Circulating Angiogenic Factors Associated with Response and Survival in Patients with Acute Graft-versus-Host Disease: Results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802

IntroductionPaediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children’s health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies.Methods and analysisWe will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer—other, cancer—skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.

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CD56 bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft- versus -host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results

Haematologica ◽

10.3324/haematol.2017.170928 ◽

2017 ◽

Vol 102 (11) ◽

pp. 1936-1946 ◽

Cited By ~ 8

Author(s):

Amina Kariminia ◽

Sabine Ivison ◽

Bernard Ng ◽

Jacob Rozmus ◽

Susanna Sung ◽

...

Keyword(s):

Natural Killer ◽

Graft Versus Host Disease ◽

Marrow Transplant ◽

Regulatory Cells ◽

Donor Blood ◽

Host Disease ◽

Graft Versus Host ◽

Blood And Marrow Transplant ◽

Study Results

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Endpoints for Clinical Trials Testing Treatment of Acute Graft-versus-Host Disease: A Joint Statement

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2009.03.012 ◽

2009 ◽

Vol 15 (7) ◽

pp. 777-784 ◽

Cited By ~ 45

Author(s):

Paul J. Martin ◽

Carlos R. Bachier ◽

Hans-Georg Klingemann ◽

Philip L. McCarthy ◽

Paul Szabolcs ◽

...

Keyword(s):

Clinical Trials ◽

Graft Versus Host Disease ◽

Host Disease ◽

Graft Versus Host ◽

Joint Statement ◽

Acute Graft

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Tools for the Precision Medicine Era: How to Develop Highly Personalized Treatment Recommendations From Cohort and Registry Data Using Q-Learning

American Journal of Epidemiology ◽

10.1093/aje/kwx027 ◽

2017 ◽

Vol 186 (2) ◽

pp. 160-172 ◽

Cited By ~ 10

Author(s):

Elizabeth F Krakow ◽

Michael Hemmer ◽

Tao Wang ◽

Brent Logan ◽

Mukta Arora ◽

...

Keyword(s):

Graft Versus Host Disease ◽

Controlled Trial ◽

Treatment Strategies ◽

Marrow Transplant ◽

Host Disease ◽

Q Learning ◽

Graft Versus Host ◽

Adaptive Treatment ◽

Blood And Marrow Transplant ◽

Multiple Assignment

Abstract Q-learning is a method of reinforcement learning that employs backwards stagewise estimation to identify sequences of actions that maximize some long-term reward. The method can be applied to sequential multiple-assignment randomized trials to develop personalized adaptive treatment strategies (ATSs)—longitudinal practice guidelines highly tailored to time-varying attributes of individual patients. Sometimes, the basis for choosing which ATSs to include in a sequential multiple-assignment randomized trial (or randomized controlled trial) may be inadequate. Nonrandomized data sources may inform the initial design of ATSs, which could later be prospectively validated. In this paper, we illustrate challenges involved in using nonrandomized data for this purpose with a case study from the Center for International Blood and Marrow Transplant Research registry (1995–2007) aimed at 1) determining whether the sequence of therapeutic classes used in graft-versus-host disease prophylaxis and in refractory graft-versus-host disease is associated with improved survival and 2) identifying donor and patient factors with which to guide individualized immunosuppressant selections over time. We discuss how to communicate the potential benefit derived from following an ATS at the population and subgroup levels and how to evaluate its robustness to modeling assumptions. This worked example may serve as a model for developing ATSs from registries and cohorts in oncology and other fields requiring sequential treatment decisions.

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