Janna Hol
,
Pediatric Blood and Bone Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, Netherlands
Annalisa Ruggeri, MD
,
Eurocord International Registry, Paris, France
Vanderson Geraldo Rocha, MD, PhD
,
Churchill Hospital, Oxford University Hospitals, Oxford, United Kingdom
Gerard Michel, MD
,
Department of Pediatric Hematology, La Timone Hospital, Marseille, France
Mouhab Ayas, MD
,
Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Tracey O'Brien, MD
,
Centre for Children's Cancer, Sydney Children's Hospital, Sydney, Australia
Gergely Krivan, MD
,
St. Laszlo Hospital, Budapest, Hungary
Victoria Bordon, MD
,
Ghent University Hospital, Ghent, Belgium
Rik Schots, MD, PhD
,
Department of Clinical Hematology, University Hospital Brussels, Brussels, Belgium
Attilio Rovelli, MD
,
San Gerardo University Hospital, Monza, Italy
Izaskun Elorza, MD
,
Hospital Vall D'Hebron, Barcelona, Spain
Jose Moraleda, MD, PhD
,
Hospital Universitario Vergen de la Arrixaca, Murcia, Spain
Peter John Shaw, MD
,
Dept. of Oncology, Children's Hospital At Westmead, Sydney, Australia
Marleen Renard, MD
,
University Hospital Gasthuisberg, Leuven, Belgium
Karl-Walter Sykora, MD
,
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany
Reuven Or, MD
,
Bone Marrow Transplantation & Cancer Immunotherapy Department, Hadassah University Hospital, Jerusalem, Israel
Tsila Zuckerman, MD
,
Hematology and Bone Marrow Transplantation, Rambam Medical Center, Haifa, Israel
Manuel Abecasis, MD PhD
,
Unidade Do Transplant Do Marrow De Osso, Instituto Portugues de Oncologia, BMT Unit, Lisboa, Portugal
Robbert Bredius, MD, PhD
,
Department of Pediatrics, Leiden University Medical Center, Leiden, Netherlands
M. Akif Yesilipek, MD
,
Departement of Pediatric Hematology, Akdeniz University Medical School, Antalya, Turkey
Miguel Angel Diaz, MD, PhD
,
Hospital Nino Jesus, Madrid, Spain
Andrew Gennery, MD
,
Paediatric Immunology, Newcastle University, Newcastle upon Tyne, United Kingdom
Eliane Gluckman, MD RFCP
,
Hospital Saint Louis, Eurocord, Paris, France
Jaap-Jan Boelens, MD, PhD
,
Blood and Marrow Transplantation Program, University Medical Center Utrecht, Utrecht, Netherlands
This study aims to describe outcomes of allogeneic cord blood transplantation (CBT) in leukodystrophies (LD). LD are rare inborn errors of metabolism in which the brain myelin is primarily affected, characterized by rapid neurological deterioration. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected leukodystrophies, including adrenoleukodystrophy (ALD), Krabbe disease (globoid cell leukodystrophy) and metachromatic leukodystrophy (MLD). Unrelated cord blood has the advantage of being rapidly available.
All patients undergoing CBT for LD in EBMT centers between 1996 and 2012 were included. HSCT data were collected from the EUROCORD database. An additional questionnaire on disease-specific clinical outcomes was sent to participating centers. Kaplan-Meier estimates were used to calculate overall survival (OS) and cumulative incidence methods for secondary outcomes, including neutrophil and platelet engraftment, incidence of graft-versus-host disease (GvHD) and disease-specific characteristics at most recent follow-up. The two-sided log-rank test was used for univariate comparisons.
Seventy patients (31 ALD, 5 Krabbe, 34 MLD) were available for analysis, with a median age at transplant of 6.5 years. Median follow-up for survivors was 46 months. OS at 4 years was 60% (±6%). Cumulative incidences of neutrophil and platelet engraftment were 88% (±4%) at day 60, and 73% (±6%) at day 180, resp. Acute-GvHD (grade II-IV) occurred in 16 patients (22% ±5%) at day 100 and chronic-GvHD in 9 patients (13% ±5%). Out of the 24 patients who died, 18 (67%) died of transplant-related causes and 6 (33%) died of disease progression. Higher OS was seen in patients who had no or 1 HLA mismatch (OS 81%), compared to patients who received a CBT with 2 HLA mismatches (OS 47%, p 0.02).
On 37 patients (53%), information on disease-specific characteristics was available. OS among these patients was 68% (±8), which was not significantly different from patients without disease-specific information (p=0,307). Nineteen patients (51%) were asymptomatic at transplant, 14 (38%) had mild disease and 4 (11%) were severely affected. Overall survival was worse in patients with severe disease at transplant; none of these 4 patients survived, versus 79% of mildly affected and 76% of asymptomatic patients. At most recent follow-up, disease status was stable in 15 (57.7%), had improved in 2 (7.7%) and worsened in 9 (34.6%) surviving patients. The majority of patients showed abnormalities on MRI-scanning pre-HSCT (n=25, 68%). In patients with normal MRI-scans pre-transplant OS was 69%; in patients with abnormal MRI-scans 75%.
In conclusion, we found an encouraging OS of 60% at 4 years, with relatively low rates of GvHD. Use of a mismatched donor (>1 HLA) negatively impacts survival. Data on clinical characteristics suggest that OS is strongly influenced by disease status at transplant.
