Radioimmunotherapy for Stem Cell Transplantation in Non-Hodgkin’s Lymphoma: In Pursuit of a Complete Response

Abstract

High-dose chemotherapy (HDC) conditioning given in association with autologous stem cell transplantation (ASCT) or reduced-intensity conditioning (RIC) with allogeneic stem cell transplantation (alloSCT) are established treatment approaches for patients with chemotherapy-sensitive, relapsed, aggressive, or low-grade non-Hodgkin's lymphoma (NHL). These approaches have been shown to be the only curative option for patients with relapsed NHL. Despite data suggesting that prolonged event-free survival can be achieved with SCT combined with HDC, there are problems that may limit the utility of this approach for a broad patient population. For example, older patients, who make up the majority of the NHL population, may not be able to withstand the toxicities associated with this intensive regimen, and this therapy combination, especially when it includes the use of total-body irradiation, has been associated with a greater risk for secondary malignancies. Furthermore, relapse is the most common cause of treatment failure after HDC with ASCT and there is a poor success rate for those patients with either chemotherapy-refractory or heavily pretreated, multiple-relapsed disease. Consequently, there is an urgent need for other effective and well-tolerated approaches that will eradicate the residual disease that may persist before SCT, thus improving outcomes for patients with this life-threatening disease. In addition, approaches with better safety profiles would allow older patients to benefit from this therapeutic option. Because lymphomas are highly sensitive to radiation, radioimmunotherapy (RIT) has been used with great success in consolidation therapy and, as a result, there is great interest in exploring the use of RIT, either as a single agent or as augmentation of HDC, as part of a conditioning regimen for ASCT. The flexibility of including RIT as part of conditioning therapy also allows it to be combined with RIC to reduce the toxic effects of HDC. This treatment option replaces any concomitant loss of chemotherapy efficacy with a gain in RIT efficacy. The data so far suggest that the use of RIT in the au-

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

“…Though it varies with B-cell NHL subtype, a significant number of patients relapse with no greatly defined standard therapies. For DLBCL, the combination of high-dose chemotherapy and stem cell transplantation is effective for relapsed NHL [7] but is clearly worse in patients with early relapse or primary failures. Patients with indolent NHL relapse even more frequently, with a subsequent shorter response to chemotherapy and often transformation over time.…”

A new approach for eradication of residual lymphoma cells by host nonreactive anti–third-party central memory CD8 T cells

“…18 For patients with advanced B-CLL or NHL, the most common treatments are either autologous BMT after intensive conditioning or allogeneic BMT following RIC. [19][20][21] The former is limited to patients who can tolerate the harsh conditioning, and therefore excludes many elderly patients who make up the majority of the B-NHL population. Thus, a recent report from the Center for International Blood and Marrow Transplant Research supports the use of the latter for such patients.…”

Tearing RAGs apart

“…Total body irradiation is likely to be more harmful although the use of targeted radioimmunotherapy to BM cells may have some utility. 5 Similarly, hematopoietic progenitor cell depletion by administration of specific antibodies may be an important development. 6 Gene therapy strategies for ARTEMIS 7 and RAG 8,9 deficiencies have shown proof of concept in murine models and clinical trial protocols are in development.…”