Nonmyeloablative allogeneic blood stem cell transplantation (NMBSCT) ± donor lymphocyte infusion (DLI) for chemorefractory advanced nasopharyngeal carcinoma (NPC)

Abstract only 2549 Background: There is emerging clinical evidence for T cell immunotherapy in NPC. We report a NMBSCT regimen that induced mixed chimerism for DLI to potentially achieve a graft-versus-tumour effect (GVT) in NPC. Methods: 15 patients with advanced pretreated NPC were accrued to this...

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Published in:Journal of clinical oncology Vol. 24; no. 18_suppl; p. 2549
Main Authors: Toh, H. C., Tan, E. H., Thng, C. H., Yap, S. P., Lee, K. M., Phoon, Y. P., Chua, S., Soe, Y., Hee, S. W., Sun, L.
Format: Journal Article
Language:English
Published: 20-06-2006
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Summary:Abstract only 2549 Background: There is emerging clinical evidence for T cell immunotherapy in NPC. We report a NMBSCT regimen that induced mixed chimerism for DLI to potentially achieve a graft-versus-tumour effect (GVT) in NPC. Methods: 15 patients with advanced pretreated NPC were accrued to this prospective clinical trial. Our regimen comprised IV cyclophosphamide 50 mg/kg on day-5,-4,-3 and IV thymoglobuline on day-1, +1, +2 and +3 (n = 9) and then revised to IV thymoglobuline day-1, +1, +2, +3 (n = 6). Thymic radiation was given on day-1. G-CSF mobilized HLA-matched (n = 14) and 1-antigen-mismatched (n = 1) sibling PBSC were infused. DLI was initiated following taper of prophylactic cyclosporine (CyA). Results: Median age (n =15) was 49 yrs, median no. of metastatic organ sites was 3, mean no. of prior chemotherapy was 4 (range 2 - 8) and 14/15 had prior radiation. Median time to engraftment was 13 days and hospital stay was 17 days. Complete removal of prophylactic CyA was achieved for all patients at a median of day +28. DLI was given in 14 patients (median = 2, range 1 to 6). 4 patients were later re-started on GVHD immunosuppressive therapy. Two (13.3%) patients had acute GVHD (one Grade II and one fatal case who died on day+91). 3 patients developed chronic GVHD (20%), all controlled with short courses of standard immunosuppressive treatment. 11/15 died of PD, and 2/15 died from sepsis. 100-day TRM was 6.6%. 3/9 patients had donor graft loss. 6/6 patients on the revised protocol had stable and/or full donor chimerism. CMV antigenemia was 9/9 for the first regimen and 3/6 for the revised regimen (p = 0.044). Tumor response (RECIST) confirmed 40% PR, 33.3% SD and 40% PD, for a disease control rate of 73.3%. > day+100 anti-tumor response were observed in 5/15 patients (33.3%), implicating a GVT effect. 1 patient achieved a delayed PR on day+111 with stable donor chimerism of 19%. The longest surviving patient (36.5 mths) with multiple nodal, bone and lung metastasis achieved full donor chimerism and further tumor shrinkage at 8 mths post-NMBSCT. Conclusions: GVT is achievable with NMBSCT ± DLI in Stage IV NPC patients with a high disease control rate and acceptable GVHD. Early complete removal of prophylactic CyA was possible in all 15 patients. No significant financial relationships to disclose.
ISSN:0732-183X
1527-7755
DOI:10.1200/jco.2006.24.18_suppl.2549