Breaking News
June 19, 2018 - Study finds elevated risk of congenital defects in lithium-exposed infants
June 19, 2018 - Test-Taking Can Be Tough for Kids With Vision Problems
June 19, 2018 - Injections for knee osteoarthritis—’subtle but significant’ impact of revisions in clinical practice guidelines
June 19, 2018 - Researchers develop new approach to assess effectiveness of Men B vaccine
June 19, 2018 - Study shows link between financial literacy and hospitalization risk in older adults
June 19, 2018 - New study examines how the brain plays role in rheumatoid arthritis inflammation
June 19, 2018 - Researchers discover new defense mechanism against oxygen radicals
June 19, 2018 - WVU researcher aims to produce updated whooping cough vaccine
June 19, 2018 - Scientists develop novel computational framework to support personalized cancer treatment
June 19, 2018 - Rate of dementia on the decline—but beware of growing numbers
June 19, 2018 - Microglia play protective role in response to retinal detachment, shows study
June 19, 2018 - Technology breakthrough could enable detection of fetal genetic abnormalities in early pregnancy
June 19, 2018 - Novel chip can be used to identify rhinovirus strains as cause of asthma
June 19, 2018 - Effects of in vitro fertilization depend on genetic variation inherited from parents
June 19, 2018 - Heart attack patients unable to resume work report depression and financial hardship
June 19, 2018 - Study combines gene editing and stem cell technologies to predict person’s risk for heart disease
June 19, 2018 - Weight loss of 20% or greater results in better outcomes for overweight, obese adults with knee osteoarthritis
June 19, 2018 - Alnylam Reports Updated Positive Results from Phase 1/2 Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1 (PH1)
June 19, 2018 - Study predicts most people with earliest Alzheimer’s signs won’t develop dementia associated with the disease
June 19, 2018 - Abnormal sleep duration linked to metabolic syndrome in new study
June 19, 2018 - Researchers develop new method to preserve fertility in boys with prepubertal cancer
June 19, 2018 - Late onset of diabetes could be indicative of pancreatic cancer
June 19, 2018 - WHO releases new International Classification of Diseases (ICD-11)
June 19, 2018 - Skin tone makes big difference in diagnosis and treatment of dermatologic conditions
June 19, 2018 - After addiction, the long road back to good health
June 19, 2018 - High blood pressure could be an early sign of dementia
June 19, 2018 - Innovative drugs and new European treatment guidelines refine, improve MS therapy
June 19, 2018 - BIDMC scientists develop new tool to benefit patients with HCV-associated liver failure
June 19, 2018 - Diabetes diagnosis may come with increased risk of pancreatic cancer for African-Americans, Latinos
June 19, 2018 - Personalized Goals, Cash Motivate Heart Patients to Exercise
June 19, 2018 - Nipah Virus (NiV) | CDC
June 19, 2018 - Genomics offers new treatment options for infants with range of soft tissue tumors
June 18, 2018 - Study shows how moderate consumption of alcohol can protect the heart
June 18, 2018 - Gene editing technology predicts heart disease risk
June 18, 2018 - Who Will and Who Won’t Get the Flu?
June 18, 2018 - Research shows effective responses to online feedback
June 18, 2018 - Scientists to focus on big data and genetics to identify risk factors for dementia
June 18, 2018 - Ultrasound-based technology for assessing overweight adolescents with liver disease
June 18, 2018 - Osteochondral knee defect treated using cell technology
June 18, 2018 - New clinical trial finds no evidence to support use of tamsulosin for kidney stones
June 18, 2018 - Study demonstrates increased levels of gum disease in people at risk of rheumatoid arthritis
June 18, 2018 - Ebola & Marburg | NIH: National Institute of Allergy and Infectious Diseases
June 18, 2018 - Brains, eyes, testes: off-limits for transplants?
June 18, 2018 - Drug used to treat myelofibrosis can awaken ‘dormant’ lymphomas in the bone marrow
June 18, 2018 - New study focuses on best, cost effective practices to bridge treatment gap for brain disorders
June 18, 2018 - New study highlights predictors that prevent from achieving remission in early RA
June 18, 2018 - Neuroscientists map feeling of cool touch to the brain’s insula in mouse model
June 18, 2018 - Study highlights potential use of blood biomarkers as diagnostic tool for sleep apnea
June 18, 2018 - Eating plant-based diet can reduce risk for heart problems in people with type 2 diabetes
June 18, 2018 - Lenabasum has acceptable safety and tolerability in diffuse cutaneous systemic sclerosis
June 18, 2018 - Study shows link between risky opioid prescriptions and increased odds of death
June 18, 2018 - Bone density scans could help determine likelihood of cardiovascular disease
June 18, 2018 - Mechanical thrombectomy appears to be important therapy for acute stroke in very old patients
June 18, 2018 - Novel compound as effective as FDA-approved antibiotics for treating deadly infections
June 18, 2018 - Ironwood Pharmaceuticals Announces FDA Orphan Drug Designation for Olinciguat for the Treatment of Sickle Cell Disease
June 18, 2018 - Surgical outcomes equivalent whether physician anesthesiologist assisted by nurse anesthetist or AA
June 18, 2018 - Studies provide insight into molecular changes prior to onset of arthritis
June 18, 2018 - Dyaco unveils specialist medical and rehabilitation equipment range in the UK
June 18, 2018 - Engineers develop algorithm to monitor joints of patients with arthritis
June 18, 2018 - Women with higher vitamin D blood levels have lower risk for breast cancer
June 18, 2018 - New studies help elucidate role of sleep in chronic pain
June 18, 2018 - Researchers link red meat sensitivity spread by ticks with heart disease
June 18, 2018 - Research explores role of autopsy in cardiovascular medicine
June 18, 2018 - Motif Bio Submits NDA for Iclaprim
June 18, 2018 - NIH-funded researchers identify target for chikungunya treatment
June 18, 2018 - Negative emotions are murkier, less distinct in adolescence
June 18, 2018 - Gut microbiome may be potential contributor to depression, anxiety in people with obesity
June 18, 2018 - Canakinumab reduces gout rate by more than half in atherosclerosis patients, study shows
June 18, 2018 - What Does the Future Hold?
June 18, 2018 - FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL)
June 18, 2018 - School cliques don’t always click
June 18, 2018 - Three experts from The Tinnitus Clinic contribute to major review on pulsatile tinnitus
June 18, 2018 - Unwieldy health costs often stand between teachers and fatter paychecks
June 18, 2018 - Link between frailty and mortality remains unchanged despite lower death rates, study finds
June 18, 2018 - Sleep disorders appear to be first sign of serious neurological diseases
June 18, 2018 - Childhood, adult obesity raise risk of developing hip and knee osteoarthritis
June 18, 2018 - Study unravels ‘blood stem cell niche’ puzzle
June 18, 2018 - People with heart problems do not take enough exercise, shows study
June 18, 2018 - Strong Link Identified Between T2DM and Parkinson’s Disease
June 18, 2018 - Early childhood interventions show mixed results on child development
Drug improves disease-free, overall survival after hematopoietic stem cell transplants

Drug improves disease-free, overall survival after hematopoietic stem cell transplants

image_pdfDownload PDFimage_print

Results from a phase 2 clinical trial, presented by Seattle Children’s Research Institute at the 59th American Society of Hematology (ASH) Annual Meeting, show that the drug Abatacept (Orencia) nearly eliminated life-threatening severe acute graft-versus-host disease (GvHD) in patients receiving hematopoietic stem cell transplants.

Abatacept, when added to the standard drug regimen used to prevent GvHD, reduced the occurrence of acute, grade III-IV GvHD from 32 to 3 percent in pediatric and adult patients who underwent mismatched unrelated donor stem cell transplants to treat advanced cancer and other blood disorders. As a result, patients receiving the post-transplant regimen with abatacept experienced improved disease-free and overall survival compared to those who did not.

Acute GvHD is the most deadly complication that can arise after stem cell transplantation. Graft-versus-host disease occurs when the donated T cells, white blood cells in the immune system that fight infection, launch a vigorous attack on a patient’s organs, including the skin, liver, kidneys, lung, and the gastrointestinal tract. For patients receiving cells from an unrelated donor, the rate of mild-to-severe forms of acute GvHD can reach as high as 80 percent, with up to half of patients dying from the most severe forms.

“Given the serious threat of graft-versus-host disease, new approaches to make stem cell transplants safer for patients remain a critical unmet need,” said Dr. Leslie Kean, the trial’s principal investigator and associate director of the Ben Towne Center for Childhood Cancer Research at Seattle Children’s. “To see such striking results in patients at extremely high risk for graft-versus-disease is incredibly encouraging.”

Kean first became interested in using abatacept to prevent GvHD based on the immunotherapy drug’s success in treating patients with rheumatoid arthritis. In rheumatoid arthritis, abatacept inhibits T-cell activation and prevents the chain of events that lead to debilitating joint inflammation.

Similarly, feasibility studies conducted by Kean found that abatacept blocks the activation of certain T cells after transplant. In their models, abatacept reduced the proliferation and activation of effector T cells. Effector T cells incite GvHD when they become overactive as the patient’s immune system starts to rebuild itself from the donor stem cells.

“Preventing graft-versus-host disease and relapse after transplant requires a difficult balance of eliminating the bad, overactive effector T cells, without suppressing the good, regulatory T cells,” said Kean, who is also an associate professor of pediatrics at the University of Washington School of Medicine and a member of the Fred Hutchinson Cancer Research Center. “As we make improvements to our toolbox of agents capable of achieving this Holy Grail of stem cell transplant, it’s essential to include targeted approaches like abatacept.”

The multicenter data presented included two patients cohorts who were enrolled across 18 sites. In the cohort of patients who received transplants from mismatched unrelated donors, all 43 patients received four doses of abatacept with a calcineurin inhibitor and methotrexate. To serve as the control, researchers looked at data from a national database of matched patients receiving two commonly used regimens to prevent GvHD – a calcineurin inhibitor and methotrexate (CNI/MTX) or a calcineurin inhibitor and methotrexate plus anti-thymocyte globulin (+ATG).

At 100 days post-transplant, the cumulative incidence of grade III-IV acute GvHD occurred in 3 percent of patients receiving abatacept compared to 32 percent receiving CNI/MTX and 22 percent receiving +ATG. Patients receiving abatacept had intact immune reconstitution, significant improvement in transplantation-related mortality, no major uncontrolled infection and no increase in disease relapse. Significant survival advantages for the abatacept group were demonstrated at one year post-transplant. Overall survival improved to 85 percent (vs. 57 percent in CNI/MTX and 68 percent in +ATG controls); 79 percent of patients experienced disease-free survival (vs. 50 percent in CNI/MTX and 63 percent in +ATG controls).

The second cohort of 140 patients with human leukocyte antigen-matched unrelated donor transplants completed enrollment in November 2017, with data expected from this randomized double-blind arm of the study in the next six months.

“As a transplant physician, it’s beyond heartbreaking to witness a patient develop severe acute graft-versus-host disease after having their leukemia cured through bone marrow transplant,” said Kean. “To have a therapy at our disposal that safely targets just the T cells causing graft-versus-host disease would represent a major step forward in stem cell transplantation. It not only offers new hope that we can prevent graft-versus-host disease upfront, but that we can also significantly improve outcomes for patients requiring high-risk transplants.”

Source:

http://www.seattlechildrens.org/

Tagged with:

About author

Related Articles