About

Selina M. Luger, M.D., FRCPC, is a Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania and an Attending Physician at the Hospital of the University of Pennsylvania. She is a member of the Abramson Cancer Center at the University of Pennsylvania. Her educational background includes an A.B. in Biochemistry from Harvard University and an M.D.CM in Medicine from McGill University. Her research expertise focuses on leukemia, myelodysplastic syndrome, and myeloproliferative disorders, including AML, MDS, CML, and ALL. Her clinical expertise encompasses hematologic malignancies, leukemia, stem cell transplantation, and bone marrow transplant. Dr. Luger has contributed to numerous publications in her field, emphasizing her active engagement in advancing understanding and treatment of hematologic cancers.

Research topics

• Computer Science
• Medicine
• Internal medicine
• Oncology
• Pediatrics
• Clinical psychology
• Psychology
• Psychiatry

Selected publications

• Survival after Chimeric Antigen Receptor T-cell Therapy Is Predicted By Fried’s Frailty Phenotype

  Transplantation and Cellular Therapy · 2026-02-01

  article
  PublisherDOI

• Major Adverse Cardiovascular Events and Cardiac Dysfunction in Patients With Acute Leukemia

  JACC CardioOncology · 2026-01-16

  articleOpen access
  PublisherDOI

• Survival after intensive therapy or clofarabine in fit older adults with acute myeloid leukemia: E2906 phase 3 trial

  Blood Neoplasia · 2026-01-14

  articleOpen access

  = .003). In contrast, MRD-positive patients assigned to clofarabine (vs high-dose cytarabine) consolidation had significantly inferior OS. Clofarabine is inferior to standard intensive therapy despite similar remission rates. Achieving MRD-negative remission is associated with high, sustained rates of OS regardless of therapy. Increasing MRD negativity and improving outcomes among MRD-positive patients remain pressing, ongoing challenges. This trial was registered at www.clinicaltrials.gov as NCT02085408.

  PublisherDOI

• 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

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  PublisherDOI

• Prospective study of patient-reported depression, and cognitive and functional impairment, and impact on survival and induction mortality in fit adults age ≥60 years receiving intensive chemotherapy (IC) for Acute Myeloid Leukemia (AML): Prospective geriatric assessment (GA) report from ECOG-ACRIN (EA) E2906 randomized study

  Blood · 2025-11-03

  article

  Abstract Background We performed a prospective study evaluating a baseline GA battery and clinical outcomes in fit older adults (age ≥60 years) with AML and normal cardiac and renal function in the recent E-A NCTN E2906 phase 3 study. A patient-reported outcomes (PRO) assessment of Depression, Activities of Daily Living (ADL), Cognitive Function, Social Support (SS) domains, and comorbidity was performed at study registration to evaluate the prevalence of vulnerabilities and their impact on overall survival (OS) and 30-day induction mortality rates (IM) in this cohort selected for fitness to receive IC. Methods E2906 study design and results have been presented previously [n=727, age ≥60 years, randomized 1:1 to ‘standard 7&3‘ & high dose cytarabine (Arm A) vs. single agent clofarabine (CLO, Arm B), as remission induction (Step 1) and consolidation (Step 2)]. There was no difference in composite complete remission (CCR, 50%) or IM (8.5%), and CLO was inferior for OS. A baseline GA was a key secondary protocol objective, offered to all patients, and n=532 (73%) participated. We assessed Geriatric Depression Scale (GDS, none vs. any depressive symptoms, n=524); cognitive screen using Mini-Mental Exam Section (MMES, score 8/8 vs. <8, n=516); ADL & Instrumental ADL (iADL), (need for assistances vs. not n=526); a Medical Outcomes Study SS Survey (MOS-SS, measured as per unit increase, n=527); a Comorbidity survey ( ≤4 vs. ≥5 patient-reported comorbidities, n=530), patient-reported prescription medications use (PM, 0-3 vs. ≥4, n=519); and a survey of Sexual Desire (n=491) and Sexual Activity (n=477) within 4 weeks of AML diagnosis. Association of GA domains with OS, IM, and achievement of CCR was evaluated using the Chi-squared, Fisher's exact, and Wilcoxon rank sum test. Survival analysis was performed using the Cox proportional hazards models, adjusted for treatment arm. All p-values are 2-sided. Results The median age among those participating in GA battery was 67 yrs (range 60-85), including 38% age ≥70. There were 42% females, and ECOG performance status was 0 (28%), 1 (54%), 2 (16%), or 3 (2%). Central Cytogenetic review was classified (ELN2017) as Favorable (3%), Intermediate (66%), and Adverse (31%) risk. There was a notable rate of GA scores outside ‘normal’ clinical cutoff, including Depression (GDS 31%), cognitive and functional impairment [MMSE (37%), ADL (25%) and iADL (32%)], ≥5 Comorbidities (23%), and ≥4 PM's (44%). 81% & 76%, respectively, reported no sexual activity and low/none sexual desire. MOS-SS tended to be high in this cohort [mean (SD) score 87 (17)]. We observed a significant association of GA domains with OS & IM. For OS, absence of depressive symptoms [GDS, Hazard Ratio (HR) 0.79, 95% confidence Intervals (CI) 0.64-0.97, p=0.025)], MMES 8/8 (HR 0.78, 95%CI 0.64-0.96, p=0.016), requiring no assistance with ADLs (HR 0.65, 95%CI 0.52-0.82, p<0.001) and iADLs (HR 0.69, 95%CI 0.57-0.85, p<0.001), and ≤4 Comorbidities (HR 0.68, 95%CI 0.54-0.84, p=0.001) were significant for superior OS; use of ≥4 PM's was associated with inferior OS (HR 1.32, 95%CI 1.09-1.61, p=0.005). There was no association of sexual activity/desire, BMI ≥30 kg/m2, or MOS-SS with OS. IM was significantly higher among those with any depression symptoms (GDS, p=0.005), any ADL (p=0.010) or iADL (p=0.013) impairment, ≥5 comorbidities (p=0.037) and ≥4 PM's (p=0.001); there was no association with MOS-SS or MMES. There was no significant association of GA scores with cytogenetic risk group or with CCR rates. Only ADL independence (p=0.048), and possibly Comorbidity ≤4 (p=0.071), were associated with proceeding to Step 2. Conclusions In this large prospective cohort of fit older adults with AML selected to receive IC, we observed high rates of PRO-assessed GA vulnerability, which was significantly associated with inferior OS and higher IM rates, and (for ADL impairment) lower rates of proceeding to consolidation therapy. This suggests that functional and cognitive impairments are prevalent and can significantly impact outcome even in fit older adults. Despite potential long-term OS advantages of IC previously observed in E2906, efforts to systematically recognize those at higher risk based on GA PROs are needed to help identify patients who may be more appropriate for study of lower intensity treatment options to mitigate impact on IM and OS. SImilarly we plan to evaluate the potential benefit of GA-driven supportive care to improve patients' outcomes.

  PublisherDOI

• UBA1a dependency leads to synthetic lethality in vacuoles, E1-ligase, x-linked, auto-inflammatory, somatic (VEXAS) syndrome

  Blood · 2025-11-03

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  Abstract VEXAS is a recently described, monogenic auto-inflammatory condition affecting approximately 1:4000 men over 50. It is characterized by severe, multi-system inflammation, cytopenias, and increased risk of myelodysplastic syndrome (MDS) and plasma cell disorders. VEXAS typically follows a progressive course with high morbidity and ~50% 5-year mortality. No clear disease-modifying therapies exist, and potentially curative allogeneic transplantation is highly toxic; better treatments are therefore urgently needed. VEXAS is caused by somatic mutations in UBA1 on the X chromosome. UBA1 encodes the primary ubiquitin E1 ligase, which catalyzes the first step in the ubiquitin-proteasome pathway. A single mRNA transcript produces 2 isoforms: a longer nuclear form (UBA1a) and a shorter cytoplasmic form (UBA1b), the latter initiated at Met41. Most cases involve Met41 mutations, resulting in reduced UBA1b and the emergence of a truncated form with reduced catalytic activity (UBA1c). This leads to impaired global ubiquitylation (Ub) and subsequent induction of the unfolded protein response (UPR) and autophagy. Interestingly, UBA1 Met41 mutations are variably tolerated throughout hematopoiesis, enriched in myeloid cells and depleted in lymphocytes. Low variant allele frequency (VAF) UBA1 Met41 mutations have been reported in asymptomatic individuals, suggesting a threshold for disease. We therefore hypothesized that even a partial reduction of the VEXAS clone might improve symptoms. Thus, our goal was to develop an ex vivo gene therapy to correct UBA1 Met41 mutations in patient-derived CD34+ hematopoietic stem and progenitor cells (HSPCs). Sinceprimary VEXAS specimens are rare, we first sought to install and correct pathogenic UBA1 Met41 mutations in healthy male HSPCs via base editing (BE). We efficiently installed the canonical Met41Thr and Met41Val mutations (avg. VAFs approx. 90% and 30%, resp.). However, due to a lack of strong PAMs, the need to use less efficient cytidine base editors, and consequential bystander edits, direct correction via BE proved impractical. Surprisingly, despite efficient installation of Met41 mutations and the expected isoform shifts, we did not observe the reported downstream phenotype (e.g., decreased Ub, UPR activation, autophagy) in the engineered VEXAS HSPCs. Closer examination revealed an increased ratio of UBA1a:UBA1b protein compared to what has been published for primary VEXAS monocytes (which uniformly display VEXAS-associated pathology). We then reasoned that the relative increase in UBA1a might buffer the loss of UBA1b and mitigate the phenotype in HSPCs. To assess this possibility, we first designed CRISPR sgRNAs to knock out UBA1a alone or in combination with UBA1b. Loss of UBA1a alone had no apparent effect on Ub or the cells' behavior in culture or clonogenic potential. In contrast, loss of UBA1a and UBA1b resulted in decreased Ub, rapid negative selection, and marked up-regulation of p53, possibly due to impaired Ub by MDM2. These results suggest that UBA1a is dispensable in wild-type (WT) HSPCs but becomes essential in the setting of UBA1b deficiency – opening the possibility of synthetic lethality in VEXAS. Specifically, we hypothesized that suppression of UBA1a will selectively kill UBA1b-deficient VEXAS cells without affecting WT hematopoiesis. Our data also provide insight into VEXAS pathogenesis: dependence on UBA1a may explain lineage-specific tolerance of Met41 mutations, while p53 activation may contribute to MDS risk. Because pathogenic Met41 mutations still produce low levels of UBA1b, complete UBA1 KO does not accurately model the disease. To specifically interrogate the interaction between UBA1a and Met41 mutations, we next suppressed UBA1a using BE to alter its start codon (Met1Thr). Like our CRISPR KO strategy, Met1Thr-mediated loss of UBA1a was tolerated by HSPCs with no apparent effect on their biology, while in combination with Met41-mediated UBA1b loss, cells demonstrated decreased Ub and underwent rapid negative selection. Collectively, these results suggest that loss of UBA1a in VEXAS may be an efficient and unique opportunity to use synthetic lethality to eliminate diseased HSPCs without affecting residual WT hematopoiesis.

  PublisherDOI

• A CHIP off the old (MDS) block

  Haematologica · 2025-09-01 · 1 citations

  articleOpen access1st authorCorresponding

  A CHIP off the old (MDS) blockWhile clonal hematopoiesis (CH) is now considered a precursor to myeloid neoplasia, this concept is relatively new.Unlike other premalignant hematologic conditions, which have been recognized for decades (e.g., monoclonal gammopathy of undetermined significance [MGUS] was first characterized in the 1960s), Steensma et al. established the framework for CH in their landmark 2015 paper. 1 This work highlights the importance of DNA sequencing to our understanding of myeloid neoplasia.Over the preceding years, researchers found that >85% of MDS harbor somatic mutations in a stereotyped set of genes.Simultaneously, similar changes were identified in healthy individuals as they aged -and although these were associated with an increased risk of blood cancer development (hazard ratio [HR]=11.1),most cases did not progress. 2Given their partial overlap, it was initially unclear how to parse these phenomena.Furthermore, if the latter group had cytopenias, they would have met the criteria for myelodysplastic syndrome (MDS), leading to overdiagnosis.In this context, Steensma et al. codified a definition for CH (Figure 1) and proposed an updated diagnostic schema for MDS.By doing so, they deconvoluted the two conditions and established a myeloid disease spectrum.Recognition of CH as a distinct entity permitted more extensive investigation and led to the identification of clinical TITLE Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes.

  PublisherOA PDFDOI

• QUANTUM-WILD: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF QUIZARTINIB IN COMBINATION WITH CHEMOTHERAPY AND AS SINGLE-AGENT MAINTENANCE IN FLT3-ITD–NEGATIVE ACUTE MYELOID LEUKEMIA

  Hematology Transfusion and Cell Therapy · 2025-10-01

  articleOpen access

  Quizartinib (Quiz) is an oral, selective, type-II FMS-related tyrosine kinase 3 (FLT3) inhibitor with potent activity against wild-type FLT3, FLT3-internal tandem duplications (ITDs), and other kinase domain variants. Quiz is approved for patients with FLT3-ITD-positive newly diagnosed (ND) acute myeloid leukemia (AML) based on the QuANTUM-First trial (ClinicalTrials.gov: NCT02668653) results. FLT3 gene mutations are observed in ∼ 30% of AML cases, most commonly as ITDs, but they are not the only mechanism affecting FLT3 activation. Elevated FLT3 receptor expression is observed in nearly all AML cases, and high levels of FLT3 gene expression are detected in 70–100% of AML blasts, independent of the presence of FLT3 mutations, potentially contributing to leukemic cell survival and proliferation. Evidence from preclinical and clinical studies supports Quiz activity in FLT3-ITD-negative AML. In the randomized, placebo-controlled, phase 2 QUIWI trial, the addition of Quiz to Induction and Consolidation chemotherapy, followed by up to 12 months of single-agent quiz Maintenance for patients achieving complete remission (CR) or CR with incomplete count recovery (CRi), significantly prolonged overall survival (OS) versus placebo in patients with ND FLT3-ITD-negative AML. QuANTUM-Wild is an ongoing, global, phase 3, double-blind, placebo-controlled trial evaluating Quiz with standard induction/consolidation chemotherapy and as maintenance monotherapy in patients with ND FLT3-ITD-negative AML (ClinicalTrials.gov: NCT06578247). Eligible patients are aged 18–70 years with ND FLT3-ITD-negative AML defined as FLT3-ITD allelic frequency < 5%. Treatment includes standard induction with cytarabine and an anthracycline plus Quiz/placebo for 14 days (up to 2 cycles), followed by up to 4 cycles of consolidation with high-dose cytarabine and Quiz/placebo for 14 days (+/– allogeneic hematopoietic stem cell transplantation at investigator discretion), and then single-agent maintenance with Quiz/placebo in 28-day cycles for up to 36 cycles. Patients are randomized 2:2:1 into 3 arms: Arm A (Quiz in all phases), Arm B (placebo in all phases), or Arm C (Quiz in induction/consolidation and placebo in maintenance). Quiz is administered at 60 mg once daily and reduced to 30 mg if combined with strong CYP3A inhibitors. The primary endpoint is OS between Arms A and B. Secondary endpoints include OS between Arm C and Arm B (descriptive), event-free survival, relapse-free survival, complete remission rate and duration, measurable residual disease (by FLT3-ITD in all patients and by NPM1/CBF if present), and safety between Arm A vs Arm B. Planned enrollment is ∼700 patients, with 280 each in Arms A and B, and 140 in Arm C. Enrollment is currently ongoing and approximately 260 sites are planned across North and South America, Europe, Asia, and Australia. This study is sponsored by Daiichi Sankyo Co., Ltd. © American Society of Hematology (2024). Reused with permission.

  PublisherDOI

• Special considerations in the management of adult patients with acute leukaemias and myeloid neoplasms in the COVID-19 era: recommendations from a panel of international experts

  UNC Libraries · 2025-06-26

  articleOpen access
  PublisherDOI

• Impact of therapy delays on outcomes in adults with BCR::ABL1 negative b-lineage acute lymphoblastic leukemia (ALL) in the ECOG-ACRIN E1910 trial randomized to conventional chemotherapy +/- blinatumomab

  Blood · 2025-11-03

  article

  Abstract Background: The addition of the CD19/CD3 bispecific T-cell engager, blinatumomab, to standard consolidation chemotherapy in adults with ALL who achieved a measurable residual disease negative (MRDneg) remission (CR), demonstrated an improvement in 3-year overall survival (OS, 85% vs 68%, HR 0.41, P=0.002) and 3-year relapse-free survival (RFS, 80% vs 64%, HR 0.53) compared to conventional chemotherapy in the ECOG-ACRIN E1910 study (Litzow et al, NEJM 2024). Given the complex therapy in this study, treatment delays and modifications are expected. We herein explored the impact of such delays on patient outcomes. Methods: In the phase 3 ECOG-ACRIN E1910 trial (NCT02003222), adults aged 30-70 years with newly diagnosedALL who had achieved MRDneg CR following induction and intensification were randomized to consolidation chemotherapy with blinatumomab (blina arm) or chemotherapy alone (chemo arm). We examined the association between the timing of the initiation of maintenance therapy and OS and RFS. The expected duration of consolidation was 252 days vs 126 days for patients on the blina and chemo arms, respectively. For this analysis, participants were classified into two groups (no/short delay or long delay) depending on whether they started on time/before or after the median time between the beginning of consolidation and start of maintenance therapy for their treatment group (medians: 335 days, range, 181-457 days vs 176 days, range, 139-265 days for blina and chemo arms, respectively). Multivariate analyses of OS and RFS were performed to examine the effect of no/short delay vs. long delay in starting maintenance. Patients were stratified according to their assigned consolidation treatment arm, and the models were further adjusted for age, sex, white blood cell count, platelets, hemoglobin, peripheral blood blasts, bone marrow blasts, performance status and genetic-genomic risk at diagnosis. Results: Of the 488 patients enrolled, 224 MRDneg patients were randomized to consolidation chemotherapy with or without blinatumomab and 135 of the 224 went on to maintenance therapy on study (N= 66 on blina arm and 69 on chemo arm, respectively). The median follow-up from the time of maintenance registration was 43.4 months. There were no significant differences in baseline characteristics between patients in either arm who experienced no/short delay or long delay. In the blina group, 60 of 66 patients (90.9%) received all 8 cycles of consolidation therapy of which 31 (45.6%) had long delays. Sixty-eight of 69 patients on the chemo arm (98.5%) received all cycles of consolidation therapy, of which 34 (50%) had a long delay. Strikingly, patients who had a long delay before initiation of maintenance had a significant improvement in OS in multivariate analysis compared to patients who had no/short delay (HR 0.31, 95% CI: 0.11-0.91; P =0.03). However, within each treatment group, OS benefit did not reach statistical significance (blina arm: HR 0.04, 95% CI: 0.001-1.64; P =0.09; chemo arm: HR 0.32, 95% CI: 0.08-1.38; P =0.13). Similar results were observed for RFS in multivariate analysis (HR 0.40, 95% CI: 0.16-1.01; P =0.05), though this impact on improved RFS was noted in the chemo arm but not in blinatumomab treated patients (blina arm: HR 0.56, 95% CI: 0.10-3.24; P =0.52; chemo arm: HR 0.19, 95% CI: 0.04-0.83; P=0.03). Additionally, patients who had no/short delay before starting maintenance experienced a longer median duration of maintenance treatment (blina arm, 548 days; chemo arm, 708 days) compared to patients who had a long delay (blina arm 488 days; chemo arm 598 days) before initiation of maintenance (P=0.0008). Conclusion: In the phase 3 randomized ECOG-ACRIN E1910 clinical trial, long delays between initiation of consolidation therapy and start of maintenance therapy were associated with improved OS compared to no/short delays. However, within each treatment group (blina or chemo), no significant difference of OS was observed. We postulate that these longer delays allowed more patients to receive all of the recommended protocol-assigned therapy thereby resulting in improved survival. Furthermore, patients who had no/short delays had a significantly longer duration of maintenance therapy. These data indicate that treatment delays during consolidation do not worsen survival. Further studies are being done to better understand why patients with long delays had better overall survival.

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Recent grants

• NIH Grant U10CA015488

  NIH · $11.8M · 2014

Frequent coauthors

• Martin S. Tallman

  Memorial Sloan Kettering Cancer Center

  337 shared

• Elisabeth Paietta

  Montefiore Medical Center

  337 shared

• Hillard M. Lazarus

  295 shared

• Mark R. Litzow

  Mayo Clinic in Arizona

  280 shared

• Jacob M. Rowe

  Rambam Health Care Campus

  227 shared

• Noelle V. Frey

  California University of Pennsylvania

  196 shared

• Edward A. Stadtmauer

  University of Pennsylvania

  190 shared

• Alison W. Loren

  University of Pennsylvania

  176 shared