ORLANDO Nonmyeloablative conditioning in combination with post-transplant cyclophosphamide and thiotepa appeared feasible for patients with severe transfusion-dependent thalassemia undergoing bone marrow transplantation, according to results of a phase 1 study presented at TCT | Transplantation & Cellular Therapy Meetings.

Researchers noted the need for a phase 2 study to identify the optimal regimen to balance improved thalassemia-free survival with the least toxicity.

We hypothesized that post-transplant cyclophosphamide would overcome the engraftment barrier, reduce rejection and improve transplant and thalassemia-related outcomes for patients with different platforms, Dilan A. Patel, MD, clinical fellow in the hematology/oncology division at Vanderbilt University Medical Center, told Healio. The most favorable thing we found was minimal acute and chronic graft-versus-host disease, no cases of extensive chronic or grade 3 to grade 4 acute GVHD, and minimal transplant-related toxicities in terms of infectious complications.

Previous studies have shown that post-transplant cyclophosphamide allows for allogeneic hematopoietic stem cell transplantation across the HLA barrier. However, allogeneic HSCT can be performed only for some patients with severe transfusion-dependent thalassemia because of limited donor availability, graft rejection and regimen-related toxicities.

Allogeneic HSCT can be performed only for some patients with severe transfusion-dependent thalassemia because of limited donor availability, graft rejection and regimen-related toxicities.

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Patel and colleagues analyzed nine patients with severe transfusion-dependent thalassemia who received a common conditioning regimen of anti-thymocyte globulin dosed at 4.5 mg/kg, fludarabine at 150/m2, cyclophosphamide at 29 mg/kg, thiotepa at 10 mg/kg 7 days before transplant, and total body irradiation at 200 cGy.

Additionally, researchers administered GVHD prophylaxis consisting of cyclophosphamide at 50 mg/kg on days 3 and 4 after transplant, mycophenolate mofetil and sirolimus.

To improve engraftment rates, patients underwent preconditioning with hydroxyurea at 30 mg/kg for 60 days.

Two patients received transplants from matched related donors, whereas four received them from haploidentical donors and three received them from matched unrelated donors.

Median follow-up was 371 days.

Results showed one case of graft failure at day 32 after transplantation in the haploidentical group. The other eight patients (89%) successfully engrafted.

Researchers observed two cases each of mild gut and skin acute GVHD, and one case each of limited gut and skin chronic GVHD.

All patients remained alive at the time of reporting, with a thalassemia-free survival rate of 100% for the matched related and matched unrelated donor groups. No statistical differences existed between groups according to neutrophil or platelet engraftment, age, total nucleated cell dose or CD34-positive cell dose.

All patients remained transfusion independent, and none who underwent engraftment needed long-term immunosuppression therapy.

The only way to know if these results apply to more patients is by doing a larger phase 2 study, Patel said. In our cohort, we have pediatric and young adult patients, but we also need to know if this applies to older adults, as well. Gene therapy is being used for thalassemia right now, but on a larger scale I think transplant is the best overall option. by John DeRosier

Reference:

Patel DA, et al. Abstract 329. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.

Disclosures:

Patel reports no relevant financial disclosures. Please see the abstract for all other authors relevant financial disclosures.

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Toxicity minimal with novel transplantation approach for transfusion-dependent thalassemia - Healio