Rhenium 188–labeled anti-CD66 (a, b, c, e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-risk acute myeloid leukemia or myelodysplastic syndrome: results of a phase I-II study

Abstract

The conditioning regimen prior to stem cell transplantation in 36 patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) was intensified by treating patients with a rhenium 188-labeled anti-CD66 monoclonal antibody. Dosimetry was performed prior to therapy, and a favorable dosimetry was observed in all cases. Radioimmunotherapy with the labeled antibody provided a mean of 15.3 Gy of additional radiation to the marrow; the kidney was the normal organ receiving the highest dose of supplemental radiation (mean 7.4 Gy). Radioimmunotherapy was followed by standard full-dose conditioning with total body irradiation (12 Gy) or busulfan and high-dose cyclophosphamide with or without thiotepa. Patients subsequently received a T-cell-depleted allogeneic graft from a HLA-identical family donor (n ‫؍‬ 15) or an alternative donor (n ‫؍‬ 17). In 4 patients without an allogeneic donor, an unmanipulated autologous graft was used. Infusion-related toxicity due to the labeled antibody was minimal, and no increase in treatment-related mortality due to the radioimmunoconjugate was observed. Day ؉30 and day ؉100 mortalities were 3% and 6%, respectively, and after a median follow-up of 18 months treatment-related mortality was 22%. Late renal toxicity was observed in 17% of patients. The relapse rate of 15 patients undergoing transplantation in first CR (complete remission) or second CR was 20%; 21 patients not in remission at the time of transplantation had a 30% relapse rate. (Blood. 2001;98:565-572)

Ibritumomab tiuxetan (Zevalin) combined with reduced-intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin's lymphoma

“…131 I linked to anti-CD45 and anti-CD33 and 188 Re linked to anti-CD66 have been used in combination with myeloablative chemotherapy and allogeneic SCT in patients with acute leukemia. [27][28][29] Radioimmunotherapy seemed to enable further intensification of the conditioning regimen by targeting radiation to the BM with no additional toxicity. A similar approach has also been tested in RIC.…”

Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia

“…In contrast to chronic hematological neoplasms like chronic lymphocytic and chronic myeloid leukemia, dose intensification of the conditioning regimen before allogeneic transplantation with rhenium 188-labeled anti-CD66 monoclonal antibody seems to be beneficial in high risk acute leukemias. 36 This concept of myeloablation without the risk of excessive organ toxicity is especially attractive for elderly patients. Apart from the conditioning therapy the introduction of pre-emptive donor lymphocyte infusion may be crucial for future trials for maintaining complete remission in acute leukemias.…”

Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

“…1 Monoclonal antibodies (mAbs) targeting hematologic-specific antigens have been used in radioimmunotherapy (RIT) studies as a means to deliver higher radiation doses prior to HSCT. [2][3][4][5][6] One such target is CD45, a cell surface antigen highly expressed on hematologic tissues (;200 000 binding sites per cell) with minimal expression on nonhematologic tissues. 7,8 CD45 is not extensively internalized after mAb binding, 9,10 further making anti-CD45 RIT a viable approach for therapy of high-risk AML.…”