Philadelphia May 20, 2025 – A collaborative team of researchers from Children’s Hospital of Philadelphia (CHOP) found that hematopoietic stem cell transplantation (HSCT) is a highly effective method for treating patients with monogenic inflammatory bowel disease (IBD), a more severe form of the illness usually affecting younger patients. More than 90% of patients achieved sustained medication-free remission. These findings, published today in Clinical Gastroenterology and Hepatology, demonstrate the importance of genetic evaluation in helping achieve curative and potentially lifesaving results.
While most forms of IBD are driven by a complex interplay between environmental exposures, immune response and genetic susceptibility, monogenic IBD is caused by single gene defects. The clinical symptoms may be similar in patients with all types of IBD. However, there are some important differences, such as the predominant younger age of disease onset in patients with monogenic IBD, commonly seen in children with very early onset (VEO-IBD). The disease can also be more aggressive and less responsive to conventional IBD therapies, and patients may experience additional complications linked to underlying immunodeficiency and associated autoimmune diseases. Together, these factors often result in more frequent illnesses, disease exacerbations and trips to the hospital.
One therapeutic option that has the potential to lead to a sustained medication free remission for children with monogenic IBD is allogenic hematopoietic stem cell transplant (HSCT). To determine the effectiveness of HSCT in a larger cohort of children with monogenic IBD, the VEO-IBD team collaborated with investigators in CHOP’s Program for Integrated Immunodeficiency and Cellular Therapy.
“The younger the patient, the more likely we are to find a single gene driving their IBD,” said first study author Alyssa Baccarella, MD, MS, an attending physician with the Division of Gastroenterology, Hepatology and Nutrition at CHOP. “By identifying these genes through genetic sequencing, we can truly personalize therapy for patients with identified defects. Stem cell transplant has become safer and more effective with protocol advances made over the last couple of decades.”
In this retrospective study, researchers studied 25 patients who were treated with allogeneic hematopoietic stem cell transplant for monogenic IBD between 2012 and 2022. Prior to receiving stem cell transplants, 76% of these children required immunosuppressive therapy and 20% underwent IBD-related surgery.
The results of the study showed that at the most recent follow up, there was 100% survival and 92% of patients achieved sustained medication-free remission of IBD. Additionally, 60% of patients who previously had surgery to create an ileostomy due to their severe disease, successfully underwent reconnection of the small bowel to the large bowel, reversing the ileostomy. Across the study population, patients experienced significant improvement in growth, were able to substantially reduce hospital visits and experienced significantly fewer severe infections.
“These results, along with similar findings in the literature, offer new hope for our patients with this severe form of IBD,” said senior study author Judith R. Kelsen, MD, Program Director of the VEO-IBD Clinic and the Richard and Ann Frankel Chair in Gastroenterology Research at CHOP. “Our experience clearly indicates that a multidisciplinary collaborative team approach is essential for identifying appropriate transplant candidates. The partnership between the VEO-IBD, immunology, and bone and marrow transplant teams at Children's Hospital of Philadelphia has been instrumental in determining suitable patients for transplant. While HSCT is currently indicated for only a subset of patients with monogenic IBD, insights gained from studying these cases may inform the development of novel therapeutic targets for the broader IBD population.”
This study was supported by National Institutes of Health grants K23 DK119585, 5T32HD043021-19, and NIH R01 DK127044, the Frank R. Wallace Endowed Chair in Infectious Diseases and the Elizabeth Paige Lavin Endowed Chair.
Baccarella et al, “Outcomes of Allogeneic Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease.” Clin Gastroenterol Hepatol. Online May 16, 2025. DOI: 10.1016/j.cgh.2025.03.018
About Children’s Hospital of Philadelphia:
A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.
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Philadelphia May 20, 2025 – A collaborative team of researchers from Children’s Hospital of Philadelphia (CHOP) found that hematopoietic stem cell transplantation (HSCT) is a highly effective method for treating patients with monogenic inflammatory bowel disease (IBD), a more severe form of the illness usually affecting younger patients. More than 90% of patients achieved sustained medication-free remission. These findings, published today in Clinical Gastroenterology and Hepatology, demonstrate the importance of genetic evaluation in helping achieve curative and potentially lifesaving results.
While most forms of IBD are driven by a complex interplay between environmental exposures, immune response and genetic susceptibility, monogenic IBD is caused by single gene defects. The clinical symptoms may be similar in patients with all types of IBD. However, there are some important differences, such as the predominant younger age of disease onset in patients with monogenic IBD, commonly seen in children with very early onset (VEO-IBD). The disease can also be more aggressive and less responsive to conventional IBD therapies, and patients may experience additional complications linked to underlying immunodeficiency and associated autoimmune diseases. Together, these factors often result in more frequent illnesses, disease exacerbations and trips to the hospital.
One therapeutic option that has the potential to lead to a sustained medication free remission for children with monogenic IBD is allogenic hematopoietic stem cell transplant (HSCT). To determine the effectiveness of HSCT in a larger cohort of children with monogenic IBD, the VEO-IBD team collaborated with investigators in CHOP’s Program for Integrated Immunodeficiency and Cellular Therapy.
“The younger the patient, the more likely we are to find a single gene driving their IBD,” said first study author Alyssa Baccarella, MD, MS, an attending physician with the Division of Gastroenterology, Hepatology and Nutrition at CHOP. “By identifying these genes through genetic sequencing, we can truly personalize therapy for patients with identified defects. Stem cell transplant has become safer and more effective with protocol advances made over the last couple of decades.”
In this retrospective study, researchers studied 25 patients who were treated with allogeneic hematopoietic stem cell transplant for monogenic IBD between 2012 and 2022. Prior to receiving stem cell transplants, 76% of these children required immunosuppressive therapy and 20% underwent IBD-related surgery.
The results of the study showed that at the most recent follow up, there was 100% survival and 92% of patients achieved sustained medication-free remission of IBD. Additionally, 60% of patients who previously had surgery to create an ileostomy due to their severe disease, successfully underwent reconnection of the small bowel to the large bowel, reversing the ileostomy. Across the study population, patients experienced significant improvement in growth, were able to substantially reduce hospital visits and experienced significantly fewer severe infections.
“These results, along with similar findings in the literature, offer new hope for our patients with this severe form of IBD,” said senior study author Judith R. Kelsen, MD, Program Director of the VEO-IBD Clinic and the Richard and Ann Frankel Chair in Gastroenterology Research at CHOP. “Our experience clearly indicates that a multidisciplinary collaborative team approach is essential for identifying appropriate transplant candidates. The partnership between the VEO-IBD, immunology, and bone and marrow transplant teams at Children's Hospital of Philadelphia has been instrumental in determining suitable patients for transplant. While HSCT is currently indicated for only a subset of patients with monogenic IBD, insights gained from studying these cases may inform the development of novel therapeutic targets for the broader IBD population.”
This study was supported by National Institutes of Health grants K23 DK119585, 5T32HD043021-19, and NIH R01 DK127044, the Frank R. Wallace Endowed Chair in Infectious Diseases and the Elizabeth Paige Lavin Endowed Chair.
Baccarella et al, “Outcomes of Allogeneic Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease.” Clin Gastroenterol Hepatol. Online May 16, 2025. DOI: 10.1016/j.cgh.2025.03.018
About Children’s Hospital of Philadelphia:
A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.
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