Bortezomib to Treat Significant Complication of HSCT

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