Allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling has been shown to cure most children with transfusion-dependent b-thalassemia major. Results obtained using an HLA-partially matched (haploidentical, haplo) donor have been historically less satisfactory, the thalassemia-free-survival (TFS) probability being ~ 60%. αβ T and B-cell depleted haplo-HSCT has been proposed as a novel strategy able to minimize the risk of graft-versus-host disease (GvHD) and to protect patients from the risk of life-threatening viral/fungal infections. However, recovery of adaptive immunity after this type of allograft is still suboptimal.

BPX-501 is an allogeneic product consisting of T cells modified to express the inducible caspase-9 (iC9) safety switch and truncated CD19 to allow monitoring and expansion of BPX-501 following transplant. The polyclonal nature of the BPX-501 provides broad virus and tumor-specific immunity, while the safety switch provides the unique ability to promptly and durably resolve graft-versus-host disease (GvHD) symptoms following the administration of rimiducid which induces dimerization and activation of iC9, inducing apoptosis of BPX-501.


To evaluate the safety and efficacy (immune recovery and risk of acute and chronic GvHD) of BPX-501 administered after a αβ T and B-cell depleted haplo-HSCT in pediatric patients with b-thalassemia.


This is a multicenter US (NCT03301168) and EU (NCT020658), prospective trial utilizing αβ-T and B-cell-depleted haplo-HSCT followed by infusion of donor lymphocytes genetically modified with iC9 (BPX-501) in patients with malignant or non-malignant disorders. A subset of patients enrolled had b-thalassemia. BPX-501 was planned to be infused on day14±4 after the allograft. No post-transplant pharmacological GvHD prophylaxis was employed. Patients who develop GvHD resistant to conventional steroid therapy can receive ≥1 dose of dimerizing rimiducid activating iC9.

The efficacy-evaluable population (EEP) was defined as any patient with b-thalassemia who received HSCT, BPX-501 infusion and had at least one follow-up assessment.


At the time of clinical cut-off (June 30, 2018) 24 patients (EU [n=22] US [n=2]; Male [n=14] Female [n= 10]; median age 9.16 yrs (2.15 - 14.34 yrs) met the EEP definition. The median follow-up was 11.3 mos (0.5-37.4 mos).

The majority (83.3%) of patients received a busulfan-based conditioning regimen. The median HSCT CD34+ and ab TCR+ cell doses were 20.5 x 106 /kg and 0.15 x 105 /kg, respectively. The donor was a parent in all children (100%).The median time to BPX-501 infusion was 17 days (10- 36 days).

Two children experienced primary graft failure (8.7% [95% CI: 0-20.3]). One patient underwent a second HSCT with successful engraftment and remains disease free with a median follow up of 31 months. In patients who obtained sustained engraftment of donor cells, the median time for neutrophil and platelet engraftment was 15 (15 - 18) and 12 (11 - 13) days, respectively. Of 22 evaluable patients 3 patients (Grade 1 [n=1] and Grade 2 [n= 2]) developed Grade 1-II aGvHD (13.6% [95% CI: 0 - 28). No patients developed Grade III-IV aGvHD or chronic GvHD. The dimerizing agent rimiducid was administered in one patient with Grade 2 Skin aGvHD who subsequently achieved a complete response.

Two of the twenty-four patients died after transplantation from infections (9.3% [95% CI: 0 - 21.6%]). Disease-free survival (DFS) was 82.2% (95% CI: 66.3 - 98%). Overall Survival (OS) was 90.7% (95% CI: 78.4 - 100). The median time from last red blood cell transfusion was 11.1 mos (1 day - 37.2 mos).

CD3+ and CD3+CD4+ T cells above 500 cells/ml were achieved by 180 and 270 days, respectively. IgA and IgM levels achieved normal values by 30 and 180 days, respectively. The percentage of circulating and median absolute BPX-501 at Day 100 were 2.53% ± 2.62% (0 - 7.6%) and 23.94 ± 28.58 cells/ml (0 - 76.5 cells/ml), respectively.


An αβ-T and B-cell depleted haplo-HSCT followed by infusion of BPX-501 is a suitable and effective option for children with transfusion-dependent b-thalassemia major lacking an HLA-identical donor. The low cumulative incidence of TRM and the absence of severe aGvHD or chronic GvHD observed support further study in this patient population.


Locatelli:Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi: Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.

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