Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Children and Adolescents with Fanconi Anemia

Abstract

We describe haploidentical bone marrow transplantation with post-transplant cyclophosphamide (PT-CY) for 30 patients with Fanconi anemia (FA). Twenty-six patients were transplanted upfront, and the preparatory regimens included fludarabine 150 mg/m + total body irradiation 200 to 300 cGy ± CY 10 mg/kg without (n = 12) or with rabbit antithymocyte globulin (r-ATG) 4 to 5 mg/kg (n = 14). Four patients were rescued after primary or secondary graft failure after related or unrelated donor transplantation with the above regimen with (n = 2) or without r-ATG (n = 2). PT-CY at 25 mg/kg/day (total dose, 50 mg/kg) followed by cyclosporine and mycophenolate mofetil was given to all patients. All patients engrafted in the subgroup of patients who did not receive r-ATG (n = 14), but their transplant course was complicated by high rates of acute and chronic graft-versus-host disease (GVHD), and only 8 patients are alive. In the subgroup that received r-ATG (n = 16), 14 patients had sustained engraftment, severe GVHD rates were lower, and 13 patients are alive. Hemorrhagic cystitis occurred in 50% of patients, whereas cytomegalovirus reactivation occurred in 75%. One-year overall survival for the entire cohort was 73% (95% CI, 64% to 81%), and all surviving patients achieved full donor chimerism. In conclusion, haploidentical donor transplantation with PT-CY is a suitable option for FA patients without a matched related or unrelated donor.

Haploidentical hematopoietic stem cell transplantation with post‐transplant high‐dose cyclophosphamide in high‐risk children: A single‐center study

“…The additional effect of ATG in a Post‐Cy‐based regimen era is controversial. Bonfim et al reported lower GVHD rates and higher survival in Fanconi anemia patients receiving ATG treatment with Post‐Cy. However, we have not found such an effect in our study.…”

“…The usual recommendation for GVHD prophylaxis in Post‐Cy practice is to administer cyclophosphamide on day 3 with or without day 4 and to start a calcineurin inhibitor the day after the last dose of cyclophosphamide, with or without mycophenolate . Our approach differs from these literature standards in two ways.…”

Transplantation of Hematopoietic Stem Cells for Primary Immunodeficiencies in Brazil: Challenges in Treating Rare Diseases in Developing Countries

“…Hence, for many years, UCB was easier and faster, and therefore used in almost 40% of our patients. More recently, haploidentical transplants with in vivo T cell depletion with post-transplant cyclophosphamide (PTCy) have been described in children and adults with hematological malignancies and non-malignant diseases [38][39][40][41][42][43]. This strategy is cheap and immediately available, and its applicability to treat PIDs has been reported in a small number of patients, but results are promising [44][45][46][47].…”

Pediatric unmanipulated haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and reduced intensity, TBI-free conditioning regimens in salvage transplantations

“…12 Similarly, Shima reported the combination of TBI with melphalan. 13 The usage of TBI as a part of haploSCT with a PTCY regimen is continued even in patients with Fanconi anemia 14,15 or in combination with busulfan. 16 Some reports in adults have investigated the possibility of a TBI-free conditioning regimen by replacing it with thiotepa and melphalan, but the trial was complicated by limited access to thiotepa and the group reversed to TBI.…”