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Validity of the Minnesota aGvHD risk score in predicting survival and response to therapy

May 6, 2022
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Learning objective: After reading this article, learners will be able to cite a new clinical development in acute GvHD.

The Minnesota acute graft-versus-host disease (aGvHD) risk score was developed to classify patients as standard- or high-risk of non-relapse mortality and response to therapy. The scoring system considers the number of organs involved and the severity of aGvHD at therapy onset, with standard-risk patients showing better outcomes.1

At the 48th Annual Meeting of the European Society for Bone and Marrow Transplantation (EBMT), Maria Teresa Lupo-Stanghellini1 presented a single-center study investigating the efficacy of this scoring system in the setting of posttransplant cyclophosphamide (PTCy). In this article we summarize the key results.

You can listen to a summary of the Minnesota risk score for GvHD in our interview with David Weisdorf here:

How do we stratify risk in patients with GvHD?

Methods

This prospective single-center study aimed to identify the accuracy of the Minnesota risk score in identifying patients at high-risk of aGvHD-associated mortality and response to steroid therapy. Inclusion criteria were:

  • allogeneic hematopoietic stem cell transplants performed at San Raffaele Hospital, IT;
  • recipients of PTCy-based GvHD prophylaxis for any disease indication;
  • any donor type;
  • and transplants performed between January 2016 and June 2020.

Results

Out of 315 eligible patients,  139 developed aGvHD, and their characteristics are summarized in Table 1.

Table 1. Characteristics of patients who developed aGvHD*

Characteristic, % (unless otherwise stated)

n = 139

Median follow-up (range), years

2.4 (1.43.5)

Median age (range), years

52.7 (15.375.6)

Sex

 

              Male

62.6

              Female

37.4

Diagnosis

 

              AML

50.4

              ALL

12.2

              NHL/HL

10.8

              MDS or MPN

23.7

              Other

2.9

Disease risk index

 

              Low-intermediate

55.4

              High

28.8

              Very high

5.8

Donor

 

              Mismatched related donor

48.2

              Matched related donor

12.9

              Matched unrelated donor

38.9

Conditioning

 

              MAC

70.5

              RIC

28.8

Graft source

 

              Bone marrow

5.8

              Peripheral blood

94.2

Minnesota risk

 

              High-risk

33.1

              Standard-risk

66.9

aGvHD, acute graft-versus-host disease; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; HL, Hodgkin lymphoma; MAC, myeloablative conditioning; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; NHL, non-Hodgkin lymphoma; RIC, reduced intensity conditioning.
*Adapted from Lupo-Stanghellini.1

Multivariate analysis of all patients indicated that:

  • the development of both Grades II–IV and III–IV aGvHD were impacted by donor source and donor age, with older donors associated with worse disease (Table 2);
  • and the development of aGvHD Grade III–IV was affected by donor source (Table 2).

Table 2. Multivariate analysis of factors associated with aGvHD incidence*

Characteristic

aGvHD Grade II–IV

aGvHD Grade III–IV

HR (95% CI)

p value

HR (95% CI)

p value

Donor source

 

0.01

 

0.003

              MRD vs MMRD

0.27 (0.130.57)

0.001

0.163 (0.050.55)

0.003

              MUD vs MMRD

0.54 (0.300.99)

0.047

0.45 (0.210.96)

0.039

Donor age

 

 

 

 

              >35 years vs ≤35 years

2.75 (1.594.76)

<0.001

aGvHD, acute graft-versus-host disease; CI, confidence interval; HR, hazard ratio; MMRD, mismatched related donor; MRD, matched related donor; MUD, matched unrelated donor.
*Adapted from Lupo-Stanghellini.1

Rates of 2-year overall survival and transplant-related mortality (TRM) stratified by Minnesota risk score revealed improved survival and lower TRM in patients with a standard risk score compared with those classified as high-risk (Figure 1).

Figure 1. The 2-year OS and TRM in Minnesota high- and standard-risk patients*

OS, overall survival; TRM, transplant-related mortality.
*Adapted from Lupo-Stanghellini.1

When stratifying by Day 28 overall response rate, improved response rates were seen in the standard-risk cohort compared with the high-risk cohort (Figure 2).

Figure 2. Day 28 ORR in patients classified as standard- and high-risk by Minnesota score*

ORR, overall response rate.
*Adapted from Lupo-Stanghellini.1

Conclusion

Results from this study validate the accuracy of using the Minnesota risk score as a tool for predicting Day 28 overall response rate, 2-year overall survival probability, and TRM in standard- and high-risk patients with aGvHD following PTCy. The authors suggested that this may be a better approach for identifying high-risk patients than using initial GvHD grade, allowing for more effective therapy.

  1. Maria Teresa Lupo-Stanghellini. Minnesota risk score defines survival at onset of aGvHD after PTCy prophylaxis. Oral abstract #OS10-07. 48th Annual Meeting of European Society for Bone and Marrow Transplantation. Mar 23, 2022; Virtual.

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