Half-Match Bone Marrow Transplant Cures 22-Year-Old with Aplastic Anemia and PNH

Jacob Huber was six years old when he was diagnosed with aplastic anemia and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow transplant wasn’t an option since no matched donors could be found. One round of immunosuppressive therapy controlled his condition — until he relapsed in 2015, at age 22.

That’s when he met Rabi Hanna, MD, Director of Pediatric Bone Marrow Transplantation at Cleveland Clinic Children’s.

“Treatment options included another cycle of immunosuppression,” says Dr. Hanna. “But that would just buy more time and increase Jacob’s risk of developing myelodysplastic syndromes or leukemia. Approximately 10 percent of patients with aplastic anemia who have PNH will get leukemia. The only true cure is bone marrow transplant.”

Dr. Hanna checked Jacob’s family members and donor registries but found no human leukocyte antigen (HLA) matches for Jacob.

“A couple of years ago, we would have settled for more immunosuppression,” says Dr. Hanna. “Fortunately, today we can do haploidentical bone marrow transplantation for both malignant and nonmalignant conditions.”

How haploidentical transplants work

Through haploidentical (half-matched) donors, bone marrow transplantation is accessible to nearly all who need it. Graft rejection and graft-versus-host disease (GvHD), once common in recipients with mismatched donors, are remarkably low due to administering cyclophosphamide shortly after transplant. This drug destroys alloreactive immune cells that can cause these complications while sparing hematopoietic stem cells.

Recipients are prepared for transplant with low-dose chemotherapy — just enough to suppress their immune system, not destroy it. As a result, side effects are fewer and milder.

Cleveland Clinic is one of few programs in the U.S. to offer haploidentical transplantation for leukemia and other malignancies as well as nonmalignant disorders such as sickle cell disease and aplastic anemia.

Jacob’s transplant procedure

Jacob’s older sister was one of his best matches, with six out of 10 HLA markers.

“Finding a donor with the highest match (at least 50 percent) is important, but other factors also are considered,” says Dr. Hanna. “Young donors are better for this procedure. That’s why siblings are usually preferred instead of parents.”

In August 2015, Jacob began a six-day, reduced-intensity conditioning regimen to prepare him to receive his sister’s bone marrow. First were low doses of chemotherapy drugs fludarabine and cyclophosphamide. Next began infusions of rabbit anti-thymocyte globulin (ATG), to help prevent acute rejection of the transplanted marrow. One day before the procedure, Jacob received low-dose total body irradiation.

On the day of the procedure, bone marrow was harvested from Jacob’s sister (under sedation) and infused into Jacob through a central line. Three days later, Jacob received another round of cyclophosphamide, this time at high dose.

Success, with only minor side effects

“For two weeks, Jacob’s blood counts remained very low,” says Dr. Hanna. “Due to the chemotherapy, he developed relatively minor mouth sores and difficulty eating, but those complications soon resolved.”

During Jacob’s recovery, chimerism testing showed an increase in the percentage of cells with Jacob’s phenotype, a potential sign of minimal residual disease. By increasing his immune-suppression medication (mycophenolate mofetil, “MMF”), cells with his sister’s phenotype were able to reclaim 100 percent.

Jacob was discharged 18 days post-transplant. His blood counts were improving and there was no evidence of PNH.

He continues to have blood draws every two weeks to check his progress. He has weaned off MMF and eventually will wean off tacrolimus as well.

“It takes about nine months to get back to normal life,” says Dr. Hanna.

Today, Jacob is preparing to return to college and resume part-time work as a groundskeeper.

Universal possibility

According to Dr. Hanna, haploidentical transplants are well tolerated by patients and have very low transplant-related mortality. Although medical teams must pay close attention to immune reconstitution after the procedure, patients typically are discharged relatively quickly.

“Bone marrow transplant requires the utmost preparation and precision, but it all starts with an available donor,” says Dr. Hanna. “Haploidentical transplantation can provide an almost universal option to people needing life-saving treatment.”