Prophylactic Peripheral Blood Stem Cell Collection in Patients with Extensive Bone-Marrow Infiltration of Neuroendocrine Tumours Prior to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

Amir Sabet,Hans Jürgen Biersack,Fadi Khreish,Frank Grünwald,Samer Ezziddin,Nicolai Mader,Jörg Thomas Bittenbring

doi:10.3390/ph14101022

Abstract

Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.

Highlights

In this paper we introduce and discuss the feasibility of peripheral blood stem-cell collection (PBSC) collection in neuroendocrine tumors (NET) patients with metastatic bone-marrow spread
Peptide receptor radionuclide therapy (PRRT) was performed with 7.6 ± 0.8 GBq 177 Lu-DOTATATE per cycle at standard intervals of 3 months using a previously described protocol [22]
(15.4 GBq) of re-PRRT and partial response (E) after additional 3 cycles (18 GBq). This preliminary report introduces the concept of PBSC in high-risk patients with. This preliminary report introduces the concept of PBSC in high-risk patients with advanced bone-marrow involvement of NET undergoing PRRT, describing a successful advanced bone-marrow involvement of NET undergoing PRRT, describing a successful procedure in five patients with bone-marrow impairment at the time of apheresis

Summary

Introduction

Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE is a longstanding systemic treatment for metastatic gastroenteropancreatic neuroendocrine tumors (GEPNET) [1,2,3]. Several studies have reported remarkable results of individualized PRRT schemes for selected patients in different settings [4,5,6,7,8,9,10,11,12,13,14]. The only conducted randomized phase III trial (NETTER-1) demonstrating the efficacy of PRRT was limited to patients with midgut NET receiving a “standard treatment scheme”. Identifying other eligible patients for PRRT, appropriate treatment individualizations, and baseline characteristics influencing the outcome mainly relies on Pharmaceuticals 2021, 14, 1022.

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