Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival.

Storb, Rainer; Prentice, Ross L.; Ed, Thomas

doi:10.1172/jci108680

Cited by 110 publications

(27 citation statements)

References 27 publications

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“…The same risk factors were found, although with an inferior statistical significance: higher patient age (Ͼ 42 years) (P ϭ .02), female patients (P ϭ .02), increased CD3 ϩ cell dose (P ϭ .04), and increased CD34 ϩ cell dose (P ϭ .1). Although the sex-mismatch combination most frequently associated with aGVHD in unmodified transplantations is male recipients from a female donor, 6,17,18 this finding has not been identified in either this or in other T-cell-depleted series.…”

Section: Resultsmentioning

confidence: 57%

“…Three groups of CD34 ϩ and CD3 ϩ cells were established (CD34 ϩ cells [ϫ 10 6 /kg]: Յ 2, Ͼ 2 to 4, Ͼ 4; CD3 ϩ cells [ϫ 10 6 /kg]: Յ 0.05, Ͼ 0.05 to 0.1, Ͼ 0.1) based on results showing that these cell doses influenced outcome in T-cell-depleted transplantations. [12][13][14][15][16][17] All prognostic variables in the cumulative incidence study with P Յ .2 were included in the stepwise proportional hazard Cox regression model (SPSS 9.0.1;1999). 16 The proportional hazard assumption was rejected for the covariate irradiation, which was included in the Cox model as a stratum.…”

Section: Methodsmentioning

confidence: 99%

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Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings

Urbano-Ispizúa¹,

Rozmán²,

Pimentel³

et al. 2002

Blood

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A study on 315 patients undergoing transplantation with CD34 ؉ selected blood cells from HLA-identical siblings was performed to determine risk factors for acute GVHD (aGVHD). Recipients of a dose of CD34 ؉ cells (؋ 10 6 /kg) of 2 or less, more than 2 to 4, and more than 4 had a cumulative incidence of aGVHD grades I-IV of 21%, 35%, and 43%, respectively (log-rank P ‫؍‬ .01); similarly, recipients of a dose of CD3 ؉ cells (؋ 10 6 /kg) of 0.05 or less, more than 0.05 to 0.1, and more than 0.1 had a cumulative incidence of aGVHD grades I-IV of 18%, 35%, and 44%, respectively (log-rank P ‫؍‬ .007). Using a Cox regression model, 4 independent factors for aGVHD I-IV were identified: increased CD34 ؉ cell dose (P ‫؍‬ .02), increased CD3 ؉ cell dose (P ‫؍‬ .02), female patients (P ‫؍‬ .01), and higher patient age (> 42 years IntroductionAcute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic stem cell transplantation. 1,2 Although widely accepted risk factors for aGVHD have been identified in patients receiving unmodified grafts, 3-6 these parameters may not have the same predictive value in patients receiving a graft in which donor T cells, the major determinant of GVHD, have been depleted. The isolation of risk factors for aGVHD in T-cell-depleted transplantations could be useful to identify individual patients at a high probability of developing this complication. The present study was directed at identifying factors predictive of aGVHD in 315 adult patients receiving an HLAidentical sibling transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells T-cell depleted by means of CD34 ϩ selection (allo-PBT/CD34 ϩ ). We observed a strong association between the incidence of aGVHD and 2 controllable variables: the number of CD34 ϩ and CD3 ϩ cells infused. Study designThis study included 315 consecutive adult patients with hematologic malignancies treated with an allo-PBT/CD34 ϩ from an HLA-identical sibling donor between March 1995 and December 2000. Granulocyte colony-stimulating factor administration and leukapheresis procedures have been previously described. 7 This study was approved by local ethic committees and by the Spanish Department of Health. Informed consent was provided according to the Declaration of Helsinki. Patient and donor characteristics are shown in Table 1. CD34 ϩ cells and CD3 ϩ cells were quantified as previously published. 7 There was no correlation between CD34 ϩ and CD3 ϩ cell dose (Pearson correlation coefficient Ϫ0.04; P ϭ .47). Phase of disease, time to engraftment, diagnosis of graft failure, and transplantation-related mortality (TRM) have been previously defined. 8 The diagnosis and grading of aGVHD was established according to the Seattle criteria. 9 Probabilities of aGVHD were calculated by the cumulative incidence method (marginal probability) and statistically compared by Gray method. 10,11 In this study, graft failure or relapse, without aGVHD, were considered competing risks. Characteristics consi...

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Section: Resultsmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings

Urbano-Ispizúa¹,

Rozmán²,

Pimentel³

et al. 2002

Blood

View full text Add to dashboard Cite

show abstract

“…Although this approach has led to a shift in the clinical paradigm stressing the necessity of HLA antibody detection and the performance of pretransplant cross-matches, the realization in clinical practice has not yet been accomplished. This has in part been due to the lack of highly sensitive diagnostic tools, although already in 1977 Storb and coworkers [40] have recognized a higher prevalence of HSCT graft rejection in pretransplant transfused patients with acquired platelet refractoriness. In contrast to solid-organ transplantations where HLA antibody monitoring posttransplant provides essential information for graft rejection, in HSCT current data suggest that HLA antibody detection of de novo DSA is restricted to the increased risk of graft failure.…”

Section: Hla Antibodies and Hematopoietic Stem Cell Transplantationmentioning

confidence: 99%

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion<sup>*</sup>

Lachmann

Todorova

Schulze

et al. 2013

Transfus Med Hemother

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The detection of antibodies against the human leukocyte antigen (HLA) complex has become indispensable in every clinical practice. The development of solid-phase assays like the Luminex allows the standardized measurement of anti-HLA antibodies (HLAab) with high sensitivity, albeit the relevance for some clinical settings remains a matter of debate. In this review we aim to describe the principle of Luminex-based antibody detection, including two modifications that allow identifying solely complement-activating antibodies. We then describe three applications for Luminex: i) detection of HLAab preceding solid-organ transplantation and monitoring of donor-specific antibodies posttransplant as a risk factor for antibody-mediated rejection; ii) presence of HLAab in recipients as a risk for graft failure in hematopoietic stem cell transplantation, especially in haploidentical or mismatched transplantations; iii) role of HLAab in blood transfusion including refractory thrombocytopenia and selection of suitable platelet donors, transfusion-related lung injury after plasma transfusion, and immunization against HLA after red blood cell transfusion despite leukodepletion. Although the Luminex platform constitutes a potent technology for HLA antibody detection, some drawbacks require the well-educated analysis and interpretation of data in critical cases. In addition, Luminex has become an important tool to identify clinically relevant antibodies.

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“…Landmark papers published in the JCI have presented elucidation of the pathophysiology of human diseases such as diabetic ketoacidosis (1) and Addison disease (2), development of radioimmunoassays for medically important peptides including ACTH and somatomedin B (3, 4), fundamental advances in understanding steroid metabolism and its role in prostatic hypertrophy and human sexuality (5-7), seminal findings linking cholesterol to heart disease (8-10), and key advances in organ transplant biology (11,12), to mention but a small sampling (Figure 1). In this context, the overriding mission of the new JCI editors is to continue publishing important and timely biomedical research of broad interest and relevance to normal biology and diseases.…”

Section: A Mission Statement For the Jci At The Dawn Of The 21st Centurymentioning

confidence: 99%

A mission statement for the JCI at the dawn of the 21st century

Marks¹

2002

J. Clin. Invest.

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Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival.

Cited by 110 publications

References 27 publications

Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings

Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings

Luminex® and Its Applications for Solid Organ Transplantation, Hematopoietic Stem Cell Transplantation, and Transfusion<sup>*</sup>

A mission statement for the JCI at the dawn of the 21st century

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