Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML.

Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes for acute myeloid leukemia (AML) patients. We evaluated 8709 AML patients from the CIBMTR database and, after selection and manual curation of cytogenetics data, 3779 patients in CR1 were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis compared to intermediate-risk patients detected an increased risk of relapse for KMT2A-rearranged and adverse-risk patients (HR 1.27, p = 0.01 and HR 1.71, p < 0.001, respectively). Leukemia-free survival (LFS) was similar for KMT2A and adverse-risk patients (HR 1.26, p = 0.002 and HR 1.47, p < 0.001), as was overall survival (OS) (HR 1.32, p < 0.001 and HR 1.45, p < 0.001). No differences in outcome could be detected when patients were stratified by KMT2A fusion partner. This is the largest study conducted to date on post-HCT outcomes in AML using manually curated cytogenetics for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A rearrangements and adverse-risk disease

Transplant Physicians’ Attitudes on Candidacy for Allogeneic Hematopoietic Cell Transplantation (HCT) in Older Patients: The Need for a Standardized Geriatric Assessment (GA) Tool

Background Despite improvements in conditioning regimens and supportive care having expanded the curative potential of HCT, underutilization of HCT in older adults persists (Bhatt VR et al, BMT 2017). Therefore, we conducted a survey of transplant physicians (TP) to determine their perceptions of the impact of older age (≥60 years) on HCT candidacy and utilization of tools to gauge candidacy. Methods We conducted a 23-item, online cross-sectional survey of adult physicians recruited from the Center for International Blood and Marrow Transplant Research between May and July 2019. Results 175/770 (22.7%) TP completed the survey; majority of respondents were 41-60 years old, male, and practicing in a teaching hospital. Over 75% were at centers performing ≥50 HCT per year. When considering regimen intensity, most (96%, n=168) had an upper age limit (UAL) for using a myeloablative regimen (MAC), with only 29 physicians (17%) stating they would consider MAC for patients ≥70 years. In contrast, when considering a reduced intensity/non-myeloablative conditioning (RIC/NMA), 8%, (n=13), 54% (n=93), and 20% (n=35) stated that age 70, 75, and 80 years respectively would be the UAL to use this approach, with 18% (n=31) reporting no UAL. TP agreed that Karnofsky Performance Score (KPS) could exclude older pts for HCT, with 39.1% (n=66), 42.6% (n=72), and 11.4% (n=20) requiring KPS of ≥70, 80, and 90, respectively. The majority (n=92, 52.5%) indicated an HCT-comorbidity index threshold for exclusion, mostly ranging from ≥3 to ≥ 5. Almost all (89.7%) endorsed the need for a better health assessment of pre-HCT vulnerabilities to guide candidacy for pts ≥60 with varied assessments being utilized beyond KPS (Figure 1). However, the majority of centers rarely (33.1%) or never (45.7%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 yrs. The largest barriers to performing GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff (Figure 2). Approximately half (n=78, 45%) endorsed GA now routinely influences candidacy. Conclusions The vast majority of TP will consider RIC/NMA alloHCT for patients ≥70 years. However, there is heterogeneity in assessing candidacy. Incorporation of GA into a standardized and easily applied health assessment tool for risk stratification is an unmet need. The recently opened BMT CTN 1704 may aid in addressing this gap

Impact of Second Primary Malignancy Post–Autologous Transplantation on Outcomes of Multiple Myeloma: A CIBMTR Analysis

The overall survival (OS) has improved significantly in multiple myeloma (MM) over the last decade with the use of proteasome inhibitor and immunomodulatory drug-based combinations, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) and subsequent maintenance therapies in eligible newly diagnosed patients. However, clinical trials using auto-HSCT followed by lenalidomide maintenance have shown an increased risk of second primary malignancies (SPM), including second hematological malignancies (SHM). We evaluated the impact of SPM and SHM on progression-free survival (PFS) and OS in patients with MM after auto-HSCT using CIBMTR registry data. Adult patients with MM who underwent first auto-HSCT in the United States with melphalan conditioning regimen from 2011 to 2018 and received maintenance therapy were included (n = 3948). At a median follow-up of 37 months, 175 (4%) patients developed SPM, including 112 (64%) solid, 36 (20%) myeloid, 24 (14%) SHM, not otherwise specified, and 3 (2%) lymphoid malignancies. Multivariate analysis demonstrated that SPM and SHM were associated with an inferior PFS (hazard ratio [HR] 2.62, P \u3c .001 and HR 5.01, P \u3c .001, respectively) and OS (HR 3.85, P \u3c .001 and HR 8.13, P \u3c .001, respectively). In patients who developed SPM and SHM, MM remained the most frequent primary cause of death (42% vs 30% and 53% vs 18%, respectively). We conclude the development of SPM and SHM leads to a poor survival in patients with MM and is an important survivorship challenge. Given the median survival for MM continues to improve, continued vigilance is needed to assess the risks of SPM and SHM with maintenance therapy post-auto-HSCT

Predictive Value of PET-CT in Patients with T-Cell Lymphoma Undergoing Autologous and Allogeneic Stem Cell Transplant

T-NHL are associated with an aggressive clinical course and poor outcomes. The role of PET-CT at the time of SCT (pre-SCT), BM biopsy, and peripheral blood (PB) flow cytometry have not been well investigated. We retrospectively analyzed 83 pts with T-NHL undergoing auto or allo SCT to determine the predictive value of pre-SCT PET-CT scan, BM and PB flow for relapse-free survival (RFS) and OS. PET CR was defined as the absence of any radiographic dz by PET-CT (5-pt score). Overall CR was defined as negative PET, BM and PB flow. Pre-SCT variables were assessed for their effects on RFS and OS: age, number of previous lines of therapy, CIBMTR dz risk, pre-SCT BM, pre-SCT PB flow, and pre-SCT PET-CT. Of 83 pts studied, 49 were autoSCT and 34 were alloSCT. Six pts who underwent alloSCT had received a prior autoSCT. Diagnosis was PTCL NOS 34, AITL 23, CTCL/Sezary syndrome 11, nasal NK-T 6, EATL 3, SPTCL 2, hepatosplenic 1, ALK-ALCL 1, HTLV-2 ATL 1, T-lymphoblastic 1. The majority of pts with AITL (16/23) underwent autoSCT upfront. Conditioning for autoSCT was BEAM. Conditioning for alloSCT was Pentostatin/TBI in all but 6 SCT. Median lines of therapy prior to SCT were 1 for auto and 4 (r 2-13) for alloSCT. Median age at SCT was 60 (r 20-75). A total of 6 out of 49 (12%) autoSCT and 8 out of 34 (24%) alloSCT had positive PET-CT (score 4-5) at the time of SCT. BM was positive in 8 out of 49 (16%) at the time of autoSCT and 7 out of 34 (21%) at the time of alloSCT. PB flow was positive in 9 out of 49 (18%) at the time of auto SCT and 6 out of 34 (12%) at the time of alloSCT. CIBMTR dz index was low in 57(69%), intermediate in 15(18%), and high in 11 (13%) of 83 SCT. The majority of allo-SCT were intermediate-high risk. The median follow-up 56 months (r 6 - 122). Twenty (24%) pts had expired. Univariate analysis of pre-autoSCT variables did not reveal statistically significant (SS) results for BM or PET positivity. Univariate analysis of pre-alloSCT variables identified positive BM and positive PET/CT scan as being SS. There was a SS lower incidence of relapse, longer RFS and OS in alloSCT pts with either negative pre-SCT PET-CT scan or negative pre-SCT BM. Other pre-SCT variables tested were not SS. In multivariate analysis, pre-alloSCT PET-CT alone retained SS. Pre-alloSCT PET-CT scan was a strong predictor of 2-yr RFS and 2-yr OS. This data indicates that in heavily pretreated pts with T- NHL undergoing alloSCT, a negative pre-SCT PET-CT is a statistically significant predictor of long-term RFS and OS regardless of dz risk and number of lines of therapy. Due to the small number of autoSCT with positive PET-CT scans, BM biopsy, or PB flow at the time of SCT, no association between the above-mentioned variables and relapse was identified. Further studies with larger numbers of pts are warranted to determine the role of pre-autoSCT PET-CT, BM and PB flow as prognostic factors in T-NHL

HLA-DP mismatch and CMV reactivation increase risk of aGVHD independently in recipients of allogeneic stem cell transplant.

HLA-DP mismatched allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with increased risk of aGVHD and decreased risk of relapse with no effects on overall survival (OS). It has been proposed that CMV-reactivation induces expression of HLA-DP molecules on GVHD target tissues by releasing inflammatory cytokines. We hypothesized that the increased GVHD incidence in HLA-DP mismatched allo-SCTs correlates with recipient CMV serostatus or CMV reactivation. In addition, CMV reactivation is associated with increased risk of GVHD with an unknown mechanism. Here, we analyzed the association between HLA-DPB1 and CMV reactivation on cumulative incidence of aGVHD and relapse as well as OS in 613 patients with AML and MDS who underwent matched related or unrelated allo-HCT at MD Anderson Cancer Center from 2005 to 2011. In multivariable analysis, HLA-DPB1 mismatching was associated with increased risk of aGVHD (hazard ratio (HR): 1.53, P &lt; 0.001) independent of CMV serostatus and CMV reactivation. Additionally, HLA-DPB1 mismatching was associated with decreased risk of relapse and no effect on OS. CMV reactivation increased risks of aGVHD (HR: 5.82, P &lt; 0.001) independent of HLA-DP mismatching with no effect on relapse or OS. In conclusion, our data suggests that HLA-DPB1 mismatching and CMV reactivation increase risk of aGVHD independently