Hematopoietic stem cell transplantation after reduced-intensity conditioning as treatment of sickle cell disease.
OBJECTIVE
Sickle cell disease generates considerable morbidity and mortality. Allogeneic hematopoietic stem cell transplantation (SCT) has the potential of curing the disease and halting end-organ damage. However, in older patients this treatment is associated with a significant risk of toxicity and death. SCT after reduced-intensity conditioning (RIC) might be a safer approach for the treatment of sickle cell disease.


METHODS
A 22-year-old male had experienced multiple, life-threatening hemolytic crises. We treated him with G-CSF-mobilized stem cells from his heterozygote, human leukocyte antigen-matched brother after RIC with fludarabine and cyclophosphamide. GVHD prophylaxis consisted of cyclosporine (CyA) and mycophenolate mofetil (MMF). Chimerism of peripheral blood mononuclear cells was evaluated using short tandem repeat analysis and hemoglobin analysis was performed by high-performance liquid chromatography.


RESULTS
There were no major treatment-related toxicities. At day +30 after transplantation the patient had mixed hematopoietic chimerism, which later converted to full chimerism. Hemoglobin analysis revealed 3.4% HbA(2), 1.0% HbF, and 41.2% HbS, which essentially is the same hemoglobin partition as in his brother's blood. MMF was discontinued on day +35 and CyA on day +120. After discontinuation of CyA the patient developed mild chronic GVHD, which resolved with continued CyA, low-dose steroids, and the retinoid isotretinoin. He is doing well on day +315 without evidence of GVHD.


CONCLUSIONS
Allogeneic SCT after RIC is feasible in adult patients with sickle cell disease. Mixed chimerism is sufficient to relieve disease-related symptoms and is possibly correlated with less acute GVHD.
Schleuning
Michael
M
Medizinische Klinik III, Klinikum Grosshadern der Ludwig-Maximilians-Universität München, München, Germany. mschleu@lrz.uni-muenchen.de
Stoetzer
Oliver
O
Waterhouse
Christine
C
Schlemmer
Markus
M
Ledderose
Georg
G
Kolb
Hans-Jochem
HJ
D000328:Adult; D000755:Anemia, Sickle Cell / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine