Long-term observations of patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation: a two-center experience
Elena V. Skorobogatova1, Kirill I. Kirgizov1, Dmitry N. Balashov2, Natalia V. Sidorova1, Ekaterina A. Pristanskova1, Natalia V. Sidorova1, Veronika V. Konstantinova1, Oxana L. Blagonravova1, Pavel E. Trakhtman2, Yulia V. Skvortsova2, Michael A. Maschan2, Aleksey A. Maschan2
1 The Russian Pediatric Clinical Hospital, Moscow
2 Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow
Fanconi anemia (FA) is a rare disease characterized by inborn anomalies, hematopoietic aplasia and high incidence of malignancies. Hematopoietic stem cell transplantation (HSCT) is the only approach to hematopoiesis correction in these patients. However, high-dose chemotherapy is highly toxic in FA patients. Our aim was to evaluate the results of a long-time follow-up which is important for individual prognosis.
Materials and methods
Twenty-nine children with FA (11 males, 18 females), median age 9,5 (3,7-15,4) years, underwent HSCT from November 1994 to April 2014. In 17 cases (58,6%), HLA-matched sibling donors (MRD), and for 12 children (41,4%), matched unrelated donors (MUD) were employed. Graft sources were as follows: bone marrow (n=18); peripheral blood stem cells (n=7), bone marrow+cord blood (n=3), umbilical cord blood (n=1). There was a 9/10-HLA match in one case of related HSCT, and in two patients subjected to MUD HSCT. Two patients were transplanted after development of a secondary myelodysplastic syndrome. The conditioning regimens included: in MUD, Busulfan, 4 mg/kg, Cyclophosphamide (20 mg/kg), Fludarabine, 150 mg/m2, and ATG treatment; with MRD, Busulfan 4 mg/kg, Fludarabine, 150 mg/m2, and ATG injections. GvHD prophylaxis was donor-dependent, i.e., CsA-based regimen for MRD HSCT, or Tacrolimus-based therapy for MUD HSCT. TCR alpha/beta transplant depletion was performed in three MUD HSC recipients.
All the patients were successfully engrafted. The rejection rate was 13,8% (n=4) which occured by 1, 2, 6, 12 months after HSCT. Second HSCT was performed in all these cases. Two patients survived after the 2nd HSCT with good engraftment; two patients deceased after 2nd HSCT, due to GvHD and adenovirus pneumonia, respectively. Direct toxicity of the conditioning regimens was minimal. No signs of GvHD were observed in 16 patients (55,2%), grade I-II aGVHD. in 8 patients (27,6%), severe GvHD was observed in 5 cases (17,2%). Limited cGvHD was diagnosed in 3 recipients, extensive cGvHD, in 2 cases. A median follow-up was 31,9 months (3,8 to 246). The estimated probability of 5-year overall survival was 67,4%, event-free survival, 62,7%. Two patients developed oral cavity malignancies. The causes of death were GvHD+infection (n=5), infection (n=3), including adenoviral pneumonia, graft-versus-host disease (n=2), and tongue cancer (n=1).
Our results suggest that HSCT is a valid therapeutic option for treating the patients with FA. Post-HSCT course is characterized by rather high incidence of GvHD and infectious complications. Second HSCT is associated with high risk of refractory infections and GvHD. Cancer may be a cause of late mortality.
Fanconi anemia, аllogeneic hematopoietic stem cell transplantation, graft-versus-host disease acute, children neurometabolic diseases