To date, allogeneic stem cell transplantation (SCT) is the only curative approach for patients with Fanconi anemia (FA) and myeloid malignancy (AML). No data exist on whether cytoreductive chemotherapy prior to SCT impacts outcome.
We retrospectively analyzed data retrieved from the AML-BFM database (Germany) regarding children with FA and AML.
Between January 1993 and May 2013 14 patients were identified, in whom AML was diagnosed at a median age of 11.6 yrs [0.9-19.6] (n=13). In 10 patients (4 not available) the diagnosis FA preceded the occurrence of AML by a median of 32.3 months [0-161].
Six of 14 patients underwent SCT achieving a 5 year overall survival of 42%. Median time to transplant after the diagnosis of AML was 2 months. One patient died after relapse, one due to severe graft versus host disease (GvHD), another of unknown cause. Of the three surviving patients two had chronic GvHD (one limited, one extended). All three surviving patients received a radiation free preparative regimen (1. fludarabine (Flu) and cyclophosphamide (Cy); 2. busulfan (Bu) and Flu; 3. Bu, Flu and Cy.) including antibodies for intensive GVHD prophylaxis. In all three cases a high cell dose of either PBSC (30.1 x 10e6 CD34+) or BM (2.13 and 3.43 x 10e8 MNC) was infused. Two surviving patients received low dose cytoreductive therapy (thioguanin and cytarabin) to bridge time to SCT. The remaining patient did not receive pre-transplant therapy.
Eight of 14 patients did not receive a SCT. Median survival for these children was 40 days. Three of 8 patients received low intensity chemotherapy (thioguanin and/or cytarabin). Two were treated with more intensive combinations (e.g. cytarabin, adriamycin and etoposide). The latter all died of complications from long lasting aplasia.
Additionally to the 14 patients described above, another patient was identified, in whom AML developed 14 months after successful SCT for bone marrow failure. Blasts were of recipient origin and the patient died of progressive disease.
The data presented are subject to selection bias. Three of 14 patients survived and 2/3 surviving patients received low dose cytoreductive therapy for disease control before going to transplant. None of them achieved complete remission (CR) before SCT. Graft failure and chronic GVHD were the main complications after transplantation. FA patients with AML should proceed to SCT. Mild cytoreductive therapy with thioguanine and cytarabine may be useful. Achieving CR pre transplant might not be necessary for OS.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.