Frontiers of Cord Blood Science by Phillip Stubblefield & Niranjan Bhattacharya

Author:Phillip Stubblefield & Niranjan Bhattacharya
Language: eng
Format: epub
Publisher: Springer London, London

Sickle Cell Disease

SCD is an inherited blood disorder with an abnormal type of hemoglobin (HbS) that results in sickle cell-shaped red blood cells causing obstructions of vessels with end organ damage causing substantial morbidity and mortality. Patients need frequent red cell transfusions to maintain HbS levels low to prevent recurrent cerebrovascular complications, hence leading to secondary complications of iron overload and alloimmunization against red cell antigens or HLA antigens. It has been known that SCD is curable by HSCT for many years, depending on severity of pre-existing symptoms the TRM is reported as 6–10% [57, 58] and chronic GVHD occurring in about 12% [59]. Previous publications with BM or PBSC from matched siblings demonstrated an OS of 90% and an EFS of 80% with rejection (8–15%) being the major cause of treatment failure [60, 61].

In the previously mentioned study of Locatelli, the EFS for SCD patients after related umbilical CBT was 90% [46] with a lower rate of graft failure than in the thalassaemic patient group, low probability of acute or chronic GVHD, and an OS of 100%.

Adamkiewicz et al. present three children with SCD and cerebrovascular accidents undergoing unrelated 4/6 mismatched CBT [62]. One patient had graft failure, two patients engrafted. All patients developed moderate to severe acute GVHD with one patient experiencing extensive chronic GVHD.

Other cases of CBT for SCD are included in Rocha 1998 [54], Wagner 1995 [10], Rocha 2000 [56] and Gluckman 1997 [33].

For both thalassemia and SCD, persistent mixed chimerism or partial engraftment has been previously reported, and unlike in aplastic anemia [63], was not always associated with graft failure. Even with a low percentage of donor cells, the amount of mature red blood cells might be sufficient enough for the patient to become clinically asymptomatic and thus transfusion independent [58, 64].

Given that we are dealing with diseases which are non-malignant, and that the aim is merely to correct the underlying problem, and the observation that mixed chimerism can correct the disease phenotype, it is logical to attempt to use non-myeloablative conditioning in such diseases; the original cohort of patients reported by Slavin’s group included thalassemia, Gaucher’s disease, Blackfan-Diamond anemia, and FA [65]. However, the observation that in some cases, stable mixed chimerism can correct the disease is not easy to achieve intentionally, and such attempts have not led to sustained engraftment even with BM or PBSC from matched siblings once immunosuppression is withdrawn [66].

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