Alternative Donor Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Kanakry, Christopher G.; Lima, Marcos J.G. de; Luznik, Leo

doi:10.1053/j.seminhematol.2015.03.005

Cited by 17 publications

(17 citation statements)

References 81 publications

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“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). 1 However, a human leukocyte antigen (HLA)-identical sibling 2 , 3 is available in only 25–35% of the patients. 4 For patients lacking a full matched sibling donor (MSD), other stem cell sources are available such as unrelated donors, 5 umbilical cord blood units, 6 or HLA-mismatched family donors (Haplo).…”

Section: Introductionmentioning

confidence: 99%

Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

et al. 2018

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Allogeneic hematopoietic stem cell transplantation is the optimal care for patients with high-risk or intermediate - acute myeloid leukemia. In patients lacking matched sibling donor, haploidentical donors are an option. We compared outcomes of unmanipulated (Haplo) to matched sibling donor transplant in acute myeloid leukemia patients in first complete remission. Included were intermediate and high-risk acute myeloid leukemia in first complete remission undergoing Haplo and matched sibling donor transplant from 2007–2015, and reported to the ALWP of the EBMT. A propensity score technique was used to confirm results of main analysis: 2 matched sibling donors were matched with 1 Haplo. We identified 2654 pts (Haplo =185; matched sibling donor =2469), 2010 with intermediate acute myeloid leukemia (Haplo=122; matched sibling donor =1888) and 644 with high-risk acute myeloid leukemia (Haplo =63; matched sibling donor =581). Median follow up was 30 (range 1–116) months. In multivariate analysis, in intermediate - acute myeloid leukemia patients, Haplo resulted in lower leukemia-free survival (Hazard Ratio 1.74; P<0.01), overall-survival (HR 1.80; P<0.01) and GvHD-free-relapse-free survival (Hazard Ratio 1.32; P<0.05) and higher graft-versus-host disease (GvHD) non-relapse mortality (Hazard Ratio 3.03; P<0.01) as compared to matched sibling donor. In high-risk acute myeloid leukemia, no differences were found in leukemia-free survival, overall-survival, and GvHD-free- relapse-free survival according to donor type. Higher grade II-IV acute GvHD was observed for Haplo in both high-risk (Hazard Ratio 2.20; P<0.01) and intermediate risk (Hazard Ratio 1.84; P<0.01). A trend for a lower Relapse-Incidence was observed in Haplo among high-risk acute myeloid leukemia (Hazard Ratio 0.56; P=0.06). The propensity score analysis confirmed results. Our results underline that matched sibling donor is the first choice for acute myeloid leukemia patients in first complete remission. On the other hand, results of Haplo transplants are similar to matched sibling donor transplants in acute myeloid leukemia patients with high risk cytogenetics.

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Section: Introductionmentioning

confidence: 99%

Outcomes of hematopoietic stem cell transplantation from unmanipulated haploidentical versus matched sibling donor in patients with acute myeloid leukemia in first complete remission with intermediate or high-risk cytogenetics: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

et al. 2018

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“…The major challenge of HLA-haploidentical HSCT is the intense bidirectional alloreactivity leading to high incidences of graft rejection and graft-versus-host disease (GVHD). Advances in graft techniques and in pharmacologic prophylaxis of GVHD have reduced the risks of graft failure and GVHD after HLA-haploidentical HSCT and have made this stem cell source a viable alternative for patients lacking an HLA-matched donor [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Review on Haploidentical Hematopoietic Cell Transplantation in Patients with Hematologic Malignancies

Ramanathan

2016

Advances in Hematology

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Allogenic hematopoietic cell transplantation (HSCT) is typically the preferred curative therapy for adult patients with acute myeloid leukemia, but its use has been reduced as a consequence of limited donor availability in the form of either matched-related donors (MRD) or matched-unrelated donors (MUD). Alternative options such as unrelated umbilical cord blood (UCB) transplantation and haploidentical HSCT have been increasingly studied in the past few decades to overcome these obstacles. A human leukocyte antigen- (HLA-) haploidentical donor is a recipient's relative who shares an exact haplotype with the recipient but is mismatched for HLA genes on the unshared haplotype. These dissimilarities pose several challenges to the outcomes of the patient receiving such a type of HSCT, including higher rates of bidirectional alloreactivity and graft failure. In the past 5 years, however, several nonrandomized studies have shown promising results in terms of graft success and decreased rates of alloreactivity, in part due to newer grafting techniques and graft-versus-host disease (GVHD) prophylaxis. We present here a summary and review of the latest results of these studies as well as a brief discussion on the advantages and challenges of haploidentical HSCT.

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“…These include suitable volunteer HLA-matched-unrelated donors (HLA-MUD), one-locus HLA-mismatched-unrelated donors (HLA-mmUD), HLA-haploidentical donors (HLAhaplo) (half matched donor, typically a parent or other relative), or umbilical cord blood (UCB) units [6][7][8].…”

Section: Transplantation As a Therapeutic Approachmentioning

confidence: 99%

“…Other important prognostic impact factors are age, sex, cytomegalovirus (CMV) serostatus, and natural-killer (NK) cells allo-reactivity [6].…”

Section: Transplantation As a Therapeutic Approachmentioning

confidence: 99%

Future Perspectives in HLA Typing Technologies

Giannopoulos¹,

Kriebardis²

2017

Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

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A wide range of malignant and nonmalignant diseases require hematopoietic stem cell transplantation (HSCT) as last resort therapeutic approach. Graft versus host disease (GVHD), which is one of the major causes of transplant-related mortality, is minimized whenever increased matching of human leukocyte antigens (HLAs) between donor and recipient is present. Suitable donor selection is determined with the utilization of HLA typing. HLAs are highly polymorphic glycoproteins encoded by a region of genes known as the major histocompatibility complex (MHC). Their biological function is to present antigenic peptides to T lymphocytes. However, they also play important role in HSCT acceptance/rejection. During the previous years, various techniques have been acquired in order to better characterize the HLA profile of transplant donors and recipients. This effort is particularly challenging due to MHC size, but most importantly due to high sequence variability in specific regions of the respective genetic loci, between individuals. Initially, HLA typing was performed using serological typing, hybridization techniques, and restriction fragment length polymorphism (RFLP) approaches. Later on, polymerase chain reaction (PCR) based techniques and direct sequencing (dideoxy-based Sanger sequencing) capillary electrophoretic analyses arose. Nowadays, 2nd and 3rd generation sequencing (NGS) technologies show great potential in effectively identifying these polymorphic regions.

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Alternative Donor Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia

Cited by 17 publications

References 81 publications

Review on Haploidentical Hematopoietic Cell Transplantation in Patients with Hematologic Malignancies

Future Perspectives in HLA Typing Technologies

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