Abstract
In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 × 109 NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 × 108 NC CliniMACS selected CD34+ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day −10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13+, CD15+), about 30% myelomonocytic cells (CD14, HLA-DR+), 5.2% megakaryocytes (CD61+) and 1.2% CD34+ cells. The proportion of T (CD3+), NK cells (CD56+) as well as dendritic cells (CD83+) was below 0.2%. The unseparated CB infused at day 0 and +1 consisted of a total of thawed 4.4 × 107 NC/kg BW, 5.8 × 104 CFU-GM/kg BW, 1.54 × 105 CD34+cells/kg BW and 7.73 × 102 LTC-IC/kg BW. In addition, the 1 × 107 NC/kg BW ex vivo expanded cells representing 1.9 × 104 CFU-GM/kg BW, 1.13 × 105CD34+ cells/kg BW and 4.37 × 102 LTC-IC/kg BW, were infused at day +1. At day +2 after transplantation the patient revealed a focal pneumonia on X-ray with generalized sepsis and became catecholamine dependent. From day +4 the patient received 280 μg/m2 G-CSF. At day +5 she developed an erythroderma, which could not be identified as acute GVHD by biopsy. Early engraftment with leukocyte counts at days 8 and 14 were 350 and 700/μl, ANC 310 and 410/μl, respectively. Donor cells determined by chimerism analysis were 97% and 98% in the periphery at this early time. Most importantly, the pneumonia as well as the septicemia subsided within a few days. Notably, as well is the clearly shortened aplastic phase observed after this simultaneous CB cell component transplantation. The patients T cell and NK cell reconstitution could be detected at day +37 with 330 CD3+ cells/μl and 40 CD56+ cells/μl, respectively. The time to reach an absolute platelet count of 20 000 (50 000)/μl was 75 (103) days. The disease-free survival now exceeds 1 year in complete remission without chronic GVHD or any other health problems. These data show that the applicability of ex vivo expanded committed progenitors and LTC-IC, even in high risk leukemia at the time of transplantation, is feasible and can provide sufficient myeloid progenitors resulting in rapid engraftment able to clear bacterial pneumonia and sepsis. In addition, accelerated hematopoietic reconstitution apparently served as a well functioning platform for definitive graft-versus-leukemia activity. This transplantation of defined ex vivo generated components presents a feasible and generally applicable approach and may open a promising new avenue for cell therapy in malignant diseases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kögler, G., Nürnberger, W., Fischer, J. et al. Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia. Bone Marrow Transplant 24, 397–403 (1999). https://doi.org/10.1038/sj.bmt.1701916
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1701916
Keywords
This article is cited by
-
Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results
Bone Marrow Transplantation (2004)
-
Unrelated donor umbilical cord blood transplantation in adults
Leukemia (2002)
-
The CD34+CD38neg population is significantly increased in haemopoietic cell expansion cultures in serum-free compared to serum-replete conditions: dissociation of phenotype and function
Bone Marrow Transplantation (2001)
-
Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood
Bone Marrow Transplantation (2001)
-
Umbilical cord blood for allogeneic transplantation in children and adults
Bone Marrow Transplantation (2001)