Skip to main content

Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center.

Publication ,  Conference
Prasad, VK; Medizabal, A; Parikh, SH; Szabolcs, P; Driscoll, TA; Page, K; Lakshminarayanan, S; Allison, J; Wood, S; Semmell, D; Escolar, ML ...
Published in: Blood
November 16, 2007

Background: Allogeneic bone marrow transplantation from related and unrelated donors leads to improvement in longevity and quality of life due to replacement of missing enzyme and engraftment of donor-derived glial cells in patients with LSD. Recently, unrelated umbilical cord blood transplant (UCBT) has yielded encouraging results but due to the rarity of LSDs, there has never been a large series of patients transplanted at a single center.Methods: Between 1995 and 2007, 159 consecutive LSD patients received unrelated UCBT at Duke after busulfan, cyclophosphamide, and antithymocyte globulin myeloablation. Cyclosporine+methylprednisolone (n=125) or cyclosporine+cellcept (n=34) was given for graft-versus-host disease (GvHD) prophylaxis. Cord blood units from 8 US public banks were screened and the unit with high-normal enzyme was selected. Engraftment, enzyme, organ function, neurodevelopmental, neuroimaging, and neurophysiologic studies were performed pre- and post-UCBT. The probabilities of engraftment, overall survival (OS) and GvHD were estimated. Multivariate models for graft and patient factors were analyzed.Results: Median patient age was 1.5 yrs (range 0.05–26.3); 19.5% were CMV seropositive; and 41.5% had a performance status<80%. The majority of grafts were 5/6 (47%) or 4/6 (46%) by intermediate-res HLA-A and -B and high-res HLA-DRB1. The median (range) cell dose/kg of TNC (pre-cryo), TNC (infused), CD34 (infused) and CFU (infused) was 9.7x107(2.2–50.4), 7.6x107(1.5–32.4), 2.1x105(0.4–104.8) and 5.7x104(0.0–105.3), respectively. ABO and ethnicity matching between donor/graft pairs were 55% and 82%, respectively. The cumulative incidence of 42 day neutrophil and 180 day platelet engraftment (50k) was 87.1% (95%CI 82%–92%) in a median of 22 days and 71.0% (95%CI 64%–78%) in a median of 87 days, respectively. In multivariate analysis, neutrophil and platelet engraftment was favored by (p< 0.05) patient age = 2 years, infused CD34 >2.1x105/kg, and infused CFU >5.7x104/kg. The probability of day+100 Grade III/IV acute GvHD was 10.3% (95%CI 5%–15%). Chronic GvHD developed in 25 (18%), 11 of whom were extensive. OS at 0.5, 1, 3, and 5 years was 79.0% (95%CI 73%–85%), 71.8% (95%CI 65%–79%), 62.7% (95%CI 55%–71%) and 58.2% (95%CI 50%–67%), respectively. In multivariate analysis, performance status 80–100 (p<0.0001), CFU infused >5.7x104/kg (p=0.02) and matched ethnicity (p=0.05) were independently associated with higher OS. In median follow-up of 4.2 years (range 0.2–11.5), all but 3 engrafted patients maintained donor chimerism >90% and all but 4 normalized enzyme level. In patients with high performance status (80–100), the OS at 1, 3 and 5 years was 88.4% (95%CI 79.6%–97.1%), 83.5% (95%CI 73.0%–94.1%) and 79.5% (95%CI 66.9%–92.1%), respectively.Conclusions: Unrelated Cord blood is an excellent graft source for treatment of patients with these fatal disorders, particularly when transplantation is performed in early stages. Pre-transplant performance status and post-thaw CFU dosing were highly predictive of overall survival.

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2007

Volume

110

Issue

11

Start / End Page

336 / 336

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Prasad, V. K., Medizabal, A., Parikh, S. H., Szabolcs, P., Driscoll, T. A., Page, K., … Kurtzberg, J. (2007). Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center. In Blood (Vol. 110, pp. 336–336). American Society of Hematology. https://doi.org/10.1182/blood.v110.11.336.336
Prasad, Vinod K., Adam Medizabal, Suhag H. Parikh, Paul Szabolcs, Timothy A. Driscoll, Kristin Page, Sonali Lakshminarayanan, et al. “Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center.” In Blood, 110:336–336. American Society of Hematology, 2007. https://doi.org/10.1182/blood.v110.11.336.336.
Prasad, Vinod K., et al. “Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center.Blood, vol. 110, no. 11, American Society of Hematology, 2007, pp. 336–336. Crossref, doi:10.1182/blood.v110.11.336.336.
Prasad VK, Medizabal A, Parikh SH, Szabolcs P, Driscoll TA, Page K, Lakshminarayanan S, Allison J, Wood S, Semmell D, Escolar ML, Martin PL, Carter S, Kurtzberg J. Analysis of the Cellular Components of the Graft and Clinical Characteristics of 159 Children with Lysosomal and Peroxisomal Disorders (LSD) Undergoing Unrelated Umbilical Cord Blood Transplantation at a Single Center. Blood. American Society of Hematology; 2007. p. 336–336.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2007

Volume

110

Issue

11

Start / End Page

336 / 336

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology