Contributions
Abstract: PB2168
Type: Publication Only
Background
Therapy of post-transplant autoimmunity manifestations remains a challenge. Many cases are steroid and rituximab refractory and continuing intensified immune suppression increase the risk of infection in the post-HSCT patient. In our institution, we have used bortezomib as our third agent after failure of steroids or rituximab, or in cases of steroid-dependence since Bortezomib appears to be effective in cases with refractory autoimmunity.
Aims
In our series, we assessed the therapeutic response to proteasome inhibitor in 4 cases of post-transplant refractory autoimmunity
Methods
Three of the 4 cases received Bortezomib for autoimmune cytopenia (autoimmune haemolytic anaemia AIHA (n=2), AIHA with acquired red Cell Aplasia (n=1)). At least 2 therapy lines had failed to resolve the cytopenia. One to two courses of Bortezomib were administered at a dose of 1.3 mg/m2 at day 1, 4, 8, 11 each course. In two cases this treatment was combined with immunosuppressive agents: Mycophenolate mofetil (MMF) alone in one case and associated with sirolimus in the other case.
Results
Resolution of autoimmune cytopenia was observed in the three cases after a median of 33 days from the first day of administration. The fourth case received 1 course of Bortezomib for persistent anti-enzyme antibodies after allogeneic transplant for Wolman disease. Therapeutic response was obtained after 25 days reflected by a complete regression of circulating anti-enzyme antibodies. In all cases, no Bortezomib related toxicity was noticed. The response was maintained in all cases.
| patients | Age at Allogeneic HSCT | Diagnosis | post-transplant bortezomib indication | Previous treatments | bortezomib courses (n) | Response | Time to response | bortezomib-related toxicity | loss of response at last follow up |
| 1 | 14 | Beta thalassemia | AIHA | IVIG, Sirolimus, Steroids, Rituximab, Cyclophosphamide, Splenectomy | 2 | Yes | 33 | None | No |
| 2 | 91 | myelodysplastic syndrome trisomy 8 | AIHA | IVIG, Steroids, Rituximab, MMF | 2 | Yes | 57 | None | No |
| 3 | 14 | Mucopolysaccharidos type 1 | AIHA with Acquired Red Cell Aplasia | Rituximab, MMF | 1 | Yes | 14 | None | No |
| 4 | 25 | Wolman disease | Anti-enzyme antibodies | None | 1 | Yes | 25 | None | No |
Conclusion
Our study shows that Bortezomib is a promising therapeutic option for refractory post-transplant autoimmunity with high tolerance and no related toxicities.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Autoimmunity, Proteasome inhibitor, Post-transplant, bortezomib
Abstract: PB2168
Type: Publication Only
Background
Therapy of post-transplant autoimmunity manifestations remains a challenge. Many cases are steroid and rituximab refractory and continuing intensified immune suppression increase the risk of infection in the post-HSCT patient. In our institution, we have used bortezomib as our third agent after failure of steroids or rituximab, or in cases of steroid-dependence since Bortezomib appears to be effective in cases with refractory autoimmunity.
Aims
In our series, we assessed the therapeutic response to proteasome inhibitor in 4 cases of post-transplant refractory autoimmunity
Methods
Three of the 4 cases received Bortezomib for autoimmune cytopenia (autoimmune haemolytic anaemia AIHA (n=2), AIHA with acquired red Cell Aplasia (n=1)). At least 2 therapy lines had failed to resolve the cytopenia. One to two courses of Bortezomib were administered at a dose of 1.3 mg/m2 at day 1, 4, 8, 11 each course. In two cases this treatment was combined with immunosuppressive agents: Mycophenolate mofetil (MMF) alone in one case and associated with sirolimus in the other case.
Results
Resolution of autoimmune cytopenia was observed in the three cases after a median of 33 days from the first day of administration. The fourth case received 1 course of Bortezomib for persistent anti-enzyme antibodies after allogeneic transplant for Wolman disease. Therapeutic response was obtained after 25 days reflected by a complete regression of circulating anti-enzyme antibodies. In all cases, no Bortezomib related toxicity was noticed. The response was maintained in all cases.
| patients | Age at Allogeneic HSCT | Diagnosis | post-transplant bortezomib indication | Previous treatments | bortezomib courses (n) | Response | Time to response | bortezomib-related toxicity | loss of response at last follow up |
| 1 | 14 | Beta thalassemia | AIHA | IVIG, Sirolimus, Steroids, Rituximab, Cyclophosphamide, Splenectomy | 2 | Yes | 33 | None | No |
| 2 | 91 | myelodysplastic syndrome trisomy 8 | AIHA | IVIG, Steroids, Rituximab, MMF | 2 | Yes | 57 | None | No |
| 3 | 14 | Mucopolysaccharidos type 1 | AIHA with Acquired Red Cell Aplasia | Rituximab, MMF | 1 | Yes | 14 | None | No |
| 4 | 25 | Wolman disease | Anti-enzyme antibodies | None | 1 | Yes | 25 | None | No |
Conclusion
Our study shows that Bortezomib is a promising therapeutic option for refractory post-transplant autoimmunity with high tolerance and no related toxicities.
Session topic: 22. Stem cell transplantation - Clinical
Keyword(s): Autoimmunity, Proteasome inhibitor, Post-transplant, bortezomib