Acute GVHD Raises Risk of Transplant-Related Mortality in Certain Patients

By Cecilia Brown - Last Updated: September 28, 2022

Acute graft-versus-host disease (GVHD) may increase the risk of transplant-related mortality by sevenfold in certain patients. New research presented at the Tenth Annual Meeting of the Society of Hematologic Oncology (SOHO) showed acute GVHD of grade 3 or higher independently raised the risk of first-year transplant-related mortality in patients who developed cytokine release syndrome after haploidentical hematopoietic stem-cell transplantation (HSCT) with posttransplant cyclophosphamide.

Alberto Hernández-Sánchez, MBBS, of the Hospital Universitario de Salamanca and the Instituto de Investigación Biomédica de Salamanca in Spain, and colleagues conducted the research and presented their findings at the SOHO meeting.

“The use of posttransplant cyclophosphamide has favored haploidentical [HSCT] when a [human leukocyte antigen]-matched donor is not available or when an urgent transplant is needed,” Dr. Hernández-Sánchez and colleagues wrote. “Although a high percentage of patients receiving [posttransplant cyclophosphamide haploidentical] HSCT develop cytokine release syndrome after infusion, it only seems to affect prognosis in the reduced proportion of patients that develop severe [cytokine release syndrome]. Literature regarding the clinical impact of this complication is scarce.”

The researchers retrospectively analyzed 150 patients who underwent allogeneic haploidentical HSCT and received posttransplant cyclophosphamide at a single center.

Most patients developed cytokine release syndrome (86%). Researchers divided patients into groups, with one group comprised of patients who developed early-onset cytokine release syndrome 24 hours or less after infusion (50%), and the other group comprised of patients who developed late-onset cytokine release syndrome or did not have cytokine release syndrome.

Acute GVHD of grade 3 or higher was an independent prognostic factor for first-year transplant-related mortality (hazard ratio [HR], 6.89; P<.001), with the risk of transplant-related morality being nearly 7 times higher than in patients who did not develop acute GVHD of grade 3 or higher. Sinusoidal obstruction syndrome (HR, 9.24; P<.001) was also an independent prognostic factor for 1-year transplant-related mortality, as were early-onset cytokine release syndrome (HR, 3.09; P=.007) and older patient age at transplantation (HR, 1.05 per year increment; P=.002).

Patients with early-onset cytokine release syndrome had a significant increase in first-year transplant-related mortality (31%) compared with those who did not have early-onset cytokine release syndrome (15%; log-rank P=.014). Those with early-onset cytokine release syndrome also had a significantly lower first-year overall survival rate (60%) than those who did not (79%; log-rank P=.008).

A modified Baltimore haploidentical HSCT platform (HR, 7.54; P<.001), active disease at transplantation (HR, 2.94; P=.015), and increased infused CD3-postive cells (HR, 1.05 per 107/kg increment; P=.002) were all independent prognostic factors for developing early-onset cytokine release syndrome. Graft cryopreservation emerged as a “protective factor” (HR, 0.14; P=.005) against early-onset cytokine release syndrome, according to the researchers.

Based on the survival differences between patients who developed cytokine release syndrome within 24 hours after transplant and those who did not, the researchers proposed defining early-onset cytokine release syndrome as developing within 24 hours after haploidentical HSCT.

“However, this is a single-center retrospective study and further studies will be required in order to confirm these findings,” Dr. Hernández-Sánchez and colleagues concluded.

Hernández-Sánchez A, Cabero A, Fonseca M, et al. Cytokine release syndrome after peripheral blood haploidentical stem cell transplantation with post-transplant cyclophosphamide: time of onset matters. Poster CT-169. Presented at the Tenth Annual Meeting of the Society of Hematologic Oncology; September 28-October 1, 2022; Houston, TX.

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