Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment

Abstract

HLA-mismatched family members may represent an important cell source for patients that require stem cell transplantation but lack both a matched sibling donor and a closely matched unrelated donor. We report the outcome of 19 transplantations from HLA two-or three-loci mismatched parental donors in which 14 pediatric patients with hematological malignancies or other disorders, received a median of 21.5 ؋ 10 6 (range, 5.4-58) highly purified CD34؉ peripheral blood stem cells (

Haploidentical SCT in children: an update and future perspectives

“…17 The low incidence of EBV-associated lymphoproliferative disease in pediatric patients with CD34 þ or CD133 þ selected grafts was related to the additional indirect depletion of mature B cells harboring the EBV. 5,9,11,13,18 However, new stem cell markers, targeting CD34 negative progenitors, have questioned whether positive selection procedures will be sufficient to identify early and pluripotent progenitor cells. 7 Further, other immune components such as natural killer (NK) cells, DCs and monocytes are lost during the separation procedure and cannot be used to generate antitumor, antiviral or graft-facilitating effects.…”

“…32 To overcome the HLA barrier, most conditioning regimens for haplotransplantation in children were myeloablative and BU or TBI (14.4 or 12 Gy) based. 2,3,5,9,11,13,18 Thiotepa was added by some groups to enhance myeloablation. 12 Alternatively, VP16 was used in patients with acute leukemias.…”

“…29 High median stem cell doses between 11.3 and 24.3 Â 10 6 /kg were infused in several studies according to the megadose concept of Reisner et al 16 To date, there is no clear clinical evidence for the optimum cell dose, and a wide range of CD34 þ selected progenitors (4.2-58 Â 10 6 /kg) was able to induce successful engraftment. 5,9,11,13,18,34 In patients with T and B cell-depleted grafts, cell doses of approximately 2 Â 10 6 /kg resulted in stable engraftment. Frequent analyses of T cell chimerism can help to predict graft rejection, either by PCR analysis of VNTR regions or by flow cytometry of lymphocyte subsets with MoAb against HLA Ags of recipient and donor.…”

“…34 The risk of acute and chronic GVHD was significantly reduced by all mentioned graft manipulation procedures and therefore comparable with that after matched unrelated donor transplantations. The rates ranged between 0-24% (acute GVHDXgrade II) and between 0-19% (chronic) 5,9,11,13,35,40 after CD34 or CD133 positive selection and between 36 and 27% (acute GVHDXgrade II) after CD3 depletion and CD20 or CD19 depletion. 7,14 In contrast to those studies, Chinese and Japanese groups investigated the use of G-CSF primed BM/PBSC without any in vitro T cell depletion on the basis of antithymocyte globulin and post-transplant immunosuppression with 3-4 agents.…”

New strategies for haploidentical transplantation

“…With this extensive T-cell depletion, almost no GvHD was seen even in the absence of any pharmacological GvHD prophylaxis, and due to the indirect B-cell depletion associated with CD34 + selection, post-transplant Epstein-Barr virus-related lymphoproliferative disorders were also absent in both pediatric (6,33) and adult patients (34). However, the experience of the transplant center with haploidentical transplantation of CD34 + stem cells had a major impact on the outcome.…”