What is a Reduced Intensity or Mini-Stem Cell Transplantation?

Historically, the preparative regimens for stem cell transplantation involved the highest tolerable doses of chemotherapy and/or radiation designed to eradicate the malignancy and provide immunosuppression to prevent graft rejection.

Unfortunately, high dose chemotherapy/radiation are associated with significant risks of treatment-related complications, sometimes fatal.

However, it is increasingly recognized that the therapeutic benefit of allogeneic marrow transplantation for many diagnoses is not only limited to the chemotherapy/radiation. The success of the transplant is also related to the presence of a potent immune-mediated graft-versus-malignancy effect. This has led to development of less toxic, reduced intensity preparative regimens to achieve engraftment and allow development of graft-versus-malignancy effects as a primary form of therapy.

Upon engraftment, an allogeneic graft-versus-hematopoietic effect occurs in which donor cells act to eradicate residual host hematopoiesis as well as the malignant cells. Some transplant physicians refer to this type of treatment as “mini-transplant.” This less toxic approach for stem cell transplantation allows treatment of older patients (up to mid-70s) and selected patients with other co-morbidities.

Disease Susceptibility to Graft versus Malignancy

There are major differences among malignancies in their susceptibility to graft-versus-malignancies effects and hence their sensitivity to reduced intensity allogeneic transplants. Strong graft-versus-tumor effects have been demonstrated in patients with chronic myelogenous leukemia, chronic lymphocytic leukemia and indolent lymphoma after an allogeneic stem cell transplant.

Several transplant groups have also reported promising results in patients with recurrent Hodgkin’s disease. Patients with acute myelogenous leukemia, multiple myeloma, and intermediate-grade lymphoma have intermediate sensitivity to graft-versus-malignancies effects but patients with acute lymphocytic leukemia and high grade lymphoma appear relatively insensitive to the graft-versus-malignancies effects. The rapid rate of proliferation of these malignancies may outpace a developing immune response.

Graft-versus-tumor effects may also occur against solid tumors, although few studies with allogeneic transplantation have been performed. Major antitumor responses have been reported in renal cell carcinoma, usually concomitant with development of acute GVHD (graft-versus-host disease). Further studies are required to assess the potential for induction of graft-versus-tumor effects against other solid tumors.

Interesting in knowing more about our program? Visit the home page for the Bone Marrow Transplant Center at Rush University Medical Center in Chicago, Illinois.