For patients with blood cancers, allogeneic hematopoietic stem cell transplantation represents a critical gateway to the possibility of a cure.
Yet for many, the end of transplantation does not mean the end of treatment. Chronic graft-versus-host disease (cGVHD), which can develop after transplantation, may attack multiple organs, including the skin, eyes, mouth, lungs and liver, disrupting patients’ lives for years.
Among the various manifestations of cGVHD, lung involvement remains one of the most difficult areas for both patients and physicians. By the time symptoms become obvious, lung function has often already deteriorated significantly.
Professor Yoon Jae-ho of the Department of Hematology at the Catholic University of Korea Seoul St. Mary's Hospital described chronic GVHD as “one of the most important post-transplant treatment challenges that determines patients’ quality of life.”
Although advances in transplant techniques and preventive strategies have reduced severe cases, many patients still face another long and difficult battle after transplantation.
Chronic GVHD patient Kim Kyung-hee (left) and Professor Yoon Jae-ho of Catholic University of Korea Seoul St. Mary's Hospital (KBR photo)
After a successful transplant, another long battle awaits
According to Professor Yoon, an estimated 3,000 to 5,000 patients undergo allogeneic stem cell transplantation each year in Korea for diseases including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome and aplastic anemia.
Chronic GVHD develops in about half of transplant recipients, with severe cases accounting for roughly 10 percent. Around 10 percent to 20 percent require second- or third-line therapies.
“In recent years, we have been implementing various preventive measures with the goal of keeping the severe incidence rate below 10 percent,” Yoon said. “Compared to the past, the overall incidence of cGVHD has decreased by 20 percent to 50 percent.”
Chronic GVHD occurs when transplanted immune cells attack the patient’s body. The disease can affect multiple organs, including the eyes, mouth, skin, lungs and liver.
“GVHD can affect the entire body, so we evaluate at least eight major organs,” Yoon explained. “No single medication can resolve symptoms across all organs.”
Lung and sclerotic skin GVHD remain difficult to control with existing therapies
Among the most challenging manifestations are lung involvement and sclerotic skin GVHD. While symptoms affecting the eyes or mouth may often respond to first- or second-line therapies, pulmonary and sclerotic skin GVHD frequently remain refractory to conventional treatments.
“Sclerotic skin GVHD is similar to the hardened skin seen in burn patients,” Yoon said. “As fibrosis progresses and the skin hardens, joint mobility can also become impaired.”
Lung involvement can severely threaten daily life. Lung function may deteriorate silently until the disease becomes difficult to reverse.
“If pulmonary GVHD is left untreated until symptoms appear, patients are often discovered in a very advanced state,” Yoon said. “That is why we perform pulmonary function tests every three months regardless of symptoms.”
Since February this year, Rezurock, which gained reimbursement coverage under the national health insurance system, has become a treatment option for patients with chronic GVHD involving the lungs or sclerotic skin that is difficult to control with existing therapies.
“Rezurock works by inhibiting the ROCK2 signaling pathway to reduce inflammation and fibrosis,” Yoon explained. “The drug suppresses fibrosis-related signaling and collagen deposition, so we expect it to be particularly effective for fibrotic manifestations, sclerotic skin GVHD and pulmonary GVHD.”
He added that physicians are increasingly considering switching therapies when patients fail to respond adequately to existing treatments.
‘I had to stop several times during the short walk from the Express Bus Terminal to the hospital’
Also present during the interview was Kim Kyung-hee, a patient living with chronic GVHD, who vividly described the burden of pulmonary involvement.
Kim was diagnosed with acute lymphoblastic leukemia in March 2023 and underwent a fully matched allogeneic stem cell transplant from her younger sister on Sept. 20 of the same year.
However, acute GVHD developed after transplantation and eventually progressed into chronic disease. She later developed severe chronic GVHD, leading to repeated emergency room visits and pleural fluid drainage procedures.
Chronic GVHD patient Kim Kyung-hee (KBR photo)
“Acute GVHD persisted after the transplant and eventually became chronic,” Kim recalled. “I was initially treated with steroids and later switched to a JAK inhibitor, but my shortness of breath continued.”
Despite stable blood test results, her breathing difficulties worsened and eventually became more distressing than chemotherapy itself.
“Other patients say chemotherapy is the hardest part, but for me, the suffering caused by GVHD was much worse,” she said.
Her symptoms devastated ordinary daily activities. Traveling from Unjeong in Paju, Gyeonggi Province, to Seoul St. Mary’s Hospital became an exhausting challenge. Even the short walk from the Express Bus Terminal to the hospital required multiple rest stops, and she often had to stop repeatedly just to reach the bus stop near her apartment.
“My legs felt weak and unstable,” she said. “There were times when I went to the emergency room struggling to breathe and had to survive with oxygen support.”
After Rezurock, both lung function and daily life changed
A turning point came when Professor Yoon recommended starting Rezurock. Kim began taking the medication before insurance reimbursement was approved, despite the significant financial burden of paying out-of-pocket.
“It was not an easy decision because the cost was substantial,” she said.
Her siblings helped share the expense and encouraged her to continue until reimbursement approval was finalized. She has now been taking the medication for about six months under insurance coverage.
“Professor Yoon encouraged me to start treatment before reimbursement was approved because he believed it would help patients,” Kim said.
Changes became noticeable after about two to three months of treatment. Professor Yoon recalled that Kim gradually began talking more during clinic visits as her breathing improved.
Pulmonary function testing also showed measurable improvement.
“Kim’s FEV1 had fallen below 40 percent, approaching nearly 20 percent,” Yoon explained.
“At that level, patients struggle to hold conversations because they are breathless even at rest,” he added. “After taking Rezurock, her FEV1 improved to 35 percent.”
Kim said the improvement she felt matched the numbers.
“The biggest change after starting Rezurock was my breathing,” she said. “Before, I had to stop multiple times while walking from the bus terminal to the hospital. Now I can walk the entire distance without resting.”
“I no longer feel short of breath, and daily life is no longer limited,” she said.
Beyond breathing, eating, sleeping, and ordinary life returned
The benefits extended beyond respiratory improvement. Severe oral ulcers gradually resolved, allowing her to eat normally again, including spicy foods she previously could not tolerate.
Her skin symptoms also improved. The rashes and bruise-like lesions that once spread across her chest and back during periods of stress disappeared. Sleep improved as well. Whereas she had previously slept only one or two hours a night, she can now sleep about five hours. Kim described the changes as “miraculous.”
Her outpatient visits have also become less frequent. Before starting Rezurock, worsening physical symptoms often forced hospital visits every one to two weeks despite stable blood test results. She now visits once a month and may eventually extend follow-ups to every three months if her condition remains stable.
“If Rezurock did not exist, I believe I would still be suffering from severe shortness of breath,” she said. “I feel deeply grateful for this medication.”
‘Patients no longer need excessive fear about transplantation’
Professor Yoon Jae-ho of Catholic University of Korea Seoul St. Mary's Hospital (KBR photo)
Professor Yoon said Kim’s experience demonstrates the importance of selecting appropriate therapies and intervening early in the treatment of chronic GVHD.
“Recently, there has been a growing tendency to use effective therapies earlier,” he said. “Rather than waiting until patients deteriorate, we try to prescribe them as early as possible whenever reimbursement criteria allow.”
At the same time, he emphasized that patients should not avoid transplantation out of excessive fear of GVHD.
“Some patients hesitate to undergo transplantation because they fear GVHD,” Yoon said. “But today we have far more treatment options, preventive strategies are being actively implemented, and transplant techniques themselves have improved dramatically. There is no need for excessive fear.”
He added that continued efforts to reduce GVHD incidence, along with the emergence of new therapies, are creating a more optimistic treatment environment for both patients and physicians.
Still, access remains critical if new therapies are to truly change patients’ lives. In Kim’s case, the financial burden before reimbursement approval had to be shared by her entire family.
Yoon pointed to Korea’s annual out-of-pocket spending cap system, under which the National Health Insurance Service reimburses medical expenses exceeding income-based annual thresholds.
“The lower a patient’s income, the lower the maximum out-of-pocket limit,” Yoon explained. “Even when medical expenses become extremely high, the system can provide meaningful financial protection.”
‘I hope my story can help other patients’
For Kim, treatment success is not simply about improved laboratory results. It is about being able to walk again, breathe comfortably and return to ordinary life.
“That is also why she agreed to share her story.
“I spent my entire life working constantly, so when I was first diagnosed, it was incredibly difficult to accept,” Kim said. “But over time, I came to see it as life telling me to pause and rest for a while.”
“There were moments in the emergency room when I wanted to give up,” she continued. “But my younger sister stayed by my side and helped me endure. Since Rezurock helped me survive those difficult times, I hope this interview can offer even a small amount of help to other patients going through the same suffering.”
Allogeneic stem cell transplantation remains a crucial treatment for blood cancers, but many patients face years of chronic GVHD afterward. Kim’s case illustrates both the burden of the disease and how newer therapies may help patients regain ordinary daily life.
Kim Yun-mi
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