Residual Disease on FDG-PET and Multiple Lines of Prior Therapy Predict Poorer Outcomes Following Autologous Hematopoietic Stem Cell Transplantation for Lymphoma

Introduction

The prognostic value of positron emission tomography using 18-fluorodeoxyglucose ([¹⁸F]FDG-PET) prior to autologous hematopoietic stem cell transplantation (HSCT) has become more established in recent years. We investigated the utility of pre-HSCT [¹⁸F]FDG-PET in patients undergoing autologous HSCT for lymphoma at our centre.

Methods

104 patients were identified as having undergone autologous HSCT for lymphoma between 2004 and 2013, who also had pre-transplant PET assessment. Patient demographic and disease-related data was collected retrospectively from electronic patient records. Contemporaneous PET-CT reports were used to document disease status prior to HSCT. Kaplan-Meier and Cox regression analyses assessed univariate and multivariate analysis of disease outcomes.

Results

The median age was 51 years (range 10-73), and 55.8% were male. 33 patients (31.7%) had Hodgkin lymphoma, the remainder non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (29.8%), mantle cell lymphoma (10.6%), follicular lymphoma (6.7%) and others (21.2%). The majority (81.7%) had advanced stage disease (III-IV). 14.4% had received four or more lines of prior therapy. At pre-transplant PET, 65 patients (62.5%) were documented to have a complete response (CR), 24 (23.1%) had a very good partial response (VGPR) and 15 (14.4%) had a partial response (PR). No patients were shown to have stable or progressive disease at the time of transplantation. All but 5 patients received pre-transplant conditioning consisting of carmustine/lomustine, etoposide, cytarabine and melphalan (BEAM). Progression-free survival (PFS) at 5 years was 43.9%, and overall survival 60.8% at 5 years. There was no difference in PFS or OS in patients with CR or VGPR on pre-transplant PET (see chart). Predictors of inferior PFS on multivariate analysis included 4 or more lines of prior therapy (hazard ratio (HR) 3.36, p=0.009), and those patients with only PR on pre-transplant PET (HR 2.93, p=0.007). Predictors of inferior OS on multivariate analysis included female gender (HR 2.51, p=0.024) and 4 or more lines of prior therapy (HR 3.36, p=0.009), with a trend towards inferior OS in those with age greater than the median (HR 2.10, p=0.081) and with PR on pre-transplant PET (HR 2.55, p=0.055). Day 100 transplant-related mortality was 2.9%.

Conclusion

In our large single-centre cohort, patients with either CR of VGPR on pre-transplant PET scan showed no difference in either PFS or OS. By contrast, those patients with less than VGPR and those who had undergone four or more prior lines of chemotherapy or radiotherapy had significantly poorer outcomes. Whether eligible patients who fail to achieve at least a VGPR prior to autograft might fare better with allogeneic transplantation remains to be proven.

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