Skip to main content
Journal cover image

Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.

Publication ,  Journal Article
Patel, SA; Allewelt, HA; Troy, JD; Martin, PL; Driscoll, TA; Prasad, VK; Kurtzberg, J; Page, KM; Parikh, SH
Published in: Biol Blood Marrow Transplant
October 2017

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune dysregulation characterized by fever, hepatosplenomegaly, cytopenias, central nervous system disease, increased inflammatory markers, and hemophagocytosis. Currently, allogeneic hematopoietic stem cell transplantation is the only curative approach for patients with HLH, with reported survival ranging from 50% to 70% with myeloablative conditioning (MAC) regimens. However, donor availability and transplantation-related mortality associated with conventional MAC are major barriers to success. Unrelated umbilical cord blood transplantation (UCBT) provides a readily available alternative donor source for patients lacking matched related donors. Accordingly, we report the results of UCBT in 14 children treated between 1998 and 2016. All children received standard HLH chemotherapy before UCBT. The median age at diagnosis was 2.7 months (range, .8 to 10.4) and at transplantation was 7.5 months (range, 3.8 to 17). Ten patients received MAC with busulfan/cyclophosphamide/etoposide /antithymocyte globulin (ATG) (n = 5), busulfan/cyclophosphamide /ATG (n = 4), or busulfan /melphalan/ATG (n = 1). Four patients received reduced-toxicity conditioning (RTC) with alemtuzumab/fludarabine/melphalan/hydroxyurea ± thiotepa. Cord blood units were mismatched at either 1 (n = 9) or 2 (n = 5) loci and delivered a median total nucleated cell dose of 11.9 × 107/kg (range, 4.6 to 27.9) and CD34+ dose of 3.1 × 105/kg (range, 1.1 to 6.8). The cumulative incidence of neutrophil engraftment by day 42 was 78.6% (95% confidence interval [CI], 42.9% to 93.4%) with a median of 19 days (range, 13 to 27), and that for platelet (50,000) engraftment by day 100 was 64.3% (95% CI, 28.2% to 85.7%) with a median of 51 days (range, 31 to 94). Six patients developed either grade II (n = 5) or grade IV (n = 1) acute graft-versus-host disease (GVHD); no extensive chronic GVHD was seen. Ten patients (71.4%) are alive and well at a median of 11.2 years after transplantation (range, .85 to 18.25), 9 of whom maintain sustained full donor chimerism after a single UCBT, whereas 1 patient with autologous recovery after first UCBT with RTC has achieved full donor chimerism after a second UCBT with MAC. This series demonstrates that, in combination with standard HLH therapy, UCBT after MAC or RTC conditioning can provide long-term survival with durable complete donor chimerism comparable to that of conventional donors. UCBT should be considered for patients with HLH lacking a fully matched related or unrelated adult donor.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

October 2017

Volume

23

Issue

10

Start / End Page

1722 / 1728

Location

United States

Related Subject Headings

  • Transplantation Conditioning
  • Lymphohistiocytosis, Hemophagocytic
  • Infant
  • Immunology
  • Humans
  • Graft vs Host Disease
  • Graft Survival
  • Fetal Blood
  • Disease-Free Survival
  • Cord Blood Stem Cell Transplantation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Patel, S. A., Allewelt, H. A., Troy, J. D., Martin, P. L., Driscoll, T. A., Prasad, V. K., … Parikh, S. H. (2017). Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience. Biol Blood Marrow Transplant, 23(10), 1722–1728. https://doi.org/10.1016/j.bbmt.2017.06.013
Patel, Sachit A., Heather A. Allewelt, Jesse D. Troy, Paul L. Martin, Timothy A. Driscoll, Vinod K. Prasad, Joanne Kurtzberg, Kristin M. Page, and Suhag H. Parikh. “Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.Biol Blood Marrow Transplant 23, no. 10 (October 2017): 1722–28. https://doi.org/10.1016/j.bbmt.2017.06.013.
Patel SA, Allewelt HA, Troy JD, Martin PL, Driscoll TA, Prasad VK, et al. Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience. Biol Blood Marrow Transplant. 2017 Oct;23(10):1722–8.
Patel, Sachit A., et al. “Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience.Biol Blood Marrow Transplant, vol. 23, no. 10, Oct. 2017, pp. 1722–28. Pubmed, doi:10.1016/j.bbmt.2017.06.013.
Patel SA, Allewelt HA, Troy JD, Martin PL, Driscoll TA, Prasad VK, Kurtzberg J, Page KM, Parikh SH. Durable Chimerism and Long-Term Survival after Unrelated Umbilical Cord Blood Transplantation for Pediatric Hemophagocytic Lymphohistiocytosis: A Single-Center Experience. Biol Blood Marrow Transplant. 2017 Oct;23(10):1722–1728.
Journal cover image

Published In

Biol Blood Marrow Transplant

DOI

EISSN

1523-6536

Publication Date

October 2017

Volume

23

Issue

10

Start / End Page

1722 / 1728

Location

United States

Related Subject Headings

  • Transplantation Conditioning
  • Lymphohistiocytosis, Hemophagocytic
  • Infant
  • Immunology
  • Humans
  • Graft vs Host Disease
  • Graft Survival
  • Fetal Blood
  • Disease-Free Survival
  • Cord Blood Stem Cell Transplantation