Donor blood stem cell infusion after ex vivo T cell purging with alemtuzumab as a treatment for poor engraftment of allogeneic blood stem cell transplant from HLA haploidentical family donor: A case of severe aplastic anemia

초록

Ex vivo T cell manipulation for dose adjustment in DLI is sophisticated. As simpler method, alemtuzumab was elected for ex vivo T cell reduction from blood stem cells (BSCs) prior to infusion. A case of poor engraftment was taken in the setting of successful allogeneic blood stem cell transplant from HLA haploidentical father for severe aplastic anemia of a 12 year old girl. After preparation with reduced intensity regimen consisting of busulfan, fludarabine and rabbit ATG, T cell replete BSCs were infused. The transplant was complicated by acute GVHD requiring steroid, post-transplant lymphoproliferative disease requiring rituximab, CMV reactivation requiring gancyclovir, hemorrhagic cystitis, BKV viruria and hypertension. Immunosuppression was off at 8 months. Despite 100% donor chimerism at 1-12 months post-transplant and complete alteration of blood type at 8 months, pancytopenia persisted requiring transfusion of 42 units of red cells and 220 units of platelet concentrates until 14 months post-transplant. DLI without T cell reduction was thought risky because of previous GVHD. G-CSF mobilized peripheral BSCs of her father were harvested (5.74x108 NMC/kg containing 1.56x108 CD3+ cells/kg and 3.41x106 CD34+ cells/kg) and incubated at 1mg of alemtuzumab per 1010 NMC for 30 minutes at 20 C. Processed BSCs were slowly infused. After incubation, T cells were reduced to 0.61x108 CD3+ cells/kg. Alemtuzumab caused severe infusion related reaction including fever up to 39 C making the drip of the infusion for a whole day. Pancytopenia disappeared and she became transfusion independent at day 10 post-DLI. The patient developed mild chronic GVHD involving skin, liver and lungs at a month post-DLI. Alemtuzumab can be used for ex vivo reduction of T cells prior to DLI. Infusion related reaction was substantial even at one tenth of usual dose. The optimal dose as well as duration is yet to be determined.