Stem cell transplantation after reduced-intensity conditioning for sickle cell disease.
Sickle cell disease (SCD) is still associated with substantial morbidity and reduced life expectancy. Disease-related mortality rises to 14% in adolescents and young adults. Overall and disease-free survival following haematopoietic stem cell transplantation (HSCT) is 90% and 95%, respectively. To reduce transplant-associated late effects, the feasibility of a highly immunosuppressive reduced-intensity conditioning (RIC) regimen was explored in children with SCD and a matched sibling donor. Eight patients (median age, 9 yr) and symptomatic SCD were included. The conditioning regimen consisted of fludarabine, melphalan and either thiotepa or total lymphoid irradiation plus antithymocyte globuline or alemtuzumab. The graft was bone marrow in seven and cord blood in one case. The conditioning regimen was well tolerated and no severe infectious complications occurred. All patients displayed mixed chimaerism on day +28. After a median follow-up of 4 yr, 3/8 patients have mixed leucocyte chimaerism and 8/8 patients have 100% donor erythropoiesis. HSCT from matched sibling donors following a RIC regimen was well tolerated and resulted in cure in all patients studied. If confirmed in larger patient cohorts, these observations will have important implications for the indications of HSCT in children with SCD.
Department of Paediatrics, St. Anna Children's Hospital, Medical University, Kinderspitalgasse 6, Vienna, Austria. susanne.matthes@stanna.at
Susanne
S
Matthes-Martin
Anita
A
Lawitschka
Gerhard
G
Fritsch
Thomas
T
Lion
Brigitte
B
Grimm
Sabine
S
Breuer
Heidrun
H
Boztug
Susanne
S
Karlhuber
Wolfgang
W
Holter
Christina
C
Peters
Milen
M
Minkov
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000628:therapy*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007223:Infant; D008297:Male; D035781:Siblings; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D055815:Young Adult