Successful Haploidentical Stemcell Transplantation In a Patient with Fanconi Anemia and AML.

Abstract 4586

Allogeneic hematopoetic transplantation is the only curative treatment in patients with fanconi anemia indicated as soon transfusion dependency occurs and a matched family or unrelated donor is available. Overall survival for matched or nearly (5/6) matched unrelated donor transplantation improved since the introduction of fludarabine-based conditioning regimens from 30% to 53%. Transplantation after malignant transformation, in heavily pretransfused patients or from alternative donors is associated with a dismal outcome. We report the case of a 7 year old girl with fanconi anemia who developed AML-M4 (monosomy 7 and gain on chromosome 3) with 24% peripheral blasts during donor search for HCT. Remission was acchieved with a mild chemotherapeutic regimen consisting of a single dose of intravenous (300mg/m²) and intrathecal (40mg) cytarabine and daily oral thioguanine (cumulative dose: 930mg/m²). 4 weeks after diagnosis of AML, the girl was transferred for allogeneic PBSCT (CD3/19 depleted) from an unrelated mismatched (7/10) donor. Conditioning regimen consisted of Fludarabine, Busulfex, ATG and OKT-3. Unfortunately, mixed chimerism was observed and on day +21 graft rejection was diagnosed. The patient underwent a second PBSCT from the same donor after conditioning with Fludarabine, Alemtuzumab and Cyclophosphamide and 12 days later received a stem-cell-boost due to poor hematological regeneration. Prolonged aplasia under treatment with G-CSF was suspicious for non-engraftment. The indication for a third PBSCT with her haploidentical father as donor was set. Conditioning in the aplastic patient with elevated autologous T-Lymphocytes consisted of ATG only for 3 days. Full engraftment was achieved on day +11. CMV-reactivation was effectively treated with a combination therapy of valganciclovir and foscavir. One year after the third PBSCT, the patient is in continuing morphologic remission with normal Cytogenetics and complete donor chimerism. Mild Graft vs. Host Disease (Grade I, Skin) dissolved after short term therapy with Prednison. Still she suffers under minor restrictions in her every day life. We demonstrate here the case of a CMV-positive patient with fanconi anemia and AML, polytransfused (27 red-cell-packs and 94 platelet-transfusions) who survived mismatched PBSCT of her CMV-positive father after two failed PBSCT from an alternative 7/10-mismatched donor. To our knowledge this is the first patient with fanconi anemia and AML, successfully transplanted from an haploidentical donor.