January 20, 2020
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Allogeneic HSCT survival outcomes show ‘striking improvement’

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George B. McDonald, MD
George B. McDonald

Patients who received allogeneic hematopoietic stem cell transplants between 2013 and 2017 demonstrated substantial improvement in survival outcomes and fewer complications than those who underwent transplantation a decade earlier, according to results of a retrospective study published in Annals of Internal Medicine.

“The most striking improvement was the continuing fall in the risk [for] nonrelapse mortality — that is, deaths that occurred from complications of the transplant procedure, unrelated to the blood cancers for which the transplants were being carried out,” George B. McDonald, MD, member emeritus at Fred Hutchinson Cancer Research Center and professor of gastroenterology at University of Washington, told Healio. “There were also reductions in the risk [for] recurrence or progression of the cancers. The sum of these reductions was improved OS over the last decade, despite a patient population that was older and sicker in the most recent cohort.”

Clinical outcomes of allogeneic HSCT have improved during the past 50 years as a result of declines in transplant-related complications. McDonald and colleagues sought to determine whether improvement in survival continued during the past decade and to identify barriers to better outcomes.

The researchers analyzed 1,148 patients (median age, 47.2 years; range, 0.4-78.9) who underwent their first allogeneic HSCT between 2003 and 2007 at Fred Hutch’s clinical care partner, Seattle Care Alliance, and 1,131 patients (median age, 50 years; range, 0.1-80.9) who received their first transplant between 2013 and 2017. They compared rates between the two cohorts of nonrelapse mortality before day 200 after transplant, cancer recurrence or progression, relapse-related mortality, and overall mortality adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen, patient and donor sex, and cytomegalovirus serostatus.

Results showed decreases in the adjusted hazards of day-200 nonrelapse mortality (HR = 0.66; 95% CI, 0.48-0.89), relapse of cancer (HR = 0.76; 95% CI, 0.61-0.94), relapse-related mortality (HR = 0.69; 95% CI, 0.54-0.87) and overall mortality (HR = 0.66; 95% CI, 0.56-0.78).

Patients who received allogeneic HSCT between 2013 and 2017 demonstrated substantial improvement in survival outcomes and fewer complications than those who underwent transplantation a decade earlier.

Researchers observed similar reductions in overall mortality among patients who received myeloablative vs. reduced-intensity conditioning, as well as among those whose allograft came from a matched sibling vs. an unrelated donor.

Jaundice, renal insufficiency, mechanical ventilation, high-level cytomegalovirus viremia, gram-negative bacteria, invasive mold infection, acute and chronic graft-versus-host disease and prednisone exposure all decreased in frequency between 2013 and 2017 compared with 2003 and 2007.

Frequency of grade 3 or grade 4 acute GVHD declined from 14% in the earlier cohort to 12% in the later cohort (adjusted HR = 0.63; 95% CI, 0.46-0.86), whereas frequency of chronic GVHD decreased by 60% (HR = 0.4; 95% CI, 0.33-0.48). These declines may be due in part to avoidance of the most toxic preparative regimens, according to the researchers.

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Improvements in outcomes may be the result of better patient selection, researchers acknowledged; however, they noted that the 2013-2017 cohort had several factors associated with increased risk for poor outcomes.

“Our approach to nonrelapse mortality from infection, organ failure and severe GVHD has always been guided by the principle ‘an ounce of prevention is worth a pound of cure,’” McDonald said. “The hazard of death associated with each of the morbid complications of transplant will be the focus of research by medical specialists in infectious disease, liver, kidney and pulmonary disease.

“Of interest are data showing that the major causes of nonrelapse mortality in the early days of transplantation have greatly decreased in frequency or disappeared altogether, for example, intestinal bleeding, cytomegalovirus disease, mold infections and liver disease,” he added. “Organ failure remains the most hazardous posttransplant complication — and an understanding of the pathobiology of liver, kidney and lung damage will be critical in designing preventive strategies.” – by John DeRosier

For more information:

George B. McDonald, MD, can be reached at gmcdonal@fredhutch.org.

Disclosures: McDonald reports consultant/advisory roles with Lucent Medical Systems and Soligenix Therapeutics and a data and safety monitoring role with Sangamo Therapeutics. Please see the study for all other authors’ relevant financial disclosures.