Abstract

Abstract 2363

Background:

Fanconi anemia (FA) is a rare, genetically and phenotypically heterogeneous inherited disorder. The natural history of FA is characterized by progressive marrow failure and an increased risk for clonal evolution. Evolution to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) is the main cause of premature mortality. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered the treatment of choice in this situation but the evolution is usually poor post-HSCT, mainly due to treatment-related mortality. We report here the outcome of 6 FA patients who received a sequential regimen strategy because of clonal evolution.

Patients, disease and methods:

From August 2006 to December 2011, 6 consecutive patients with FA who received a sequential treatment with chemotherapy and reduced-intensity conditioning for clonal evolution in four different French institutions were reviewed. Five patients presented an AML (3 high risk and 2 standard risk according to Medical Research Council) and 1 a myelodysplastic syndrome considered high risk according to the International Pronostic Scoring System. The sequential strategy consisted in a pre-transplant chemotherapy by fludarabine 30 mg/m2/d 5 days and cytarabine 1gr/m2x2/d 5 days with granulocyte-colony stimulating factor injections (FLAG) followed early after by a reduced-intensity conditioning [4 days cyclophosphamide 10 mg/kg (low dose cyclophosphamide because of FA), 4 days fludarabine 30 mg/m2, 2 days anti-thymocyte globulin (3.75 mg/kg) and TBI (2 Gy)]. The source of stem cells was cord blood for three patients (Double units in 2 patients) and bone marrow for others. Graft versus host disease (GvHD) prophylaxis consisted in cyclosporine (CSA) plus MMF (except 1 patient who received CSA plus methotrexate).

Results:

Median age of the patients at HSCT was 20.5 years (5–28). Pre-transplant chemotherapy as well as conditioning regimen were well tolerated. The median time between the first day of chemotherapy and the date of HSCT was 30 days (range 12 to 80). During evolution, all patients engrafted. Median time to engraftment was 21 days (range 14 to 35) for neutrophils and 29 days for platelets (range 21 to 42). Donor chimerism was complete at day 100 for 5 patients. Septicemias were encountered in three patients (Staphylococcus, Enterobacter, and Candida) at 1, 3 and 4 months after HSCT, respectively. One patient developed a diarrhea to Campylobacter jejuni one month after HSCT and another patient underwent meatotomy for chronic maxillary sinusitis six months post-HSCT. Acute GvHD (1 grade I and 1 grade II) occurred in 2 patients. Both responded to steroid therapy. Chronic GvHD occurred in two patients. After a median follow-up (FU) of 30 months (8–72), all patients are still alive in complete remission from the clonal evolution.

Conclusion:

We report here 6 FA patients (5 AML and 1 MDS) who were successfully treated by a sequential strategy approach (FLAG and RIC HSCT). With a median FU of 30 months, all patients are alive and free from their original AML or MDS. The number of patients is little but the usual evolution is very poor post-HSCT in this particular situation. We thus believe this study supports the use of a sequential strategy (FLAG and RIC HSCT) in FA patients with AML or MDS.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.