1.
Fludarabine-Based Low-Intensity Conditioning for Fanconi Anemia is Associated with Good Outcomes in Aplastic Anemia but not in MDS - a Single-Center Experience
Chattopadhyay, S., Lionel, S., Selvarajan, S., Devasia, A. J., Korula, A., Kulkarni, U., Na, F., Sindhuvi, E., Lakshmi, K. M., Srivastava, A., et al
Mediterranean journal of hematology and infectious diseases. 2023;15(1):e2023039
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with Fanconi Anemia (FA) with hematological abnormalities. MATERIALS AND METHODS This is a retrospective analysis of patients with FA who underwent a matched-related donor HSCT. RESULTS Sixty patients underwent 65 transplants between 1999-2021 using a fludarabine-based low-intensity conditioning regimen. The median age at transplant was 11 years (range: 3-37). Aplastic anemia (AA) was the underlying diagnosis in 55 (84.6%), while 8 (12.4%) had myelodysplastic syndrome (MDS) and 2 (3%) had acute myeloid leukemia (AML). The conditioning regimen used was Fludarabine with low-dose Cyclophosphamide for aplastic anemia and Fludarabine with low-dose Busulfan for MDS/AML. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine and methotrexate. Peripheral blood was the predominant stem cell graft source (86.2%). Engraftment occurred in all but one patient. The median time to neutrophil and platelet engraftment was 13 days (range: 9-29) & 13 days (range: 5-31), respectively. Day 28 chimerism analysis showed complete chimerism in 75.4 % and mixed chimerism in 18.5%. Secondary graft failure was encountered in 7.7%. Grade II-IV acute GVHD occurred in 29.2%, while Grade III-IV acute GVHD occurred in 9.2%. Chronic GVHD was seen in 58.5% and was limited in most patients. The median follow-up is 55 months (range: 2-144) & the 5-year estimated overall survival (OS) is 80.2 ± 5.1%. Secondary malignancies were noted in 4 patients. The 5-year OS was significantly higher in patients undergoing HSCT for AA (86.6 + 4.7%) as compared to MDS/AML (45.7+16.6%) (p= 0.001). CONCLUSION SCT using a fully matched donor provides good outcomes with low-intensity conditioning regimens in patients with FA who have aplastic marrow.
2.
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
Lin, F., Zhang, Y., Han, T., Cheng, Y., Mo, X., Wang, J., Chen, Y., Wang, F., Tang, F., Han, W., et al
Clinical transplantation. 2022;36(1):e14514
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.