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ctt-journal > Urban et al. (Abstract)

Urban et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 12
doi: 10.3205/ctt-2011-No12-abstract68

© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "5th Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation in Children and Adults", Saint Petersburg, Russia, September 18–20, 2011

Preliminary Program

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The influence of conditioning and graft manipulation on prevention of graft rejection and GvHD in alternative donor hematopoietic stem cell transplantation (HSCT) for refractory severe aplastic anemia (SAA)

Christian Urban, Wolfgang Schwinger, Petra Sovinz, Martin Benesch, Volker Strenger, Ewa Müller, Herwig Lackner

Division of Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria

Correspondence: Christian Urban, Division of Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Auenbruggerplatz 34/2, A-8036 Graz, Austria, E-Mail: christian.urban@spam is badmedunigraz.at


HSCT from a matched sibling donor (MSD) is the treatment of choice for children with SAA, however it is limited by donor availability. Immunosuppression (IS) as the other option has the disadvantage of high treatment failures. In our study, 7 patients with SAA without MSD and refractory to previous IS, median age 11 years (5–16), median interval from diagnosis to HSCT 12 months (3–155) and median number of transfusions before HSCT 55 (18–116) underwent alternative donor HSCT. Donors were matched unrelated (MUD) (n= 4), mismatched unrelated (n=2), and haploidentical (n=1). The conditioning regimens contained cyclophosphamide and either muromonab-CD3 or anti-thymocyte globulin (ATG) in 7/7, thiotepa (THT) in 6/7, fludarabine (FLU) in 5/7, and total lymphoid irradiation in 2/7 patients. Grafts were either CD 34+ selected and/or CD 3/19 depleted using the Miltenyi CliniMACS device. The median yield of purified CD 34 + cells was 10.17 x 10E6/kg (7.85–24.3) and median CD 3+ number was 5.5 x 10E4/kg (0.84–10). All patients had WBC-engraftment on median day 10 (8–12). There was no GVHD prophylaxis in 2 patients and either cyclosporine-A or mycophenolate mofetil up to day +60 in 5 patients. One patient with 6 previous IS courses and the longest interval to MUD-HSCT (13 yrs), who received the highest CD 3+ dose (10x 10E4/kg), developed GVHD (grade II) on day +125 with progressive kidney failure due to microangiopathic hemolytic anemia. All patients are alive with a median follow-up of 20 months (10–149) with stable chimerism of median 98.5% (90.65–100).

Conclusion: A long interval to transplant, multiple transfusions and long-term immunosuppression before HSCT are associated with poor alternative donor HSCT-outcomes in SAA. Cyclophosphamide conditioning including FLU, THT, and ATG but without TLI, high doses of purified 34+ cells and/or CD 3/19 depletion may prevent graft rejection and GVHD and hasten engraftment. This may facilitate the decision for the earlier use of unrelated stem cells, preventing complications from prolonged and multiple immunosuppressive therapies and presumably increasing the survival of patients with refractory SAA without a matched sibling donor.

Keywords: alternative donor stem cell transplantation, refractory severe aplastic anemia, graft manipulation