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Review
. 2023 Sep 1:14:1237782.
doi: 10.3389/fimmu.2023.1237782. eCollection 2023.

The two-step approach to allogeneic hematopoietic stem cell transplantation

Sikemi Ibikunle  1 , Dolores Grosso  1 , Usama Gergis  1
Affiliations
Review

The two-step approach to allogeneic hematopoietic stem cell transplantation

Sikemi Ibikunle et al. Front Immunol. .

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) provides the only potentially curative option for multiple hematological conditions. However, allogeneic HSCT outcomes rely on an optimal balance of effective immune recovery, minimal graft-versus-host disease (GVHD), and lasting control of disease. The quest to attain this balance has proven challenging over the past few decades. The two-step approach to HSCT was conceptualized and pioneered at Thomas Jefferson University in 2005 and remains the main platform for allografting at our institution. Following administration of the transplant conditioning regimen, patients receive a fixed dose of donor CD3+ cells (HSCT step one-DLI) as the lymphoid portion of the graft on day -6 with the aim of optimizing and controlling T cell dosing. Cyclophosphamide (CY) is administered after the DLI (days -3 and -2) to induce donor-recipient bidirectional tolerance. On day 0, a CD34-selected stem cell graft is given as the myeloid portion of the graft (step two). In this two-step approach, the stem cell graft is infused after CY tolerization, which avoids exposure of the stem cells to an alkylating agent, allowing rapid count recovery. Here, the two-step platform is described with a focus on key results from studies over the past two decades. Finally, this review details lessons learned and current strategies to optimize the graft-versus-tumor effect and limit transplant-related toxicities.

Keywords: cyclophosphamide tolerization; haploidentical; matched related; stem cell transplantation; two-step approach.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The two-step approach to allogenic HSCT. After conditioning the donor lymphocyte infusion containing 2x108 CD3 +cells/kg is infused (step 1) followed by 2 rest days and then 2 days of high-dose cyclophosphamide. Tacrolimus and MMF are initiated on day -1.CD34+ stem cells are then infused (step 2) followed by GM-CSF on day +1.
See this image and copyright information in PMC

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