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New research suggests the immunosuppressant sirolimus may be a promising treatment option for patients with refractory autoimmune cytopenias.
The drug proved particularly effective in children with autoimmune lymphoproliferative syndrome (ALPS), producing complete responses in all of the ALPS patients studied.
On the other hand, patients with single-lineage autoimmune cytopenias, such as immune thrombocytopenia (ITP), did not fare as well.
David T. Teachey, MD, of The Children’s Hospital of Philadelphia in Pennsylvania, and his colleagues reported these results in Blood.
The group studied sirolimus in 30 patients with refractory autoimmune cytopenias who were 5 to 19 years of age. All of the patients were refractory to or could not tolerate corticosteroids.
Twelve patients had ALPS, 6 had single-lineage autoimmune cytopenias (4 with ITP and 2 with autoimmune hemolytic anemia [AIHA]), and 12 patients had multi-lineage cytopenias secondary to common variable immune deficiency (n=2), Evans syndrome (n=8), or systemic lupus erythematosus (n=2).
The patients received 2 mg/m2 to 2.5 mg/m2 per day of sirolimus in liquid or tablet form for 6 months. After 6 months, those who benefited from the drug were allowed to continue treatment with follow-up appointments to monitor toxicities.
Of the 12 children with ALPS, 11 had complete responses—normalization of blood cell counts—from 1 to 3 months after receiving sirolimus. The remaining patient achieved a complete response after 18 months.
All ALPS patients were successfully weaned off steroids and discontinued all other medications within 1 week to 1 month after starting sirolimus.
The patients with multi-lineage cytopenias also responded well to sirolimus. Eight of the 12 patients had complete responses, although these occurred later than for most ALPS patients (after 3 months).
The 6 patients with single-lineage cytopenias had less robust results—1 complete response and 2 partial responses. One child with ITP achieved a partial response but had to discontinue therapy.
One of the patients with AIHA had a complete response by 6 months and was able to stop taking other medications within a month. The other child with AIHA achieved a partial response.
For all patients, the median time on sirolimus was 2 years (range, 1–4.5 years).
The most common adverse event observed in this study was grade 1-2 mucositis (n=10). Other toxicities included elevated triglycerides and elevated cholesterol (n=2), acne (n=1), sun sensitivity (n=1), and exacerbation of gastro-esophageal reflux disease (n=1).
One patient developed hypertension 2 years after starting sirolimus, but this was temporally related to starting a new psychiatric medication.
Another patient (with Evans syndrome) developed a headache with associated white matter changes (4 different lesions). The changes were attributed to disease-associated vasculitis, and the lesions resolved over a few months with the addition of steroids. The patient was eventually diagnosed with a primary T-cell immune deficiency and underwent hematopoietic stem cell transplant.
“This study demonstrates that sirolimus is an effective and safe alternative to steroids, providing children with an improved quality of life as they continue treatment into adulthood,” Dr Teachey said. “While further studies are needed, sirolimus should be considered an early therapy option for patients with autoimmune blood disorders requiring ongoing therapy.” 
New research suggests the immunosuppressant sirolimus may be a promising treatment option for patients with refractory autoimmune cytopenias.
The drug proved particularly effective in children with autoimmune lymphoproliferative syndrome (ALPS), producing complete responses in all of the ALPS patients studied.
On the other hand, patients with single-lineage autoimmune cytopenias, such as immune thrombocytopenia (ITP), did not fare as well.
David T. Teachey, MD, of The Children’s Hospital of Philadelphia in Pennsylvania, and his colleagues reported these results in Blood.
The group studied sirolimus in 30 patients with refractory autoimmune cytopenias who were 5 to 19 years of age. All of the patients were refractory to or could not tolerate corticosteroids.
Twelve patients had ALPS, 6 had single-lineage autoimmune cytopenias (4 with ITP and 2 with autoimmune hemolytic anemia [AIHA]), and 12 patients had multi-lineage cytopenias secondary to common variable immune deficiency (n=2), Evans syndrome (n=8), or systemic lupus erythematosus (n=2).
The patients received 2 mg/m2 to 2.5 mg/m2 per day of sirolimus in liquid or tablet form for 6 months. After 6 months, those who benefited from the drug were allowed to continue treatment with follow-up appointments to monitor toxicities.
Of the 12 children with ALPS, 11 had complete responses—normalization of blood cell counts—from 1 to 3 months after receiving sirolimus. The remaining patient achieved a complete response after 18 months.
All ALPS patients were successfully weaned off steroids and discontinued all other medications within 1 week to 1 month after starting sirolimus.
The patients with multi-lineage cytopenias also responded well to sirolimus. Eight of the 12 patients had complete responses, although these occurred later than for most ALPS patients (after 3 months).
The 6 patients with single-lineage cytopenias had less robust results—1 complete response and 2 partial responses. One child with ITP achieved a partial response but had to discontinue therapy.
One of the patients with AIHA had a complete response by 6 months and was able to stop taking other medications within a month. The other child with AIHA achieved a partial response.
For all patients, the median time on sirolimus was 2 years (range, 1–4.5 years).
The most common adverse event observed in this study was grade 1-2 mucositis (n=10). Other toxicities included elevated triglycerides and elevated cholesterol (n=2), acne (n=1), sun sensitivity (n=1), and exacerbation of gastro-esophageal reflux disease (n=1).
One patient developed hypertension 2 years after starting sirolimus, but this was temporally related to starting a new psychiatric medication.
Another patient (with Evans syndrome) developed a headache with associated white matter changes (4 different lesions). The changes were attributed to disease-associated vasculitis, and the lesions resolved over a few months with the addition of steroids. The patient was eventually diagnosed with a primary T-cell immune deficiency and underwent hematopoietic stem cell transplant.
“This study demonstrates that sirolimus is an effective and safe alternative to steroids, providing children with an improved quality of life as they continue treatment into adulthood,” Dr Teachey said. “While further studies are needed, sirolimus should be considered an early therapy option for patients with autoimmune blood disorders requiring ongoing therapy.”
New research suggests the immunosuppressant sirolimus may be a promising treatment option for patients with refractory autoimmune cytopenias.
The drug proved particularly effective in children with autoimmune lymphoproliferative syndrome (ALPS), producing complete responses in all of the ALPS patients studied.
On the other hand, patients with single-lineage autoimmune cytopenias, such as immune thrombocytopenia (ITP), did not fare as well.
David T. Teachey, MD, of The Children’s Hospital of Philadelphia in Pennsylvania, and his colleagues reported these results in Blood.
The group studied sirolimus in 30 patients with refractory autoimmune cytopenias who were 5 to 19 years of age. All of the patients were refractory to or could not tolerate corticosteroids.
Twelve patients had ALPS, 6 had single-lineage autoimmune cytopenias (4 with ITP and 2 with autoimmune hemolytic anemia [AIHA]), and 12 patients had multi-lineage cytopenias secondary to common variable immune deficiency (n=2), Evans syndrome (n=8), or systemic lupus erythematosus (n=2).
The patients received 2 mg/m2 to 2.5 mg/m2 per day of sirolimus in liquid or tablet form for 6 months. After 6 months, those who benefited from the drug were allowed to continue treatment with follow-up appointments to monitor toxicities.
Of the 12 children with ALPS, 11 had complete responses—normalization of blood cell counts—from 1 to 3 months after receiving sirolimus. The remaining patient achieved a complete response after 18 months.
All ALPS patients were successfully weaned off steroids and discontinued all other medications within 1 week to 1 month after starting sirolimus.
The patients with multi-lineage cytopenias also responded well to sirolimus. Eight of the 12 patients had complete responses, although these occurred later than for most ALPS patients (after 3 months).
The 6 patients with single-lineage cytopenias had less robust results—1 complete response and 2 partial responses. One child with ITP achieved a partial response but had to discontinue therapy.
One of the patients with AIHA had a complete response by 6 months and was able to stop taking other medications within a month. The other child with AIHA achieved a partial response.
For all patients, the median time on sirolimus was 2 years (range, 1–4.5 years).
The most common adverse event observed in this study was grade 1-2 mucositis (n=10). Other toxicities included elevated triglycerides and elevated cholesterol (n=2), acne (n=1), sun sensitivity (n=1), and exacerbation of gastro-esophageal reflux disease (n=1).
One patient developed hypertension 2 years after starting sirolimus, but this was temporally related to starting a new psychiatric medication.
Another patient (with Evans syndrome) developed a headache with associated white matter changes (4 different lesions). The changes were attributed to disease-associated vasculitis, and the lesions resolved over a few months with the addition of steroids. The patient was eventually diagnosed with a primary T-cell immune deficiency and underwent hematopoietic stem cell transplant.
“This study demonstrates that sirolimus is an effective and safe alternative to steroids, providing children with an improved quality of life as they continue treatment into adulthood,” Dr Teachey said. “While further studies are needed, sirolimus should be considered an early therapy option for patients with autoimmune blood disorders requiring ongoing therapy.”