HLA-haploidentical umbilical cord blood stem cell transplantation in a child with advanced leukemia: Clinical outcome and analysis of hematopoietic recovery

R. Miniero, A. Busca, M. G. Roncarolo, M. Saitta, A. Iavarone, F. Timeus, A. Biondi, A. Amoroso, L. Perugini, E. Ciuti, P. Saracco, L. Ruggieri, E. Vassallo, V. Gabutti, E. Madon

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Growing attention has been focused on cord blood as a source of transplantable hematopoietic stem cells. However, clinical experience is rather limited. In this study we describe a child with advanced acute lymphoblastic leukemia who received an HLA-haploidentical cord blood transplant. The patient was transplanted in third complete remission after conditioning with fractionated total body irradiation, thiotepa and cyclophosphamide. Forty-one milliliters of cryopreserved umbilical cord blood, containing 0.15 x 108 nucleated cells/kg and 0.25 x 104 CFU-GM/kg, were infused. Cyclosporine and prednisone were administered for graft-versus-host disease (GVHD) prophylaxis. The patient received G-CSF from day +1 to day +35, but no improvement in granulocyte counts was observed. Therefore, administration of GM-CSF was started on day +36 to day +59, which resulted in a significant increase in white blood cells and granulocyte counts. Sustained myeloid engraftment was evidenced by a granulocyte count >0.5 x 109/l by day +41. The presence of donor-derived cells could be documented in the peripheral blood and bone marrow of the patient by cytogenetic analysis, HLA phenotyping and DNA studies. Forty-one days after transplant, clonogenic bone marrow assays showed the presence of low frequencies of primitive hematopoietic progenitor cells (BFU-E = 19/105 and CFU-GM = 8/105). The chimerism was complete and no host-derived cells could be detected. However, the engraftment was restricted to the myeloid lineage whereas lymphoid and megakaryocytic engraftments were inadequate. The immunophenotype of the patient's peripheral blood showed the presence of T lymphocytes expressing an immature phenotype (CD2+ CD3-) at day +21. Among the subset of T cells expressing the CD3 antigen, the majority were CD45RO+ memory cells and a significant proportion was positive for the activation markers CD25, CD69̄ and HLA-DR, suggesting that these T cells had been activated in vivo. On day +41, a mild cutaneous rash consistent with grade I acute GVHD resolved with steroid treatment. Unfortunately, the patient died of hepatic insufficiency and renal failure 84 days after transplantation. Autopsy showed a multiorgan failure with hepatic veno-occlusive disease (VOD). Overall, this study shows that (1) cord blood transplantation from an HLA-mismatched donor can be performed with a low risk of acute GVHD, and (2) a small volume of cord blood containing a reduced number of CFU-GM is sufficient to achieve engraftment.

Original languageEnglish
Pages (from-to)229-240
Number of pages12
JournalBone Marrow Transplantation
Issue number2
Publication statusPublished - 1995


  • ALL
  • Cord blood
  • HLA-haploidentical
  • Stem cell transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation


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