Blog | HemaCare

Improved Outcome for Stem Cell Transplantation in Leukemia

Sep 28, 2015 1:00:14 PM / by Daisy Goodrich

About 50% of stem cell transplant patients develop GVHD. A clinical trial using a modified stem cell graft reduced this hazard to 9%.

Stem cell transplantation is often curative for leukemia patients, especially with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). However, risks associated with the procedure can be high. It is therefore highly recommended that patients select transplant centers equipped to manage complications.

stem cell T cells in the stem cell graft influence outcome following transplantation. Image credits: https://commons.wikimedia.org/wiki/File:US_Navy_021204-N-0696M-171_Surgical_technician_Amina_Sherali_places_recently_transfused_bone_marrow_from_Aviation_Electronics_Technician_1st_Class_Michael_Griffioen_into_a_sterile_bag_in_preparation_for_transplant.jpg

Given the dire alternative, common hazards of stem cell transplantations are acceptable. Still, the hematology community strives to improve the procedure. Due to the substantial influence of transplantation on patient survival, there is much impetus for reducing complications and improving the benefits of the procedure.

Scientists have already tested several modifications that have led to advances in the overall survival of stem cell transplant recipients. One variation that modifies outcome is altering the number of T cells in the stem cell graft transplanted into the patient.

Research has shown that donor T cells present in the graft (T cell-replete graft) promote the establishment of the graft in the recipient. T cells also have a graft vs. leukemia effect whereby donor T cells eliminate the recipient’s leukemia cells. However, donor T cells can often times also recognize the recipient as being foreign and consequently mount a graft versus host disease (GVHD), attacking the patient’s “foreign” organs (previously discussed here).

If T cells are depleted from the graft (T cell-deplete graft), it alleviates potential GVHD, but at the cost of delayed immune reconstitution. This leaves the stem cell transplant patient without a functioning immune system – making him or her vulnerable so that even common infections can have a fatal outcome.

Is there a fine balance between a T cell-deplete and a T cell-replete graft? In a clinical trial that enlisted 35 patients, clinicians tested transplanting T cell-deplete stem cell grafts and then adding back a defined dose of T cells.[1] More importantly, the donor T cells were sorted before introduction so that naïve T cells were eliminated and only memory T cells were given.

Experiments in mice had previously established the benefit of removing naïve T cells and adding memory T cells to stem cell grafts. In line with these preclinical observations, all patients in the clinical trial had successful grafting of donor cells with the modified T cell infusion. Of notable significance, incidences of chronic GVHD was down to 9%, in sharp contrast to the ~50% historical rates. Excessive rates of infection or relapse did not occur, and overall survival was 78% at 2 years.

At HemaCare, we are delighted to highlight another step forward in the stem cell transplantation procedure. We provide stem cells for research and applaud all work that translates from bench to bedside.

Reference

  1. Bleakley M, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015 Jul 1; 125(7):2677-89.

Topics: Bone Marrow, clinical trial, leukemia, Stem Cells, T Cells, Basic Research

Daisy Goodrich

Written by Daisy Goodrich

      Subscribe Here!

      Posts by Topic

      see all

      Recent Posts