Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy

Jiang, Hua; Jiang, Mao Fa; Li, Sha; Cai, Yamei; Liang, Cuili; Liu, Li

doi:10.1016/j.pediatrneurol.2015.05.002

Cited by 7 publications

(7 citation statements)

References 15 publications

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“…Due to the rapid progression of the disease, it is not possible to identify, in a suitable time, an appropriately matched marrow donor, sibling or unrelated, for many patients. In these urgent situations, the use of alternative sources, such as the umbilical cord blood units from unrelated donors and partially mismatched related donors (haploidentical), might be considered [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, it has been shown by several groups that cyclophosphamide at high doses after HSCT (post transplant cyclophosphamide (PT/ Cy)) can regulate the alloreactivity associated with partially matched donors in pre-clinical [15] and clinical studies [16]. The administration of PT/Cy may selectively deplete the T cells from the alloreactive donor that are responsible for the GVHD, preserving the non-alloreactive, resting memory T cells that can facilitate engraftment and accelerate immune reconstitution [14][15][16][17]. Studies using the nonmyeloablative (NMA) regimen with PT/Cy have shown good outcomes mostly in adults with hematological malignancies, while the experience with children and nonmalignant disorders are scarce [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Fernandes

Bonfim

Kerbauy

et al. 2018

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment that enhances survival and stabilizes neurologic symptoms in X-linked adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide (PT/Cy) has been performed in patients with malignant and nonmalignant diseases showing similar outcomes compared to other alternative sources. We describe the outcomes of transplants performed for nine X-ALD patients using haploidentical donors and PT/Cy. Patients received conditioning regimen with fludarabine 150 mg/m, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and mycophenolate mofetil. One patient had a primary graft failure and was not eligible for a second transplant. Three patients had secondary graft failure and were successfully rescued with second haploidentical transplants. Trying to improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for 4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37 months after transplant). Haploidentical HSCT with PT/Cy is a feasible alternative for X-ALD patients lacking a suitable matched donor. Graft failure has to be addressed in further studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Fernandes

Bonfim

Kerbauy

et al. 2018

Bone Marrow Transplant

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“…Dysfunction of ABCD1 increases the levels of VLCFAs in the sera of X‐ALD patients, and the levels of C26:0 did not always become normal range but tend to be decreased after BMT 7,16‐18 . The serum levels of C26:0 in the KO mice (1.64 μmol/L serum) were higher than in the WT mice (0.66 μmol/L serum), and the levels of C26:0 in GFP‐KO/KO mice (2.07 μmol/L serum) were similar to those in the KO mice (Figure 1B).…”

Section: Resultsmentioning

confidence: 78%

Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice

Morita

Kaizawa

Yoda

et al. 2021

J of Inher Metab Disea

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X‐linked adrenoleukodystrophy (X‐ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues, especially the brain. At present, bone marrow transplantation (BMT) at an early stage of the disease is the only effective treatment for halting disease progression, but the underlying mechanism of the treatment has remained unclear. Here, we transplanted GFP‐expressing wild‐type (WT) or Abcd1‐deficient (KO) bone marrow cells into recipient KO mice, which enabled tracking of the donor GFP+ cells in the recipient mice. Both the WT and KO donor cells were equally distributed throughout the brain parenchyma, and displayed an Iba1‐positive, GFAP‐ and Olig2‐negative phenotype, indicating that most of the donor cells were engrafted as microglia‐like cells. They constituted approximately 40% of the Iba1‐positive cells. Unexpectedly, no decrease of VLCFA in the cerebrum was observed when WT bone marrow cells were transplanted into KO mice. Taken together, murine study suggests that bone marrow‐derived microglia‐like cells engrafted in the cerebrum of X‐ALD patients suppress disease progression without evidently reducing the amount of VLCFA in the cerebrum.

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“…30 Haploidentical stem cell transplant combined with UCB units was also studied as a new treatment regimen but the longterm result is still NA yet. 31,32 There are now more donor sources available for transplantation of TM, nearly all patients could be able to find a suitable donor for transplant. However, families should be counseled carefully about the pros and cons of various options.…”

Section: Discussionmentioning

confidence: 99%

“…Recently there are reports of using haploidentical family donors for treatment of hematological malignancies and other non‐malignant diseases 30 . Haploidentical stem cell transplant combined with UCB units was also studied as a new treatment regimen but the long‐term result is still NA yet 31,32 . There are now more donor sources available for transplantation of TM, nearly all patients could be able to find a suitable donor for transplant.…”

Section: Discussionmentioning

confidence: 99%

Double‐unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA‐identical sibling bone marrow transplantation

Feng

Lee²,

Lam³

et al. 2020

Pediatric Transplantation

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UCBT recipients with TM are at high risk of EF related to low number of stem cells and prior alloimmunization after multiple blood transfusions. Here, we evaluated the safety and efficacy of double-unit UCBT using TT-containing conditioning regimens in TM. Retrospective analysis of children who underwent double-unit UCBT for TM in the Prince of Wales Hospital between August 2007 and January 2017, and outcome of double-unit UCBT for TM was compared with outcome of HLA-matched sibling BMT. Ten patients, median age 4.2 years, received double-unit UCBT. All patients except one engrafted at a median of 19 days. None of the patients with successful engraftment had grade III or IV aGVHD. Among nine patients with successful engraftment, six of nine patients evaluable after day 100 developed cGVHD.All patients with cGVHD were well controlled after treatment with steroids and/ or supportive care and maintained good quality of life. In comparison with patients receiving BMT, those given UCBT had slower platelet recovery, and more cGVHD.With a median follow-up of 272 months after BMT and 84 months after UCBT, the 8-year OS after BMT and UCBT was 92% and 90% (P = .84), whereas 8-year DFS after BMT and UCBT was 87% and 80% (P = .54). UCB could be an acceptable source of stem cells for transplantation of TM patients when HLA-matched family bone marrow donors are NA.

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Combination of a Haploidentical Stem Cell Transplant With Umbilical Cord Blood for Cerebral X-Linked Adrenoleukodystrophy

Cited by 7 publications

References 15 publications

Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Haploidentical bone marrow transplantation with post transplant cyclophosphamide for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent situation

Bone marrow transplantation into Abcd1‐deficient mice: Distribution of donor derived‐cells and biological characterization of the brain of the recipient mice

Double‐unit unrelated cord blood transplantation for thalassemia major: Comparison with HLA‐identical sibling bone marrow transplantation

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