Table 1.

Comparison of current methods for T-cell depletion.

	Protocol name	Biological hypothesis underlying clinical effects	Reported clinical outcomes
	Principle
Ex-vivo T-cell depletionTCD platforms	CD34+ megadose Positive CD34+ selection	Use of G-CSF mobilized PBSC as graft source allows the collection of high numbers of stem cells that are isolated using immune magnetic strategies.	Engraftment 91% Grade II–IV aGVHD 8%/cGVHD 7% TRM 37%–44%
		Slow immune reconstitution leads to high incidence of infection and high relapse rates
	Specific alloreactive T-cell depletion ⇔ Selective CD3+/CD19+ cell depletion	NK cells, monocytes and dendritic cells are retained, which may contribute to a better immune reconstitution after transplantation	Engraftment 95% Grade II–IV aGVHD 46%/cGVHD 18% 2y TRM 42% 2y relapse rate 31% 2y OS 28%
		Significantly increase of the risk of GVHD compared with positive CD34+ selection
	Designed graft ⇔ Specific removal of alloreactive cells	Depletion of TCRαβ+/CD19+ cells/depletion of CD45RA+ naive T cells	Engraftment 97.5% Grade I–II aGVHD 30%/no cGVHD TRM 5% Relapse 24%
		Low incidence of GVHD and NRM, excellent relapse-free survival
	Adoptive T-cell add-back	– Donor-derived Tregs decrease aGVHD	Engraftment 95%, 46 months DFS 56% Grade II–IV aGVHD 15%/no cGVHD
	⇔ Treg/Tcons infusion following haplo-HSCT	– Co-infusion of Treg + conventional T cells fosters immune reconstitution and prevents aGVHD
		→ Low incidence of GVHD, optimal immune reconstitution, and very low relapse rate
	Genetically engineered TK cells add-back	TK-cell infusions would confer GVL activity and early protective immune reconstitution after haplo-HSCT, while the suicide gene allow the control of GVHD which could be induced by the TK-cells	3y NRM 40% for patients with de-novo AML in CR at haplo-HSCT/41% for patients in relapse at haplo-HSCT 3y OS: 49% for patients with de-novo leukemias in any CR No GVHD-related deaths or long-term complication (10 of 22 immune reconstituted patients developed aGVHD + 1 patient developed cGVHD)
	⇔ Infusion of donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) following haplo-HSCT (14)
In-vivo T-cell depletion TCR platforms	Baltimore protocol	High-dose PT-Cy	Non-myeloablative conditioning
	T-cell replete (TCR), unmanipulated graft + High doses PT-Cy: 50 mg/kg/day on day +3/+4	– Selectively eliminates the alloreactive donor T cells (mainly naive T cells) without exerting toxic effects on hematopoietic stem cells	Engraftment 85%–90%, OS 40%–45%, Relapse >40%
		↘ Proliferation of alloreactive CD4+ effector T cells	Myeloablative regimen
		↘ Survival of alloreactive CD4+ and CD8+ alloreactive T cells	Decreased relapse compared to NMAC CR1 11%/CR2 26%/active disease 40% Increased OS compared to NMAC CR1 77%/CR2 49%/active disease 38%
		–Preferentially encourages recovery of regulatory T cells
		→Host regulatory T cells thereby expand shifting the Treg:T-cell ratio in favor of an immunotolerant balance
	Beijing protocol	G-CSF
	T-cell replete (TCR), unmanipulated and G-CSF primed graft + ATG + Intensive post-graft IS (MTX, CsA, MMF)	Induces T-cell hyporesponsiveness Induces Th2 polarization in BM and PBSC harvests Induces proliferative expansion of regulatory cells, including regulatory T cells, myeloid-derived suppressor cells, and regulatory B cells	Engraftment 99%, Grade II–IV aGVHD 40%/3y cGVHD 50% 3y NRM 17%, 3y relapse 17%, 3y DFS 67%, 3y OS 70%

Adapted from “Evolution of the Role of Haploidentical ´ Stem Cell Transplantation: Past, Present, and Future”, Kwon et al. (7) and “Update on Current Research Into Haploidentical Hematopoietic Stem Cell Transplantation”, Sun et al. (15).

aGVHD, acute GVHD; AML, acute myeloid leukemia; ATG, anti-thymoglobulin; BM, bone marrow; cGVHD, chronic GVHD; CR(#), complete remission (number #); CsA, ciclosporin-A; DFS, disease-free survival; G-CSF, granulocyte colony-stimulating factor; GVL: graft versus leukemia; IS, immunosuppression; MMF, mycophenolate mofetil; MTX, methotrexate; NRM, non-relapse mortality; OS, overall survival; PBSC, peripheral blood stem cell; PFS, progression-free survival; PT-Cy, post-transplant cyclophosphamide; TCD, T-cell depleted; TCR, T-cell replete; TRM, transplant-related mortality; NMAC, non myeloablative conditioning; #y, # years.