HLA-DR-matched Parental Donors for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-risk Acute Leukemia

Abstract

The immunomodulating effect of human leukocyte antigen (HLA)-DR and the central role of CD4 T cells in alloimmunity provide clues suggesting that HLA-DR-matched, partially mismatched related donors could be feasible alternative donors of allogeneic hematopoietic stem cells for transplantations (allo-HSCT). We describe our experience with allo-HSCT in eight patients with high-risk acute leukemia; donors included one of each of the parents. Among the eight patients, seven were identical HLA-DR matches with the donors. The stem cells were not manipulated in vitro. Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, cyclosporine, and methotrexate. All patients had successful trilineage engraftment. Only one patient had grade 2-4 acute GVHD. Two patients died before day +100 due to complications. At the end of follow-up, four patients had survived for 18-48 months and three are alive and without relapse. Our results suggest that HLA-DR fully-matched parents are feasible alternative donors for allo-HSCT in patients with high-risk acute leukemia under an intensive conditioning regimen.

The hollow fiber bioreactor as a stroma‐supported, serum‐free ex vivo expansion platform for human umbilical cord blood cells

“…Based on current clinical experience, the recommended minimum cell dose numbers for successful CB HSC transplantation are 3.5 × 10 7 total nucleated cells (TNC)/kg and 2 × 10 5 CD34 + HSC/kg [17]. Due to the large number of HSCs needed for transplantation (range 1.5 -14.0 × 10 6 /kg) in clinical applications [18,19], largescale ex vivo expansion systems have captured the interest of many researchers [14,[20][21][22][23]. Bioreactor systems such as perfusion chambers [24], stirred bioreactors [25][26][27], rotating wall bioreactors [28], membrane-based bioreactors [29], and packed or fluidized bed reactors [30,31] have been developed and widely tested for ex vivo expansion of HSCs.…”

Donor-Derived Solid Malignancies after Hematopoietic Stem Cell Transplantation

“…Afteralongprocessandlargeamountsofclinicalpractice,it is now considered a novel therapeutic strategy benefiting patientswithvarioushematologicalmalignancies [1][2][3],solid malignancies [4], or inherited stem cell disorders [5][6][7]. In recentyears,therehasbeenagrowingnumberoflong-term recipients as the technique and quality of allo-HSCT is improving;however,thiscohortstillsuffersfromahighriskof potential late allo-HSCT complications, including the developmentofsecondaryneoplasms [8],graftversushostdisease (GVHD) [9], and infections [10].…”

Three dimensional platforms for ex vivo hematopoietic cell bioprocesses

“…The (TNC)/kg and 2.0×10 5 CD34 + HSC/kg. Due to the large number of HSCs needed for transplantation (Range: 1.5-14.0×10 6 /kg) in clinical application [233,234], large-scale ex vivo expansion systems have captured many researchers' interests [129,230,[235][236][237]. Development of bioreactor systems like perfusion chambers [1], stirred bioreactors [2,3], rotating wall bioreactors [4], membrane based bioreactors [5], and packed or fluidized bed reactors [6,7] grew and were widely tested for ex vivo expansion of HSCs.…”