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. 2019 Dec 10;3(23):4034-4042.
doi: 10.1182/bloodadvances.2019000791.

V体育安卓版 - The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease

Hrishikesh K Srinagesh  1 , Umut Özbek  2 , Urvi Kapoor  1 , Francis Ayuk  3 , Mina Aziz  1 , Kaitlyn Ben-David  1 , Hannah K Choe  4 , Zachariah DeFilipp  5 , Aaron Etra  1 , Stephan A Grupp  6 , Matthew J Hartwell  1 , Elizabeth O Hexner  7 , William J Hogan  8 , Alexander B Karol  1 , Stelios Kasikis  1 , Carrie L Kitko  9 , Steven Kowalyk  1 , Jung-Yi Lin  2 , Hannah Major-Monfried  1 , Stephan Mielke  10   11 , Pietro Merli  12 , George Morales  1 , Rainer Ordemann  13 , Michael A Pulsipher  14 , Muna Qayed  15 , Pavan Reddy  16 , Ran Reshef  17 , Wolf Rösler  18 , Karamjeet S Sandhu  19 , Tal Schechter  20 , Jay Shah  1 , Keith Sigel  1 , Daniela Weber  21 , Matthias Wölfl  22 , Kitsada Wudhikarn  23 , Rachel Young  1 , John E Levine  1 , James L M Ferrara  1
Affiliations

The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease

"VSports" Hrishikesh K Srinagesh et al. Blood Adv. .

Abstract

The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD) VSports手机版. We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < . 0001) and nonresponders (65% vs 25%, P < . 0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0. 290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials. .

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Conflict of interest statement

Conflict-of-interest disclosure: U. M. , J. E. L. , and J. L. M. F. are coinventors on a GVHD biomarker patent V体育ios版. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Prediction of NRM by MAP and clinical responses after 4 weeks of systemic therapy for GVHD. (A) Cumulative incidence of NRM for patients according to clinical response to GVHD therapy (left) and no response (right) analyzed by high (red dash) or low (blue dash) MAP. (B) Crude proportion of 6-month NRM (± standard error) for each clinical GVHD grade after 4 weeks of treatment according to response (light green box) or no response (purple box) of clinical symptoms (left), or low (blue box) or high (red box) MAP (right).
Figure 2.
Figure 2.
Prediction of 6-month NRM during first month of GVHD therapy. AUCs of ROC curves (±95% CI) for MAPs (red circle), clinical responses (green circle), and a new algorithm combining biomarkers and clinical responses (blue circle) after 1, 2, and 4 weeks of treatment of GVHD. Patients with both clinical responses and biomarker values were included at each timepoint (week 1: n = 321; week 2: n = 323; week 4: n = 367). The difference between MAP and clinical responses alone was P < .0001 at all time points. The AUC of MAPs at week 1 (0.81) is significantly greater than that of clinical response at week 4 (0.70) (P = .0029).
Figure 3.
Figure 3.
Changes in MAP after 4 weeks according to initial Ann Arbor score. (A) Reverse waterfall plots of changes in MAP and (B) box-and-whisker plots of changes in MAP in consecutive patients who provided samples before and after 4 weeks of treatment according to initial Ann Arbor score in patients with (red line) and without (blue line) 6-month NRM. (Left) Ann Arbor 1 patients (MAP < .141 at treatment initiation). (Center) Ann Arbor 2 patients (0.141 ≤ MAP ≤ .290 at treatment initiation). (Right) Ann Arbor 3 patients (MAP > .290).
Figure 4.
Figure 4.
Long-term mortality by MAP threshold (0.290) after 4 weeks of treatment. (A) Crude proportions of 6-month nonrelapse mortality (± standard error) and (B) Kaplan-Meier estimates of overall survival according to Ann Arbor score for patients whose MAP after 4 weeks of treatment rose/remained above (red line) or fell/remained below (blue line) the threshold of 0.290. Ann Arbor scores were determined as in Figure 3.
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V体育ios版 - References

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