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A comparison between low intensity and reduced intensity conditioning in allogeneic hematopoietic stem cell transplantation for solid tumors

¹ Department of Laboratory Medicine, Division of Clinical Immunology;
² Center for Allogeneic Stem Cell Transplantation;
³ Department for Clinical Science, Intervention and Technology, Division of Radiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden

Correspondence: Réka Conrad, Karolinska Institutet, Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska University Hospital Huddinge F79, SE-141 86 Stockholm, Sweden. E-mail: reka.conrad{at}ki.se

Background: Following different types of conditioning, allogeneic hematopoietic stem cell transplantation produces a graft-versus-tumor effect in patients with solid tumors. We performed a non-randomized study comparing low intensity conditioning with reduced intensity conditioning after stem cell transplantation to demonstrate the graft-versus-tumor effect.

Design and Methods: Allogeneic stem cell transplantation was performed in 48 patients with metastatic renal cell cancer (n=17), colo-rectal cancer (n=15), non-metastatic advanced primary liver cancer after orthotopic liver transplantation (n=11), and other solid tumors (n=5). Tumor response was determined based on the international response evaluation criteria for solid tumors (RECIST).

Results: No significant difference in the incidence of graft rejection was found between the low intensity conditioning and reduced intensity conditioning groups. Engraftment occurred earlier in the low intensity conditioning group than in the reduced intensity conditioning group (median 0 vs. 16 days, respectively; p<0.001). Complete donor chimerism in B cells occurred earlier after low intensity conditioning than after reduced intensity conditioning (median 28 vs. 97 days, respectively; p<0.001). No significant difference in the incidence of tumor response was found between groups receving the different types of the conditioning. The most favorable tumor response rate was found in patients who received donor lymphocyte infusions and de-veloped chronic graft-versus-host disease (75% vs. 34%, p=0.003). The best graft-versus-tumor effect was demonstrated in patients with advanced primary liver cancer who had previously undergone liver transplantation (p=0.018). Patients receiving reduced intensity conditioning had a tendency to better overall survival compared to the low intensity conditioning group (30% vs. 17%, p=0.005).

Conclusions: Adjuvant cell therapy with donor lymphocyte infusion may augment the graft-versus-tumor effect of cronic graft-versus-host disease. Patients with limited tumor load are indicated for allogeneic stem cell transplantation and reduced intensity conditioning may be favorable compared to low intensity conditioning.

Key words: allogeneic hematopoietic stem cell transplantation, liver transplantation, reduced intensity conditioning, graft-versus-tumor effect, solid tumor.