Bortezomib to Treat Significant Complication of HSCT

Use of Bortezomib to Treat Refractory Autoimmune Cytopenia(s) in Allogeneic Stem Cell Transplantation

The purpose of this trial is to study the safety and effectiveness of a drug called Bortezomib for the treatment of low blood cell counts after bone marrow transplant.

The purpose of this research study is to study the safety and effectiveness of a drug called bortezomib for the treatment of autoimmune cytopenia(s) (low blood cell counts) after bone marrow transplant that are not responding to standard treatments. Autoimmune cytopenias are low blood counts due to antibodies or proteins produced against an individual's own blood cells. Having a low red blood cell count (anemia) can make a person feel tired and require blood transfusions frequently. A low platelet count (blood cells that help blood to clot) can make a person bleed or bruise easily. A low neutrophil (white blood cell) count can make a person have infections.

All of these things can be a serious complication after bone marrow transplant and can cause prolonged hospital stay. Bortezomib is being used in children with certain types of blood cancer, however, bortezomib has not been used in children with autoimmune cytopenia(s) and its use in this study is investigational.

Inclusion Criteria:

• All patients, having undergone allogeneic stem cell transplantation at our center.
• Should have failed at least 2 standard treatments for autoimmune cytopenias. Standard treatments include corticosteroids, rituximab, IVIG, plasmapheresis, withdrawal of cyclosporine, cyclophosphamide and MMF. Definition of "failed" treatment will be no response of cytopenia after 2 weeks of continued treatment OR requirement of daily GCSF at 10 mcgs/kg/day for autoimmune neutropenia despite 2 weeks of treatment, transfusions of packed red blood cells or platelets 3 times weekly for 2weeks despite continued treatment OR 5days/week plasmapheresis for 2 weeks and inability to wean the duration.
• Definition of autoimmune hemolytic anemia- development of anemia, where there is a hemoglobin drop of >2 g/dL/48 hours or an absolute value of hemoglobin < 8 g/dL, and evidence of hemolysis by positive direct Coombs test with compatible peripheral blood cell morphology, reticulocyte count and bilirubin level.
• Definition of autoimmune neutropenia - absolute neutrophil counts < 500 for 2 weeks and presence of anti-neutrophil antibodies.
• Definition of autoimmune thrombocytopenia- Platelet counts < 20,000 cells/uL for 2 weeks and presence of anti-platelet antibodies.

Exclusion Criteria:

• Ongoing life threatening infections
• Documented anaphylaxis to bortezomib
• Failed engraftment
• Relapse of primary malignancy
• ≥6/8 matched or haploidentical transplants