Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma

Abstract

Many patients with lymphoma relapse after autologous stem cell transplantation (AutoSCT). These patients are often considered for allogeneic stem cell transplantation (AlloSCT) if remission can be achieved. If a tandem approach was organized, some cases of relapse might be prevented. We conducted a phase II trial of tandem AutoSCT followed by reduced-intensity conditioning (RIC) AlloSCT for patients with high-risk lymphoma. High-dose chemotherapy was given with busulfan, cyclophosphamide, and etoposide. AlloSCT was composed of RIC with busulfan/fludarabine and tacrolimus, sirolimus, and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Donors were fully matched related or unrelated donors. AlloSCT was performed any time between 40 days and 6 months after AutoSCT. Forty-two patients were enrolled, and all patients underwent AutoSCT. RIC AlloSCT was performed in 29 patients. In the 29 patients who underwent tandem transplant, median time from AutoSCT to AlloSCT was 96 days (range, 48 to 169). The 6-month cumulative incidence of grades II to IV acute GVHD was 13.8% (90% confidence interval [CI], 5.3% to 26.3%). Cumulative incidence of chronic GVHD at 1 year was 37.9% (90% CI, 23.1% to 52.7%). Nonrelapse mortality at 2 years after AlloSCT was 11.1% (90% CI, 3.5% to 23.6%). At a median follow-up of 30 months (range, 17.1 to 51.5) for the entire group, the 2-year progression-free survival rate was 64% (90% CI, 50% to 75%) and the 2-year overall survival rate was 69% (90% CI, 43% to 85%). For the 29 patients who underwent tandem SCT, the 2-year progression-free survival rate was 72% (90% CI, 55% to 83%) and the 2-year OS rate was 89% (90% CI, 74% to 96%). Tandem AutoSCT-RIC AlloSCT appears to be safe and effective in patients with high-risk lymphoma. Prospective trials using such an approach in specific lymphoma subtypes are warranted.

How I manage patients with relapsed/refractory diffuse large B cell lymphoma

“…With a better definition of the prognostic factors and poor results obtained with HDT/ASCT in early relapse, high secondary IPI, and double‐hit translocation (Herrera et al , ), we can now discuss whether, in the case of a response, these patients should be transplanted directly with RIC‐allo or ASCT or treated with a tandem approach of ASCT followed by RIC‐allo (Chen et al , ). Nevertheless, it should be underscored again that RIC‐allo should not be proposed to refractory patients who are not responding to salvage chemotherapy.…”

Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee

“…In general, BU TDM should be conducted in adults receiving BU/ CY, FLU/BU/Thymoglobulin ± TBI, and any novel regimens developed using BU TDM (eg, vorinostat/gemcitabine/BU/ melphalan [37]). However, the use of BU TDM has varied with FLU/BU [49,50], clofarabine/BU [32,51,52], and BU/CY/ etoposide (BuCyE) regimens mostly based on the magnitude of the BU dose [53,54].…”

Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes

“…50 Chen et al compared outcomes after ASCT across different conditioning regimens and among patients with HL, and busulfan-based regimens were also associated with inferior outcomes. 51 …”