aGvHD

Response to MSC treatment at one week predicts probability of survival in patients with acute graft-versus-host disease

Previous studies have shown that mesenchymal stromal cells (MSCs) may be a possible novel strategy for the treatment of steroid-resistant acute graft-versus-host disease (SR aGvHD). Despite these encouraging findings, clinicians are faced with the difficult task of choosing which patients will be either sensitive or resistant to therapy. In order to establish criteria for the use of MSCs, a study was conducted to analyze a cohort of SR aGvHD patients receiving MSCs in several centers in the United Kingdom. This retrospective study, published in the January edition of British Journal of Haematology, conducted by Antonio Galleu from King’s College, London, UK, and colleagues, used MSCs manufactured at Imperial College Healthcare NHS Trust and administered for compassionate use.

Patients and characteristics
  • N = 60 patients with aGvHD were included in the analysis
  • Patients received bone-marrow derived MSCs between May 2008 and December 2014
  • aGvHD was defined as steroid-refractory if patients failed to respond to ≥ 2 mg/kg methylprednisolone
Key findings
  • Median time from transplantation to MSC treatment: 62 days (range, 12–929)
  • Median time from diagnosis of GvHD to MSC treatment: 60 days (range, 11–905)
  • Median dose of MSCs: 2.6 x 106/kg per infusion
  • Thirty-two patients (53%) responded to therapy
    • CR: 1 patient
    • PR: 31 patients
  • Median overall survival: 104 days (95% CI, 0–215)
  • Overall survival of responders was significantly improved in comparison with non-responders, P < 0.0001
  • Median survival in responders and non-responders: not reached vs 20 days (95% CI 11–29 days)
  • Factors associated with responses:
    • Organ involvement
    • Age at transplantation
    • Dose of MSCs infused
  • Patients receiving MSC doses > 3 x 106/kg achieved higher response rates

In summary, this analysis showed that clinical responses at week 1 following MSC treatment may be a feasible early predictor of clinical outcome. Dr Galleu added that this data strengthened “the role of MSC recipient rather than the one of MSC donor or source in prediciting clinical responses.”

Reference
  1. Galleu A. et al. Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival. Br J Haematol. 2019 Jan 13. DOI: 10.1111/bjh.15749. [Epub ahead of print].

Expert Opinion

The use of Mesenchymal Stromal Cells holds great potentials to treat GvHD. So far more than 800 GvHD patients have been treated with MSCs with more than 1000 doses administered. Based on this experience, we can conclude that MSCs are safe and well tolerated, with no or minimal adverse reactions. Furthermore, despite the potent immunosuppressive activity, MSC use does not lead to an increase in both infection severity or frequency, or number of relapses in MSC treated patients.

Outcomes of patients treated with MSCs are encouraging but highly variable in the different studies reported in the literature, with response rates ranging from 33% to almost 100% in few studies. Importantly, OS higher than 50% at 2 years has been consistently reported in patients who responded to MSCs.

The results reported in our paper confirm that the achievement of any kind of response significantly prolong the OS of the patients, despite the very poor prognosis of the cohort treated. Importantly, the assessment of the response at one week after MSC treatment can be used as early predictor of treatment failure. Younger age, absence of liver involvement and higher MSC doses were associated with better response rates. If confirmed in controlled prospective studies, these data will guide to a better patient stratification and improvement of the administration regimen of MSCs in GvHD.

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