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Nonmyeloablative haploidentical allogeneic bone marrow transplant feasible for sickle cell disease
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SALT LAKE CITY — Among patients with severe hemoglobinopathies, greater total body irradiation followed by nonmyeloablative haploidentical allogeneic bone marrow transplant and posttransplant cyclophosphamide appeared associated with decreased graft failure, according to study results presented at the BMT Tandem Meetings.
In a previous study, using total body irradiation of 200 cGy showed high graft failure.
“Severe haemoglobinopathies, such as sickle cell disease and thalassemia, are much more prevalent among people that belong to ethnic groups underrepresented in the donor registry,” Javier Bolaños Meade, MD, associate professor of oncology and clinical director of the BMT Program at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, told HemOnc Today. “At the same time, they usually have siblings affected. Therefore, finding an HLA-matched donor is a rare occurrence, perhaps close to only 10%. The majority of patients who potentially can benefit from a transplant never will find a donor.”
Due to related toxicity, adults with sickle cell disease and -thalassemia are not usually offered myeloablative bone marrow transplant.
Previously, Bolaños Meade and colleagues showed these patients could be offered haploidentical donors and nonmyeloablative conditioning, which is less toxic. However, the success rate was only 60%.
Researchers enrolled 12 patients with severe sickle cell disease and five with -thalassemia who underwent nonmyeloablative haploidentical allogeneic bone marrow transplant (median age, 16 years; range, 6-31 years; female, n = 12).
Prior to bone marrow transplant, patients received ATG (rabbit) 0.5 mg/kg on day –9 and 2 mg/kg on days –8 and –7; fludarabine 30 mg/m2 on days –6 to –2; cyclophosphamide 14.5 mg/kg on days –6 and –5; and total body radiation 400 cGy on day –1.
GVHD prophylaxis included 50 mg/kg daily cyclophosphamide on days +3 and +4, sirolimus (levels of 5 ng/dl to 10 ng/dl) from days 5 to 365, and mycophenolate mofetil 1g every 8 hours from days 5 to 35.
Only one patient had graft failure. Thirteen patients achieved full donor chimerism and three had mixed chimeras.
Toxicities included grade 2 acute GVHD (n = 2), grade 3 acute GVHD (n = 1) and chronic GVHD (n = 3). Other toxicities included sirolimus-inducted diabetes, worsening of Meniere’s and BK cystitis (n = 1 each).
At the median follow-up of 15 months (range, 3-34), all patients remained alive.
Of the 11 patients with sickle cell disease and donor engraftment, nine achieved full donor chimerisms and all but one achieved transfusion independence. The one exception had a major ABO-mismatched donor.
Among patients with -thalassemia, four out of five achieved full donor chimerism and all five were transfusion independent at a median follow-up of 11 months (range, 5-16).
Of the eight engrafted patients with more than 1 year of follow-up, six were no longer on systemic immunosuppression.
“In our previous study, we achieved success in only close to 60%,” Bolaños Meade said. “After some modifications in the schema, it looks like we drastically reduced the risk [for] graft failure improving outcomes. So, it looks like we can, in fact, use haploidentical donors and nonmyeloablative conditioning schemas in these people with acceptable toxicities.” – by Cassie Homer
Reference:
Bolaños-Meade J, et al. Abstract LBA3. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.
Disclosures: Bolaños-Meade reports receiving honoraria from Incyte for data and safety monitoring board participation. Please see the abstract for all other authors’ relevant financial disclosures.