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Survivors of childhood leukemias and other serious hematologic diseases requiring allogeneic blood or marrow transplant (BMT) remained at elevated risk for death, even 25 years post-transplant, according to a retrospective cohort study.

An analysis of 1,388 cases where patients lived 2 years or longer following allogeneic BMT revealed a standardized mortality ratio of 14.4 versus the general population (95% CI 12.8-16.1), reported Smita Bhatia, MD, MPH, of the University of Alabama at Birmingham, and colleagues in .

At the 20-year mark following BMT, there were 295 deaths for an overall survival rate of 79.3%, the investigators found.

Compared with the general U.S. population, relative mortality was highest among patients 2 to 5 years following allogeneic BMT (standardized mortality ratio [SMR] 522.0, 95% CI 439.9-613.6). And while the rate then rapidly decreased, it remained significantly elevated 25 years or more following transplant (SMR 2.9, 95% CI 2.0-4.1).

"Allogeneic (related or unrelated donor) BMT is used with a curative intent for life-threatening malignant and non-malignant diseases of childhood," Bhatia told 番茄社区app in an email. "While there are several reports describing early outcomes (i.e., within the first 5 years), long-term risk of premature death is not known, nor do we know whether this risk has changed over the past 3 decades."

The cohort consisted of patients (median age at transplantation, 14.6 years) who had undergone allogeneic BMT between 1974 and 2010. Medical record data on their vital status and cause of death were gathered from the National Death Index Plus Program and Accurint databases.

The most common reasons for BMT were acute lymphoblastic leukemia (ALL, 25.1%) and acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS, 23.5%), followed by inborn errors of metabolism, severe aplastic anemia, Fanconi anemia, chronic myeloid leukemia (CML), immune disorders, sickle cell disease or thalassemia, and other malignant and nonmalignant diseases.

The 20-year survival rates were:

• 72.7% for ALL
• 81.1% for AML or MDS
• 76.1% for inborn errors of metabolism
• 91.0% for severe aplastic anemia
• 68.5% for Fanconi anemia
• 77.2% for CML
• 92.4% for immune disorders
• 82.3% for sickle cell anemia or thalassemia

The study results are "consistent" with what medical professionals often see clinically, Sogol Mostoufi-Moab, MD, MSCE, of Children's Hospital of Philadelphia in Pennsylvania, explained to 番茄社区app.

While clinicians generally care for patients from a risk perspective regardless of whether it's at the time of diagnosis or treatment, Mostoufi-Moab said, it is important to also address care from "a survivorship perspective."

"There are certain subgroups of patients that need to be highlighted which specifically deserve more medical focus and attention, and I think that's one of the highlights of this paper," she said. "In severe aplastic anemia, for example, there's subgroups within the indications for bone marrow transplantations where there has been improvement and/or patients were no longer experiencing the higher mortalities or some of the chronic complications."

Consistent with past studies looking at cause-specific late mortality after allogeneic BMT, Bhatia's group found that primary disease (24.6%), infection and/or chronic graft-versus-host disease (cGVHD, 49.6%), and subsequent malignant neoplasms (18.4%) were the most common causes of death. Deaths from cGVHD or infection occurred primarily in the first 2 to 9 years following transplant (79% for cGVHD, 78% for infection).

Improvements over time, however, were seen with regard to the 10-year cumulative incidence of late mortality (18.9% prior to 1990, 12.8% from 1990-1999, 10.9% from 2000-2010, P=0.002), and these improvements remained statistically significant even after adjusting for various factors.

In their conclusion, the study authors wrote that follow-up care following childhood allogeneic BMT needs to focus on "surveillance and early management of infections, cGVHD, and disease recurrence during the first decade after transplantation, as well as screening for early detection of subsequent malignant neoplasms and other complications throughout life."

Among the study's limitations were a lack of information on pretransplant treatments and the prospect of misclassification on death certificates. In an effort to address the latter, the investigators reviewed the causes of death recorded to look for possible misclassifications.

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