Email this article Transplantation of the bone marrow from a HLA-compatible unrelated donor after immunoablative conditioning in children with acquired aplastic anemia unresponsive to combined immunosuppressive therapy: Preliminary results
- Authors: Novichkova GA1, Maschan MA1, Shipitsyna IP2, Skvortsova Y.V2, Persiantseva MI1, Lebedeva LL2, Bobrynina VO1, Baidildina DD2, Goronkova OV2, Solopova GG2, Khachatryan LA1, Petrova UN1, Suntsova EV2, Kalinina II1, Sinitsyna VV1, Skorobogatova EV2, Balashov DN3, Dyshlevaya ZM2, Shelikhova LN2, Kurnikova EE2, Trakhtman PE2, Maschan AA1
-
Affiliations:
- Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
- Russian Children's Hospital, Moscow
- Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow
- Issue: Vol 82, No 7 (2010)
- Pages: 41-47
- Section: Editorial
- URL: https://ter-arkhiv.ru/0040-3660/article/view/30622
- ID: 30622
Cite item
Full Text
Abstract
Subjects and methods. The study enrolled 14 children aged 2-16 years (median 9 years). A control group comprised 26 patients in whom IST was continued. The median interval between the diagnosis of AA and transplantation was 26 months (9-156 months). The conditioning regimen consisted of thoracoabdominal irradiation in a dose of 2 Gy, fludarabin (Flu) 100-150 mg/m2, cyclophosphamide (Cy) 100-200 mg/kg, antithymocyte globulin (ATG) in 11 patients and Flu, Cy, and ATG in 3. A graft-versus-host reaction was prevented with mycophenolate mefetil in all the patients, tacrolimus in 11, and cyclosporin A in 3. Donors were compatible for high-resolution typing of 10/10 and 9/10 alleles in 8 and 6 patients, respectively; the source of a transplant was bone marrow in 13 patients and granulocyte colony-stimulating factor-mobilized peripheral blood precursors in one case.
Results. Thirteen patients achieved primary engraftment after single transplantation; one patient did after repeat transplantation. Grades I to II graft-versus-host reaction (GVHR) developed in 9 patients; postengraftment life-threatening infections in 3, extensive chronic GVHR in 2, circumscribed GVHR in 7. All fourteen hemopoietic cell transplant recipients followed for a median 17.5 months (range 1-71 months) were survivors.
Conclusion. The likelihood of good survival after unrelated transplantations in AA is much higher than that after continued IST: 100% versus 15±11%.
About the authors
G A Novichkova
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
M A Maschan
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
I P Shipitsyna
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
Yu V Skvortsova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
M I Persiantseva
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
L L Lebedeva
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
V O Bobrynina
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
D D Baidildina
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
O V Goronkova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
G G Solopova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
L A Khachatryan
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
U N Petrova
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
E V Suntsova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
I I Kalinina
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
V V Sinitsyna
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
E V Skorobogatova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
D N Balashov
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, MoscowFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationRussian Children's Hospital, Moscow
Z M Dyshlevaya
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
L N Shelikhova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
E E Kurnikova
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
P E Trakhtman
Russian Children's Hospital, MoscowRussian Children's Hospital, Moscow
A A Maschan
Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian FederationFederal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of the Russian Federation
References
- Kojima S., Hibi S., Kosaka Y. et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood 2000; 96 (6): 2049-2054.
- Fuhrer M., Burdach S., Ebell W. et al. Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group. Klin. Pädiatr. 1998; 210 (4): 173-179.
- Fuhrer M., Rampf U., Baumann I. et al. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood 2005; 106: 2102-2104.
- Scheinberg P., Wu C. O., Nunez O., Young N. S. Long-term outcome of pediatric patients with severe aplastic anemia treated with antithymocyte globulin and cyclosporine. J. Pediatr. 2008; 153 (6): 814-819.
- Di Bona E., Rodeghiero F., Bruno B. et al. Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO) Br. J. Haematol. 1999; 107 (2): 330-433.
- Scheinberg P., Nunez O., Young N. S. Retreatment with rabbit antithymocyte globulin and cyclosporin for patients with relapsed or refractory severe aplastic anaemia. Br. J. Haematol. 2006; 133 (6): 622-627.
- Tichelli A., Passweg J., Nissen C. et al. Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia. Br. J. Haematol. 1998; 100 (2): 393-400.
- Führer M. Risk-adapted procedures for HSCT from alternative donor in children with severe aplastic anaemia. Bone Marrow Transplant. 2008; 42 (suppl. 2): S97-S100.
- Gupta V., Gordon-Smith E. C., Cook G. et al. A third course of antithymocyte globulin in aplastic anaemia is only beneficial in previous responders. Br. J. Haematol. 2005; 129 (1): 110-117.
- Camitta B., Ash R., Menitov J. et al. Bone marrow transplantation for children with severe aplastic anemia: use of donors other than HLA-identical siblings. Blood 1989; 74: 1852- 1857.
- Hows J. M., Yin J. L., Marsh J. et al. Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia. Blood 1986; 68: 1322-1328.
- Margolis D., Camitta B., Pietryga D. et al. Unrelated donor bone marrow transplantation to treat severe aplastic anemia in children and young adults. Br. J. Haematol. 1996; 94: 65-72.
- Locasciulli A., Oneto R., Bacigalupo A. et al. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation. Haematologica 2007; 92: 11-18.
- Viollier R., Socie G., Tichelli A. et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplant. 2008; 41: 45-50.
- Storb R., Blume K. G., O'Donnell M. R. et al. Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers. Biol. Blood Marrow Transplant. 2001; 7: 39-44.
- Kahl C., Leisenring W., Deeg H. J. et al. Cyclophosphamide and antithymocyte globulin as a conditioning regimen for allogeneic marrow transplantation in patients with aplastic anaemia: a long-term follow-up. Br. J. Haematol. 2005; 130 (5): 747-751.
- Bacigalupo A., Locatelli F., Lanino E. et al. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant. 2005; 36: 947-950.
- Kosaka Y., Yagasaki H., Sano K. et al. Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia. Blood 2008; 111: 1054-1059.
- Camitta B. M., Thomas E. D., Nathan D. G. et al. A prospective study of androgens and bone marrow transplantation for treatment of severe aplastic anemia. Blood 1979; 53 (3): 504- 514.
- Glucksberg H., Storb R., Refer A. et al. Clinical manifestation of graft versus host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation 1974; 18: 295-304.
- Shulmann H., Sullivan K. M., Weiden P. L. et al. Chronic graft-versus-host disease in man: a clinic pathologic study of 20 long term Seattle patients. Am. J. Med. 1980; 69: 204-217.
- Deeg H. J., Amylon M. D., Harris R. E. et al. Marrow transplants from unrelated donors for patients with aplastic anemia: Minimum effective dose of total body irradiation. Biol. Blood Marrow Transplant. 2001; 7: 208-215.
- Yagasaki H., Seiji Kojima S., Yabe H. et al. Tacrolimus/methotrexate versus cyclosporine/methotrexate as graft-versus-host disease prophylaxis in patients with severe aplastic anemia who received bone marrow transplantation from unrelated donors: Results of matched pair analysis. Biol. Blood Marrow Transplant. 2009; 15: 1603-1608.
- Buyck H. C. E., Ball S., Junagade P. et al. Prior immunosuppressive therapy with antithymocyte globulin increases the risk of EBV-related lymphoproliferative disorder following allo-SCT for acquired aplastic anaemia. Bone Marrow Transplant. 2009; 43: 813-816.
Supplementary files
