Hematopoietic Stem Cell Mobilization for Gene Therapy of Adult Patients with Severe β-thalassemia: Results of Clinical Trials Using G-CSF or Plerixafor in Splenectomized and Nonsplenectomized Subjects

Overview

Journal Mol Ther

Publisher Cell Press

Specialties Molecular Biology
Pharmacology

Date 2011 Sep 29

PMID 21952171

Citations 34

Authors

Evangelia Yannaki

Thalia Papayannopoulou

Erica Jonlin

Fani Zervou

Garyfalia Karponi

Angeliki Xagorari

Pamela Becker

Nikoleta Psatha

Ioannis Batsis

Panayotis Kaloyannidis

Varvara Tahynopoulou

Varnavas Constantinou

Asimina Bouinta

Konstantia Kotta

Aglaia Athanassiadou

Achilles Anagnostopoulos

Athanasios Fassas

George Stamatoyannopoulos

Affiliations

Soon will be listed here.

Abstract

The safety and efficacy of hematopoietic stem cell (HSC) mobilization was investigated in adult splenectomized (SPL) and non-SPL patients with thalassemia major, in two clinical trials, using different mobilization modes: granulocyte-colony-stimulating factor (G-CSF)-alone, G-CSF following pretreatment with hydroxyurea (HU), plerixafor-alone. G-CSF-mobilization was both safe and effective in non-SPL patients. However, in SPL patients the procedure resulted in excessive response to G-CSF, expressed as early hyperleukocytosis necessitating significant dose reduction, and suboptimal CD34(+) cells yields. One-month HU-pretreatment prevented hyperleukocytosis and allowed successful CD34(+) cell collections when an optimal washout period was maintained, but it significantly prolonged the mobilization procedure. Plerixafor resulted in rapid and effective mobilization in both SPL and non-SPL patients and was well-tolerated. For gene therapy of thalassemia, G-CSF or Plerixafor could be used as mobilization agents in non-SPL patients whereas Plerixafor appears to be the mobilization agent of choice in SPL adult thalassemics in terms of safety and efficacy.

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References

Devine S, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N . Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood. 2008; 112(4):990-8. DOI: 10.1182/blood-2007-12-130179. View

Gratwohl A, Baldomero H, Frauendorfer K, Urbano-Ispizua A . EBMT activity survey 2004 and changes in disease indication over the past 15 years. Bone Marrow Transplant. 2006; 37(12):1069-85. DOI: 10.1038/sj.bmt.1705377. View

Cappellini M, Motta I, Musallam K, Taher A . Redefining thalassemia as a hypercoagulable state. Ann N Y Acad Sci. 2010; 1202:231-6. DOI: 10.1111/j.1749-6632.2010.05548.x. View

Stiff P, Bensinger W, Abidi M, Gingrich R, Artz A, Nademanee A . Clinical and ultrasonic evaluation of spleen size during peripheral blood progenitor cell mobilization by filgrastim: results of an open-label trial in normal donors. Biol Blood Marrow Transplant. 2009; 15(7):827-34. DOI: 10.1016/j.bbmt.2009.03.015. View

Dincer A, Gottschall J, Margolis D . Splenic rupture in a parental donor undergoing peripheral blood progenitor cell mobilization. J Pediatr Hematol Oncol. 2004; 26(11):761-3. DOI: 10.1097/00043426-200411000-00015. View

Rosenbaum C, Peace D, Rich E, Van Besien K . Granulocyte colony-stimulating factor-based stem cell mobilization in patients with sickle cell disease. Biol Blood Marrow Transplant. 2008; 14(6):719-23. DOI: 10.1016/j.bbmt.2008.03.001. View

Platzbecker U, Prange-Krex G, Bornhauser M, Koch R, Soucek S, Aikele P . Spleen enlargement in healthy donors during G-CSF mobilization of PBPCs. Transfusion. 2001; 41(2):184-9. DOI: 10.1046/j.1537-2995.2001.41020184.x. View

Basak G, Knopinska-Posluszny W, Matuszak M, Kisiel E, Hawrylecka D, Szmigielska-Kaplon A . Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)-Polish compassionate use experience. Ann Hematol. 2010; 90(5):557-68. PMC: 3070880. DOI: 10.1007/s00277-010-1098-7. View

Champlin R, Schmitz N, Horowitz M, Chapuis B, Chopra R, Cornelissen J . Blood stem cells compared with bone marrow as a source of hematopoietic cells for allogeneic transplantation. IBMTR Histocompatibility and Stem Cell Sources Working Committee and the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2000; 95(12):3702-9. View

10.

Brown S, Dale D . Spontaneous splenic rupture following administration of granulocyte colony-stimulating factor (G-CSF): occurrence in an allogeneic donor of peripheral blood stem cells. Biol Blood Marrow Transplant. 1998; 3(6):341-3. View

11.

De Odorico I, Spaulding K, Pretorius D, Bailey T, Nelson T . Normal splenic volumes estimated using three-dimensional ultrasonography. J Ultrasound Med. 1999; 18(3):231-6. DOI: 10.7863/jum.1999.18.3.231. View

12.

Falzetti F, Aversa F, Minelli O, Tabilio A . Spontaneous rupture of spleen during peripheral blood stem-cell mobilisation in a healthy donor. Lancet. 1999; 353(9152):555. DOI: 10.1016/S0140-6736(99)00268-8. View

13.

Lindemann A, Rumberger B . Vascular complications in patients treated with granulocyte colony-stimulating factor (G-CSF). Eur J Cancer. 1993; 29A(16):2338-9. DOI: 10.1016/0959-8049(93)90236-9. View

14.

Arruda V, Lima C, Saad S, Costa F . Successful use of hydroxyurea in beta-thalassemia major. N Engl J Med. 1997; 336(13):964. DOI: 10.1056/NEJM199703273361318. View

15.

Larochelle A, Krouse A, Metzger M, Orlic D, Donahue R, Fricker S . AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood. 2006; 107(9):3772-8. PMC: 1895780. DOI: 10.1182/blood-2005-09-3592. View

16.

Balaguer H, Galmes A, Ventayol G, Bargay J, Besalduch J . Splenic rupture after granulocyte-colony-stimulating factor mobilization in a peripheral blood progenitor cell donor. Transfusion. 2004; 44(8):1260-1. DOI: 10.1111/j.1537-2995.2004.00413.x. View

17.

Picardi M, De Rosa G, Selleri C, Scarpato N, Soscia E, Martinelli V . Spleen enlargement following recombinant human granulocyte colony-stimulating factor administration for peripheral blood stem cell mobilization. Haematologica. 2003; 88(7):794-800. View

18.

Abboud M, Laver J, Blau C . Granulocytosis causing sickle-cell crisis. Lancet. 1998; 351(9107):959. DOI: 10.1016/S0140-6736(05)60614-9. View

19.

Saxon B, Rees D, Olivieri N . Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassaemia. Br J Haematol. 1998; 101(3):416-9. DOI: 10.1046/j.1365-2141.1998.00719.x. View

20.

Li K, Wong A, Li C, Shing M, Chik K, Tsang K . Granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in beta-thalassemia patients: kinetics of mobilization and composition of apheresis product. Exp Hematol. 1999; 27(3):526-32. DOI: 10.1016/s0301-472x(98)00045-9. View