Severe aplastic anemia is a rare and serious form of bone marrow failure related to an immune-mediated mechanism that results in severe pancytopenia and high risk for infections and bleeding. Patients with matched sibling donors for transplantation have a 80-90% chance of survival; however, a response rate with just immunosuppression for those patients lacking suitable HLA-matched related siblings is only 60%. With immunosuppression, only 1/3 of patients are cured, 1/3 are dependent on long term immunosuppression, and the other 1/3 relapse or develop a clonal disorder. Recent studies have shown that using a haploidentical donor for transplantation has good response rates and significantly lower rates of acute and chronic GVHD.
Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor who must have negative HLA cross-match in the host vs. graft direction
Age <= 65 years for previously treated and <= 75 years for previously treated patients
KPS >= 70%
<500 PMN/mm3
poor cardiac function (LVEF <40%)
poor pulmonary function (FEV1 & FVC <50% predicted)
poor liver function (bili >= 2mg/dL)
poor renal function (creatinine >= 2.0mg/dL or creatinine clearance <40mL/min)
Single group
Fludarabine
Drug30 mg/m2 IV QD x 5 days (Days -6 to -2)
Cyclophosphamide
Drug14.5 mg/kg/day IV x 2 doses (Days -6 \& -5)
Total Body Irradiation
Radiation300 cGy x1 dose (Day -1)
Rabbit ATG
Drug1.5 mg/kg/day x 3 days (Days -3 to -1)
Cyclophosphamide
DrugPost-transplant: 50 mg/kg IV QD (Day +3 to +4)
Demonstrate sustained engraftment after T-cell replete HLA-mismatched haploidentical bone marrow transplantation by collecting chimerism tests monthly following transplant
Hypothesis is that following preparative regimen and bone marrow transplantation, the 30-day graft failure rate will be \<30%.
Determine the incidence of regimen-related mortality at 100 days post transplantation by recording treatment-related adverse events
Determine the incidence of grade 2-4 and 3-4 acute graft versus host disease at 100 days post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course
Determine incidence of chronic GVHD at 6 months and 1 year post transplantation by assessing signs and symptoms of GVHD throughout post-transplant course
Estimate overall survival at 100 days and 1 year post transplantation by collecting survival information at those time points
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