297: Salvage Transplantation for Allograft Failure Utilizing Fludarabine and Alemtuzumab as the Conditioning Regimen (2008)

Graft failure remains a cause for elevated morbidity and mortality after myeloablative allogeneic stem cell transplantation. This report includes the outcome of nine patients that received a salvage allogeneic stem cell transplant after failing (rejecting) one (n = 8) or two (n = 1) previous transplants. Three were males and the median age was 48.5. Diagnoses included: CMML 2, AML 2, CML 1, CLL 1, HL 1, NHL 1 and MDS 1. Median time between failed and salvage transplant was 62 days (range 43–84). Patients received fludarabine 30 mg/m2 IV and alemtuzumab 20 mg IV every day from day -6 to day -2. On day -2 they started cyclosporine 5 mg/kg IV over 6 hours every day (n = 8) or tacrolimus 1 mg PO every 12 hours (keeping levels 5–15 ng/mL after 72 hours)(n = 1). Day 0 was the infusion of donor stem cells. By day +3, cyclosporine was decreased to 2.5 mg/kg IV and eventually switched to oral form once tolerated. Patients received G-CSF support until neutrophil recovery. Grafts consisted of allogeneic HLA identical PBSC from a sibling in 6 cases, MUD PBSC in 2 and MUD BM in 1. All the patients received the grafts from the same donor as in their previous transplant except 1. All patients engrafted. Neutrophil recovery was seen at a median of 12 days. Seven patients achieved 100% chimerism by restriction length fragment polymorphism by day 60, 1 by day 30, and 1 died before chimerism evaluation but with neutrophil recovery. The therapy was well tolerated with low toxicity. There are so far only two cases of GVHD; one patient had skin only (acute grade II), and the second had acute of the skin (grade II) and later chronic of the skin (mild chronic/limited). With a median overall survival of 191 days (range 37–738), six patients are alive and in complete remission, three patients have died: two of relapse and one of a fungal infection in the setting of GVHD therapy. The combination of fludarabine and alemtuzumab appears to be an effective and well tolerated conditioning regimen for reconditioning patients suffering from graft failure. Graft failure remains a cause for elevated morbidity and mortality after myeloablative allogeneic stem cell transplantation. This report includes the outcome of nine patients that received a salvage allogeneic stem cell transplant after failing (rejecting) one (n = 8) or two (n = 1) previous transplants. Three were males and the median age was 48.5. Diagnoses included: CMML 2, AML 2, CML 1, CLL 1, HL 1, NHL 1 and MDS 1. Median time between failed and salvage transplant was 62 days (range 43–84). Patients received fludarabine 30 mg/m2 IV and alemtuzumab 20 mg IV every day from day -6 to day -2. On day -2 they started cyclosporine 5 mg/kg IV over 6 hours every day (n = 8) or tacrolimus 1 mg PO every 12 hours (keeping levels 5–15 ng/mL after 72 hours)(n = 1). Day 0 was the infusion of donor stem cells. By day +3, cyclosporine was decreased to 2.5 mg/kg IV and eventually switched to oral form once tolerated. Patients received G-CSF support until neutrophil recovery. Grafts consisted of allogeneic HLA identical PBSC from a sibling in 6 cases, MUD PBSC in 2 and MUD BM in 1. All the patients received the grafts from the same donor as in their previous transplant except 1. All patients engrafted. Neutrophil recovery was seen at a median of 12 days. Seven patients achieved 100% chimerism by restriction length fragment polymorphism by day 60, 1 by day 30, and 1 died before chimerism evaluation but with neutrophil recovery. The therapy was well tolerated with low toxicity. There are so far only two cases of GVHD; one patient had skin only (acute grade II), and the second had acute of the skin (grade II) and later chronic of the skin (mild chronic/limited). With a median overall survival of 191 days (range 37–738), six patients are alive and in complete remission, three patients have died: two of relapse and one of a fungal infection in the setting of GVHD therapy. The combination of fludarabine and alemtuzumab appears to be an effective and well tolerated conditioning regimen for reconditioning patients suffering from graft failure.