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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multi-state models have proved versatile and useful in the statistical analysis of the complicated course of events after bone marrow transplantation. Working from data from the International Bone Marrow Transplant Registry, we show that summary probability calculations may be useful to explore hypothetical scenarios where some transition intensities are set by the researcher. A multi-state Markov process model is specified with six states: the initial state 0; acute; chronic and both acute and chronic graft-versus-host disease A, C and AC; relapse R and death in remission D. Transition rates between the states are estimated using Nelson-Aalen estimators and Cox regression models and combined to transition probability estimators using Aalen-Johansen product integration. Besides the estimated transition probabilities to D and R we explore hypothetical probabilities obtained by artificially changing certain transition intensities, with the general purposes of getting summary views of the development for actual patients 'in this world' and of exploring the intrinsic information from real patients about consequences of various changed conditions.
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PMID:Multi-state models and outcome prediction in bone marrow transplantation. 1140 47

We propose nonparametric estimators of the stage occupation probabilities and transition hazards for a multistage system that is not necessarily Markovian, using data that are subject to dependent right censoring. We assume that the hazard of being censored at a given instant depends on a possibly time-dependent covariate process as opposed to assuming a fixed censoring hazard (independent censoring). The estimator of the integrated transition hazard matrix has a Nelson-Aalen form where each of the counting processes counting the number of transitions between states and the risk sets for leaving each stage have an IPCW (inverse probability of censoring weighted) form. We estimate these weights using Aalen's linear hazard model. Finally, the stage occupation probabilities are obtained from the estimated integrated transition hazard matrix via product integration. Consistency of these estimators under the general paradigm of non-Markov models is established and asymptotic variance formulas are provided. Simulation results show satisfactory performance of these estimators. An analysis of data on graft-versus-host disease for bone marrow transplant patients is used as an illustration.
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PMID:Estimation of integrated transition hazards and stage occupation probabilities for non-Markov systems under dependent censoring. 1249 33

After allogeneic stem cell transplantation, the establishment of the donor's immune system in an antigenically distinct recipient confers a therapeutic graft-versus-malignancy effect, but also causes graft-versus-host disease (GVHD) and protracted immune dysfunction. In the last decade, a molecular-level description of alloimmune interactions and the process of immune recovery leading to tolerance has emerged. Here, new developments in understanding alloresponses, genetic factors that modify them, and strategies to control immune reconstitution are described. In Section I, Dr. John Barrett and colleagues describe the cellular and molecular basis of the alloresponse and the mechanisms underlying the three major outcomes of engraftment, GVHD and the graft-versus-leukemia (GVL) effect. Increasing knowledge of leukemia-restricted antigens suggests ways to separate GVHD and GVL. Recent findings highlight a central role of hematopoietic-derived antigen-presenting cells in the initiation of GVHD and distinct properties of natural killer (NK) cell alloreactivity in engraftment and GVL that are of therapeutic importance. Finally, a detailed map of cellular immune recovery post-transplant is emerging which highlights the importance of post-thymic lymphocytes in determining outcome in the critical first few months following stem cell transplantation. Factors that modify immune reconstitution include immunosuppression, GVHD, the cytokine milieu and poorly-defined homeostatic mechanisms which encourage irregular T cell expansions driven by immunodominant T cell-antigen interactions. In Section II, Prof. Anne Dickinson and colleagues describe genetic polymorphisms outside the human leukocyte antigen (HLA) system that determine the nature of immune reconstitution after allogeneic stem cell transplantation (SCT) and thereby affect transplant outcomethrough GVHD, GVL, and transplant-related mortality. Polymorphisms in cytokine gene promotors and other less characterized genes affect the cytokine milieu of the recipient and the immune reactivity of the donor. Some cytokine gene polymorphisms are significantly associated with transplant outcome. Other non-HLA genes strongly affecting alloresponses code for minor histocompatibility antigens (mHA). Differences between donor and recipient mHA cause GVHD or GVL reactions or graft rejection. Both cytokine gene polymorphisms (CGP) and mHA differences resulting on donor-recipient incompatibilities can be jointly assessed in the skin explant assay as a functional way to select the most suitable donor or the best transplant approach for the recipient. In Section III, Dr. Nelson Chao describes non-pharmaceutical techniques to control immune reconstitution post-transplant. T cells stimulated by host alloantigens can be distinguished from resting T cells by the expression of a variety of activation markers (IL-2 receptor, FAS, CD69, CD71) and by an increased photosensitivity to rhodamine dyes. These differences form the basis for eliminating GVHD-reactive T cells in vitro while conserving GVL and anti-viral immunity. Other attempts to control immune reactions post-transplant include the insertion of suicide genes into the transplanted T cells for effective termination of GVHD reactions, the removal of CD62 ligand expressing cells, and the modulation of T cell reactivity by favoring Th2, Tc2 lymphocyte subset expansion. These technologies could eliminate GVHD while preserving T cell responses to leukemia and reactivating viruses.
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PMID:New developments in allotransplant immunology. 1463 90