Late mortality among allogeneic bone marrow transplant (BMT) recipients has decreased over the past 40 years, but only among those who received a BMT under the age of 18 years as well as among those who received a bone marrow transplant as opposed to a peripheral blood stem cell (PBSC) transplant, a retrospective cohort study has shown.
In a study involving 4741 patients who survived 2 or more years after undergoing a BMT, all-cause mortality dropped by 33% between the reference era of 1974 to 1989 and 1990 to 2004 at a hazard ratio (HR) of 0.67 (95% CI, 0.53-0.85), Smita Bhatia, MD, MPH, University of Alabama at Birmingham, Alabama, and colleagues reported in JAMA Oncology.
By 2005 to 2014, late mortality had declined by 48% at a HR of 0.52 (95% CI 0.39-0.69; P<0.001), again relative to the earliest era, investigators added.
However, BMT recipients were still at a 8.8-fold (95% CI, 8.4-9.3-fold) higher risk for all-cause mortality with a relative 8.7 years reduction in life expectancy compared with the general population.
At 30-years, 57.8% of BMT recipients were still alive.
“The data showed an improvement in outcomes over 4 decades of allogeneic transplantation among individuals who underwent transplantation at a young age and those who received bone marrow,” Bhatia and colleagues noted.
“[But t]here is [still] a need to address the causes of late mortality among the older BMT recipients as well as those who receive PBSCs to improve outcomes,” the authors concluded.
The Blood or Marrow Transplant Survivor Study is a cohort study designed to examine the long-term outcome of patients who survive 2 or more years after undergoing a BMT.
The transplants were done between January 1974 and December 2014 at the City of Hope, University of Minnesota, and the University of Alabama at Birmingham.
Time periods from 1974-1989; 1990-2002, and 2005-2014 were used to examine mortality trends over time.
“Relative mortality was highest in the 2-to 5-year period post-BMT,” the authors noted, at a standardized mortality ratio (SMR) of 34.3 (95% CI, 31.7-36.9).
After this time period, all-cause mortality decreased but remained significantly higher at 30 years post-BMT compared to the general population at a SMR of 5.4 (95% CI, 4.0-7.1), they added.
Risk factors associated with 10-year, all-cause late mortality included:
- Older age (18-45) at the time of BMT: HR: 1.42 (95% CI, 1.14-1.76) compared with patients under the age of 18
- Over the age of 45 at the time of BMT: HR: 2.37 (95% CI, 1.87-3.01) compared with patients under the age of 18
- Male sex: HR 1.24 (95% CI, 1.09-1.42)
- High-risk disease (HR: 1.44 (95% CI, 1.24-1.67)
- Use of PBSC as the stem cell source: HR: 1.30 (95% CI, 1.07-1.58) compared with bone marrow
- History of chronic graft-versus-host-disease (GVHD): HR: 2.11 (95% CI, 1.80-2.49)
As the authors pointed out, the median age on BMT receipt increased across the 3 eras from 19.5 years for those transplanted in the earliest era to a median of 43 years for those transplanted during the latest era.
So, too, did the proportion of patients receiving an unrelated BMT, which increased from 4.8% during the earliest era to 55.7% during the latest era as did the proportion of patients receiving a BMT for high-risk disease, which increased from 17.9% for those undergoing BMT during the earliest era to 33.6% for those receiving a BMT in the last era analyzed.
However, the decrease in late mortality by transplant era was only statistically significant among patients who received a BMT under the age of 18 years, dropping by 38% (95% CI, 0.40-0.96) by 1990-2004 (P<0.001) and by 70% (95% CI, 0.16-0.54) by 2005-2014 compared to the reference era of 1974-1989.
Similarly, the decline in late mortality by transplant era was again only significant among patients who received a bone marrow transplant, not a PBSC or cord blood transplants, dropping by 30% (95% CI, 0.54-0.90) by 1990-2004 and by 55% (95% CI, 0.29-0.69) by 2005 -2014 compared with 1974-1989 (P<0.001).
The 30-year cumulative incidence for recurrence-related mortality was also substantially lower at only 12.2% (95% CI, 11%-13.4%) compared with non-recurrence-related (NRM) mortality which at 30 years was 22.3% (95% CI, 20.4%-24.3%).The leading causes of NRM included infection; subsequent malignant neoplasms; cardiovascular disease, and pulmonary disease.
Commenting on the findings, Lohith Gowda, MD and Stuart Seroplan, MD, both from Yale University School of Medicine, New Haven Connecticut, pointed out that the risk of recurrence-related mortality appeared to plateau at 10 years. In contrast, the risk of NRM continued to increase with time.
Furthermore, “a decrease in late mortality was significant for infections and secondary neoplasms but not for cardiovascular or pulmonary disease,” the editorialists wrote.
“This finding should be underscored, given that the years of life at risk following a high-risk procedure, such as allografting, are highest in younger patients,” Gowda and Seroplan emphasized.
As to how findings from this study should inform the transplant and medical community at large, the editorialists suggested that the fact that relapse-related mortality may take 10 years to plateau is “notable”.
“The concept of using pre-emptive maintenance drugs posttransplant is gaining traction and future research should be tailored to address high-risk patient populations and optimal timelines to adopt such approaches,” they wrote.
Another finding of note was the association between the use of PBSCs with NRM independent of the presence of chronic GVHD.
The high incidence of late pulmonary-related NRM suggest that some patients may have unrecognized chronic pulmonary GVHD or related immune lung injury—although this finding will probably not change physician preferences for graft sources before transplantation, the editorialists noted.
The main limitation of the study includes the usual caveats regarding retrospective studies but that limitation does not detract from its conclusions.
“Transplantation gives patients a new lease on life…[and p]atients take a leap of faith when they select transplantation, hoping for long-term survival,” Gowda and Seroplan wrote. “Patients are obviously in it for the long haul [and] findings from this…study…tell us the transplant community must be in it for the long haul as well.”
Late mortality among allogeneic BMT recipients has decreased over the past 40 years but only among patients who received a BMT at a young age as well as those who received a bone marrow transplant and not those who received a peripheral blood stem cell or cord blood transplant.
The risk of recurrence-related mortality appeared to plateau at 10 years whereas the risk of non-recurrence-related mortality largely continued to increase over time especially from cardiovascular and pulmonary disease.
Pam Harrison, Contributing Writer, BreakingMED™
The work was supported in part by grants from the National Cancer Institute and the Leukemia and Lymphoma Society.
Bhatia had no conflicts of interest to declare.
The editorialists had no conflicts of interest to declare.
Cat ID: 118
Topic ID: 78,118,730,118,935,192,925
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