Successful Treatment of Secondary Graft Failure Following Unrelated Cord Blood Transplant with Hematopoietic Growth Factors in a Patient with Fanconi Anemia

Background:

Graft failure following unrelated cord blood transplantation (UCBT) in patients with Fanconi anemia is associated with significant mortality. Second transplantation may be considered; however, the limited toxicity profile of hematopoietic growth factors makes them an option for the treatment of graft failure. We describe a 7-year-old female with Fanconi anemia and marrow failure treated with UCBT utilizing a 6 /6 HLA matched cord blood unit. The course was complicated by secondary graft failure treated with hematopoietic growth factors including granulocyte colony stimulating factor (GCSF), erythropoietin (EPO), and romiplostim with reversal of pancytopenia and transfusion dependence.   The use of hematopoietic growth factors in the treatment of secondary graft failure following UCBT in pediatric patients with Fanconi anemia might be considered as alternative to re-transplantation.   

 Methods:

The preparative regimen included total body irradiation (3 Gy), fludarabine (35 mg/m2/day x 4 days), cyclophosphamide (10 mg/kg/day x 4 days), and thymoglobulin (3 mg/kg/day x 4 days).  Graft-versus-host disease (GVHD) prophylaxis included cyclosporine and mycophenolate mofetil.  A total of 11.6 x 10^7 TNC / kg and 0.9 x 10 ^6 CD34 / kg cell were infused.  Engraftment occurred on Day +18.  No evidence of GVHD was noted and immunosuppression was discontinued on Day +110.  Post-HSCT complications included: mucositis, respiratory syncitial virus infection, adenovirus viremia, hemorrhagic cystitis, and cytomegalovirus (CMV) reactivation.  On Day +79 CMV reactivation reoccurred and valganciclovir was started on Day +87.  On Day +103 leukopenia was noted and Bactrim was stopped.  On Day +110, CMV was undetectable and valganciclovir was stopped due to evolving cytopenias.

Results:

Transfusion with packed red blood cell and platelets were provided.  A bone marrow examination demonstrated a hypocellular marrow (< 5%) and a normal cytogenetic evaluation.  On Day +188, engraftment analysis using whole blood still demonstrated 98% donor DNA suggesting that the few remaining stem cells were of donor origin.   In order to avoid the toxicity associated with second transplant, GCSF (5 mcg/kg/day), romiplostim (10 mcg/kg/week), and EPO (150 units/kg/dose three times per week), was started on Day +114, +117, and Day +119; respectively.  By Day +130 the absolute neutrophil count was > 500 / uL and platelet count was > 25,000 / uL. By Day +149, the cytopenias and need for transfusion support had resolved off of hematopoietic growth factors.

Conclusion:

To our knowledge, this is the first description of a successful application of hematopoietic growth factors as initial therapy in a patient with secondary graft failure following UCBT for Fanconi anemia.   We found that the use of hematopoietic growth factors to be an alternative to the morbidity and mortality associated with the use of second transplantation.