Stem cell transplantation after reduced‐intensity conditioning for sickle cell disease

Abstract

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.

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

“…92 In Austria, a cohort of 8 patients underwent matched sibling HSCT following conditioning with fludarabine, melphalan, thiotepa and ATG or Campath-1H with a disease-free survival of 100% and stable engraftment. 93 …”

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease

“…[17][18][19][20] A RIC regimen augmented with host immunoablation by alemtuzumab was previously successful in achieving donor engraftment. 21,22 In that report of HLA-matched sibling donor bone marrow transplant (BMT) in 52 children with hemoglobinopathies, acute and chronic GVHD rates were 23% and 13%, respectively. 21 The regimen was adopted for a phase 2 URD transplant trial with bone marrow or umbilical cord blood grafts through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN #0601; NCT 00745420).…”

Cyclophosphamide improves engraftment in patients with SCD and severe organ damage who undergo haploidentical PBSCT

“…7 Because stable mixed chimerism with donor chimerism levels as low as 11% was found to reverse the sickle phenotype and was not associated with GVHD, 8 and because adults with subclinical and overt organ damage cannot tolerate myeloablative conditioning, we and others sought to develop a successful nonmyeloablative conditioning regimen for SCD. [9][10][11][12][13][14] Our nonmyeloablative HLA-matched sibling peripheral blood stem cell transplantation (PBSCT) regimen used alemtuzumab 300 cGy total body irradiation (TBI) and sirolimus, which led to the achievement of donortype hemoglobin in 25 (83%) of 30 patients at 1 year posttransplant and the reversal of SCD in 26 (87%) of 30 patients and no GVHD at most recent follow-up. 15 Although this HLA-matched sibling PBSCT protocol has been successful, the vast majority of patients with SCD do not have an HLA-matched sibling.…”