A modified conditioning regimen based on low‐dose cyclophosphamide and fludarabine for haploidentical hematopoietic stem cell transplant in severe aplastic anemia patients at risk of severe cardiotoxicity

Abstract

Severe cardiotoxicity is a fatal complication during high-dose cyclophosphamide (Cy)based conditioning in hematopoietic stem cell transplant (HSCT) for severe aplastic anemia (SAA). This study aimed to evaluate the feasibility and efficacy of a modified conditioning regimen in haploidentical HSCT (haplo-HSCT) for severe-cardiotoxic-risk SAA patients. This BuCy low Flu conditioning utilized busulfan (Bu, 3.2 mg/kg for 2 days), low-dose Cy (100 mg/kg), fludarabine (150 mg/m 2 ), and rabbit antithymocyte globulin (rATG, 10 mg/kg). Compared to BuCy conditioning using high-dose Cy of 200 mg/kg, Bu of 3.2 mg/kg for 2 days, and rATG of 10 mg/kg, the incidence of severe cardiotoxicity of BuCy low Flu conditioning was significantly decreased (2.17% vs 12.80%, p = .032).The engraftment rates (100% for neutrophil and 84.44% for platelet) were favorable. The probabilities of 100-day transplant-related mortality were similar in the BuCy low Flu and the BuCy group (8.75% vs 10.53%, p = .671). Both 1-year overall survival (88.79% vs 84.66%, p = .357) and 1-year failure-free survival (84.78% vs 81.70%, p = .535) were comparable. The BuCy low Flu group had higher rates of cytomegalovirus and Epstein-Barr virus reactivation. In conclusion, the BuCy low Flu provided reduced severe cardiotoxicity, and achieved favorable engraftment and survival. Our results suggest BuCy low Flu conditioning can be a feasible alternative for haplo-HSCT recipients at risk of severe cardiotoxicity.

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

“…In contrast, Japanese colleagues reported a higher incidence of sPGF of 15% in 49 pediatric AA patients, which included 3 transplantations from matched sibling donors (20.0%), 3 from unrelated donors (10.3%), and 1 from haploidentical donor (20%) ( 25 ). Similar to the study of Kako et al ( 8 ), Flu was suggested to be responsible for the increased incidence of sPGF, which was denied by our studies ( 11 ). The discrepancy in results can be explained by the difference in conditioning regimen instead of HSCT type, as Liu and we additionally applied 2 days of Bu to ensure successful engraftment and stable full donor chimerism in the haplo-setting ( 26 ).…”

“…All patients received mixed graft infusion of granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow (BM) and peripheral blood (PB) stem cells except for three cases (0.67%) in which only PB grafts were infused. The conditioning regimen for acquired AA patients included: (1) BuCy-ATG conditioning including busulfan (Bu, 3.2 mg/kg daily on days -8 and -7), cyclophosphamide (Cy, 50 mg/kg daily on days -5 to -2), and rabbit antithymocyte globulin (rATG, 2.5 mg/kg daily on days -5 to -2, from SangStat, France); and (2) the BuCy low Flu-ATG regimen consisting of Bu (0.8 mg/kg 4 times daily on days -8 and -7), Cy (25 mg/kg daily on days -5 to -2), Flu (30 mg/m2 daily on days -6 to -2), and rATG (2.5 mg/kg daily on days -5 to -2) ( 10 , 11 ). The prophylaxis of GvHD was described elsewhere ( 10 ).…”

Efficacy and safety of mesenchymal stem cells treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation

“…2,22,24 For patients with severe aplastic anemia, the preconditioning regimen mainly included busulfex, cyclophosphamide, fludarabine, and ATG. 33 We used cyclosporine A (CSA), mycophenolate mofetil (MMF), and methotrexate (MTX) to prevent GVHD. 34 As it was reported by Chen et al 35 that the co-infusion of an unrelated cord blood unit may potentially improve the engraftment of HID HSCT, two patients with relatively higher donor-specific anti-human leukocyte antigen (HLA) antibodies levels (2000 ⩽ median fluorescent intensity ⩽ 10,000) received umbilical cord blood in their graft in this study.…”