Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution

Abstract

Summary:A total of 11 high-risk Korean acute myeloid leukemia (AML) patients received stem cell transplantation from human leukocyte antigen (HLA) haploidentical donors. Specifically, for eight patients with 2-3 mismatched antigens and bidirectional vectors, we used a newly designed conditioning regimen that consists of total body irradiation, busulfex, ATG, and fludarabine. The median number of CD34 þ cells infused was 15.4 Â 10 6 /kg (range, 8-21.2). These patients received neither graftversus-host disease (GvHD) prophylaxis nor post transplantation G-CSF. All of the patients who were followed up for a median of 6 months (range, 17 days-28 months) showed stable primary engraftment and had no acute GvHD or transplant-related mortality for 100 days post transplant. Three patients with high-risk or refractory disease eventually died in relapse, even with GvH-directed NK alloreactivity. However, the patients in complete remission (CR), with the exception of one patient who is alive at 18 months EFS, died at 4, 6, and 8 months post transplantation due to infections that were associated with delayed immune recovery. Our findings suggest that haploidentical transplantation represents a feasible treatment for patients with high-risk AML in CR, provided that a plan for the enhancement of immune recovery is implemented. Bone Marrow Transplantation (2005) 35, 959-964.

Comparison of Allogeneic Stem Cell Transplantation from Familial-Mismatched/Haploidentical Donors and from Unrelated Donors in Adults with High-Risk Acute Myelogenous Leukemia

“…Thus, further well-controlled studies of larger numbers of patients are needed to address this issue. In addition, the relatively higher proportion of patients with CR1 at time of transplantation (75%) in the present study compared with previous studies of FMT, including variable proportions of patients in CR1 at transplantation but\50% (14%-45%) in acute leukemia, might have contributed to the relatively higher survival rate in our FMT group [15][16][17][18][32][33][34][35][36]38], suggesting the benefit of FMT in patients with favorable disease status at the time of transplantation.…”

“…We reported our previous experience of FMT using MAC with ex vivo T cell depletion in patients with high-risk AML without further GVHD prophylaxis, the majority of whom were in advanced disease status at transplantation (CR1, n 5 2; CR2, n 5 1; CR3, n 5 1; refractory, n 5 4) [38]. The conditioning regimens differed from the current FMT regimen with respect to doses of TBI (1200 cGy versus 800 cGy) as well as busulfan (3.2 mg/kg/day for 3 days versus for 2 days) and fludarabine (40 mg/m 2 /day for 4-5 days versus 30 mg/m 2 /day for 5 days).…”

Feasible Outcomes of T Cell–Replete Haploidentical Stem Cell Transplantation with Reduced-Intensity Conditioning in Patients with Myelodysplastic Syndrome

“…However, early studies on haploidentical SCT resulted in unacceptably high incidences of graft rejection and graft-versus-host disease (GVHD) [2][3][4]. To overcome these bidirectional barriers of HLA incompatibilities, T celledepleted haploidentical SCT was attempted with the infusion of megadose peripheral blood (PB) stem cell grafts after intensive conditioning [5][6][7]. Although this strategy was effective in reducing the incidences of graft rejection and GVHD, the high infection-related mortality rate due to a delayed immune reconstitution remained a challenge.…”

Temporal, quantitative, and functional characteristics of single-KIR–positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation

“…3,10,13,14 However, subsequent studies failed to confirm the protective effect of NK alloreactivity on leukemia relapse after haploidentical HSCT. 15,16 In particular, Nguyen et al 15 provided evidence for a role of CD94:NKG2A, the inhibitory receptor specific for HLA-E, in limiting the antileukemic effect of NK cells that reconstitute at an early stage after haploidentical HSCT.…”