Alpha BETA T-Cell Depletion for Patients with Hematologic Malignancies with Targeted ATG Dosing

Children’s Wisconsin is currently enrolling patients with hematologic cancers on a Pilot trial, coupling bone marrow transplant with α/β (alpha/beta) T-cell depletion with targeted dosing of AntiThymocyte Globulin (ATG) in patients with hematologic malignancies including:

• Acute myeloid leukemia
• Acute lymphoblastic leukemia
• Chronic myelogenous leukemia
• Mixed lineage or biphenotypic acute leukemia
• Lymphoblastic lymphoma
• Burkitt’s lymphoma/leukemia
• Myelodysplasia

Drs. Amy Moskop and Julie Talano, are the co-primary investigators of this investigator initiated trial.

Allogeneic stem cell transplant is curative for many patients with leukemias in which chemotherapy has <20% chance of achieving long-term remission. However, only 25-30% of patients will have an HLA identical sibling donor. A well matched unrelated donor, or mismatched related donor may be considered for these patients. However, acute and chronic graft vs. host disease (GVHD) are significant risks for patients who receive these alternative donor transplants. To overcome the risk of GVHD, various methods of T-cell depletion have been developed.

T-cell depletion of unrelated and Haploidentical donors has been done for over 25 years at Children’s Wisconsin for patients who lack matched related donors. This has enabled us to transplant patients who do not have either a matched related donor who represent more than 75 percent of patients who may benefit from an allogeneic transplant.

The technology used for T-cell depletion (TCD) has changed through the years. The technology of T- cell depletion has evolved from methods that remove all of the T-cells, to more precise methods. Newer methods have become available using magnet-activated cell sorting including, depletion of α/β T lymphocytes. In this method, γ/δ+ T cells are retained. Those cells have potential anti-infectious and anti-tumor properties and are not considered to cause GVHD.

We are also using personalized medicine to dose one of the medicines used for Bone Marrow Transplant in this study. Targeted Anti-thymocyte Globulin (ATG) is dosed based on a patient’s weight and white blood cell count on the day of admission. By giving targeted ATG to each patient, we hope to reduce infections and improve the anti-leukemic affect of the BMT. 

Our blood and marrow transplant program is FACT (Foundation for the Accreditation of Cellular Therapy) accredited and has one year survival rates for allogeneic transplant >90%. Children’s Wisconsin was ranked in the U.S. News & World Report Best Children’s Hospitals list