Soluble CD44 Is Increased in Haematopoietic Stem Cell Grafts of Patients with Acute Myeloid Leukemia, Multiple Myeloma and Non-Hodgkin’s Lymphoma.

Autologous haematopoietic stem cell transplantation (autoHSCT) after high dose chemotherapy is a widely used form of therapy for patients with leukemia, lymphoma and multiple myeloma. Malignant cells remaining in the graft, however, may reengraft leading to relapse of the original disease. CD44, a transmembrane glycoprotein, which is overexpressed in many malignancies, including most haematological malignancies, and which plays a role in the engraftment of leukemia-initiating cells, is shed from the surface of malignant cells. In order to establish whether there is a correlation between the amount of CD44 shed from the surface of the malignant cells with the number of contaminating cells remaining in the graft, the engraftment potential of the malignant cell population, or clinical outcome after autoHSCT, we measured soluble CD44 (sCD44) in 86 haematopoietic stem cell grafts from patients with haematological malignancies by enzyme-linked immunosorbent assay (ELISA) and compared the results to sCD44 levels in the HSC grafts from 33 healthy donours. The levels of sCD44 were almost 2fold higher in the grafts of patients with acute myeloid leukemia (AML) (mean: 30,015 ng/ml ± 8524), multiple myeloma (mean: 27,564 ng/ml ± 7,801) and diffuse large B-cell Non-Hodgkin-Lymphomas (mean: 22,539 ng/ml ± 8,382) than in healthy HSC donour grafts (mean: 13,035 ng/ml ± 10,075). As expected, levels of sCD44 were highest in auto HSCT grafts of patients with AML. The majority of patients who achieved a complete remission after autoHSCT had relatively low sCD44 values (mean: 22,610 ng/l ± 7439). Levels of sCD44 were greatest in patients who experienced progressive disease (mean: 28,918 ng/ml ± 10,431), and somewhat less elevated in patients with relapsed disease after auto HSCT (mean: 26,171 ng/ml ± 7616). In addition, patients who had levels of sCD44 <25,500 ng/ml had increased survival (33% at 120 months after autoHSCT versus 18% in patients with sCD44 levels of >25,500 ng/ml). These results argue that the levels of soluble CD44 in an HSC graft could serve as a biomarker for the engraftment potential of contaminating malignant cells in the graft, and may correlate with clinical outcome after autoHSCT. Further, these results raise the possibility that CD44 blocking strategies may be beneficial in autoHSCT.