番茄社区

Outcomes have improved over the last quarter-century for patients undergoing allogeneic hematopoietic cell transplantation for treating their cancer, a single-center cohort study indicated.

Reported in the , an adjusted analysis revealed that patients who had a transplant from 2013-2017 had a 34% lower risk of dying within 200 days after transplantation from a cause unrelated to disease relapse compared with patients who had a transplant from 2003-2007 (HR 0.66, 95% CI 0.48-0.89).

These patients from the later era also had an adjusted lower risk of disease relapse (HR 0.76, 95% CI 0.61-0.94), dying from relapse (HR 0.69, 95% CI 0.54-0.87), and dying from any cause (HR 0.66, 95% CI 0.56-0.78), according to George McDonald, MD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

The improvement in overall mortality was seen regardless of whether patients had myeloablative conditioning therapy versus reduced-intensity conditioning therapy or whether the transplant was from a matched sibling or unrelated donor.

"This is good news," Ryotaro Nakamura, MD, co-director of the Center for Stem Cell Transplantation at City of Hope in Duarte, California, told 番茄社区. Nakamura, who was not involved in the research, said the study shows at least "some progress" but the outcomes are still "far from perfect."

The results of the cohort study are based on data from 1,148 patients who had their first transplant from 2003-2007 and 1,131 patients who had their first transplant from 2013-2017, all of whom were treated at Seattle Cancer Care Alliance. Most patients had acute lymphocytic leukemia, acute myeloid leukemia, or myelodysplastic syndrome.

Although the results are from a single institution, Nakamura believes they are "largely applicable to the field in general."

These latest data show a trend in improved outcomes over not just the past 10 years, but 25. Previously, the study researchers showed in a 2010 study that 30% of patients who had a transplant from 1993-1997 died within 200 days after transplantation. The incidence has declined to 16% for patients from the 2003-2007 era and 11% for patients from the 2013-2017 era.

In addition, rate of relapse and overall mortality also improved over the three time periods, but the greatest improvement was seen for the rate of non-relapse mortality within 200 days. Relapse-related mortality was not assessed in the previous study for the 1993-1997 era.

Although the current cohort study cannot identify what caused the improvement in outcomes, "we can speculate about what changes in our transplant practices have contributed to better outcomes," McDonald told 番茄社区.

For starters, the risk of infection through 100 days after transplant was lower for patients treated from 2013-2017 compared with 2003-2007. These later-era patients had a lower risk of invasive mold infection (HR 0.55, 95% CI 0.33-0.92) and gram-negative bacteremia (HR 0.42, 95% CI 0.29-0.60).

Also, while the risk of any cytomegalovirus (CMV) infection did not decrease for later-era patients (HR 1.15, 95% CI 0.88-1.52), the risk of having a higher CMV viremia did. Specifically, the risk of CMV infection of more than 250 IU/mL (HR 0.78, 95% CI 0.55-1.10) or more than 1,000 IU/mL (HR 0.46, 95% CI 0.28-0.74) declined.

McDonald said that the lower frequency of serious infection may be due to the emergence of molecular methods of diagnosis and newer treatments. Also, the practice of treating graft-vs-host disease (GVHD) has changed.

Patients from the 2013-2017 era received lower initial doses of prednisone on average to treat GVHD (mean 0.58 vs 0.83 mg/kg, P<0.001) as well as had a lower total prednisone exposure (mean 0.08 vs 0.05, P<0.001). These reductions in prednisone allowed patients to avoid "many" of the side effects of prednisone, including loss of muscle mass, diabetes, and hypertension, explained McDonald.

In addition, the odds of a grade 3/4 GVHD event was lower among later-era patients compared with earlier-era patients (OR 0.63, 95% CI 0.46-0.86), as was the odds of chronic GVHD (OR 0.40, 95% CI 0.33-0.48).

Patients from the 2013-2017 period also had less frequent acute kidney injury, respiratory failure, and liver dysfunction during the first 100 days after transplant.

"The gradual shift from very high-dose conditioning therapy to less intense myeloablative therapy and to reduced-intensity conditioning was likely responsible for a reduction in damage to the liver, lungs, and kidneys over the last 10 years," McDonald said.

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