A case series recently published in The Mediterranean Journal of Hematology and Infectious Diseases suggests that gastrointestinal symptoms before allogeneic stem cell transplantation may be a warning sign for severe transplant-related complications in patients with advanced systemic mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults. (SM).
Allogeneic stem cell transplantation replaces a patient’s blood-forming stem cells with cells from a donor. In the report, two patients who underwent this treatment developed severe gastrointestinal graft-versus-host disease (GvHD) and died, while the third remained in complete remission 64 months after the transplant.
GvHD is a potentially serious complication of allogeneic transplantation in which immune cells from the donor attack the recipient’s tissues, causing inflammation and damage that can affect organs such as the skin, liver and gastrointestinal tract.
Allogeneic transplantation remains controversial in advanced SMAdvanced SM In these subtypes of SM, mast cells begin to damage organs. Advanced SM includes the subtypes aggressive SM, mast cell leukemia and SM with an associated hematological neoplasm. and is usually considered only when conventional treatments are no longer effective. Although it may provide long-term disease control, it also carries substantial risks, such as severe infections and GvHD.
Read more about SM treatment and care
The patients who died had gastrointestinal involvement before transplantation and later developed severe gastrointestinal GvHD.
In one patient, biopsies confirmed mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. infiltration in the colon and gastroduodenal tract. In the other, an upper endoscopy showed chronic inflammation but no detectable mast cell infiltration.
Both deaths occurred early after transplantation. The first patient died about 60 days after the procedure from progressive intestinal GvHD and multiple infections. The second died about 120 days after transplantation following severe gastrointestinal GvHD and progressive clinical deterioration.
“Pre-transplant gastrointestinal involvement may be a clinical warning sign requiring careful assessment and monitoring,” the researchers wrote.
All three patients had received multiple treatments before transplantation. The surviving patient was the only one treated with avapritinib, a tyrosine kinase inhibitorTyrosine kinase inhibitor Targeted therapies designed to block the KIT D816V mutation that drives most cases of SM. Includes avapritinib, midostaurin and imatinib., which reduced the mast cell burden and made the KIT D816V mutation undetectable before the procedure.
What is a KIT D816V mutation?
KIT D816V is an acquired change in the KIT gene found in most people with SM. It causes the KIT protein to remain continuously active, promoting the abnormal growth and accumulation of mast cells.
His bone marrow function recovered slowly, taking 18 months to fully return. At the latest follow-up, 64 months after transplantation, he remained in complete remission, although bone pain and moderate fatigue persisted.
Researchers said that transplantation should be performed when the disease is under the best possible control. They also cited previous research showing that patients whose disease had not responded to treatment before transplantation had worse outcomes afterward.
The report highlighted previous transplant studies that found that about 40% to 50% of patients experienced disease progression within three years and nearly half died. However, many of those patients were treated before newer targeted therapies and advances in transplant care became widely available.
The authors concluded that “More data are warranted to better understand the potential correlation between mast cell infiltration and GvHD severity.”
