An injectable bone marrow–like scaffold enhances T cell immunity after hematopoietic stem cell transplantation

The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor is that almost every patient who does not have a HLA-identical donor or who urgently needs hematopoietic stem cell transplantation (HSCT) has at least one family member with whom shares one haplotype (haploidentical) and who is promptly available as a donor. The major challenge of haplo-HSCT is intense bi-directional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft processing and in pharmacologic prophylaxis of GVHD have reduced these risks and have made haplo-HSCT a viable alternative for patients lacking a matched donor. Indeed, the haplo-HSCT has spread to centers worldwide even though some centers have preferred an approach based on T cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs), others have focused on new strategies for GvHD prevention, such as G-CSF priming of bone marrow and robust post-transplant immune suppression or post-transplant cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted PBPCs or standard dose of unmanipulated bone marrow and/or PBPCs. Although haplo-HSCT modalities are based mainly on high intensity conditioning regimens, recently introduced reduced intensity regimens (RIC) showed promise in decreasing early transplant-related mortality (TRM), and extending the opportunity of HSCT to an elderly population with more comorbidities. Infections are still mostly responsible for toxicity and non-relapse mortality due to prolonged immunosuppression related, or not, to GVHD. Future challenges lie in determining the safest preparative conditioning regimen, minimizing GvHD and promoting rapid and more robust immune reconstitution.

Download Full-text

Haploidentical Hematopoietic Stem Cell Transplantation in Children Leukemia and Lymphoma with G-CSF Mobilized Marrow Grafts without T Cell Depletion: A Single Center Report of 45 Cases.

Blood ◽

10.1182/blood.v112.11.3282.3282 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3282-3282

Author(s):

HengXiang Wang ◽

Hong-Min Yan ◽

Lian-Ning Duan ◽

Ling Zhu ◽

Mei Xue ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

T Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Platelet Recovery ◽

Hematopoietic Malignancies

Abstract Haploidentical hematopoietic stem cell transplantation (Haplo-SCT) has been increasingly used in the treatment of patients with hematopoietic malignancies without immediate HLA-matched donors. Here, we describe a protocol for the management of hematopoietic malignances in children and adolescents who received T cell replete G-CSF-mobilized bone marrow grafts from HLA-mismatched parents. The donors were administered G-CSF for 7 consecutive days before marrow grafts containing a medium nucleated cells of 8.1×108/kg (range: 6.1–11.5×108/kg) were collected. 45 patients were pre-conditioned with high-doses of cytarabine and cyclophosphamide plus total body irradiation or BU for chronic myeloid leukemia patients. The regimen for acute graft versus host disease (aGvHD) prophylaxis included antithymocyte globulin, monoclonal antibody against CD25 (Simulect), CsA, MTX and mycophenolate mofetil. Three of forty-five patients died of engraftment failure, multiple organ failure and TTP, others achieved complete donor chimerism with the medium days for neutrophil (>0.5′109/L) and platelet recovery (>20′109/L) were 17(12–23 days) and 19(12–27days). Of the 42 evaluable patients, 3 cases developed grade III/IV aGvHD, and 9 of 32 cases who survived longer than 3 months developed chronic GvHD. Twenty-one patients died within a medium follow-up of 36 months(24–63 months), including 2 of transplantation related death, 11 of leukemia relapse, 4 of CMV and fungal infections, and 2 of aGvHD and 2 cases died of other reasons. The disease-free survival rate was 53%. Multivariate analysis demonstrated that the overall survival was not significantly reduced in refractory leukemia and seemed not associated with the mismatch numbers of HLA loci. These results indicate that T cell replete SCT with mobilized bone marrow from HLA-2 or -3-antigen mismatched parents could be an optional strategy for children with hematopoietic malignancies who lack immediate access to a HLA-matched stem cell source.

Download Full-text