Allogeneic hematopoietic cell transplant (HCT) remains the best option for a cure for many patients with hematologic malignancies, but is associated with significant morbidity and mortality, particularly for older patients. In the absence of a matched related or unrelated donor, a mismatched unrelated donor (MMUD) increases donor options, particularly for Black and Latinx patients. MMUD HCTs have historically been associated with an increased risk of severe acute graft-versus-host-disease (aGVHD), resulting in increased transplant related mortality (TRM) and decreased overall survival (OS) when compared with matched related or unrelated donor HCTs [1–4].
Abatacept, cytotoxic T-cell lymphocyte-4-immunoglobulin (CTLA4-Ig), is a T-cell co-stimulation blockade agent [5] that was granted FDA approval for the prevention of aGVHD in patients receiving unrelated donor HCT in part based on results of the Abatacept 2 trial (ABA2, NCT01743131). ABA2 was a multicenter phase II trial that evaluated abatacept in addition to standard GVHD prophylaxis with a calcineurin inhibitor and methotrexate (CNI/MTX) for GVHD prevention in 8/8 HLA-matched unrelated donor (MUD) HCT and 7/8 MMUD HCT. Patients in the 7/8 MMUD cohort were assigned to a single arm open label stratum compared to a prespecified Center for International Blood and Marrow Transplant Research (CIBMTR) cohort and demonstrated a significant reduction in grade 3–4 aGVHD compared with the CIBMTR cohort receiving CNI/MTX alone. The lower rates of grade 3–4 aGVHD translated into significant improvement in TRM and OS at 2 years for patients receiving abatacept [6].
The ABA2 trial enrolled patients 6–76 years of age in the 7/8 MMUD analysis, but outcomes were not reported separately for patients over 60 years of age. This age group is at increased risk of TRM [7, 8] that is further compounded by a MMUD HCT and the epidemiology of myeloid malignancies. Therefore, the goal of this analysis was to evaluate outcomes in patients 60 years and older undergoing MMUD HCT for hematologic malignancies.
More than 90% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients receive red blood cell (RBC) or platelet transfusions in the peritransplantation period. We tested the hypothesis that transfusions are associated with the development of severe (grade III-IV) acute graft-versus-host disease (aGVHD) or mortality after allo-HSCT in a retrospective study of 322 consecutive patients receiving an allogeneic bone marrow or granulocyte colony-stimulating factor-mobilized blood stem cell graft for a hematologic malignancy. Counting transfused RBC and platelet units between day −7 pretransplantation and day +27 post-transplantation, but excluding transfusions administered after a diagnosis of aGVHD, yielded medians of 5 RBC units and 2 platelet units transfused. Sixty-three patients (20%) developed a maximal grade III-IV aGVHD with onset up to day +150 post-transplantation (median aGVHD onset of 28 days). HLA mismatch (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.2 to 4.7; P =.01), and transfusion of more than the median number of RBC units (HR, 2.1; 95% CI, 1.1 to 3.7; P =.02) were independently associated with greater risk of grade III-IV aGVHD in a multivariable analysis model. Disease risk strata (HR, 1.7; 95% CI, 1.2 to 2.4 for high risk versus low risk; P =.005) and transfusion of more than the median number of RBC units (HR, 1.4; 95% CI, 1.0 to 2.0; P =.054) were independently associated with inferior overall survival. These data support our hypothesis that peritransplantation RBC transfusions are associated with the risk of developing severe aGVHD and worse overall survival following allo-HSCT, and suggest that strategies to reduce routine RBC transfusion may favorably reduce the incidence and severity of GVHD.
Background: Large linked databases (LLDB) represent a novel resource for cancer outcomes research. However, accurate means of identifying a patient population of interest within these LLDBs can be challenging. Our research group developed a fully integrated platform that provides a means of combining independent legacy databases into a single cancer-focused LLDB system. We compared the sensitivity and specifi city of several SQL-based query strategies for identifying a histologic lymphoma subtype in this LLDB to determine the most accurate legacy data source for identifying a specifi c cancer patient population.
Methods: Query strategies were developed to identify patients with follicular lymphoma from a LLDB of cancer registry data, electronic medical records (EMR), laboratory, administrative, pharmacy, and other clinical data. Queries were performed using common diagnostic codes (ICD-9), cancer registry histology codes (ICD-O), and text searches of EMRs. We reviewed medical records and pathology reports to confirm each diagnosis and calculated the sensitivity and specificity for each query strategy.
Results: Together the queries identified 1538 potential cases of follicular lymphoma. Review of pathology and other medical reports confirmed 415 cases of follicular lymphoma, 300 pathology-verifi ed and 115 verified from other medical reports. The query using ICD-O codes was highly specific (96%). Queries using text strings varied in sensitivity (range 7–92%) and specifi city (range 86–99%). Queries using ICD-9 codes were both less sensitive (34–44%) and specific (35–87%).
Conclusions: Queries of linked-cancer databases that include cancer registry data should utilize ICD-O codes or employ structured free-text searches to identify patient populations with a precise histologic diagnosis.
Fludarabine and melphalan (Flu/Mel) has emerged as a more tolerable chemotherapy-based conditioning regimen compared with busulfan and cyclophosphamide (Bu/Cy) for allogeneic stem cell transplant (allo-hematopoietic stem cell transplantation (HSCT)) patients with acute myelogenous leukemia (AML). We conducted a retrospective review of a single-institution database including patients with AML who received allo-HSCT following conditioning with Mel/Flu or Bu/Cy-based regimens. We performed descriptive statistical analysis to examine patient demographics and clinical outcomes. We identified 156 patients meeting criteria between 2005 and 2014. Overall, patients conditioned with Bu/Cy were significantly younger, but more likely to be treated in an earlier era than those receiving Flu/Mel. Regimen choice was not associated with relapse rates (RR), relapse-free survival (RFS), or overall survival (OS) on both univariate and multivariable analyses. Bu/Cy was associated with increased non-relapse mortality (NRM) on multivariable analysis. These findings demonstrate that Flu/Mel provides non-inferior disease control and could be an appropriate regimen for selected patients.