Currently Viewing:
Currently Reading
Surgical Site Infections Common After Gastrointestinal Surgeries Worldwide
February 18, 2018 – Kaitlynn Ely
USPSTF Recommends Against Screening for Ovarian Cancer in Asymptomatic Women
February 18, 2018 – Jaime Rosenberg
Study Finds Merkel Cell Carcinoma Incidence Has Increased Since 2000
February 17, 2018 – Kaitlynn Ely
New ECPR Protocol Shows Increase in Survival of Some Cardiac Arrest Patients
February 17, 2018 – Samantha DiGrande
Anthem Changes to ED Payment Policy Leaves Some Unsatisfied
February 16, 2018 – Allison Inserro
5 Things Being Discussed and Addressed in Healthcare Spending
February 16, 2018 – Jaime Rosenberg
This Week in Managed Care: February 16, 2018
February 16, 2018
AJMC® in the Press, February 16, 2018
February 16, 2018 – AJMC Staff
Survey Identifies Barriers to Achieving Value-Based Care Models
February 16, 2018 – Kaitlynn Ely

Reducing GVHD Following Transplant in Lymphoma

Surabhi Dangi-Garimella, PhD
Researchers from the Memorial Sloan Kettering Cancer Center have developed a novel method using modified donor T cells to make stem cell transplants both safer and more effective for treating blood cancers
While allogenic hematopoietic stem cell transplants (ASCT) is curative, it is associated with complications of relapse and graft-versus-host disease (GVHD). Researchers from the Memorial Sloan Kettering Cancer Center (MSKCC) have developed a novel method using modified donor T cells ways to make stem cell transplants both safer and more effective for treating blood cancers.

Led by Marcel van den Brink, MD, PhD, head of the Division of Hematologic Oncology and co-director of the Parker Institute for Cancer Immunotherapy at MSKCC, and Michel Sadelain, MD, PhD director of the Center for Cell Engineering at MSKCC, this preliminary research suggests that genetically engineered immune cells from a donor cause less GVHD than unmodified donor immune cells.

A bone marrow transplant is often the last, best chance at a cure for people with advanced blood cancers. But the procedure is not without risks. The most significant risk is GVHD, when donor white blood cells attack healthy tissues in the recipient. In severe cases, it can be fatal.

CD19, a protein expressed on the surface of normal as well as malignant B cells, has been used in chimeric antigen receptor (CAR) T-cell treatments. Allogeneic CAR-T cells can increase the risk of the occurrence of GVHD, although this has not been reported in selected patients infused with donor-derived CD19 CAR T cells after ASCT. To better understand the mechanism whereby allogeneic CD19 CAR T cells may mediate anti-lymphoma activity without increasing the incidence of GVHD, the team at MSKCC studied donor-derived CD19 CAR T cells in ASCT and lymphoma models in mice. Specifically, the model used CD19-specific CD28z CARs.

The data showed that alloreactive T cells expressing CD19-specific CD28z CARs undergo cumulative activation in response to dual-specificity T cell receptor and CAR signaling, resulting in loss of T cell function and the possible deletion of these cells. Presence of CD19+ targets can mediate the inhibition of the potential of m1928z t cells to cause GVHD.

The clinical implications of these results are that relapse following a bone marrow transplant (BMT) can be safely and effectively treated with CAR modified donor T cells instead of unmodified T cells, which is the existing standard treatment in these patients. The authors are planning a phase I study of using donor-derived CAR T cells to prevent relapse after BMT is being planned and is scheduled to open at MSK later this year.


Ghosh A, Smith M, James SE, et al. Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity [published online January 9, 2016]. Nat Med. doi: 10.1038/nm.4258.

Copyright AJMC 2006-2018 Clinical Care Targeted Communications Group, LLC. All Rights Reserved.
Welcome the the new and improved, the premier managed market network. Tell us about yourself so that we can serve you better.
Sign Up

Sign In

Not a member? Sign up now!