ABSTRACT
BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment. PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi. RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle. CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Nucleophosmin , Sulfonamides , Humans , Hematopoietic Stem Cell Transplantation/methods , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/mortality , Male , Female , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Middle Aged , Adult , Aged , Retrospective Studies , Young Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , RecurrenceABSTRACT
INTRO: The high rates of gun violence in the United States are a recognized public health concern with increased attention since the 1990's. The predominant studies used in gun violence research have been epidemiological approaches and quantitative analyses. This study, instead, examines lived experiences of gunshot wound survivors to better understand their situations. This study also compared the different census categories and their types of gunshot wound injuries. Ethnographic informed analyses may inform public health interventions to decrease firearm injuries. METHODS: Data was collected through a series of semi-structured interviews at the emergency department of an urban, Level-1, academic trauma center. 96 patients with gunshot wounds (GSWs) from 2018-2022 were included in the study. Thematic analysis was conducted after coding interview responses. RESULTS: There was a significant difference found between the 2 census categories (White and Minority populations). Those who self-identified as white had more self-inflicted GSWs (6) than other groups. Those who self-identified in the minority population had more GSWs as a result of an altercation (36) or as an innocent bystander (20). Interview data also demonstrated a trend in changing opinions about firearms in a group of participants with remote previous gunshot wounds (pGSW). When compared to the acute gunshot wound group (aGSW) the previous gunshot wound group (pGSW) responses showed support for increased gun safety and policies that limit firearm access. CONCLUSION: Different injury patterns between census groups demonstrates that multiple public health approaches will be needed to decrease firearm violence. Ethnographically informed approaches, including the support of people with previous GSW injuries, may help craft those interventions to reduce injury. Matched peer support programs represent one potential intervention to decrease secondary injury and firearm violence.