Treatment of Fanconi Anemia Patients Using Fludarabine and Low-dose TBI, Followed by Unrelated Donor Hematopoietic Cell Transplantation

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2010 Jun 29

PMID 20581880

Citations 10

Authors

M S Thakar

P Kurre

R Storb

M Kletzel

H Frangoul

M A Pulsipher

W Leisenring

M E D Flowers

B M Sandmaier

A Woolfrey

H-P Kiem

Affiliations

Soon will be listed here.

Abstract

A nonmyeloablative conditioning regimen consisting of fludarabine (FLU) and 2 Gy TBI has been used extensively and with substantial engraftment success without promoting excessive nonrelapse mortality in medically infirm patients requiring hematopoietic cell transplantation. In this paper, we studied this same low-toxicity regimen as a means of promoting engraftment of unrelated donor hematopoietic cell transplantation in patients with Fanconi anemia (FA). All patients tolerated the regimen well with no mucositis or other severe toxicities. Of six patients transplanted, five achieved stable mixed or full donor chimerism. Acute and chronic GVHD occurred in four and three patients, respectively. Three patients are alive and well at a median of 45.9 (range, 20.9-68.1) months after transplant. In summary, this FLU-based regimen facilitates stable engraftment of unrelated PBSCs, but is associated with significant chronic GVHD.

Citing Articles

A non-myeloablative conditioning approach for long-term engraftment of human and mouse hematopoietic stem cells.

Du W, Liu W, Mizukawa B, Shang X, Sipple J, Wunderlich M Leukemia. 2018; 32(9):2041-2046.

PMID: 29959415 PMC: 6128741. DOI: 10.1038/s41375-018-0200-3.

A Combined HSC Transduction/Selection Approach Results in Efficient and Stable Gene Expression in Peripheral Blood Cells in Mice.

Wang H, Richter M, Psatha N, Li C, Kim J, Liu J Mol Ther Methods Clin Dev. 2017; 8:52-64.

PMID: 29255741 PMC: 5722719. DOI: 10.1016/j.omtm.2017.11.004.

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

Pietzner J, Merscher B, Baer P, Duecker R, Eickmeier O, Fussbroich D Bone Marrow Transplant. 2016; 51(4):560-7.

PMID: 26752140 DOI: 10.1038/bmt.2015.334.

Fanconi anemia and the cell cycle: new perspectives on aneuploidy.

Nalepa G, Clapp D F1000Prime Rep. 2014; 6:23.

PMID: 24765528 PMC: 3974572. DOI: 10.12703/P6-23.

DNA damage responses and oxidative stress in dyskeratosis congenita.

Pereboeva L, Westin E, Patel T, Flaniken I, Lamb L, Klingelhutz A PLoS One. 2013; 8(10):e76473.

PMID: 24124565 PMC: 3790691. DOI: 10.1371/journal.pone.0076473.

References

Bonfim C, de Medeiros C, Bitencourt M, Zanis-Neto J, Funke V, Setubal D . HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide. Biol Blood Marrow Transplant. 2007; 13(12):1455-60. PMC: 2174905. DOI: 10.1016/j.bbmt.2007.08.004. View

Maris M, Niederwieser D, Sandmaier B, Storer B, Stuart M, Maloney D . HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood. 2003; 102(6):2021-30. DOI: 10.1182/blood-2003-02-0482. View

Rosenberg P, Greene M, Alter B . Cancer incidence in persons with Fanconi anemia. Blood. 2002; 101(3):822-6. DOI: 10.1182/blood-2002-05-1498. View

Tan P, Wagner J, Auerbach A, DeFor T, Slungaard A, MacMillan M . Successful engraftment without radiation after fludarabine-based regimen in Fanconi anemia patients undergoing genotypically identical donor hematopoietic cell transplantation. Pediatr Blood Cancer. 2005; 46(5):630-6. DOI: 10.1002/pbc.20538. View

Flowers M, Doney K, Storb R, Deeg H, Sanders J, Sullivan K . Marrow transplantation for Fanconi anemia with or without leukemic transformation: an update of the Seattle experience. Bone Marrow Transplant. 1992; 9(3):167-73. View

Yabe H, Inoue H, Matsumoto M, Hamanoue S, Koike T, Ishiguro H . Allogeneic haematopoietic cell transplantation from alternative donors with a conditioning regimen of low-dose irradiation, fludarabine and cyclophosphamide in Fanconi anaemia. Br J Haematol. 2006; 134(2):208-12. DOI: 10.1111/j.1365-2141.2006.06128.x. View

Wagner J, Eapen M, MacMillan M, Harris R, Pasquini R, Boulad F . Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia. Blood. 2006; 109(5):2256-62. PMC: 1801062. DOI: 10.1182/blood-2006-07-036657. View

Chaudhury S, Auerbach A, Kernan N, Small T, Prockop S, Scaradavou A . Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia. Br J Haematol. 2008; 140(6):644-55. DOI: 10.1111/j.1365-2141.2007.06975.x. View

Blaise D, Kuentz M, Fortanier C, Bourhis J, Milpied N, Sutton L . Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Société Française de Greffe de Moelle. J Clin Oncol. 2000; 18(3):537-46. DOI: 10.1200/JCO.2000.18.3.537. View

10.

Masserot C, Peffault de Latour R, Rocha V, Leblanc T, Rigolet A, Pascal F . Head and neck squamous cell carcinoma in 13 patients with Fanconi anemia after hematopoietic stem cell transplantation. Cancer. 2008; 113(12):3315-22. DOI: 10.1002/cncr.23954. View

11.

Bitan M, Or R, Shapira M, Aker M, Resnick I, Ackerstein A . Fludarabine-based reduced intensity conditioning for stem cell transplantation of Fanconi anemia patients from fully matched related and unrelated donors. Biol Blood Marrow Transplant. 2006; 12(7):712-8. DOI: 10.1016/j.bbmt.2006.03.002. View

12.

Motwani J, Lawson S, Darbyshire P . Successful HSCT using nonradiotherapy-based conditioning regimens and alternative donors in patients with Fanconi anaemia--experience in a single UK centre. Bone Marrow Transplant. 2005; 36(5):405-10. DOI: 10.1038/sj.bmt.1705071. View

13.

Deeg H, Socie G, Schoch G, Henry-Amar M, Witherspoon R, Devergie A . Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood. 1996; 87(1):386-92. View

14.

McSweeney P, Niederwieser D, Shizuru J, Sandmaier B, Molina A, Maloney D . Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 2001; 97(11):3390-400. DOI: 10.1182/blood.v97.11.3390. View

15.

Gyurkocza B, Cao T, Storb R, Lange T, Leisenring W, Franke G . Salvage allogeneic hematopoietic cell transplantation with fludarabine and low-dose total body irradiation after rejection of first allografts. Biol Blood Marrow Transplant. 2009; 15(10):1314-22. PMC: 2757150. DOI: 10.1016/j.bbmt.2009.06.011. View

16.

de la Fuente J, Reiss S, McCloy M, Vulliamy T, Roberts I, Rahemtulla A . Non-TBI stem cell transplantation protocol for Fanconi anaemia using HLA-compatible sibling and unrelated donors. Bone Marrow Transplant. 2003; 32(7):653-6. DOI: 10.1038/sj.bmt.1704219. View

17.

Glucksberg H, Storb R, Fefer A, Buckner C, Neiman P, Clift R . Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974; 18(4):295-304. DOI: 10.1097/00007890-197410000-00001. View

18.

Guardiola P, Pasquini R, Dokal I, Ortega J, Marsh J, Ball S . Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. Blood. 2000; 95(2):422-9. View

19.

Luznik L, ODonnell P, Symons H, Chen A, Leffell M, Zahurak M . HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008; 14(6):641-50. PMC: 2633246. DOI: 10.1016/j.bbmt.2008.03.005. View

20.

Burroughs L, Storb R, Leisenring W, Pulsipher M, Loken M, Torgerson T . Intensive postgrafting immune suppression combined with nonmyeloablative conditioning for transplantation of HLA-identical hematopoietic cell grafts: results of a pilot study for treatment of primary immunodeficiency disorders. Bone Marrow Transplant. 2007; 40(7):633-42. DOI: 10.1038/sj.bmt.1705778. View