February 5, 2024

Haploidentical Bone Marrow Transplant Has Durable Engraftment in Patients With Sickle Cell Disease

Two-year event-free survival comparable to matched sibling donor myeloablative transplant

CQD-CHP4445461-hanna-sickle-650×450

Reduced-intensity haploidentical bone marrow transplantation (BMT) for sickle cell disease has resulted in durable engraftment with low mortality, according to the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1507 study.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Presented at the 2023 American Society of Hematology conference, the findings from the adult cohort of the multicenter, phase 2, prospective trial suggest that haploidentical BMT is an important way to increase the donor pool for patients with sickle cell disease and enable access to this lifesaving therapy. Results from the trial’s pediatric cohort are expected by the end of 2024.

“At two years, the overall post-transplant survival rate for adult patients was 95%, and the event-free survival rate was 88%, which are comparable to the outcomes reported after matched sibling donor myeloablative BMT,” says the study’s co-investigator Rabi Hanna, MD, Chair of the Department of Pediatric Hematology, Oncology and Bone Marrow Transplant at Cleveland Clinic.

Sickle cell disease affects approximately 100,000 U.S. patients, making it the most common hemoglobinopathy in the nation. The event-free survival rate is more than 90% in children with sickle cell disease who undergo myeloablative BMT from a matched sibling donor. However, fewer than 17% of patients with the disease have such a donor, and the myeloablative conditioning (MAC) necessary before BMT can be prohibitively toxic in adults with sickle cell disease, who already may have end-organ damage and may not tolerate the intensity of MAC.

BMT CTN 1507 at a glance

BMT CTN 1507 was launched in 2017, after small studies of reduced-intensity human leukocyte antigen (HLA)-haploidentical BMT with post-transplant cyclophosphamide (PTCy) produced encouraging results. Event-free survival at two years after haploidentical BMT was the primary objective. Secondary objectives included determining the impact on clinical and laboratory manifestations of sickle cell disease and other transplant outcomes at two years.

Over a three-year period, 54 eligible participants ages 15 to 46 were enrolled at 19 sites. Of those, 38 completed the study as planned.

Advertisement

Preconditioning consisted of hydroxyurea 30 mg/kg/day on day -70 to day -10 to suppress the bone marrow. The conditioning regimen consisted of thymoglobulin, thiotepa, fludarabine, cyclophosphamide and total body irradiation. Prophylaxis for graft-versus-host disease (GVHD) included PTCy, sirolimus and mycophenolate.

Of the participants, 59.3% were male, 92.6% were Black and 3.7% were Hispanic. The median age was 22.8 years. Eighty-seven percent had hemoglobin SS disease, 74.1% had a Lansky/Karnofsky score of 90 to 100 at baseline, and 75.9% had an HLA match score of 4 of 8.

The most common indications for transplant were recurrent vaso-occlusive pain episodes (38.9%), acute chest syndrome (16.8%) and overt stroke (16.7%). Only 31% of participants achieved the intended dosing of hydroxyurea preconditioning.

Well tolerated, with good rates of engraftment and chimerism

Of the participants, only two had primary graft failure, and one had secondary graft failure before day +100. Cumulative incidence of grades II to IV acute GVHD at day 100 was 26.2% (95% CI: 14.0%-40.2%) — 4.8% for grades III to IV (95% CI: 0.9%-14.4%).

“These results show that a reduced-intensity regimen with thiotepa is very well tolerated, with good rates of engraftment and chimerism and low rates of severe GVHD,” says Dr. Hanna. “The other benefits of this approach are that the technology is well-established, the medication is widely available, and the cost is less than gene therapy, making it accessible to more patients.”

Advertisement

Examining rates of mortality, the investigators noted that two deaths occurred in the first year post-BMT (one due to organ failure and another due to acute respiratory distress syndrome). No deaths occurred in year 2.

“Despite the study’s great outcomes, we still have an approximately 5% mortality rate, and there will be long-term side effects from the chemotherapy,” notes Dr. Hanna. “Ideally we will be able to have a chemotherapy-free or less intense regimen in future studies to enable this life-transformative therapy in more patients.”

Related Articles

How antibody drug conjugates work
February 13, 2024
Real-World Use of Trastuzumab Deruxtecan

Key learnings from DESTINY trials

CQD-4445459-rotz-650×450
February 7, 2024
Advances in Bone Marrow Transplant Have Improved Outcomes in Fanconi Anemia

Overall survival in patients treated since 2008 is nearly 20% higher than in earlier patients

24-CNR-4545611-CQD-Podcast-967×544
February 1, 2024
Possibilities of CRISPR Technology (Podcast)

Gene editing technology offers promise for treating multiple myeloma and other hematologic malignancies, as well as solid tumors

CQD-CHP4445460-hanna-sickle-650×450
January 30, 2024
Gene Therapy Trials Show Positive Results in Sickle Cell Disease and Thalassemia

First-in-human trials of CRISPR-Cas12a gene editing demonstrate safety and meaningful event-free survival

photo of Elekta Esprit Gamma Knife machine
January 26, 2024
The Evolution of Gamma Knife Technology (Podcast)

Improvements enable targeting of brain tumors with single-session, fractionated or neoadjuvant approaches

Disparities in multiple myeloma
January 25, 2024
Major Study Identifies Global Disparities in Drug Toxicity for Multiple Myeloma Treatment

Study of 401,576 patients reveals differences in cancer burdens as well as overall survival

Treating older patients with diffuse large B-cell lymphoma (DLBCL)
January 18, 2024
Trial for Patients 75 and Older with Diffuse Large B-Cell Lymphoma Helps Address Care Inequities

Multiple Cleveland Clinic sites to participate in National Cancer Institute trial comparing treatment regimens for newly diagnosed patients

virtual anemia clinic
January 8, 2024
Advanced Practice Provider-Led Virtual Anemia Clinic Improves Patient Access

Consult program a valuable tool that benefits both patients and clinicians

Ad