Leading Complication of Stem Cell Transplants Require Improved Diagnoses

Graft-versus-host disease (GVHD) is a common, and sometimes life-threatening, complication of allogeneic bone marrow transplant (BMT), also known as stem cell transplant. Cancer patients who undergo allogeneic BMT as part of their cancer treatment could develop GVHD, which occurs when the donor stem cells, known as the graft, attack a patient’s healthy cells, or the host cells. Depending on the severity, GVHD could result in a range of health problems affecting the gut, liver, skin, and other organs. GVHD is the most common cause of treatment-related mortality or severe illness after a bone marrow or stem cell transplant, and there have been no advances in how to prevent GVHD in several decades.

In the absence of established  biomarkers—blood tests that will predict which patients are more likely than others to develop GVHD and which patients are more likely than others to respond to therapies—the diagnosis of acute GVHD remains clinical, relying mainly on the symptoms a patient develops after transplantation. A new study published in the Journal of Clinical Oncology, demonstrates a novel framework for the assessment of patients’ symptoms and clinical findings which was successful in improving the accuracy of GVHD diagnosis.

“This study is the largest observational study that was conducted in allogeneic bone marrow transplant in the U.S. to date. It followed more than a 1,700 patients across several dozen institutions and collected data on their GVHD symptoms and blood samples that are being used to develop biomarkers,” says Ran Reshef, MD, first author of the study and deputy director of the BMT and Cell Therapy Program at NewYork-Presbyterian/Columbia University Irving Medical Center. “We hope that this framework can be used in future GVHD clinical trials and may help improve their chance of success.”

Dr. Reshef and collaborators at the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) observed 1,709 patients who underwent an allogeneic BMT at multiple institutions, and studied the real-time data that led to the diagnosis of GVHD at the onset of symptoms. During the first 100 days of transplant, symptoms consistent with GVHD developed in 90% of cases but were often determined by centers to be due to causes other than GVHD. Diagnostic biopsies were obtained in 40% of cases, but treatment often was inconsistent with the findings of those biopsies and 10.5% of biopsies were actually unclear.

The study found that overall the incidence of GVHD had been inaccurately estimated; more patients were diagnosed due to the GVHD-like symptoms they presented clinically, but in actuality, the study determined that some of those cases did not have GVHD.

The researchers implemented a structured framework for more accurate identification of GVHD, consisting of improved data-capture of the start of acute GVHD in patients by systematically reporting detailed symptoms in GVHD organs, rather than a diagnosis determined per investigator; high frequency of reporting (weekly); review of the data by an adjudication committee; and meticulous annotation of GVHD events with confidence levels (probable case, possible case, negative) to reflect that the clinical observation was consistent with a GVHD diagnosis. This method was originally developed by MAGIC, a consortium of centers that investigates GVHD, its diagnosis, and its outcomes.

“We hope this improved framework for diagnosis and severity grading of GVHD will allow an easier and more accurate diagnostic process for these patients,” says Dr. Reshef, “so we can identify clearly which of them has GVHD and how it should be treated.”