Matched‐related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research

Abstract

SummaryWe report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)‐matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso‐occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty‐seven percent of patients had a poor performance score at transplantation. Ninety‐four percent received busulfan and cyclophosphamide‐containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post‐transplant period. Rates of acute and chronic graft‐versus‐host disease were 10% and 22% respectively. Sixty‐four of 67 patients are alive with 5‐year probabilities of disease‐free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle‐related events. This report confirms and extends earlier reports that HCT from HLA‐matched related donors offers a very high survival rate, with few transplant‐related complications and the elimination of sickle‐related complications in the majority of patients who undergo this therapy.

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

“…Although the sample size is small, these results are comparable to those seen in children and adolescents with SCD after MAC and lower than the incidence in those with malignant conditons. 5,7,8,[27][28][29][30][31] Methods to decrease GVHD are paramount, especially since many of the patients in this cohort had less severe disease.…”

Hematopoietic SCT for the Black African and non-Black African variants of sickle cell anemia

“…[15][16][17][18][19][20][21][22][23] The results of several major studies summarized in Table 5 show an OS of 490% and an EFS of 480%.…”

“…Panepinto et al 20 (n = 67) Lucarelli et al 9 (n = 11) 93% 94% 100% 92% 97% 90% DFS 85% 84% 90% 86% 85% 90% Rejection 10% 10% 9% 5% 13% 10% Abbreviation: DFS = disease-free survival; OS = overall survival.…”

Outcome of hematopoietic cell transplantation in children with sickle cell disease, a single center's experience

“…Although the majority of patients with SCD achieve complete donor chimerism after a myeloablative HCT, the cumulative incidence of graft rejection or recurrence of SCD remains at about 10%. [7][8][9]15 Follow-up chimerism studies in patient No 10 showed some evidence of durable mixed donor chimerism; however, with the elevated HbS% fraction and the history of two hospitalizations for pneumonia (or possible acute chest syndrome), it was decided to proceed with a second transplant using a RIC regimen to minimize toxicity. This second transplant may have provided the extra bone marrow space required to 'boost' the low mixed donor chimerism and sustain normal erythropoiesis.…”