Allogeneic Hematopoietic Stem Cell Transplantation With A Reduced-Intensity Conditioning Regimen (RIST) For The Treatment Of Solid Tumors: A Single-Institute Experience

Objective. RIST has been established as a standard therapy for various hematologic malignancies. However, its feasibility in patients with solid tumors has not been well evaluated, and thus we conducted a single-institute, retrospective study. Patients and Methods. A total of 44 patients with various advanced solid tumors underwent RIST from a related donor (41 sibling donors; 38 HLA-matched and 6 one-locus-mismatched donors) between April 2000 and August 2006. Most were enrolled in various prospective studies, and efficacy data for colorectal cancer and renal cancer have been published previously (Transplantation 78:1740, 2004; Exp Hematol 32:599, 2004). This follow-up retrospective analysis particularly focused on the overall feasibility of the procedure. The median age of the patients was 43.5 years (range 20-61). Their diseases were renal cell cancer (RCC: 8 mixed cell, 6 clear cell, 2 granular cell and 1 papillary), pancreatic cancer (4), rhabdomyosarcoma (3), colorectal cancer (2), bile duct cancer (2), Bellini duct cancer (2), and others(13). All but one patient, who had PR small cell lung cancer, were in recurrent or primary refractory tumor. The conditioning regimens were Flu (180 mg/m2)/BU(8 mg/kg po)/ATG (Thymoglobulin 5 mg/m2) (19), Flu/BU (10), cladribine(0.66 mg/kg)/BU (9) and cladribine/BU/ATG (6). The primary agent for GVHD prophylaxis was cyclosporine, and 4 patients also received short-term methotrexate. Results. All patients achieved hematological engraftment at a median of 11 days (range, 6-20). At 30 days and 90 days after transplantation, 10 of the 18 and 10 of the 11 evaluable patients achieved complete donor chimerism. Twenty-one patients developed acute GVHD at a median of 28 days (range, 8-157), including 19 grade 2-4 and 10 grade 3-4. Seventeen developed chronic GVHD at a median of 114 days (range, 94-277). Therapy-related mortality (TRM) was 9% (2 acute GVHD, 1 ARDS and 1 hemorrhagic shock), and 40 died from tumor progression. The median follow-up time was 167 days (range 14-1449). The overall survival rate at 2 years was 11% in the whole group, while patients with RCC (clear cell 33%, all other types 22%) had a higher rate of 25% (p<0.0001). Conclusion. Although these findings suggest that RIST is feasible in patients with refractory solid tumor, the ultimate usefulness of RIST should be balanced against recently developed promising new agents.