Optimization of the immunomagnetic selection in microcythemic donors enrolled for haploidentical transplantation

Abstract Profound depletion of T and B cells is a fundamental prerequisite for haploidentical transplantation. Here, we compare hematopoietic engraftment and occurrence of GvHD after two different positive selection procedures (with anti-CD34 coated or anti-CD133 coated beads) and after a direct depletion procedure with CD3/CD19 coated microbeads in children with leukemias (ALL, AML, CML) and lymphomas. Median purity of stem cells was comparable after CD34+ selection and CD133+ selection, whereas stem cells were only slightly enriched after CD3+/CD19+ depletion (97.5%, 93.4% and 1.02%). Indirect depletion of T cells was better after CD34+ selection than after CD133+ selection (4.1log vs. 3.75log, p<0.001). Direct T cell depletion with anti-CD3 coated microbeads produced results comparable to CD34+ selection. Those grafts comprised also remarkable amounts of effector cells such as NK cells (median number: 40 x106/kg), dendritic cells and monocytes (median number: 120 x106/kg). Recovery of stem cells was similar in all three methods (77.3%, 80.6%, and 70% respectively). Primary engraftment occurred in 85% (44/52) of patients with CD34+ selected stem cells and in 78% (11/14) of patients with CD133+ selected cells. After reconditioning, sustained engraftment was achieved in 98% and 100%. All patients (10/10) with CD3+/CD19+ depleted grafts had primary engraftment. Recovery of platelets was rapid especially in patients with CD133+ selected grafts (median time to reach independence from substitution = 14.5 days). GvHD grade II occurred in 6%, 7% and 25%, respectively. Only one patient had severe GvHD grade III-IV (CD34+).Conclusions: CD34+ selection and CD133+ selection resulted in similar engraftment and GvHD rates. CD3+/CD19+ depletion resulted in better engraftment but produced slightly more GvHD. Thus, the methods may be individually used according to the patient’s requirements.

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Faculty Opinions recommendation of Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10163956.11436064 ◽

2011 ◽

Author(s):

Armand Keating ◽

Brent Williams

Keyword(s):

Immune Reconstitution ◽

Haploidentical Transplantation

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Decrease post-transplant relapse using donor-derived expanded NK-cells

Leukemia ◽

10.1038/s41375-021-01349-4 ◽

2021 ◽

Author(s):

Stefan O. Ciurea ◽

Piyanuch Kongtim ◽

Doris Soebbing ◽

Prashant Trikha ◽

Gregory Behbehani ◽

...

Keyword(s):

Nk Cells ◽

Nk Cell ◽

Ex Vivo ◽

Disease Free Survival ◽

Dependent Manner ◽

Post Transplant ◽

Haploidentical Transplantation ◽

High Doses ◽

High Level

AbstractIn this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 105–1 × 108 cells/kg/dose) were administered on days −2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database.After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype.Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 (https://clinicaltrials.gov/ct2/show/NCT01904136).

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