Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

Abstract

Despite overall improvements in outcomes of patients with diffuse large B cell lymphoma (DLBCL), B30-40% of patients develop relapsed or refractory disease. For patients with chemo refractory disease, or recurrent disease following autologous hematopoietic SCT (auto-HCT), the prognosis is poor, with no consensus on the optimal therapy. Currently, owing to the graft vs lymphoma effect, hematopoietic allogeneic hematopoietic cell transplantation (allo-HCT) is the only potentially curative option for such patients. In addition, many patients who are considered today for auto-HCT actually have a low likelihood of benefit. For example, a patient with prior rituximab exposure who relapses within 1 year of diagnosis and has a second-line age-adjusted International Prognosis Index of 2 or 3 at relapse has a o25% chance of being cured by auto-HCT. It is possible that such patients may be better served with an allo-HCT. Unfortunately, in many cases, allo-HCT applicability is limited by patient age, comorbidities, performance status and treatment-related toxicities. Recent attempts to improve the efficacy of auto-HCT, such as incorporating radio-immunotherapy into the conditioning regimen, have not resulted in improved outcomes. However, incorporation of novel agents such as antiprogrammed death-1 antibodies as maintenance therapy after auto-HCT show promise. Allo-HCT in relapsed/refractory DLBCL patients can result in a 30-40% PFS rate at 3 years, in part due to a graft vs DLBCL effect. While reduced-intensity/nonmyeloablative conditioning is increasingly being used, certain patients may benefit from myeloablative conditioning. We present an algorithm intended to discriminate which relapsed and refractory DLBCL patients are most likely to benefit from auto-HCT vs allo-HCT. New approaches, using novel agents that target the molecular heterogeneity in DLBCL, will be an essential component of moving the field forward. Lastly, we propose a prospective registry-based study as the only feasible mechanism to define the optimal position of allo-HCT in the overall treatment strategy for DLBCL. It is hoped that this review will promote the development of prospective multicenter efforts to determine whether such patients do, in fact, benefit from earlier and/or more effective implementation of allo-HCT.

Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM)–Campath Allogeneic Stem Cell Transplantation for Aggressive Non-Hodgkin Lymphoma: An Analysis of Outcomes from the British Society of Blood and Marrow Transplantation

“…In this series, a complete response to DLI was seen in 1 of the 5 patients treated for relapse/progression. The rapid growth kinetics of aggressive NHL may allow the malignant clone to escape the potential GVL effect and, at least in part, explain the higher relapse rates seen after allograft when compared with indolent histologies [34].…”

Impact of induction regimen and stem cell transplantation on outcomes in double-hit lymphoma: a multicenter retrospective analysis

“…15,18,19 There are both randomized 20,21 and single-arm phase 2 data 22 suggesting that intensive induction and/or consolidation therapy may improve outcomes for selected patients with DLBCL, though none have assessed outcome with respect to DHL. Similarly, consolidation with either high-dose chemotherapy with autologous stem cell transplant (HDT-ASCT) 23 or allogeneic (allo) stem cell transplant (SCT), 24 may also improve outcomes in patients with aggressive B-cell malignancies, although the role of each in DHL remains undefined.…”

Stammzelltransplantation bei malignen Lymphomen

“…Diese Beobachtungen unterstützen die Existenz eines Graftvs.-DLBCL-Effekts. Vermutlich profitieren am meisten jüngere Patienten mit chemosensiblem DLBCL-Rezidiv von einer allogenen SZT [36]. Sogar therapierefraktäre DLBCL-Patienten können dauerhafte Remissionen nach allogener SZT erreichen [37].…”

“…Wenngleich die Strategien noch im Fluss sind, scheint für jüngere Patienten mit DLBCL-Rezidiv die allogene SZT eine bessere Option darzustellen [36]. Auch für Patienten mit FL zeigen sich klare Hinweise für die Existenz eines GvL-Effekts [41].…”