The two-step approach to allogeneic hematopoietic stem cell transplantation
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 d...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237782/full |
| _version_ | 1797729309809442816 |
|---|---|
| author | Sikemi Ibikunle Dolores Grosso Usama Gergis |
| author_facet | Sikemi Ibikunle Dolores Grosso Usama Gergis |
| author_sort | Sikemi Ibikunle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T11:27:20Z |
| format | Article |
| id | doaj.art-83ed31b3982843328292c4b6685a1505 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T11:27:20Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-83ed31b3982843328292c4b6685a15052023-09-01T07:09:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12377821237782The two-step approach to allogeneic hematopoietic stem cell transplantationSikemi IbikunleDolores GrossoUsama GergisAllogeneic 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237782/fulltwo-step approachhaploidenticalmatched relatedstem cell transplantationcyclophosphamide tolerization |
| spellingShingle | Sikemi Ibikunle Dolores Grosso Usama Gergis The two-step approach to allogeneic hematopoietic stem cell transplantation Frontiers in Immunology two-step approach haploidentical matched related stem cell transplantation cyclophosphamide tolerization |
| title | The two-step approach to allogeneic hematopoietic stem cell transplantation |
| title_full | The two-step approach to allogeneic hematopoietic stem cell transplantation |
| title_fullStr | The two-step approach to allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | The two-step approach to allogeneic hematopoietic stem cell transplantation |
| title_short | The two-step approach to allogeneic hematopoietic stem cell transplantation |
| title_sort | two step approach to allogeneic hematopoietic stem cell transplantation |
| topic | two-step approach haploidentical matched related stem cell transplantation cyclophosphamide tolerization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237782/full |
| work_keys_str_mv | AT sikemiibikunle thetwostepapproachtoallogeneichematopoieticstemcelltransplantation AT doloresgrosso thetwostepapproachtoallogeneichematopoieticstemcelltransplantation AT usamagergis thetwostepapproachtoallogeneichematopoieticstemcelltransplantation AT sikemiibikunle twostepapproachtoallogeneichematopoieticstemcelltransplantation AT doloresgrosso twostepapproachtoallogeneichematopoieticstemcelltransplantation AT usamagergis twostepapproachtoallogeneichematopoieticstemcelltransplantation |