Shah et al. studied matched cohorts of patients 1 over 64 (N = 446) and the other patients aged 55-64 (n-1183) who had non-Hodgkin’s lymphoma.1 In a multivariant analysis, the 4-year probabilities of relapse or progression, progression free survival, and overall survival were only different in nonrelapse mortality with an increased mortality in the older group. There were no significant differences in the other measures. Their conclusion was that “Age alone should not determine allo-HCT eligibility in NHL.”
Muffly et al. reviewed the use of allo-HCT in patients 70 and over as reported to the transplant registry. They found that 1,106 patients ≥70 years underwent HCT across 103 transplant centers.2 The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < 0.001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = 0.003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = 0.54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = 0.006), umbilical cord blood graft (HR, 1.97; P = 0.0002), and myeloablative conditioning (HR, 1.61; P = 0.0002) as adverse factors.
They concluded that over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant. They also state that allo-HCT is not the only therapeutic option available to older patients with relapsed/refractory or high-risk NHL. The intent of our analysis is not to prove superiority of allo-HCT in older NHL patients relative to other available tools (e.g., novel agents, autologous HCT, gene-modified T-cell therapies). Rather, we aim to demonstrate that, in any given NHL patient 2:65 years old, if after consideration of multiple variables, the treating physician has decided that allo-HCT is the next best therapy, an arbitrary age cutoff and lack of third-party (e.g., CMS) reimbursement should not remain a barrier against transplantation. Our study utilizing a large contemporary dataset suggests that survival outcomes of such Medicare-age eligible patients are not dramatically inferior to a decade-younger patient cohort undergoing similar allo-HCT procedures.
Majhail et al. published the guidelines for autologous and allogeneic hematopoietic cell transplant from the American Society for Blood and Marrow Transplantation.3 The guidelines state that “age by itself should not be a contraindication to transplantation in patients who may benefit from this procedure. Selected older patients with limited comorbidities and good functional status can safely receive HCT with a relatively low and acceptable risk of non-relapse mortality. Instead of chronological patient age, evaluations such as functional status, HCT Comorbidity Index (HCT CI) score, EBMT risk score and Pre-transplantation Assessment of Mortality (PAM) risk score can assist in determining risks of non-relapse mortality and transplant candidacy for individual patients.” Included in this article is a table (table 3) listing the indicated diseases for allogenic transplant.
D’Souza et al. noted that “the number of both autologous and allogeneic transplants for treatment of malignant diseases in older patients continues to increase.”4 To illustrate this trend, between 1991 and 1997, 7% of allogeneic HCTs were performed in patients age ≥50 years; between 2000 and 2015, this percentage increased to 38%. In 2015, 25% of all allogeneic HCT recipients were age ≥60 years, up from 5% in 2000; 4.4% were age ≥70 years in 2015, compared with 0.4% in 2000.
Kanate et al. stated in the section on patient selection and treatment: With the addition of reduced intensity/nonmyeloablative conditioning and improved supportive care, the use of HCT to include older and more frail patients has indeed widened. Chronologic age by itself should no longer be a contraindication to transplantation in patients who may otherwise be eligible and benefit from this procedure. Carefully selected older patients can safely receive HCT with a relatively low and acceptable risk of nonrelapse mortality (NRM) [59-61]. Instead of patient age, evaluations such as functional status, patient frailty, HCT-specific comorbidity index score, European Society for Blood and Marrow Transplantation risk score, and pre-transplantation assessment of mortality risk score can assist in determining risks of NRM and transplant candidacy for individual patients. The ongoing Blood and Marrow Transplant Clinical Trials Network 1704 CHARM (Composite Health Assessment Model) study is prospectively evaluating pretransplant comorbidity, geriatric assessments, and biomarkers in older patients to predict post allograft NRM (NCT03992352).
This article includes a listing of the appropriate indications for allogeneic stem cell transplants, which includes multiple forms of both B and T cell lymphoma. In the comments for that listing they state, “Lymphoma: For Hodgkin lymphoma and high-grade B cell lymphoma, the subsection positron emission tomography positive complete remission was removed because updated response criteria for these lymphoma essentially require normalization of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography to be assessed as a first complete remission [20]. An additional subsection was added to incorporate double-/triple-hit, high-grade B cell lymphoma and primary central nervous system lymphoma. The subsection of anaplastic T- cell lymphoma was removed to be included with T cell lymphoma under pediatric indications. Follicular lymphoma patients with early treatment failure defined as relapse or progression of disease within 2 years of initial therapy undergoing autologous HCT have a low NRM (5%) with good OS (70%) at 5- years compared with historical control subjects (50%) [23,24]. Matched sibling donor HCT led to lower relapse rates but higher NRM and, ultimately, similar OS (73%). These data have been acknowledged under follicular lymphoma/first relapse, sensitive”.
