Unrelated Donor Stem Cell Transplantation for 36 Patients(pts) with Fanconi Anemia(FA): A Single Center Experience.
Authors: Bonfim Carmem M.S. , Bitencourt Marco A. , Setubal Daniela C. , Funke Vaneuza A. , deMedeiros Carlos R. , Ruiz Jefferson , Flowers Mary E. , Zanis-Neto Jose , Pasquini Ricardo 
Published: April 2020

Introduction: FA is an autossomal recessive syndrome that usually presents with congenital abnormalities, progressive pancytopenia and an increased risk of cancer.The first stem cell transplant for FA was performed in Latin America in 1983 and since then the BMT center from Curitiba, Brazil became a reference center for this disease. From 1983 until June 2004, 140 pts received a stem cell transplant for FA and most of them were in aplastic phase. In this study we performed a retrospective analysis of 36 patients who received an unrelated stem cell transplant for FA in our BMT center.

Patients and methods: Period: 04/1996 to 06/2004, age 4 to 19 year old (median: 9y), sex: 20F/16M. Disease duration: 7 to 122 months (Median: 45), Previous transfusions: 0 to 400 (Median of 21). Aplastic phase: 35 pts. Myelodysplastic syndrome:1pt.Stem cell source : bone marrow 15 pts ( 6/6 : 12pts; 5/6 : 3pts) , cord blood : 20 pts ( 6/6: 3pts , 5/6 :8 pts and 4/6 : 9 pts) and peripheral stem cell : 1 pt ( 6/6). Preparatory regimen: 9 pts received only Cyclophosphamide (CY), 15 pts received CY + Fludarabine + Thimoglobuline, 4 pts received Fludarabine + TBI (200cGy), 4 pts received CY+ TBI ± ATG and 4 pts Fludarabine + CY. GVHD prophylaxis: Cyclosporine (Csa) + MTX: 18 pts, Csa + steroids: 14 pts and other: 4pts. All pts received prophylactic antibiotics according to common practice.

Results: 13 pts are alive and well 45 to 1579 days after transplant (median 303 days). 34 pts were evaluable for engraftment (2 pts died before day 28 due to bacterial sepsis and CNS hemorrhage). Median time to reach PMN&gt; 500/uL was 21 days after transplant (+ 12 to + 57) and platelets&gt; 20.000/uL was 22, 5 days (+14 to + 49). Pts who received CY + Fludarabine + Thimoglobuline had a better survival (56%) but it did not reach statistical significance when compared to other preparatory regimens. Acute graft versus host disease (A-GVHD) occurred in 9 pts (grade III: 4 pts, grade IV: 5 pts). Three pts with grade III A-GVHD developed C-GVHD (2 were extensive and severe). VOD was diagnosed in 3 pts (moderate/severe). Mucosytis grade III- IV occurred in 16 pts. Twenty-three pts died at a median time of 58 days after transplant (7 to 226 d). All pts with primary graft failure (11) and 5 pts with only a neuthrophil engraftment died. Causes of death: 15 pts: infections or hemorrhage related to rejection; 4 pts: GVHD, 3 pts:VOD , 1 pt: P carinii and 1 pt EBV lymphoproliferative disease. Transplant related mortality (TRM) was 55% for the whole group (38% for the pts who received CY+ Fludarabine + ATG). It was also lower (35%) for the pts who received cord blood transplants but it did not reach statistical significance regarding survival rate.

Conclusions: Treatment of FA pts with unrelated stem cell transplant must be directed at a more effective control of rejection and GVHD. Transplant related mortality is still very high in this group of pts. Our study shows that the use of CY + Fludarabine + Thimoglobuline may improve survival but we still need more pts and a longer follow up to confirm this data.