Hetty E. Carraway
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View article: Genomics of Acute Myeloid Leukemia at Diagnosis and Remission
Genomics of Acute Myeloid Leukemia at Diagnosis and Remission Open
Accurate and comprehensive genetic characterization of acute myeloid leukemia (AML) is essential for diagnosis, prognostication, and treatment selection. We report here, in 255 adults with AML enrolled in a prospective clinical protocol at…
View article: Clone wars: Evidence of clonal stability in a longitudinal prospective cohort of cancer survivors with serial NGS analysis
Clone wars: Evidence of clonal stability in a longitudinal prospective cohort of cancer survivors with serial NGS analysis Open
Introduction: Hematopoietic stem and progenitor cells with preleukemic mutations (mutns), collectively termed clonal hematopoiesis (CHIP) serve as the cellular origin of myeloid neoplasms (MN). While risk of MN development varies, its natu…
View article: Ivosidenib leads to durable responses in IDH1 mutated clonal cytopenias of undetermined significance: A phase II decentralized clinical trial
Ivosidenib leads to durable responses in IDH1 mutated clonal cytopenias of undetermined significance: A phase II decentralized clinical trial Open
BACKGROUND Ivosidenib is an oral inhibitor of mutant isocitrate dehydrogenase type I (IDH1) currently approved for the treatment of IDH1 mutated acute myeloid leukemia and myelodysplastic syndrome (MDS). Hematopoietic stem and progenitor c…
View article: IDH1/2-mutant clonal hematopoiesis: A novel driver of autoinflammatory disease
IDH1/2-mutant clonal hematopoiesis: A novel driver of autoinflammatory disease Open
Somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis) are known to alter the immune milieu and can result in autoimmune disorders including VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) synd…
View article: Risk of therapy-related acute lymphoblastic leukemia (t-ALL) in cancer patients secondary to either chemotherapy, radiation, or both: A retrospective cohort study from 1975-2021 using SEER registry
Risk of therapy-related acute lymphoblastic leukemia (t-ALL) in cancer patients secondary to either chemotherapy, radiation, or both: A retrospective cohort study from 1975-2021 using SEER registry Open
Background: The incidence of therapy-related leukemias is exponentially increasing with the widespread use of chemotherapy (CTX) and radiation (RT). Therapy-related Acute Lymphoblastic Leukemia (t-ALL) is a separate entity from de novo ALL…
View article: Spliceosome mutations in AML: Prevalence, clinical features, and treatment outcomes in a contemporary cohort
Spliceosome mutations in AML: Prevalence, clinical features, and treatment outcomes in a contemporary cohort Open
Background Spliceosomes are intranuclear proteins that splice pre-mRNA into mature mRNA. Somatic mutations in genes encoding spliceosome components are found in acute myeloid leukemia (AML) and can occur in SRSF2, U2AF1, SF3B1, ZRSR2, and,…
View article: ANKRD26-related thrombocytopenia: Hematologic malignancy characteristics, clinical outcomes, and precursor states
ANKRD26-related thrombocytopenia: Hematologic malignancy characteristics, clinical outcomes, and precursor states Open
Introduction Heterozygous germline pathogenic variants (PVs) in the 5' untranslated region of ANKRD26 cause inherited thrombocytopenia and predisposition to hematologic malignancy (HM). The estimated lifetime HM risk is ~10% based on famil…
View article: Impact of cohesin complex gene mutations on clinical outcomes in Acute Myeloid Leukemia
Impact of cohesin complex gene mutations on clinical outcomes in Acute Myeloid Leukemia Open
Background: The cohesin complex is a tetramer that plays a key role in chromatin interactions, DNA loop formations, and regulation of gene transcription. Cohesin subunit mutations occur in epigenetic regulator genes SMC1A, SMC3, RAD21, & S…
View article: A phase II study of eltrombopag in patients with low-risk MDS and CMML harboring TET2 mutations
A phase II study of eltrombopag in patients with low-risk MDS and CMML harboring TET2 mutations Open
Study Rationale. TET2 is one of the most commonly mutated genes in clonal hematopoiesis and myeloid malignancies, including low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Loss-of-function mutations in …
View article: Comparative risk of major adverse cardiovascular events in polycythemia vera patients treated with ruxolitinib, hydroxyurea, or interferon: A real-world, propensity-matched cohort study
Comparative risk of major adverse cardiovascular events in polycythemia vera patients treated with ruxolitinib, hydroxyurea, or interferon: A real-world, propensity-matched cohort study Open
Background: Vascular complications are the primary cause of morbidity and mortality in patients with polycythemia vera (PV), yet consensus is lacking on the optimal cytoreductive therapy to reduce risk. Hydroxyurea (HU) is used commonly, t…
View article: Clinical significance of RAS-MAPK pathway mutations in Acute Myeloid Leukemia: Insights from a retrospective cohort
Clinical significance of RAS-MAPK pathway mutations in Acute Myeloid Leukemia: Insights from a retrospective cohort Open
Background Dysregulation of the RAS-MAPK signaling pathway is among the most common molecular abnormalities observed in neoplastic processes and leads to uncontrolled cell proliferation and resistance to apoptosis. Somatic mutations in key…
View article: Is PPM1D a potential driver of myeloid malignancy transformation in neuroendocrine tumor (NET) patients: An underrecognized malignant CHIPeRpetRaTor?
Is PPM1D a potential driver of myeloid malignancy transformation in neuroendocrine tumor (NET) patients: An underrecognized malignant CHIPeRpetRaTor? Open
Background: Building on our prior work showing high baseline CHIP prevalence and cytopenias in NET patients (pts) receiving PRRT, we used NANETS support to analyze a new cohort with matched pre- (pre-tx) and post-treatment (post-tx) periph…
View article: Clinical implications of TP53 mutations (TP53MT) in patients (pts) with higher risk Myelodysplastic Syndromes (HR-MDS) treated with hypomethylating agents (HMA) and allogeneic hematopoietic transplantation (allo-HCT): An analysis from the international consortium of MDS (icMDS) validate database
Clinical implications of TP53 mutations (TP53MT) in patients (pts) with higher risk Myelodysplastic Syndromes (HR-MDS) treated with hypomethylating agents (HMA) and allogeneic hematopoietic transplantation (allo-HCT): An analysis from the international consortium of MDS (icMDS) validate database Open
Introduction TP53MT are associated with poor outcomes in MDS, especially in the context of biallelic MT. We have previously reported on outcomes of pts with HR-MDS with TP53MT who received HMA in the VALIDATE dataset (Kewan T et al, ASH 20…
View article: Machine learning uncovers invariant evolutionary molecular trajectories in MDS.
Machine learning uncovers invariant evolutionary molecular trajectories in MDS. Open
Distinct molecular underpinnings in diverse cases of MDS may result in similar prognosis and therefore outcome-supervised prognostic systems are unlikely to reflect common pathogenesis within such risk groups. We used unbiased autoencoder-…
View article: Outcomes of patients (pts) with higher-risk myelodysplastic syndromes (HR-MDS) treated with hypomethylating agents (HMA) + venetoclax (VEN) – a large analysis from the international consortium for MDS (icMDS) validate database
Outcomes of patients (pts) with higher-risk myelodysplastic syndromes (HR-MDS) treated with hypomethylating agents (HMA) + venetoclax (VEN) – a large analysis from the international consortium for MDS (icMDS) validate database Open
Introduction: HMA monotherapy (HMAm) continues to be the standard of care for HR-MDS. While the addition of VEN to azacitidine (AZA) improved overall survival (OS) and complete remission (CR) rates among older pts with acute myeloid leukem…
View article: Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts
Wide variability and inconsistency in reporting of results of Myelodysplastic Syndromes/neoplasms (MDS) clinical trials: An icMDS systematic review of published manuscripts Open
Introduction: Standardized reporting of clinical trials results for MDS is essential to improve clinical interpretation and cross-study comparison. However, reporting of patient characteristics, response criteria, and endpoints in publicat…
View article: Survival and risk of second primary malignancies in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors: A retrospective US population-level analysis
Survival and risk of second primary malignancies in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors: A retrospective US population-level analysis Open
INTRODUCTION The introduction of tyrosine kinase inhibitors (TKIs) has significantly increased the survival of patients (pts) with chronic myeloid leukemia (CML). With a growing population of long-term CML survivors, there are now question…
View article: Serum erythropoietin level as a selective pressure in clonal hematopoiesis: Insights into the mutational landscape of myeloid neoplasias
Serum erythropoietin level as a selective pressure in clonal hematopoiesis: Insights into the mutational landscape of myeloid neoplasias Open
Outgrowth of a founder mutant clone is an initial event in leukemogenesis. The corresponding somatic hit likely conveys a fitness advantage over a polyclonal background. Several factors may modulate the competitiveness of hematopoietic ste…
View article: HOPE (Hematology/Oncology Practical Education)
HOPE (Hematology/Oncology Practical Education) Open
Introduction Patients with hematologic malignancies are living longer than ever before, thanks, in part, due to advances in diagnostic tools, the development of novel therapies, and enhanced supportive care. As survival improves, a broader…
View article: Risk of second primary malignancies and leukemic transformation in patients with Philadelphia chromosome-negative myeloproliferative neoplasms: A population-level US retrospective cohort study
Risk of second primary malignancies and leukemic transformation in patients with Philadelphia chromosome-negative myeloproliferative neoplasms: A population-level US retrospective cohort study Open
INTRODUCTION There is sparse population-level data on the risk of second primary malignancy (SPM) and leukemic transformation in Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) patients (pts) in the US. In this retr…
View article: Major adverse cardiovascular events (MACE) in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: A target trial emulation study
Major adverse cardiovascular events (MACE) in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: A target trial emulation study Open
Background: Since tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) into a chronic disease with near-normal life expectancy, cardiovascular toxicity has emerged as a leading cause of non-CML mortality. Yet, …
View article: Myeloablative and Reduced Intensity Allogeneic Transplant in Patients with Myeloproliferative Neoplasms
Myeloablative and Reduced Intensity Allogeneic Transplant in Patients with Myeloproliferative Neoplasms Open
Background Allogeneic hematopoietic cell transplant (allo-HCT) is the only potentially curative treatment for myelofibrosis (MF) and chronic myelomonocytic leukemia (CMML). Older age, comorbidities, and often advanced disease make patient …
View article: Impact of Cytogenetic Response to Therapy on Long‐Term Survival in Acute Myeloid Leukemia
Impact of Cytogenetic Response to Therapy on Long‐Term Survival in Acute Myeloid Leukemia Open
Prognostication in acute myeloid leukemia (AML) relies on clinical, molecular, and cytogenetic factors. In this retrospective study, we examined the impact of different levels of cytogenetic response on overall survival (OS) and event‐free…
View article: A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia
A phase 1 study of IO-202, an anti-LILRB4 antibody, in chronic myelomonocytic leukemia and acute myeloid leukemia Open
IO-202 is a humanized immunoglobulin G1 monoclonal antibody with high affinity and specificity for leukocyte immunoglobulin-like receptor B4 (LILRB4; ILT3), which is predominantly expressed in monocytes and monocytic blasts. IO-202 induces…
View article: Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS
Pivotal results of SELECT-MDS-1 phase 3 study of tamibarotene with azacitidine in newly diagnosed higher-risk MDS Open
Higher-risk myelodysplastic syndrome (HR-MDS) with RARA gene overexpression is a subset of patients (pts) with an actionable target for tamibarotene, an oral and a selective retinoic acid receptor-α (RAR-α) agonist. Tamibarotene with azaci…
View article: Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement
Reducing clinical trial eligibility barriers for patients with MDS: an icMDS position statement Open
Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to in…