Gemcitabine-Based Salvage Chemotherapy as a Bridge to Allogeneic Hematopoietic Stem Cell Transplantation for the Patients with Relapse of Hodgkin Lymphoma After Autologous Hematopoietic Stem Cell Transplantation.
Authors: Czyz Anna , Nowicki Adam , Gil Lidia , Dytfeld Dominik , Lojko-Dankowska Anna , Styczynski Jan , Komarnicki Mieczyslaw 
Published: October 2019

Abstract
Abstract 2822
An optimal therapy for patients with Hodgkin lymphoma (HL) who experience relapse after autologous hematopoietic stem cell transplantation (autoHSCT) has not been established. Gemcitabine has been shown to be effective in patients with relapsed or refractory lymphoma. We evaluated the efficacy and safety of gemcitabine-based chemotherapy in 22 patients (median age 33 years, range 23–56 years) with relapse of HL at a median of 7 months (range 3–82) after autoHSCT preceded by a median of 3 (range 2–6) previous chemotherapy lines. Two patients relapsed after autoHSCT followed by allogeneic hematopoietic stem cell transplantation (alloHSCT). The patients received a median of 3 (range 1–4) gemcitabine-based chemotherapy courses with filgastrim support. Fourteen of patients received regimen which consisted of gemcitabine 1000 mg/m2 and vinorelbine 25 mg/m2 on days 1, 8 and 15 given every 28 days and eight of patients received gemcitabine 1000 mg/m2 on days 1, 8 and 15, cisplatin 100 mg/m2 on day 1 and methylprednisolone 1000 mg/m2 on days 1–4 of a treatment cycle repeated every 28 days. Twenty of the 22 patients were treated with the intent to proceed to reduced intensity alloHSCT. Two patients with relapse of HL after autoHSCT followed by alloHSCT were treated with the intent to proceed to donor lymphocyte infusion (DLI).

Results:
A toxicity of a total 60 gemcitabine-based cycles was analyzed. The dose of gemcitabine was omitted, delayed or reduced due to neutropenia or thrombocytopenia in 22/60 (33%) cycles. Neutropenia < 0,5 G/L occurred in 20/60 (33%) and thrombocytopenia < 20 G/L in 19/60 (32%) cycles. Two patients were thrombocytopenic before gemcitabine treatment. Seven of the 60 (12%) cycles were complicated by infection grade 3–4 according to NCI CTC (neutropenic febrile- 2 episodes, pneumonia- 5 episodes). Transient liver enzymes elevation grade 2 occurred in 2/60 (3%) cycles in 1 patient. The overall response rate was 64% (14/22 pts), with 6 CR confirmed by PET/CT and 8 PR. At the time of analysis 9 patients have proceeded to reduced intensity alloHSCT and 2 patients after prior autoHSCT and alloHSCT to DLI. After a median follow-up of 8 months (range 3–38) 11/22 patients remain alive. OS for all 22 patients was 39% (95% CI 14–64) at 24 months estimated with the Kaplan-Meier method. OS according to the response to gemcitabine-based salvage chemotherapy was 47% for patients who achieved CR/PR after treatment and 23% for refractory patients (p ns). Median of PFS for patients with response to gemcitabine-based chemotherapy was 8 (95% CI 5–11) months.

Conclusion:
Our observational study confirms that gemcitabine-based chemotherapy is a feasible regimen with significant response rate and acceptable toxicity profile in heavily pre-treated patients with relapse of HL after autoHSCT. However, the response duration is short and gemcitabine-based chemotherapy appears to be a treatment option to provide a bridge to alloHSCT.

Disclosures:
No relevant conflicts of interest to declare.