Successful Outcome in Patients with Fanconi Anemia Undergoing T Cell-Replete Mismatched Related Donor Hematopoietic Cell Transplantation Using Reduced-Dose Cyclophosphamide Post-Transplantation

Abstract

Allogeneic hematopoietic cell transplantation (HCT) has been shown to restore normal hematopoiesis in patients with Fanconi anemia (FA), with excellent results in matched related donor HCT. Outcomes of alternative donor HCT are less favorable, however. In patients without FA, several reports have documented stable engraftment and/or a low risk of graft-versus-host disease (GVHD) using unmanipulated HLA-mismatched related donors and post-HCT cyclophosphamide (PT-CY) for GVHD prophylaxis. Data on the use of this approach in patients with FA are scarce, and thus we launched a study of HLA-mismatched related donor HCT in these patient. Here we report our findings in 19 patients. The conditioning was fludarabine 30 mg/m 2 /day for 5 days, antithymocyte globulin 5 mg/kg/day for 4 days, and total body irradiation (total dose, 200 cGy). GVHD prophylaxis was cyclosporine and mycophenolate and reduced doses of PT-CY, 25 mg/kg, on days +3 and +5. All patients exhibited absolute neutrophil count recovery. Grade III-IV acute GVHD occurred in 3 patients, and chronic GVHD occurred in 1 patient. At a mean follow-up of 38.3 § 5.8 months, the 5-year probability of overall survival for our patients was 89.2% § 7.2%. The regimen was well tolerated; hemorrhagic cystitis occurred in 7 patients, and severe mucositis occurred in 5 patients. There were 2 deaths; the primary cause of death was severe GVHD in 1 patient and leukemia recurrence in the other. We conclude that in patients with FA lacking a matched related donor, the use of mismatched related HCT with low-dose PT-CY is a viable option; it is well tolerated, with a high rate of engraftment and an acceptable incidence of GVHD.

Fanconi anemia and haploidentical stem cell transplantation

“…There were no severe complications, liver or kidney involvement, and mucositis in both cases was mild. Satisfactory clinical evolution and grafting were obtained in both patients, similar to that reported in the literature 9 …”

“…Satisfactory clinical evolution and grafting were obtained in both patients, similar to that reported in the literature. 9 Various protocols have been described internationally, like that by Thakar et al 15 that describe the outcomes of six patients subjected to HSCT with a conditioning regimen based on CY (5 mg/ kg) on days −6 and −5, FLU (30 mg/m 2 ) on days −6 to −2 and 2 Gy TBI on day −1. After that, PTCY was used (25 mg/kg/day on days +3 and +4), and in the last three patients, pretransplant CY was not used.…”

“…Reduced‐intensity conditioning was performed for FA 9 modified with fludarabine 150 mg/m 2 days −6 to −2, which included using TBI radiotherapy (2Gy single dose) day −7 and rabbit ATG Genzyme 10 mg/kg between days −5 and −1. This was followed by infusion of hematopoietic progenitors from donor bone marrow cells (Volume: 600 ml, nucleated cells: 51 kg/10 7 , CD34 cells: 20 kg/10 5 , CD3 cells: 26 kg/10 6 , viability: 97.8%) without complications.…”

Recent Advances in Hematopoietic Stem Cell Transplantation for Inherited Bone Marrow Failure Syndromes

“…Bonfim et al demonstrated a one-year OS of 73% (95% CI, 64% to 81%) using a modified haplo-PTCY platform [24]. These results were also achieved by Ayas et al using a similar haplo-PTCY platform with an overall survival of almost 90% in 19 patients [25].…”

Reduced-dose of Posttransplant Cyclophosphamide and Cotransplantation of Peripheral Blood Stem Cells and Human Umbilical Cord-derived Mesenchymal Stem Cells in Severe Aplastic Anemia

“…Therefore, some studies have reported the outcomes of reduced doses of PTCY in malignant and nonmalignant hematological disorders [14,20]. Furthermore, UC-MSCs are popular in allo-HSCT for SAA because of several bene cial effects, including facilitating engraftment and decreasing GVHD.…”