ISSN 1866-8836
Клеточная терапия и трансплантация

NM-02. Long-term outcomes following hematopoietic stem cell transplantation in patients with Fanconi anemia: results from a single center

Anastasia V. Doronina, Elena B. Machneva, Ludmila V. Olkhova, Yulia A. Nikolaeva, Mariia S. Kuricina, Michail M. Antoshin, Ekaterina A. Pristanskova, Elena V. Skorobogatova

Russian Children’s Clinical Hospital, a Branch of N. I. Pirogov Russian National Research Medical University, Moscow, Russia

Contact: Dr. Anastasia V. Doronina, phone: +7 (926) 785-37-07, e-mail:

doi 10.18620/ctt-1866-8836-2023-12-3-1-176


Fanconi anemia (FA) is an inherited autosomal recessive disease characterized by congenital developmental abnormalities and bone marrow failure leading to severe anemia, neutropenia and thrombocytopenia. The only curative option of correction of bone marrow failure in AF is the hematopoietic stem cells transplantation (HSCT).

Materials and methods

Over the period of November 1994 to December 2022, HSCT was performed in 38 patients (16 boys and 22 girls) with FA: 36 patients had severe bone marrow failure; 2 patients had myelodysplastic syndrome transformation. The average age of patients was 9.5 years (3.7-15.0). 24 patients (63%) had a matched related donor, while the remaining 14 patients (37%) had a transplant from a matched unrelated donor (MUD). The following sources of hematopoietic stem cells were used: umbilical cord blood and bone marrow, in 3 patients (7.5%); umbilical cord blood in one case (2.5%); peripheral blood stem cells, in 5 patients (13.0%), bone marrow, in 29 patients (77.0%). Conditioning regimens included busulphan at the doses of 2-8 mg/kg combined with cyclophosphamide (20-40 mg/kg). Since 2001, implementation of fludarabine 150 mg/m2 and anti-thymocyte globulin enabled reduced busulphan doses and eliminated cyclophosphamide from related matched HSCT. Prophylaxis of graft-versus-host disease (GvHD) included calcineurin inhibitors (CNI) in 2 patients as monotherapy; CNI combined with daclizumab in 11 patients (29%); CNI combined with methotrexate in 23 patients (60%), and mycophenolic acid in 13 patients (34%).


All patients were successfully engrafted. The median recovery for leukocyte lineage was 16 days (9-38), for platelet lineage it was 15.5 days (9-27). 23 patients (60%) developed acute GvHD, of which 15 (40%) had mild course and 8 patients had 3-4 degrees GvHD (21%). Chronic GvHD developed in 12 patients, with 6 of them experiencing extensive GvHD. Six patients (15%) received second HSCT, i.e., due to secondary graft failure in five cases, and because of severe graft hypofunction with persistent mixed chimerism in one patient. The median period until second transplantation was 3.7 months (1.5-14.0). Five patients received a 2nd transplant of peripheral blood stem cells from the same donor. One patient developed secondary immune graft failure after HSCT from MUD (9/10 HLA), followed by repeated HSCT from a haploidentical donor with successful outcome.

For the conditioning during the 2nd HSCT for FA, thoraco-abdominal irradiation of 2-4 Gy was used in 4 patients; fludarabine (90-150 mg/m2) and thymoglobulin (5-10 mg/kg) in 5 patients; cyclophosphamide (10-20 mg/kg) in 3 patients; melphalan (30 mg/kg) in 1 case, and alemtuzumab (1 mg/kg) in one patient. Prior to the haploidentical HSCT, a combination of fludarabine, thymoglobulin, melphalan, and low doses of cyclophosphamide was used aiming for in vivo graft lymphodepletion with cyclophosphamide at a total dose of 50 mg/kg.

Two patients died after 2nd HSCT due to refractory GvHD and severe infectious complications. Acute GvHD after the 2nd HSCT was observed in 4 patients, chronic GvHD was developed in 3 patients.

The overall survival at 30 years was 71%, with event-free survival rate of 57.8%. Four patients suffered the oropharyngeal squamous cell cancer at late terms (138 to 170 months) after HSCT. A total of 11 patients died: 8 deaths were associated with infectious complications and/or GvHD, and three lehtalities resulted from the progression of squamous cell cancer. The overall survival at 10 years after second HSCT was 67.0%.


HSCT is a radical therapy for the FA patients. However, it is associated with high risks of severe complications, including fatal outcomes. In our study, both infectious and immune post-transplant complications were observed, with a post-HSCT mortality rate of 29%. Graft failure and hypofunction of the transplant is a frequent complication of HSCT in the FA patient, thus requiring second transplantation. Allo-HSCT from a haploidentical donor using post-transplant cyclophosphamide is a curative option in the absence of an alternative donor.


Congenital aplasia, Fanconi anemia, hematopoietic stem cell transplantation, children.

Supplement 12-3

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doi 10.18620/ctt-1866-8836-2023-12-3-1-176

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