Female marrow donors increase the risk of acute graft‐versus‐host disease: effect of donor age and parity and analysis of cell subpopulations in the donor marrow inoculum

Atkinson, K; Farrell, C.; Chapman, Graeme; Downs, K; Penny, Ronald; Biggs, J. C.

doi:10.1111/j.1365-2141.1986.tb05545.x

Cited by 85 publications

(26 citation statements)

References 15 publications

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“…[1][2][3][4] Older donor age has been shown to be associated with poorer outcome of CI-HSCT through a combination of higher treatment-related mortality (TRM) and relapse. [5][6][7][8] However, it is not known if donor age affects the outcome of RI-HSCT.…”

Section: Introductionmentioning

confidence: 99%

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Mehta

Tallman

et al. 2006

Bone Marrow Transplant

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Sixty three patients aged 27-66 years (median 52) were allografted from HLA-matched sibling (n ¼ 47), 10 of 10 allele-matched unrelated (n ¼ 19), or one-antigen/allelemismatched (n ¼ 7) donors aged 24-69 years (median 46) after a conditioning regimen comprising 100 mg/m 2 melphalan. Cyclophosphamide (50 mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and diseasefree survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age 445 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age 445 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age 445 years. Our data suggest that younger donor age is associated with better outcome after submyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.

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Section: Introductionmentioning

confidence: 99%

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Mehta

Tallman

et al. 2006

Bone Marrow Transplant

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“…This was unexpected since previous studies have shown that a female donor to a male recipient resulted in worse outcomes due to a higher incidence of GVHD. 27 However, female sex has been identified as a favorable risk factor for long-term survival after treatment for AML. 28 We also found that a donor graft derived from PBSCs predicted a worse outcome than a graft derived from BM.…”

Section: Discussionmentioning

confidence: 99%

Elevated lactate dehydrogenase is an adverse predictor of outcome in HLA-matched sibling bone marrow transplant for acute myelogenous leukemia

Kalaycio

Rybicki

Pohlman

et al. 2007

Bone Marrow Transplant

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Prognostic factors for survival following allogeneic BMT for AML include age, disease status and cytogenetic risk classification. Lactate dehydrogenase (LDH) levels have not been studied as a potential risk factor. We reviewed our experience with BMT for AML and included LDH at the time of admission in an analysis of prognostic factors for survival. We found that LDH 4330 U/l (1.5 times the upper limit of normal at our institution), older age, active disease, peripheral stem cell graft and male-to-male transplant were significant adverse predictors of survival. After accounting for LDH, other factors such as disease status and cytogenetics were not significantly associated with the outcome of BMT. All but one patient with an LDH 4330 U/l had active disease. However, when patients in CR were excluded, LDH 4330 U/l remained a significant adverse predictor of overall survival (hazard ratio 2.70, 95% confidence interval 1.41-5.16, P ¼ 0.003). We conclude that LDH is an important adverse risk factor for survival and should be included in future studies of risk performed on larger patient cohorts.

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“…6,7 These responses must in general be well tolerated but HY immunization may also have harmful effects as indicated in SCT. [37][38][39][40] In late pregnancy, apoptotic syncytiotrophoblast debris is normally shed in large quantities (several grams per day) from the placenta, 41 and after being processed, peptides derived from HLA, HY and other minor HY antigens are presented to CD4 + and CD8 + T lymphocytes 42 in local lymph nodes. This presentation usually takes place under non-inflammatory conditions; resulting in T lymphocytes being tolerized against fetally derived peptides.…”

Section: Discussionmentioning

confidence: 99%

Anti‐HY Responses in Pregnancy Disorders

Christiansen¹,

Steffensen²,

Nielsen³

2011

American J Rep Immunol

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Problem Cellular and humoral immune responses against male-specific minor histocompatibility (HY) antigens are important in the pathogenesis of graft-versus-host reactions and can be detected in women who have previously given birth to a boy. However, the importance of these responses for pregnancy outcome is unclear. Method of study Review of the current knowledge about the impact of anti-HY immunity on pregnancy outcome in terms of risk of miscarriage, placental abrup-tion and low birth weight. Results Women with secondary recurrent miscarriage (RM) more often have given birth to a boy compared with a girl prior to a series of miscarriages (P < 0.0001) and a firstborn boy seems significantly to reduce the chance of a subsequent live in these patients (P = 0.0003). Human leu-kocyte antigen (HLA) class II alleles known to restrict CD4 T-cell-mediated anti-HY responses were investigated among 358 patients with secondary RM and 203 of their children born prior to the miscarriages. The chance of a subsequent live birth in secondary RM patients with firstborn boys compared with firstborn girls was significantly lower in women with HY-restricting HLA class II alleles [OR: 0.17 (0.1-0.4), P = 0.0001]. In patients without these alleles, the chance of live birth was similar in those with firstborn boys and girls, respectively. In early pregnancy, both antibodies against HLA and HY antigens were found with increased prevalence in secondary patients with RM and in particular in those with a firstborn boy compared with controls (P = 0.005). The presence of these antibodies was associated with a low subsequent live birth rate, and the presence of HY antibodies was associated with a low male ⁄ female ratio (12% boys versus 88% girls) in subsequent live births (P = 0.03). Register-based population studies suggested that births of boys also are associated with subsequent adverse obstetric outcomes also in the background population. Conclusion Findings strongly indicate that aberrant maternal immune reactions against fetal HY antigens playing a role in secondary RM and other pregnancy complications. We propose pathogenetic pathways for these conditions that in our view best explain the findings.

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Female marrow donors increase the risk of acute graft‐versus‐host disease: effect of donor age and parity and analysis of cell subpopulations in the donor marrow inoculum

Cited by 85 publications

References 15 publications

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Elevated lactate dehydrogenase is an adverse predictor of outcome in HLA-matched sibling bone marrow transplant for acute myelogenous leukemia

Anti‐HY Responses in Pregnancy Disorders

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