐Alemtuzumab‐HSCT between 2000 and 2012. Median follow‐up time for survivors was 64 months. Five‐year overall survival, relapse incidence, GvHD/relapse‐free survival and non‐relapse mortality were 47%, 33%, 37% and 28% respectively. Cumulative incidence of grade II‐IV acute and extensive chronic GvHD was 22% and 21% at 100 days and 5 years respectively. On multivariate analysis, presence of GvHD (P = 0·03) and unrelated donor type (P = 0·03) were protective of relapse. 62/288 patients received DLI for either mixed donor chimerism (prophylactic DLI, n = 37) or clinical relapse (therapeutic DLI, n = 25). Prophylactic and therapeutic DLI successfully converted the patient to full or stable mixed donor chimerism in 78% and 56% of patients respectively. These data demonstrate good long‐term outcomes and support the concept of the graft‐vs‐lymphoma effect as a key protective factor against relapse following RIC‐Alemtuzumab allo‐HSCT for patients with mature lymphoid malignancies.

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

“…Nevertheless chimerism monitoring, post RIC allo-SCT is an important way of identifying patients at high risk of relapse in whom intervention with pre-emptive DLI may be beneficial. Patients who achieve full donor chimerism (FDC) with DLI have a comparable outcome to those who reach FDC spontaneously ( 148 , 149 ).…”

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

“…The addition of rituximab to augment the effects of DLI has been evaluated in two studies with conflicting results; in one report, 20/43 (47%) patients achieved complete responses which tended to be durable, whereas in the second study a sustained remission was achieved in only 2/13 (15%) patients (148,153). The potential benefit of DLI must also be weighed against the substantial risks of inducing clinically significant GVHD in up to 38-48% of patients (148,153,154). BTK and BCL2 inhibitors represent other highly effective treatment options for patients relapsing after allogeneic HCT who have not previously developed resistance to these therapies (155)(156)(157)(158).…”

Reappraising the Role of Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed and Refractory Hodgkin’s Lymphoma: Recent Advances and Outcomes

“…AlloHSCT is also associated with significant toxicities, including graft-versus-host disease (GVHD), which could increase non-relapse mortality risk. GVHD, and especially the chronic GVHD, has been shown to be associated with lower risk of relapse, which may reflect the benefits of graft-mediated immune surveillance in the prevention of lymphoma relapse [10,29]. Given the lack of randomized prospective trials evaluating the role of AlloHSCT in cHL, multiple retrospective, small prospective phase 2 and registry studies have shown the benefit of this procedure in selected fit patients with relapsed disease [30].…”

“…More than a decade of progress has made this modality safer and accessible to more patients worldwide [7]. The benefits of AlloHSCT go beyond the anticancer effects of high-dose chemotherapy and radiotherapy, to the more durable graft-versus-lymphoma phenomenon [8][9][10]. Furthermore, the recognition of the benefits of graft-versus-lymphoma effects has allowed clinicians to use lower doses of chemo-or radiotherapy (reduced-intensity conditioning, RIC) with a reduction in toxicity while achieving good outcomes.…”