Alemtuzumab, fludarabine and melphalan as a conditioning therapy in severe aplastic anemia and hypoplastic myelodysplastic syndrome--single center experience.
BACKGROUND
Allogeneic hematopoietic stem cell transplantation is the treatment of choice in young patients with severe aplastic anemia. The main causes of failure after this procedure are graft versus host disease, infections and graft failure, often exacerbated by large numbers of transfusions and prolonged disease duration before transplant.


METHODS
We report the results of allografting following conditioning with fludarabine, alemtuzumab and melphalan in: five patients with severe aplastic anemia and one with hypoplastic myelodysplastic syndrome. All patients had matched sibling donors. Source of hematopoietic stem cell was: bone marrow-2, blood-3, bone marrow and blood-1. The age of recipients was 18-26 years. Four patients received their graft as the first line therapy and two after failure of cyclosporine and antithymocyte globulin treatment. Number of transfused units including red blood cells and platelets before transplantation was 8-100 (median: 22) and 10-32 (median: 11), respectively. All donors and recipients were CMV-seropositive. Conditioning consisted of: alemtuzumab 30 mg/d (day -7 to -5), fludarabine 30 mg/m(2) (days -7 to -3) and melphalan 140 mg/m(2) at the day -2.


RESULTS
The time to granulocytes and platelets recovery was 15 and 25 days, respectively. All patients achieved full donor chimerism on day +60. Only two patients needed ganciclovir as preemptive therapy. Recurrent parvovirus B19 infection with pure red cell aplasia and acute viral B hepatitis was observed in one case. Pure red cell aplasia was successfully treated with immunoglobulins and cyclosporine discontinuation. With a follow-up of 16-39 (median: 29) months all patients are alive, and neither graft failure nor graft versus host disease, or any no other severe complications, was observed.


CONCLUSIONS
Our study suggests that transplantation of hematopoietic stem cell using alemtuzumab, fludarabine and melphalan as a conditioning therapy is safe, inexpensive and effective treatment for patients with severe aplastic anemia, including multi-transfused adults having their disease for a long time.
Rzepecki
Piotr
P
Department of Clinical Oncology, BMT Unit, Central Clinical Hospital Ministry of National Defence, 128 Szaserow Street, 00-909 Warsaw, Poland. piotr_rzepecki1@poczta.onet.pl
Sarosiek
Tomasz
T
Szczylik
Cezary
C
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000191:economics; D003365:Costs and Cost Analysis; D004359:Drug Therapy, Combination; D018380:Hematopoietic Stem Cell Transplantation / Q000191:economics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D019520:Living Donors; D008558:Melphalan / Q000008:administration & dosage*; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D019172:Transplantation Conditioning / Q000191:economics / Q000379:methods*; D014184:Transplantation, Homologous / Q000191:economics; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan