Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report

Boucher, Alexander A.; Miller, Weston; Shanley, Ryan; Ziegler, Richard; Lund, Troy; Raymond, Gerald; Orchard, Paul J.
August 2015
Orphanet Journal of Rare Diseases;Aug2015, Vol. 10 Issue 1, p1
Academic Journal
Background: Metachromatic Leukodystrophy (MLD) is a rare, fatal demyelinating disorder with limited treatment options. Published outcomes after hematopoietic stem cell transplantation (HSCT) are scant and mixed. We report survival and function following HSCT for a large, single-center MLD cohort. Methods: Transplant-related data, survival and serial measures (brain MRI, nerve conduction velocity (NCV), neurologic and neuropsychology evaluations) were reviewed. When possible, parental interviews informed current neurologic status, quality-of-life, and adaptive functioning. Gross motor and expressive functions for late-infantile (LI-MLD) and juvenile (J-MLD) patients were described using previously reported, MLD-specific scales. Results: Forty patients with confirmed MLD have undergone HSCT at our center. Twenty-one (53 %) survive at a median 12 years post-HSCT. Most deaths (n = 17) were treatment-related; two died from disease progression. Survival did not depend upon MLD subtype or symptom status at transplant. LI-MLD patients survive beyond reported life expectancy in untreated disease. Abnormal brain MRI and peripheral nerve conduction velocities (NCV) were common before HSCT. Following transplant, fewer patients experienced MRI progression compared to NCV deterioration. Sixteen LI-MLD and J-MLD survivors were evaluable for long-term gross motor and/or expressive language functioning using existing MLD clinical scoring systems. While most J-MLD patients regressed, the aggregate cohort demonstrated superior retention of function compared to published natural history. Seventeen LI-MLD, J-MLD and adult subtype (A-MLD) survivors were evaluable for long-term adaptive functioning, activities of daily living, and/or cognition. Relative cognitive sparing was observed despite overall global decline. Five sibling pairs (one LI-MLD and four J-MLD), in which at least one underwent transplant in our cohort, were evaluable. Within each familial dyad, survival or function was superior for the treated sibling, or if both siblings were transplanted, for the pre-symptomatic sibling. Conclusions: HSCT is a viable treatment option for MLD, but has significant limitations. Later-onset phenotypes may benefit most from early, pre-symptomatic transplant. Until superior, novel treatment strategies are demonstrated, MLD patients should be carefully considered for HSCT.


Related Articles

  • Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy. Bambach, B J; Moser, H W; Blakemore, K; Corson, V L; Griffin, C A; Noga, S J; Perlman, E J; Zuckerman, R; Wenger, D A; Jones, R J // Bone Marrow Transplantation;2/15/97, Vol. 19 Issue 4, p399 

    To date, in utero bone marrow transplantation (BMT) has had limited success, largely because of poor donor engraftment. The poor engraftment is probably the result of performing the procedure late in gestation after significant fetal immunocompetence has developed and/or transplanting...

  • Hematopoietic Stem Cell Transplantation for Thalassemia. Gaziev, Javid; Lucarelli, Guido // Current Stem Cell Research & Therapy;Jun2011, Vol. 6 Issue 2, p162 

    Hematopoietic stem cell transplantation (HSCT) represents the only cure for patients with thalassemia. At present, HSCT in younger patients from an HLA- matched sibling donor offers 80% to 87% probability of cure according to risk classes. However, results of HSCT in adult patients continue to...

  • Unrelated hematopoietic stem cell transplantation in the pediatric population: single institution experience. Marinho, Daniela Hespanha; Neto, José Zanis; Sales Bonfim, Carmem Maria; Moreira Funke, Vaneuza Araujo; Ribeiro, Lisandro Lima // Revista Brasileira de Hematologia e Hemoterapia;Jul/Aug2015, Vol. 37 Issue 4, p236 

    Objective: Hematopoietic stem cell transplantation has been successfully used to treat the pediatric population with malignant and non-malignant hematological diseases. This paper reports the results up to 180 days after the procedure of all unrelated hematopoietic stem cell transplantations in...

  • Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know. Ogata, M; Fukuda, T; Teshima, T // Bone Marrow Transplantation;Aug2015, Vol. 50 Issue 8, p1030 

    Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after...

  • A strategy for enhancing the engraftment of human hematopoietic stem cells in NOD/SCID mice. Lee, Soo Hyun; Kim, Dae Seong; Lee, Myoung Woo; Noh, Yoo Hun; Jang, In Keun; Kim, Dong Hyun; Yang, Heung-Mo; Kim, Sung-Joo; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Chueh, Hee Won; Son, Meong Hi; Jung, Hye Lim; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe // Annals of Hematology;Dec2013, Vol. 92 Issue 12, p1595 

    To overcome the limitations of allogeneic hematopoietic stem cell transplantation (HSCT), we conducted a study to identify a strategy for enhancing hematopoietic stem cell (HSC) engraftment during HSCT. Co-transplantation experiments with mesenchymal stem cells (MSCs) derived from adult human...

  • Improved peripheral nerve conduction, EEG and verbal IQ after bone marrow transplantation for adult metachromatic leukodystrophy. Solders, G; Celsing, G; Hagenfeldt, L; Ljungman, P; Isberg, B; Ringdén, O // Bone Marrow Transplantation;12/1/98, Vol. 22 Issue 11, p1119 

    A 28-year-old woman with a 4 year history of slowly progressing ‘frontal dementia’ was diagnosed as having adult metachromatic leukodystrophy and was followed for 4 years after bone marrow transplantation (BMT). MRI, neurophysiological tests (EEG, ENeG, VEP, SEP and BAEP) and...

  • The Neuropsychological Course of Acute Delirium in Adult Hematopoietic Stem Cell Transplantation Patients. Beglinger, Leigh J.; Mills, James A.; Vik, Stacie M.; Duff, Kevin; Denburg, Natalie L.; Weckmann, Michelle T.; Paulsen, Jane S.; Gingrich, Roger // Archives of Clinical Neuropsychology;Mar2011, Vol. 26 Issue 2, p98 

    Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem...

  • Metachromatic leukodystrophy: two sides of a coin. Jeffery, Robert; Jeffery, Alison // BMJ: British Medical Journal (International Edition);12/18/93-12/25/93, Vol. 307 Issue 6919, p1631 

    Focuses on the characterization of a child with metachromatic leukodystrophy. Effect of bone marrow transplantation on the mortality of a patient; Gradual progression of the disease; Impact of the disease on the emotional conditions of the family.

  • Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results. Benito, A. I.; Diaz, M. A.; González-Vicent, M.; Sevilla, J.; Madero, L. // Bone Marrow Transplantation;Apr2004, Vol. 33 Issue 7, p675 

    Summary:Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost 70?000 CB units are available for transplantation and more than 2000 CB transplants (CBT) have...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics