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Haploidentical BMT appears safe, effective for older patients with hematologic malignancies
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Nonmyeloablative HLA-haploidentical blood or marrow transplantation followed by cyclophosphamide demonstrated safety and promising survival outcomes for older patients with hematologic malignancies, according to the results of a retrospective analysis.
The results of the analysis support consideration of this approach in patients otherwise fit for allogeneic blood or marrow transplantation (BMT) despite advanced age, according to the researchers.
Yvette L. Kasamon
“Although allogeneic BMT is the only potentially curative approach for many patients with hematologic malignancies, the inability to identify a matched donor and the sometimes prohibitive delays with matched unrelated donor BMT have historically been major barriers,” Yvette L. Kasamon, MD, assistant professor of oncology and medicine at Johns Hopkins School of Medicine, and colleagues wrote. “In contrast, partially HLA-mismatched related, or HLA-haploidentical, donors can be promptly identified for most patients.”
Kasamon and colleagues sought to determine the effect of age on the appropriateness of nonmyeloablative (NMA), related HLA-haploidentical BMT, followed by high-dose cyclophosphamide after transplantation to reduce the risk for graft-versus-host disease (GVHD), graft failure and nonrelapse mortality.
The analysis included data from 271 consecutive patients (median age, 61 years; range, 50-75) with hematologic malignancies treated at Johns Hopkins University. Forty-eight percent of patients (n = 129) were aged between 60 and 69 years at time of BMT.
Eighty-four percent of patients (n = 227) had intermediate-risk or high-/very high-risk disease. Aggressive non-Hodgkin’s lymphoma (n = 83) and acute myeloid leukemia (n = 65) served as the most common diagnoses.
Median follow-up was 4 years (range, 0.02-10.2).
Overall, the population had a 3% 6-month probability for grade 3 or grade 4 GVHD and 8% 6-month probability of nonrelapse mortality.
Patients aged in their 60s (n = 129) had a 6-month nonrelapse mortality probability of 9%, whereas patients aged 50 to 59 years (n = 115) had a 6-month nonrelapse mortality probability of 8%, and patients aged 70 to 75 years (n = 27) had a 6-month nonrelapse mortality probability of 7%.
The 3-year PFS probabilities were 39% for patients aged 50 to 59 years, 35% for patients aged 60 to 69 years and 33% for patients aged 70 to 75 years.
Further, rates for 3-year OS probability were 48% for patients aged 50 to 59 years, 45% for patients aged 60 to 69 years and 44% for patients aged 70 to 75 years.
Patients with aggressive non-Hodgkin’s lymphoma had a 3-year PFS probability of 39% and patients with AML had a 3-year PFS probability of 40%. Patients with indolent or mantle-cell lymphoma (n = 65) had a 3-year PFS probability of 37%.
Patients aged 60 years or older faced a significantly higher risk for grade 2 to grade 4 acute GVHD (subdistribution HR = 1.67; 95% CI, 1.05-2.65). However, older patient age did not correspond with increased risk for grade 3 to grade 4 acute or chronic GVHD.
Older age did not appear significantly associated with nonrelapse mortality, relapse or survival.
The researchers acknowledged limitations of their study, including the retrospective, single-institution design and the potential for selection bias. Further, they noted that recently performed transplantations included in the study may not have accounted for time-related factors.
“Our institution no longer has an upper age limit for NMA haploidentical BMT with post-transplant cyclophosphamide,” Kasamon and colleagues wrote. “Strategies to treat and reduce disease relapse are intensively being studied.” – by Cameron Kelsall
Disclosure: Kasamon reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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