Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 9;7(3):95-100.
doi: 10.31547/bct-2024-006. eCollection 2024 Aug 25.

Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for Fanconi anemia with/without anti-thymocyte globulin

Ramya Uppuluri  1 , Venkateswaran Vellaichamy Swaminathan  1 , Kavitha Ganesan  1 , Suresh Duraisamy  1 , Anupama Nair  1 , Vijayshree Muthukumar  1 , Anuraag Reddy Nalla  1 , Logesh Balakrishnan  2 , Revathi Raj  1
Affiliations

Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for Fanconi anemia with/without anti-thymocyte globulin

Ramya Uppuluri et al. Blood Cell Ther. .

Abstract

Background: We present comparative data of children with Fanconi anemia undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with or without the addition of rabbit anti-thymocyte globulin (r-ATG) to the conditioning regimen.

Patients and methods: This retrospective study included children with Fanconi anemia aged up to 18 years who underwent haploidentical HSCT between January 2015 and December 2022. The children were included in two cohorts in this study. Cohort 1 included children who received conditioning with fludarabine/cyclophosphamide/single fraction of 2 Gy TBI. The children in cohort 2 received the same conditioning along with r-ATG. Post-transplant cyclophosphamide was administered at a dose of 25 mg/kg on day3 and day4 in both cohorts.

Results: A total of 35 children were included in the study, 25 in cohort 1 and 10 in cohort 2. Neutrophil engraftment was documented around day 14-16 post infusion in 21 children (84%) in cohort 1 and in 8 children (80%) in cohort 2. There was a significant difference in the incidence of the severity of graft versus host disease (GVHD) between the two cohorts (p = 0.003). In cohort 1, acute GVHD was documented in 17 children (68%), with grade 1/2 skin GVHD in 10 children, and grade 3/4 skin and gut GVHD in 7 children. Grade 4 gut GVHD was the cause of death in three children in cohort 1. In cohort 2, acute GVHD was documented in one child (10%) who had grade 4 skin and gut GVHD and succumbed to the above. Chronic GVHD was noted in nine (36%) children in cohort 1, and in one child (10%) in cohort 2. Cytomegalovirus reactivation was documented in 11 children (44%) in cohort 1 and three children (30%) in cohort 2. Overall survival was found to be 16/25 (64%) in cohort 1, with a median follow-up of 49 months, and 7/10 (70%) in cohort 2, with a median follow-up of 12 months.

Conclusion: Serotherapy with r-ATG significantly reduced the incidence of GVHD from 68% to 10% in children with Fanconi anemia, with an increase in overall survival from 64% to 70%, although it did not affect graft failure. Further studies should focus on decreasing graft failure rates with early HSCT before multiple transfusions.

Keywords: Fanconi anemia; GVHD; haploidentical HSCT; post-transplant cyclophosphamide; rabbit ATG.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website.

Figures

Figure 1.
Figure 1.
Conditioning regimen schedule for Fanconi anemia
Figure 2.
Figure 2.
Kaplan-Meier survival curve depicting overall survival was 16/25 (64%) in cohort 1 with a median follow-up of 49 months, and 7/10 (70%) in cohort 2 with a median follow-up of 12 months
See this image and copyright information in PMC

References

    1. Fink O, Even-Or E, Avni B, Grisariu S, Zaidman I, Schejter YD, et al. Two decades of stem cell transplantation in patients with Fanconi anemia: Analysis of factors affecting transplant outcomes. Clin Transplant. 2023; 37: e14835. - PMC - PubMed
    1. Cancio M, Troullioud Lucas AG, Bierings M, Klein E, de Witte MA, Smiers FJ, et al. Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia. Bone Marrow Transplant. 2024; 59: 34-40. - PMC - PubMed
    1. Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Kanakry CG. Optimized Timing of Post-Transplantation Cyclophosphamide in MHC-Haploidentical Murine Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2020; 26: 230-41. - PMC - PubMed
    1. Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res. 2010; 47: 65-77. - PMC - PubMed
    1. Iwamoto M, Ikegawa S, Kondo T, Meguri Y, Nakamura M, Sando Y, et al. Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease. Bone Marrow Transplant. 2021; 56: 956-9. - PubMed

LinkOut - more resources