Early and late outcomes after cord blood transplantation for pediatric patients with inherited leukodystrophies

Abstract

Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking. In this study, we define risk factors and describe the early and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood transplantation (CBT) at an European Society for Blood and Marrow Transplantation center or at Duke University Medical Center from 1996 to 2013. Factors associated with higher overall survival (OS) included presymptomatic status (77% vs 49%; = .006), well-matched (≤1 HLA mismatch) CB units (71% vs 54%; = .009), and performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%, respectively; = .003). For patients with PS≤60 (n = 20) or 60 to 80 (n = 24) pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS>80 pre-CBT, 50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an encouraging OS was found for LD patients after CBT, especially for those who are presymptomatic before CBT and received adequately dosed grafts. Early identification and fast referral to a specialized center may lead to earlier treatment and, subsequently, to improved outcomes.

Early clinical course after hematopoietic stem cell transplantation in children with juvenile metachromatic leukodystrophy

“…While the long-term outcome of HSCT in children with juvenile MLD has already been investigated systematically in recent years [5,12,[15][16][17][18][30][31][32], early outcome has been reported for MRI characteristics [9,19,22,[33][34][35], but not with respect to functional clinical parameters. In this paper, we analyzed clinical, electrophysiological, and MRI outcome parameters over the first 2 years after HSCT in children with juvenile MLD.…”

“…The main reason for a good outcome in children with the juvenile form is considered to be the early clinical disease stage at transplantation, with sufficient time until severe disease progression. Patients who underwent transplantation at an early disease stage, with low motor and neurocognitive impairment, or at a pre-symptomatic stage, exhibited a better long-term outcome than patients in advanced stages of the disease [5,6,[12][13][14][15][16][17][18]. Nevertheless, due to variable outcomes [8][9][10][19][20][21][22] and the frequent lack of comparisons between the outcomes in transplanted and non-transplanted patients, whether HSCT is an option for treatment of MLD remains controversial [5,6,13,23].…”

Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases

“…The natural history of a particular disease may lead to organ compromise that may make the patient less tolerant to preparative regimens with specific toxicities. For instance, patients with leukodystrophies with substantial demyelination of the CNS may not tolerate TBI or high doses of neurotoxic chemotherapy such as busulfan (66,67). A patient with sickle cell disease who has acquired substantial renal injury may handle agents cleared by the kidney poorly leading to heightened toxicity (81,82).…”

Prognostic assessment of cryosensitivity level for umbilical cord blood hemopoietic tissue with the help of markers of prooxidant activity processes

“…Показаннями для застосування є аплазія ГТ внаслідок захворювання або після жорстких режимів хіміотерапії та/ або радіотерапії, а також при деяких вроджених хворобах [5]. Спектр застосування трансплантацій ПК постійно розширюється [7]. У зв'язку з тим, що кріоконсервування (за температур нижче мінус 120 °С) дозволяє зберігати трансплантаційний матеріал тривалий період часу, забезпечення клінічних потреб зазвичай здійснюється через громадські (суспільні) донорські низькотемпературні банки фенотипованої ПК [8].…”