Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre’s experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x10 9 /l (1-23), which increased to 41x10 9 /l (6-150). The median platelet count increment was 29.5x10 9 /l ( p = 0.001). The pre-treatment median neutrophil count was 1.19x10 9 /l (0.39-5.1), which increased to 2.35 x10 9 /l (0.1-5.33) ( p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl ( p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.
Introduction:High-dose Melphalan followed by autologous hematopoietic cell transplantation (ASCT) compared to conventional chemotherapies has been shown to improve survival and progression free survival (PFS) in eligible patients with multiple myeloma (MM). However cells that are resistant to the high-dose therapy and remaining in the patient and/or PBSC grafts may eventually lead to relapse. Over the past decade, data have been published on the role of circulating plasma cells (CPCs) as a poor prognostic feature at the time of diagnosis and prior to auto HSCT. But these studies have not sought this issue exclusively in PBSC grafts. The aim of this study was to analyze the impact of flow cytometric measurement of residual clonal cells within the apheresis products on outcome following ASCT. Materials and Methods:Patients with a diagnosis of MM who underwent auto HSCT at our center between January 2008- Mart 2018 were prospectively analyzed. PBSC grafts were tested for the presence of abnormal PCs (APC) and the number of normal PCs (NPC) by multi-parameter flow cytometry (FCM). Standard panel was set up with CD138FITC/CD38PE/CD45ECD/CD56PC5, CD45-CD56+PCs were identified as APC if any aberrant expression (including; CD20(loss)CD27(loss)CD28(gain)CD33(loss)CD34(gain)CD81(loss) CD117(gain)) is detected at diagnosis, the corresponding antibody was also added to the panel. Since maintenance was not an approved treatment in myeloma most patients did not receive any. Outcome was determined as response to transplant, PFS and overall survival (OS) in months by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit. Results: A total of 209 patients with MM with routine assessment for APC in the apheresis product were included in the analysis. Of these patients, 195 who underwent ASCT, met the predetermined criteria for inclusion. There were 81 (41.5%) female and 114 (58.5%) male patients. The median age at diagnosis of MM was 56 years (range, 31-71 years). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). Among 195 patients, 36 (18.5%) had evidence of APC contamination in the PBSC grafts ranging between 1x10-4-12.8 x10-4of total cells. Subtypes of MM were similar among those w/wo APC. Seventy-four patients had pre and post ASCT PET-CT imaging done with 28.2% still active lesions post-ASCT. There was no correlation between PET-CR and absence of APC in grafts. Neither was there a statistically significant association between disease response <VGPR at mobilization and the number of APC in the apheresis product. Post-transplant responses were closely associated with pre-transplant responses. A total of 25 and 57 patients relapsed/progressed in respectively 6 and 12 months after ASCT. Post-transplant response was significantly associated with relapse at 6 months (≥VGPR vs. <VGPR; 37.5% vs. 62.5%, p=0.000). Estimated median OS was significantly different between patients w/o APC contamination; 20.4±8.1 and 63.3±3.8, respectively (p=0.000) (Figure 1). There were no differences in OS among the patients achieving VGPR/CR at the time of mobilization and also two months after the ASCT. We performed a subgroup analysis of patients in grouping together VGPR/CR or only CR and among those patients presence of APC was correlated with worse OS (Figure 1). PFS at 2 years were 60.3±4.3% and 75.6±9.7% in patients receiving APC free PBSC grafts compared with grafts with evidence of APC contamination, respectively (p=0.595). Discussion:PostASCT immune response was predictive for OS only when combined with APC results. Our study provides new insight suggesting a survival advantage value of residual APC detected by FCM, even at a low sensitivity level, on OS but not PFS following ASCT. The impact of such analysis may be more relevant on PFS with better assessment of residual APC with next generation flow cytometric/sequencing approaches while taking into account maintenance. Disclosures Ilhan: Roche: Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Celgene: Speakers Bureau.
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