Alison Wakoff Loren
· MD, MSCEVerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1986–2026
About
Alison Wakoff Loren, MD, MSCE, is the C. Willard Robinson Professor of Hematology-Oncology at the University of Pennsylvania's Perelman School of Medicine. She serves as an Associate Scholar at the Center for Clinical Epidemiology and Biostatistics and is the Director of the Blood and Marrow Transplantation, Cell Therapy, and Transplant (CTT) program at the Abramson Cancer Center. Additionally, she is the Chief of the Division of Hematology & Oncology at the University of Pennsylvania. Her research expertise includes clinical trials, alloimmunity, chimerism, leukemia, myelodysplasia, bone marrow and stem cell transplantation, pregnancy, fertility, and survivorship. Her clinical practice focuses on leukemia, myelodysplasia, and bone marrow and stem cell transplantation. Dr. Loren's educational background includes a cum laude A.B. in Biology from Harvard University, an M.D. from Washington University, and an M.S.C.E. in Clinical Epidemiology from the University of Pennsylvania.
Research signals
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Research topics
- Medicine
- Biology
- Genetics
- Family medicine
- Internal medicine
- Demography
- Surgery
- Cancer research
- Nursing
- Immunology
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- RETRACTED
Journal of the American Academy of Dermatology · 2026-01-01
article Transplantation and Cellular Therapy · 2026-02-01
articleTransplantation and Cellular Therapy · 2026-02-01
article- RETRACTED
Journal of the American Academy of Dermatology · 2026-01-01
article JAMA Dermatology · 2026-01-21 · 1 citations
articleOpen accessImportance: Clinician-reported and patient-reported outcomes are critical measures of therapeutic efficacy in cutaneous chronic graft-vs-host disease (cGVHD) but are not always correlated. Discordance in treatment response between clinicians and patients hinders interpretation of outcomes in clinical trials and complicates therapeutic decision-making in clinical practice. Objective: To identify factors associated with discordance in clinician-reported and patient-reported treatment response assessments and to evaluate the association of clinician-reported and patient-reported responses with survival. Design, Setting, and Participants: This multicenter longitudinal cohort study included adults 18 years and older with cutaneous cGVHD at study enrollment, assembled from 2 observational studies and 1 randomized clinical trial. Data were collected from August 2007 to March 2024, and data were analyzed from July 2024 to May 2025. Main Outcomes and Measures: A global 8-point cutaneous cGVHD treatment response assessment (with 1 indicating resolved and 8 indicating very much worse) was reported by clinicians and patients 3 to 6 months after study enrollment. Clinician-reported and patient-reported treatment responses were categorized into improved, stable, and worse from the 8-point scale, and discordance was defined as a difference in response between clinicians and patients. Positive clinician discordance indicates the clinician reported a better response than the patient, and negative clinician discordance indicates the clinician reported a worse response than the patient. The association of clinician-reported and patient-reported responses with survival was measured by nonrelapse mortality. Results: Of 489 adults with cutaneous cGVHD, 192 (39.3%) were female, 297 (60.7%) were male, and the median (IQR) age was 55 (43-62) years. A total of 321 adults (65.6%) had concordant responses and 168 (34.4%) had discordant responses between clinician-reported and patient-reported treatment responses. Patients with sclerotic cGVHD had greater odds of discordance compared with those without sclerosis, with clinicians reporting both better and worse treatment response than patients (positive clinician discordance: adjusted odds ratio, 3.14; 95% CI, 1.41-6.95; P = .005; negative clinician discordance: adjusted odds ratio, 2.33; 95% CI, 1.19-4.56; P = .01). Worsening compared with improved overall cutaneous cGVHD was associated with nonrelapse mortality when reported by clinicians (adjusted hazard ratio, 2.28; 95% CI, 1.46-3.54; P < .001) and patients (adjusted hazard ratio, 1.86; 95% CI, 1.12-3.08; P = .02), while only patient-reported worsening was significantly associated with nonrelapse mortality in patients with sclerotic disease (adjusted hazard ratio, 2.00; 95% CI, 1.02-3.90; P = .04). Conclusions and Relevance: In this cohort study, discordance in treatment response assessments between clinicians and patients was common in cutaneous cGVHD, yet clinician-reported and patient-reported treatment responses were both associated with survival. In patients with sclerosis who were more likely to experience discordance, patient-reported response was a critical treatment end point, and approaches should be developed to bridge discordance.
Blood · 2025-11-03
articleOpen accessAbstract Chimeric antigen T-cell receptor (CART) therapy is highly effective for pts (pts) with relapsed/refractory (R/R) lymphoma/multiple myeloma (MM). However, due to concerns regarding tolerability, older pts are underrepresented in CART trials and real-world studies indicate that CART is underutilized in older adults. Methods to assess fitness for CART are ECOG, clinician gestalt and age. There is interest in improving risk stratification of older adults using objective measures. Fried's frailty phenotype (FP) uses subjective (exhaustion, reported weight loss, activity level) and objective (gait speed, grip strength) measures to categorize pts into fit, pre-frail, and frail. We have previously shown that FP predicts for overall survival (OS) in older stem cell transplant (SCT) recipients. We hypothesize that FP will be associated with progression-free survival (PFS) and OS in older pts with lymphoma/MM undergoing CART therapy. We prospectively enrolled pts ≥ 60 years planned for CART for R/R lymphoma/MM from May 2019 – 2023 on a clinical trial. We performed FP prior to CART infusion, and at 7 days (d), 14d, 21d, 1 month (mo), 3mo, 6mo and 12mo post-infusion. 36 pts were enrolled with a median age at CART infusion of 69 years (Range 60-81). 53% of pts had MM, of whom 63% had intermediate or high-risk disease by R-ISS. The remainder had lymphoma (diffuse large B-cell or follicular lymphoma) with IPI &gt; 2 at diagnosis in 59%. Idecagtagene vicleucel and tisagenlecleucel were the most frequently administered CART products. Median follow up was 33mo. Median prior lines of therapy (LOT) was 3 (Range 1-7) and 47% had prior auto-SCT. Pre-infusion, majority had low ECOG scores (0-1, 81%), including 71% categorized as frail by FP. At pre-infusion FP, 35% of pts were fit (score 0), 44% were prefrail (score 1-2) and 21% were frail (score 3-5). Frail pts were more likely to be admitted for &gt;7d for their CART infusion (OR 7.0, 95% CI 1.02-47.97, p=0.04). Frailty was not associated with risk of CRS, ICANS or 30-day hospital readmission. 13 pts had died by the time of analysis; all but 2 deaths were related to progressive disease. 2 non-disease related deaths were 1 death from COVID and 1 ICANS-related death from teclistamab after relapse 1 year and 2 years after infusion, respectively. At Day 21 post-infusion, 21% were fit, 57% were prefrail, and 21% were frail. At 1mo post-infusion, 25% were fit, 63% were prefrail, and 13% were frail. Being frail by FP at pre-infusion (p&lt;0.001), Day 21 (p=0.03) or 1 month (p=0.009) post-infusion was associated with inferior OS from that time point. Median PFS in pre-infusion fit, prefrail, and frail pts were 23.4mo (95% CI 17.1-NR), 18.4mo (95% CI 6.8-13.8) and 4.0mo (95% CI 2.5-8.4), respectively. 2-year OS estimates were 100%, 93% and 14%, in fit, prefrail and frail pts respectively. 14 of 36 pts maintained or improved their FP from pre-infusion to 1mo; all but 3 received physical therapy (PT) while in hospital with 5 pts continuing PT outpatient. Notably, pts who maintained or improved their FP from pre-infusion to 1mo post-infusion had significantly better OS (p=0.05) than pts who had declines in their scores. Along with pre-infusion, day 21 and 1mo post-infusion FP scores, LDH (Mean 182 U/L) at the time of CART infusion was significantly associated with OS in the univariate Cox proportional hazards model (HR 5.22, 95% CI 1.43-19.18, p=0.013). Several factors including disease type, number of prior lines of therapy, use of bridging, stage at CART, IPI/RISS at diagnosis, HCT-CI, ECOG, presence of extra-nodal disease, CRS, ICANS, gender, age by decade, and BMI did not correlate with outcome. In pts ≥ 60 with R/R lymphoma/MM undergoing CART, 21% were frail by FP prior to CART. Frailty by FP pre-infusion, day 21 and 1mo post-infusion was associated with inferior OS as opposed to ECOG, HCT-CI, age or several disease related risk factors. FP may improve risk stratification in older adults undergoing CART. Pts with improvement in FP within 1mo post-infusion also had better outcomes. While better disease control could contribute to improved FP scores, most pts received PT to reverse frailty. Our future work aims to implement an exercise regimen to improve outcomes and to determine whether frailty is associated with adverse disease biology. Future work to uncover biologic mechanisms of frailty and adverse disease biology may identify novel targets for intervention to improve outcomes for frail pts.
Blood · 2025-11-03
articleOpen accessAbstract Emerging evidence implicates tissue resident memory T-cells (TRM) in chronic graft-versus host disease (cGVHD) immunopathology. While traditionally considered confined to tissues, recent studies indicate TRM can re-enter the circulation as “ex-TRM” in inflammatory conditions. However, the role of ex-TRM in cGVHD, and the link between peripheral blood (PB) and tissue-based immunopathology in cGVHD are not well understood. To identify and characterize ex-TRM in cGVHD, we utilized 10X Genomics 5' GEM-X technology to perform single-cell RNA sequencing (scRNA-Seq) and single-cell TCR sequencing (scTCR-Seq) on T-cell selected PBMC samples from patients with newly diagnosed, treatment-naive cGVHD (n=8) and post-allogeneic stem cell transplant (ASCT) matched controls (MC; n=5) who did not develop relapse or acute/chronic GVHD. Quality control (QC), normalization, clustering, principal component analysis, dimensionality reduction, and integration were performed with Seurat v5.2.1 in R v4.4.2. CD8+ effector memory (EM) subsets were re-clustered to enhance resolution for ex-TRM. TCR clonality was assessed in ScRepertoire, and antigen specificity was determined for alpha/beta TCR amino acid sequences using ImmuneWatch DETECT. Differences in continuous variables were assessed using the Wilcoxon rank-sum test, and Bonferroni correction was applied for differential gene expression (DGE) analysis. Significance was set at p &lt; 0.05 All patients received matched donor transplants and tacrolimus and methotrexate for GVHD prophylaxis. There were no significant differences between cGVHD and MC for age, sex, donor type (related vs. unrelated), CMV serostatus, conditioning regimen, or sample timepoint post-ASCT. After QC, 29,107 CD8+ T-cells (17,938 cGVHD and 11,1169 MC) were analyzed. Re-clustering of CD8+ EM cells revealed a distinct cluster expressing canonical TRM markers (CXCR6, ITGA1, ITGAE, CD69) as well as TRM-associated genes CXCL13 and CRTAM, consistent with ex-TRM. To further validate the TRM-like signature, we performed cluster-based module scoring using: 1) the top 100 upregulated genes from our recent publication in TRM vs. non-TRM in explanted lung tissue from pulmonary cGVHD and 2) the top 200 upregulated genes from an external dataset comparing lung TRM to circulating EM T-cells in healthy controls. Module scores for both gene sets were highest in the ex-TRM cluster, confirming TRM-like identity. The ex-TRM cluster included all cGVHD patients and MC in similar proportions. We then compared abundance and gene expression of ex-TRM in cGVHD patients and MC. Ex-TRM as a fraction of CD8+ EM was similar between groups (0.08 vs 0.09). However, cGVHD ex-TRM showed upregulation of cytotoxicity genes (GZMB, GNLY, PRF1), NK-like (NKL) markers (KLRD1, FGFBP2, NKG7), and T-cell exhaustion (Tex)-associated genes (DUSP4, HAVCR2). The median module score for an external Tex gene signature was higher in cGVHD than MC (0.029 vs 0.016, p &lt;0.001). DGE results were consistent after stratification by CMV serostatus. TCR analysis showed similar proportions of hyperexpanded (&gt;100 cells/clonotype) and large (20-100 cells/clonotype) clones in ex-TRM between conditions (30% versus 28%). Normalized entropy scores for ex-TRM were identical (0.92), indicating comparable repertoire diversity. However, hyperexpanded and large clones in cGVHD exhibited even greater upregulation of cytotoxicity, NKL, and Tex genes by log2 fold change than the overall ex-TRM population. Finally, ImmuneWatch DETECT did not find viral epitope-specific clonotypes in ex-TRM from cGVHD patients, suggesting that expansion may reflect alloantigen recognition. In conclusion, we identified circulating ex-TRM during post-ASCT immune reconstitution using canonical TRM markers and module scoring. In cGVHD, ex-TRM had a distinct cytotoxic, NKL, and Tex gene signature, supporting possible antecedent tissue antigen exposure and pathogenicity. Future work will explore protein level validation and assess phenotypic and clonal overlap between ex-TRM and bona fide TRM in affected tissues. With further validation, ex-TRM may provide a surrogate for tissue-resident populations and the foundation for non-invasive biomarkers in cGVHD.
Blood · 2025-11-03
articleOpen accessAbstract Introduction: Graft Failure (GF) is a rare but devastating outcome of HCT. Primary GF (PGF), defined as a failure of neutrophil recovery by Day+28, is straightforward to diagnose. Diagnosing secondary GF (SGF) is more challenging, with its broad time-range, multiple confounding diagnoses, and lack of predictive biomarkers. In BMT CTN1703/1801, we analyzed patients receiving RIC HCT for heme malignancies with either Tac/MTX (n=159) or PT-Cy (n=165) GVHD prophylaxis. SGF was defined as donor chimerism &lt;5% after initial donor engraftment. With Tac/MTX, there were 3 PGF and 1 SGF diagnoses. With PT-Cy, there were 4 PGF and 6 SGF. Median SGF diagnosis was Day +64 (range: Day+28-215). There were too few Tac/MTX patients to analyze SGF, but sufficient events with PT-Cy. To identify PT-Cy SGF predictors, we leveraged lymphocyte, T, B, and NK cell reconstitution analysis. In SGF we found an early, profound deficit in the reconstitution of all major lymphocyte populations, including total lymphocytes, T, B, and NK cells, as early as Day+28. This enabled the modeling of a SGF risk classifier based on the Absolute Lymphocyte Count (ALC). Methods: Clinical ALC measurements were performed on all SGF patients (n=6) and on non-GF controls with ALCs available (146 of 155 non-GF patients). Flow cytometry was performed on all PT-Cy SGF patients (n = 6) and from a subset of non-GF controls (n = 18: controls were chosen as patients without relapse or severe GVHD, to reduce confounders introduced by immunologic interventions, and for whom all samples, including from the graft infusion, were available). T, B, and NK counts, as well as T cell subsets, were compared (using Welch's T test) on Days 7, 14, 21, 28, 42, 63, 98, 180, 270, 365, 730, with SGF patients censored on the day of GF diagnosis. To interrogate the optimal ALC cutoff, the cumulative incidence of SGF was computed at Days +28 and +42, with death without GF as a competing risk. Results: We have previously demonstrated that, compared to Tac/MTX, PT-Cy patients exhibited an early decrease in reconstitution of all T cell populations (with normal NK and B cell reconstitution). Here we focused specifically on PT-Cy patients with or without SGF. Graft CD34 counts/kg were not different between SGF patients and non-GF patients (mean CD34/kg = 1.38 x10e6 (SGF) vs 0.67 x10e6 (non-GF, p = 0.61) However, even amidst the overarching early suppression in T cell reconstitution with PT-Cy, SGF patients could be easily distinguished from the larger PT-Cy cohort, based on more profound deficits in ALC, T, B and NK cells reconstitution, measured using 2 strategies: (1) SGF patients demonstrated significant early (Day +28) quantitative defects in the reconstitution of the ALC (mean +/- SEM 262+/-32 cells/µL (non-GF) vs 60 +/- 25 (SGF, p&lt;0.0001), CD4 T cells (62 +/- 12 cells/µL vs 19+/-15, p=0.048), CD8 T cells (15 +/-3 cells/µL vs 3.5 +/-1 p=0.0009), all CD8 T cell subpopulations, as well as NK cells (116+/-31 cells/µL vs 2.9+/-1.4 cells/µL, p= 0.002) and B cells (3.5 +/-1.4 cells/µL vs 0.16+/-0.07 p =0.03). (2) In SGF, there was a significant deficit in the rate of rise of all major lymphocyte populations between Days 28-42-60 vs non-GF, including CD4 T cells (p&lt;0.0001), CD8 T cells (p = 0.0002), B cells (p&lt;0.0001), and NK cells (p =0.048). These discoveries suggested that a classifier could be identified to risk-stratify patients for SGF. We explored an ALC cutpoint, amenable to standard clinical lab analysis. A statistically significant threshold was identified at both Days+28 and +42, with Day+42 being most predictive: A threshold of 120 cells/µL was identified as optimal, with landmark analysis documenting a SGF rate of 34.7% below the cutpoint, and SGF of 1% above it (HR = 45.9, 95% CI 5.7 - 366). Conclusions: Despite the small number of events, PT-Cy patients with SGF demonstrated a distinctive reconstitution trajectory that encompassed an early, substantial, and sustained deficit in all lymphocyte counts, as well as a lack of their longitudinal expansion. This enabled the discovery of a candidate ALC biomarker cutpoint at Day+42 that could distinguish patients who were more likely to develop SGF. If confirmed, these data could generate a predictive biomarker for SGF, which would enable the design of trials evaluating early interventions (e.g. CD34+ boosts, DLI, modification of immunosuppression) to improve outcomes for these patients.
Journal of Clinical Oncology · 2025-06-16 · 20 citations
articleOpen accessPURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD. METHODS: This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD. RESULTS: A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles. CONCLUSION: PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588).
Frequent coauthors
- 176 shared
Selina M. Luger
- 139 shared
Edward A. Stadtmauer
University of Pennsylvania
- 117 shared
Noelle V. Frey
California University of Pennsylvania
- 105 shared
Elizabeth O. Hexner
University of Pennsylvania
- 99 shared
Alexander E. Perl
University of Pennsylvania
- 87 shared
David Porter
University of Pennsylvania
- 84 shared
David L. Porter
University of Pennsylvania
- 74 shared
Sunita D. Nasta
University of Pennsylvania
Education
- 1992
B.A., Biology
Harvard University
- 1996
M.D., Medicine
Washington University
- 2003
Other, Clinical Epidemiology
University of Pennsylvania
Awards & honors
- C. Willard Robinson Professor of Hematology-Oncology
- Associate Scholar, Center for Clinical Epidemiology and Bios…
- Director, Blood and Marrow Transplantation, Cell Therapy and…
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