About

Daria V Babushok, MD, PhD, is an Assistant Professor of Medicine in the Hematology-Oncology department at the University of Pennsylvania's Perelman School of Medicine. She serves as an Attending Physician at the Hospital of the University of Pennsylvania, where she is involved in multiple clinical services including the Allogeneic Bone Marrow Transplant Service, Classical Hematology Consultation Service, Outpatient Bone Marrow Failure Clinic, and the Housestaff Liquid Oncology Service. Her clinical expertise focuses on bone marrow failure syndromes, acquired aplastic anemia, paroxysmal nocturnal hemoglobinuria, telomere biology disorders, clonal hematopoiesis, and predisposition syndromes related to myelodysplastic syndromes and myeloproliferative neoplasms. Her research interests are centered on understanding the fundamental mechanisms of bone marrow failure, how such failure can lead to pre-malignant genetic changes, and the development of leukemia. She leads the Babushok Lab, which conducts basic and translational research utilizing genome analysis, molecular biology, immunogenetics, and in vitro and in vivo models. Her work aims to elucidate immune-mediated marrow failure, the emergence of clonal hematopoiesis, and the genetic predispositions involved in these processes. Dr. Babushok's contributions include investigating the genetic and immunological underpinnings of marrow failure syndromes, with a focus on telomere biology, clonal evolution, and immune autoimmunity, advancing the understanding of these complex hematologic conditions.

Research topics

• Medicine
• Biology
• Immunology
• Internal medicine
• Genetics

Selected publications

• Clonal hematopoiesis in telomere biology disorders

  Seminars in Hematology · 2026-02-01

  articleSenior author
  PublisherDOI

• Ravulizumab for treatment of paroxysmal nocturnal hemoglobinuria during pregnancy

  Blood Advances · 2026-01-29 · 3 citations

  articleOpen access

  ABSTRACT: Ravulizumab, a humanized, long-acting monoclonal antibody against complement factor C5, is a widely used treatment for paroxysmal nocturnal hemoglobinuria (PNH). Given that pregnant women with PNH are at increased risk for complications and the safety and efficacy of ravulizumab in pregnancy is not known, we performed an international multicenter retrospective analysis of 16 patients with PNH with 19 pregnancies managed with ravulizumab and compared outcomes to 8 earlier pregnancies in the same patients treated with eculizumab. Of the 8 eculizumab-treated pregnancies, 3 resulted in miscarriages and 1 in early preterm delivery for threatened fetal demise and massive fetal growth retardation. All 19 pregnancies on ravulizumab resulted in the birth of live infants, with a median gestational age of 267 days (interquartile range [IQR], 259-275) and median birth weight of 3115 g (IQR, 2458-3349). Cord blood testing in 2 pregnancies receiving intensified ravulizumab dosing revealed detectable ravulizumab levels consistent with transplacental transfer. After a median follow-up of 16.2 months (IQR, 4.4-40.1), no developmental abnormalities or severe infectious complications were observed in the children. This retrospective analysis provides evidence for the safety and effectiveness of ravulizumab in managing PNH during pregnancy and breastfeeding with favorable maternal and fetal outcomes.

  PublisherOA PDFDOI

• Intermediate-Dose Post-Transplantation Cyclophosphamide (ID-PTCy) after Reduced Intensity Conditioning (RIC) HLA-Mismatched Donor Allogeneic Hematopoietic Cell Transplantation (HCT)

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• Development and Validation of the PASS Score: A Simplified Tool to Diagnose Acquired Aplastic Anemia in Adults

  Research Square · 2026-01-22

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• High-resolution single-cell mapping of clonal hematopoiesis and structural variation in aplastic anemia

  Nature Genetics · 2026-05-01

  article
  PublisherDOI

• Predicting secondary myeloid neoplasms in acquired aplastic anemia using machine learning models

  Blood Neoplasia · 2025-08-25

  articleOpen access

  Machine learning models can predict leukemic evolution in acquired aplastic anemia patients using retrospective clinical data. Acquired aplastic anemia (AA) patients treated with immunosuppressive therapy (IST) face up to a 20% long-term risk of developing secondary myeloid neoplasms (sMNs), including acute myeloid leukemia and myelodysplastic syndromes. Although hematopoietic stem cell transplantation (HSCT) is curative and prevents sMNs, older patients and those lacking suitable donors have historically received IST as first-line therapy. Recent improvements in HSCT outcomes have expanded transplant eligibility, highlighting the need for tools to better identify patients at high risk for sMN. Validated predictive models could help guide early HSCT consideration or tailor surveillance strategies. We developed two binary machine learning models to predict sMN development in AA patients at clinically relevant time points: diagnosis (Model 1) and six months after IST response (Model 2). We analyzed data from 275 adult AA patients treated at UT Southwestern, Cleveland Clinic, and the Hospital of the University of Pennsylvania between 1975 and 2023. Seventy-nine clinical variables were collected, including demographics, somatic mutations, and treatment response. Neural networks were trained with leave-one-out cross-validation. Both models achieved strong performance (AUC 0.82, sensitivity 0.82, specificity 0.73). Shared key predictors included DNMT3A mutation, CUX1 mutation, total mutation count, and age. TET2 mutation was specific to Model 1; PNH clone presence was unique to Model 2. High-risk classification was significantly associated with worse overall survival (p < 0.0001). These findings support the feasibility of machine learning–based sMN risk prediction in AA. With training on larger datasets and external validation, these models may support individualized decision-making around HSCT and post-IST surveillance.

  PublisherDOI

• Toward risk-adjusted hematologic surveillance for telomere biology disorders

  Blood · 2025-11-03

  articleSenior author

  Abstract Telomere biology disorders (TBDs) are a heterogeneous group of diseases caused by inherited defects in telomere maintenance, which can lead to dysfunction of several organs that worsens with age. TBDs can lead to bone marrow failure (BMF) and have an increased risk of myeloid neoplasms (MNs). The current TBD Diagnosis and Management Guidelines (2nd ed.) recommend a baseline bone marrow (BM) evaluation for all TBD patients. Historically, the guidelines recommended annual BM biopsies for children with genetically confirmed TBD starting at age 10, while in adults (age 22 and over) routine annual BM surveillance has not been recommended. However, optimal MN surveillance in TBD remains unknown due to the lack of formal studies of BM surveillance in TBD. To address this gap, we analyzed 344 TBD patients (166 pediatric and 178 adult) from our centers and published data from the National Institutes of Health. Of these, 29 (8.4%) developed MNs. 67 (19.5%) underwent HSCT—5 for MNs (8.5%), and 62 for other indications, with 33 (49%) died post-HSCT; 13 of 33 (39%) were from transplant-related complications. Among adults with TBD, 26/178 (14.6%) had a myeloid neoplasm compared to 3/166 (1.8%) of children (RR = 8.2, 95% CI 2.5-26.5; p&amp;lt;0.001). We next reviewed serial BM biopsy outcomes at our pediatric/adult BMF center. Among 53 pediatric TBD patients with accessible health records, 29 had individual BM biopsy data spanning 140 person-years (median 4.5 years) of follow-up. No MN transformations occurred; four children died (liver failure, complications of kidney disease, post-HSCT infections). Among 69 BM biopsies (median 2 per patient, range 1-6), 27 (39%) were for routine surveillance without clinical change. Clonal hematopoiesis (CH) was identified on clinical testing in 3 children, and contributed to the decision to proceed to HSCT in two: 1) a child with TERC-mutant TBD whose U2AF1 variant VAF rose from 3% to 11% on surveillance at age 14; 2) a patient with telomeres &amp;lt;1st percentile without identified germline mutation who had a 3% VAF PTEN variant identified at age 6 that rose to 5% and had a transient 7% del(20q) detected by FISH at age 7. The third patient with telomeres &amp;lt;1st percentile without identified germline mutation had a 6% VAF KMT2C variant identified on surveillance at age 9, and is being monitored. Overall, of the 53 children, 12 (23%) underwent HSCT at a median age of 7.7 years (two with CH, nine for BMF, one for immunodeficiency). Three died from post-HSCT infections, and the fourth died at age 22 from pulmonary fibrosis, having been declined a lung transplant despite full hematopoietic recovery post-HSCT 21 years prior because of other organ complications. Eight patients are alive post-HSCT (median post-transplant follow-up 1.9 years, range 0.18-5.65 years). Among 46 adult TBD cases with available health records, six initially presented with MN prior to the diagnosis of TBD. 3 additional adults were subsequently diagnosed with MN after TBD diagnosis: one on the initial biopsy, and two on biopsies prompted by new clinical findings. The median age of MN diagnosis was 56 (range 28-67). Of the 40 patients without MN at presentation, 39 had individual-level BM biopsy data, contributing 169 person-years of follow-up (median 3.6 years). Of 71 BM biopsies (median 1 per patient, range 1-8), 26.8% (19 biopsies) were for routine surveillance in 11 patients, 4 of whom had new or changing chromosomal or mutational alterations. 19/46 (41%) adults died. Leading causes were respiratory failure (42%), progressive/relapsed MN (16%), septic shock/infection (16%), and decompensated cirrhosis (11%). Our analysis shows that the MN risk in TBD increases with age, from under 2% in children to ~15% in adults, peaking in middle age, amid competing risks of pulmonary and other TBD complications. Our data suggest that current guidance of intensifying routine BM surveillance at age 10-21 in the absence of evolving clinical or laboratory abnormalities may offer limited benefit for early detection of MN for most children, while potentially missing that opportunity in young and middle-aged adults. Future studies are needed to identify subgroups of TBD patients most likely to benefit from routine BM surveillance, and to incorporate non-invasive monitoring allowing for a personalized surveillance strategy more closely aligned with dynamic changes in MN risk and the availability and risks of early intervention in this lifelong systemic disease.

  PublisherDOI

• RIT1 mutations in myeloid neoplasms

  Blood · 2025-11-03

  articleOpen accessSenior author

  Abstract Background: Constitutive activation of the RAS/MAPK cascade due to mutations in canonical RAS-family proteins, upstream tyrosine kinases, or downstream regulators is a hallmark of myeloid malignancies. Ras-like without CAAX 1 (RIT1) is a non-canonical RAS GTPase, with germline mutations accounting for 5–10% of Noonan syndrome cases. Somatic RIT1 mutations have also been reported in myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDS); however, their pathologic and clinical implications remain poorly defined. Methods: We queried the University of Pennsylvania's institutional archive of ~16,000 blood, bone marrow aspirate, and paraffin-embedded tissue samples tested for hematologic malignancy-associated mutations from April 2015 - June 2025 to identify cases of myeloid neoplasms with pathogenic/likely pathogenic or uncertain significance variants in RIT1. All included variantswere confirmed to be somatic based on time of acquisition, low variant allele fraction (VAF) or VAF decline in remission. Subjects were annotated for diagnosis, treatment, death, and disease progression (for acute myeloid leukemia (AML) - relapsed or refractory disease; for MDS - development of MDS with excess blasts (MDS-EB1, -EB2) or AML; for MPN - evolution to myelofibrosis (MF) or AML; and for chronic myelomonocytic leukemia (CMML) - progression to CMML-2 or AML). Co-mutations and outcomes were summarized by disease type and overall. We built a Cox proportional hazards model controlling for age and diagnosis, with RIT1 acquisition as a time-varying covariate, to test the association between RIT1 acquisition and progression or death. Results: Somatic RIT1 variants were identified in 38 subjects (10 AML, 10 CMML, 8 MPN, 6 MDS, and 4 MDS/MPN), with a median age of 62 years (range: 33–85) and a median duration of follow-up of 2.2 years (range: 0.3–21.4 years). No subjects had clinical features of Noonan syndrome. Of the 29 subjects tested for RIT1 at presentation, 18 had RIT1 variants identified at diagnosis, while 11 had them later in the disease course. Median RIT1 variant allele fraction (VAF) at diagnosis was 11.5% (range: &amp;lt;7%–50%); those acquiring RIT1 did so at a median of 1.1 years (range: 0.2–7.1 years), with a median VAF of 21% (range: &amp;lt; 7–45%). In all subjects, a single RIT1 variant was detected, with 33/38 (86.8%) involving hotspots within the switch II region of the GTPase domain: A77T (n=2), E81G (n=2), F82L/I/C/V (n=17), and M90I/V (n=12). Common co-occurring mutations throughout the duration of follow up included ASXL1 (n= 24 patients, 61.5%), SRSF2 (n=18, 46.2%), and TET2 (n=13, 33.3%). Other RAS/MAPK signaling pathway genes—including NRAS (n=8), KRAS (n=2), PTPN11 (n=3), and CBL (n=5)—were co-mutated in 18 patients (46.2%). Eight subjects (20.5%) had co-occurring JAK2 V617F mutations (4 with MPN, 2 with CMML, and 2 with MDS). Of the 8 MPN subjects (6 with myelofibrosis and 2 with polycythemia vera), 4 had JAK2 mutations (2 of which diminished with the rise of the RIT1-mutant clone), 1 had a CALR mutation, and 3 had triple-negative disease. A pattern of combined epigenetic (ASXL1 or TET2) and SRSF2 mutations at time of RIT1 detection predominated in CMML (7/10) and was also observed in AML (3/10), MDS (2/6), and MPN (3/8). Median time to progression or death in subjects exhibiting this pattern was shorter (1.1 vs 3.2 years, log-rank p = 0.021). Amongst the cohort with available baseline RIT1 testing, acquisition of RIT1 as a time-dependent covariate was not significantly associated with increased hazard of progression or death (HR 1.1; CI 0.8–10.8; p = 0.10). 25 of 38 subjects died (66%) at a median time of 2.2 years (range 0.1 – 20.1 years). These were predominantly patients with higher-grade neoplasms (MDS, CMML, AML). Cases where RIT1 occurred early without other co-occurring variants had a more indolent course resembling chronic-phase MPN. Conclusion: RIT1 variants span the myeloid malignancy spectrum, often arising in molecular contexts analogous to canonical RAS variants. Co-mutational profiles mirrored those associated with RAS-driven disease, including epigenetic and splicing events (ASXL1, TET2, and SRSF2) and late clonal drivers (RIT1), and were associated with poorer prognosis. Early acquisition of RIT1 without co-mutations appears to confer a more indolent course, potentially representing a molecularly distinct subset of triple-negative MPN-like disease and will be subject of future study.

  PublisherOA PDFDOI

• Evaluation of a screening protocol for telomere biology disorders in individuals with interstitial lung disease undergoing lung transplant evaluation

  ERJ Open Research · 2025-02-20 · 2 citations

  articleOpen access

  Background: Because of the potential for extrapulmonary disease, it is important for lung transplant programmes to identify telomere biology disorder (TBD)-related interstitial lung disease (ILD). The aim of this study was to evaluate a TBD phenotype screen among ILD patients undergoing lung transplant evaluation, including the sensitivity and specificity of individual phenotype screening questions and the characteristics of patients with TBD identified outside of the screening protocol. Methods: This was a retrospective cohort study of adults with ILD who underwent lung transplant evaluation from 1 January 2018 to 28 February 2023. The TBD phenotype screen included early greying, family history of ILD and unexplained liver disease, cytopenias or macrocytosis. TBD screen-positive patients underwent telomere length (TL) testing. Results: Among 383 patients evaluated, 92 (24.0%) had a positive phenotype screen. 58 (63.0%) had early greying, 39 (42.4%) had a first-degree relative with ILD and 29 (31.5%) had unexplained macrocytosis or cytopenias. Using granulocyte and lymphocyte TL <10th percentile, 51 (55.4%) patients met criteria for a TBD. Early greying had the highest sensitivity for TBD (72.5%) with specificity increasing with the number of positive screening questions. Among the 23 patients who underwent TL testing outside of the screening protocol, most commonly because of an early age of onset of ILD, eight (34.8%) had TL between the 1st and 10th percentile. Conclusions: Lymphocyte and granulocyte TL <10th is common among TBD phenotype screen-positive ILD patients undergoing transplant evaluation. Inclusion of additional screening questions related to age of onset of ILD could improve the sensitivity of the protocol for short TL.

  PublisherDOI

• Origins of T‐cell‐mediated autoimmunity in acquired aplastic anaemia

  British Journal of Haematology · 2025-01-21 · 1 citations

  reviewOpen accessSenior authorCorresponding

  Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T-cell-mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T-cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T-cell repertoires in AA. We will highlight new insights gained from recent in vitro studies of candidate autoreactive T cells isolated from AA patients and will discuss efforts to identify shared T-cell clonotypes in AA. Finally, we will discuss emerging evidence on the potential T-cell cross-reactivity between HSPC and common viral epitopes that may contribute to the development of AA in some patients. We conclude by highlighting the areas of consensus and limitations, as well as the ongoing uncertainties, and we identify promising directions for future research in the field.

  PublisherOA PDFDOI

Recent grants

• The effects of somatic HLA class I allele mutations on antigen presentation in acquired aplastic anemia

  NIH · $163k · 2022–2024

• Early Clonal Evolution in Acquired Aplastic Anemia

  NIH · $992k · 2016–2022

Frequent coauthors

• Timothy S. Olson

  128 shared

• Monica Bessler

  108 shared

• Selina M. Luger

  96 shared

• Jaclyn A. Biegel

  90 shared

• Philip J. Mason

  81 shared

• Nieves Perdigones

  77 shared

• Helge Hartung

  74 shared

• Joshua D. Cockroft

  University of Cincinnati Medical Center

  72 shared

Labs

• The Babushok LabPI