Histocompatibility Testing for Clinical Bone Marrow Transplantation and Prospects for Identification of Donors Other than HLA Genotypically Identical Siblings

Dupont, Bo; O’Reilly, Richard; Pollack, Marilyn S.; Good, Robert A.

doi:10.1007/978-3-642-67319-1_12

Cited by 8 publications

(2 citation statements)

References 25 publications

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“…Following similar reports in children with severe combined immunodeficiency, 24 outcomes of 39 patients who received haploBMT between 1974–1979 using bone marrow from donors who were partially to fully phenotypically matched with the recipients in terms of the unshared haplotypes were published (Figure 1, Box 3). 25 Among 10 patients with aplastic anaemia, five had graft failure, four died of GVHD, and one died of infection.…”

Section: Early Studies Of Haplobmtmentioning

confidence: 97%

Modern approaches to HLA-haploidentical blood or marrow transplantation

2015

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Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately one-third of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival. Several novel approaches to HLA-haploidentical alloBMT have yielded encouraging results with high rates of successful engraftment, effective GVHD control and favourable outcomes. In fact, outcomes of several retrospective comparative studies seem similar to those seen using other allograft sources, including those of HLA-matched-sibling alloBMT. In this Review, we provide an overview of the three most-developed approaches to HLA-haploidentical alloBMT: T-cell depletion with ‘megadose’ CD34+ cells; granulocyte colony-stimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We review the preclinical and biological data supporting each approach, results from major clinical studies, and completed or ongoing clinical studies comparing these approaches with other alloBMT platforms.

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Section: Early Studies Of Haplobmtmentioning

confidence: 97%

Modern approaches to HLA-haploidentical blood or marrow transplantation

2015

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“…Bone marrow transplantation using matched sibling donors was developed as a therapeutic modality in 1968, in order to make possible the first successful treatment of SCID [74]. Studies of patients with SCID have also enabled the development of new approaches to cellular engineering that first used fetal liver transplants [75] and then matched relative donor marrow transplants [76], Finally, bone marrow transplan tation was successfully attempted using marrow purged of T lymphocytes and T precursors to permit parental haploidentical marrow transplantation [77,78], Each of these approaches has enabled full immunologic recon struction in some patients with SCID. Full immunologic restoration has protected these patients against the regu larly lethal bacterial, fungal, protozoal or viral infections that could have developed if these patients had not under gone immunologic reconstruction.…”

Section: Treatment Of the Immunodeficiency Diseasesmentioning

confidence: 99%

Introduction

Good¹

1986

Vox Sanguinis

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HLA Compatibility for patients with thalassemia: Implications for bone marrow transplantation

Delfini¹,

Donati²,

D³

et al. 1986

The International Journal of Cell Cloning

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In order to evaluate the possibility of a patient with thalassemia finding an HLA‐identical sibling donor, we performed an analysis of HLA antigens in families of thalassemic patients. The pattern distribution was not significantly different from the expected ratio 25:50:25. When the siblings were subdivided according to the age of the patients (under or over 5 years), the above pattern remained unmodified for both the age groups. The average size of the 129 thalassemic families was 2.4. Thus, taking into account that thalassemic patients have an average of 1.4 siblings and that the HLA genotype distribution is expected as such, HLA‐matched siblings are available for 33% of the patients. Because an additional 8.5 % of the patients were found HLA‐phenotypically identical to one parent, the chance for a patient with thalassemia to find a suitable donor for bone marrow transplantation would be increased to 41.5 %. Our preliminary data cannot be extrapolated to the overall Italian thalassemic population; however, it can be inferred that for a patient with thalassemia, the chance of finding a suitable donor for bone marrow transplantation is not reduced.

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Histocompatibility Testing for Clinical Bone Marrow Transplantation and Prospects for Identification of Donors Other than HLA Genotypically Identical Siblings

Cited by 8 publications

References 25 publications

Modern approaches to HLA-haploidentical blood or marrow transplantation

Modern approaches to HLA-haploidentical blood or marrow transplantation

Introduction

HLA Compatibility for patients with thalassemia: Implications for bone marrow transplantation

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