J Korean Med Sci.  2008 Feb;23(1):146-148. 10.3346/jkms.2008.23.1.146.

Unrelated Bone Marrow Transplantation with a Reduced Toxicity Myeloablative Conditioning Regimen in Wiskott-Aldrich Syndrome

• Kang HJ
• Shin HY
• Ko SH
• Park JA
• Kim EK
• Rhim JW
• Kim JG
• Ahn HS

• KMID: 1786863
• DOI: http://doi.org/10.3346/jkms.2008.23.1.146

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked congenital immune-deficiency syndrome, and bone marrow transplantation (BMT) has become a curative modality. However, the transplant with the alternative donor needed more intensive conditioning with increased treatment-related toxicities. Recently, fludarabine-based reduced toxicity myeloablative conditioning regimens have been developed for adult myeloid malignancies with promising results of good engraftment and low treatment-related toxicities. To increase the engraftment potential without serious complications, a boy with WAS received successful unrelated BMT with a reduced toxicity myeloablative conditioning regimen composed of fludarabine (40 mg/m(2) on days -8, -7, -6, -5, -4, -3), busulfan (0.8 mg/kg i. v. q 6 hr on days -6, -5, -4, -3), and thymoglobulin (2.5 mg/kg on days -4, -3, -2). This novel conditioning regimen could improve the outcome of allogeneic transplantation for other non-malignant diseases such as congenital immune-deficiency syndromes or metabolic storage diseases.

Keyword

Wiskott-Aldrich Syndrome; Bone Marrow Transplantation; Busulfan; Fludarabine

MeSH Terms

*Bone Marrow Transplantation/adverse effects
Child, Preschool
Graft vs Host Disease/etiology
Humans
Male
*Transplantation Conditioning
Wiskott-Aldrich Syndrome/*surgery

Figure

• 

  Fig. 1 A patient diagnosed as Wiskott-Aldrich syndrome with a large deletion in the exon 1 to 11 of the WAS gene (B), compared with a normal control (A) by polymerase chain reaction (PCR) method, received bone marrow transplantation with a reduced toxicity myeloablative conditioning regimen. Bone marrow examination at one month post-transplantation revealed normal PCR pattern for all exons of the WAS gene (C).

Reference

1. Filipovich AH, Stone JV, Tomany SC, Ireland M, Kollman C, Pelz CJ, Casper JT, Cowan MJ, Edwards JR, Fasth A, Gale RP, Junker A, Kamani NR, Loechelt BJ, Pietryga DW, Ringden O, Vowels M, Hegland J, Williams AV, Klein JP, Sobocinski KA, Rowlings PA, Horowitz MM. Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program. Blood. 2001. 97:1598–1603.

2. Kim DS. Management of primary immune deficiency. J Asthma Allergy Clin Immunol. 2000. 20:447–458.

3. Russell JA, Tran HT, Quinlan D, Chaudhry A, Duggan P, Brown C, Stewart D, Ruether JD, Morris D, Glick S, Gyonyor E, Andersson BS. Once-daily intravenous busulfan given with fludarabine as conditioning for allogeneic stem cell transplantation: study of pharmacokinetics and early clinical outcomes. Biol Blood Marrow Transplant. 2002. 8:468–476.

4. Bornhauser M, Storer B, Slattery JT, Appelbaum FR, Deeg HJ, Hansen J, Martin PJ, McDonald GB, Nichols WG, Radich J, Woolfrey A, Jenke A, Schleyer E, Thiede C, Ehninger G, Anasetti C. Conditioning with fludarabine and targeted busulfan for transplantation of allogeneic hematopoietic stem cells. Blood. 2003. 102:820–826.

5. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, Shpall EJ, Shahjahan M, Pierre B, Giralt S, Korbling M, Russell JA, Champlin RE, Andersson BS. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004. 104:857–864.

6. Kang HJ, Shin HY, Choi HS, Ahn HS. Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. Bone Marrow Transplant. 2004. 34:939–943.

7. Longhurst HJ, Taussig D, Haque T, Syndercombe-Court D, Cavenagh J, Edgar JD, Helbert MR. Non-myeloablative bone marrow transplantation in an adult with Wiskott-Aldrich syndrome. Br J Haematol. 2002. 116:497–499.

8. Horwitz ME, Barrett AJ, Brown MR, Carter CS, Childs R, Gallin JI, Holland SM, Linton GF, Miller JA, Leitman SF, Read EJ, Malech HL. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001. 344:881–888.