Jaroslaw Jedrych’s research while affiliated with Johns Hopkins University and other places

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Publications (58)


Improved Overall Survival with Checkpoint Inhibition and Allogeneic Transplantation in Relapsed Hodgkin Lymphoma
  • Article

December 2024

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8 Reads

Blood Advances

Nadeem Tabbara

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Marianna L Zahurak

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Cole Sterling

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[...]

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Patients with relapsed classic Hodgkin lymphomas receive salvage therapy with immune checkpoint inhibitors (ICI) or chemotherapy (no-ICI). Patients responding to therapy often undergo consolidation with allogeneic blood or marrow transplantations (alloBMT). We previously reported that relapsed cHL patients treated with ICI followed by alloBMT experienced improved 3-year progression-free survival (PFS) compared to patients treated with salvage chemotherapy without ICI, followed by alloBMT. In this retrospective analysis, we report the 5-year OS, PFS, and GVHD incidence in cHL patients treated with ICI before alloBMT with post-transplantation cyclophosphamide (PTCy) GVHD prophylaxis. Among the 147 relapsed/refractory patients with cHL, 71 (48.3%) received ICIs and 76 (51.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. We observed an improved 5-year estimated OS of 91% (ICI) versus 66% (no-ICI), (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.16 to 0.98; P = 0.046) and a 5-year estimated PFS of 84% (ICI) versus 53% (no-ICI) (HR, 0.4; 95% CI, 0.2 to 0.81; P = 0.011). The 12-month cumulative incidence of grade III-IV GVHD was 20% (ICI) and 7% (no-ICI) (SDHR 3.16; 95% CI, 1.13 to 8.81 p = 0.03. More frequent grade III-IV acute GVHD was likely due to the higher incidence of grade III-IV acute GVHD in the subset of patients with pre-transplant exposure to ICI and shortened duration (60 days) of immunosuppression versus patients with long immunosuppression (day 180). These data suggest that cHL patients treated with ICI and alloBMT experience improved OS and the GVHD risk can be mitigated by immunosuppression until day 180.






Concurrent autoimmune blistering diseases in VEXAS syndrome: a report of two cases

July 2024

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4 Reads

Clinical and Experimental Dermatology

VEXAS (Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently characterized autoinflammatory condition driven by myeloid cell dysregulation. We report two patients with concurrent diagnoses of VEXAS syndrome and autoimmune blistering diseases - pemphigus vulgaris and dermatitis herpetiformis - highlighting a previously undescribed association between innate immune dysregulation and autoantibody-mediated skin diseases.


Pan-tumor harmonization of pathologic response assessment for standardized data collection in neoadjuvant IO trials (PATHdata): Final analysis of a multi-institutional reproducibility study.

June 2024

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15 Reads

Journal of Clinical Oncology

2515 Background: Immunotherapeutic agents are now being investigated for treating earlier-stage cancers. Radiographic assessment by RECIST, widely used to assess treatment response in clinical trials for advanced cancers, has limitations in the neoadjuvant setting; and pathologic response assessment is increasingly being used as a primary and/or secondary endpoint. To that end, a pan-tumor scoring system for assessing pathologic response was developed (1,2). This scoring system allows for the quantitative assessment of residual viable tumor (RVT) in multiple locations: i.e. primary and lymph node (LN) or distant metastases, akin to RECIST. %RVT scored using this system been associated with patient outcomes after treatment with anti-PD-1-based therapies. Additionally, %RVT in LN has been shown to have additive value to %RVT in the primary tumor when predicting patient survival (3). As a result, pathologists are now being asked to score pathologic response in the primary tumor and LN as a part of ongoing clinical trials and routine clinical care. Here, we evaluated the reproducibility of %RVT scoring using pan-tumor immune-related pathologic response criteria (irPRC). Methods: A multi-institutional, international study led by the Society for Immunotherapy of Cancer was initiated to assess the concordance of pathologic response assessment in resection specimens from patients treated with anti-PD-1-based therapies. Online lecture-based modules for irPRC scoring were developed, and 14 pathologists from multiple institutions, including academic and industry partners, were trained to score H&E-stained slides. The pathologists have scored n=37 pathology cases from resection specimens and on-treatment biopsies from >10 different tumor types, in part derived from phase II/III clinical trials. %RVT in the primary tumor and LN from patient specimens were scored separately (total of n=374 slides scored by each pathologist). Results: At the first interim analysis, scoring of pathologic response using irPRC was shown to be highly reproducible, irrespective of disease location (i.e. primary tumor vs lymph node metastasis). The second half of the study is nearing completion, and these reproducibility numbers will be finalized and presented in the final abstract. Extended analyses will also be presented that include subset analyses by tumor type. Conclusions: The results will be interpreted and presented in the context of the larger field for pathologic response assessment. A post-study survey completed by the participating pathologists will be used to refine irPRC training materials prior to dissemination to the wider immuno-oncology community. 1. Cottrell et al. Ann Oncol2018. 2. Stein et al. Clin Can Res 2020. 3. Deutsch, et al. Nat Med 2023.


The dermatopathologist-patient consultation program: A pilot study on patient perspectives and interest

April 2024

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7 Reads

Journal of Cutaneous Pathology

Background: Despite the integral contribution of dermatopathologists in diagnosing skin lesions, their role often remains unclear to patients, likely due to little face-to-face interaction. More healthcare systems have begun introducing patient-pathologist consultation programs that allow patients to discuss results with a pathologist and view tissue under a microscope. To our knowledge, only one study has been published exploring patient perspectives of these programs and no studies exist regarding interest in dermatopathology. Methods: An anonymous survey was distributed via online support groups for various dermatologic diagnoses. Results: Patients demonstrated a high level of interest in the dermatopathologist-patient consultation program, with 81.3% expressing at least moderate interest in discussing their diagnosis with a dermatopathologist and 79.2% expressing at least moderate interest in examining their tissue under the microscope with a dermatopathologist. The rationale for interest included various themes: (1) knowledge/understanding, (2) empowerment, (3) emotional support, (4) general interest, and (5) improved trust. Conclusions: Patients with cancerous and non-cancerous dermatologic diagnoses demonstrate high interest in a dermatopathologist-patient consultation program. Efforts to pilot this type of program can build upon the infrastructure of current pathologist consultation programs. Future efforts should be taken by hospital leadership, clinicians, and dermatopathologists to determine physician interest and address logistical challenges to the implementation of these programs.


Participant Demographics
Genes Implicated in Canonical Pathway Overlapping with Downregulated Proteins Canonical Pathway (P-Value) Genes
Proteomic profiling of CCCA reveals role of humoral immune response pathway and metabolic dysregulation
  • Article
  • Full-text available

January 2024

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34 Reads

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1 Citation

JID Innovations

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1–mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

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Ruxolitinib for Refractory PL-12 Antisynthetase Syndrome–Associated Angioedema-Like Panniculitis With Clonal T-Cell Receptor Gene Rearrangement

December 2023

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56 Reads

JAMA Dermatology

This case report describes a woman in her 30s who presented with a 3-year history of anti–PL-12 antisynthetase syndrome characterized by interstitial lung disease, arthritis, and myositis and was diagnosed with antisynthetase syndrome–associated panniculitis.


Citations (30)


... 65 The authors speculated that metformin's effects on CCCA could be attributed to its known agonistic effects on the adenosine monophosphate-activated protein kinase (AMPK) pathway with subsequent reduction in inflammation-induced fibrosis. 65,66 Microarray 67 and proteomic 68 analysis have shown that AMPK is known to be downregulated in CCCA , making it an interesting therapeutic target in this disease. A recent retrospective case series demonstrated that 67% (8/12) of patients with refractory CCCA had symptomatic improvement, and 50% (6/12) showed hair regrowth after 6 months of low-dose (500 mg/d) oral metformin treatment. ...

Reference:

Dermatologic Implications of Glycemic Control Medications for Patients with Type 2 Diabetes Mellitus
Proteomic profiling of CCCA reveals role of humoral immune response pathway and metabolic dysregulation

JID Innovations

... In several clinical trials, including the CheckMate-816 trial, which demonstrated the efficacy of neoadjuvant ICI combination chemotherapy, a pCR or major pathological response (MPR) was associated with a favorable postoperative prognosis [1][2][3]10]. Therefore, the pathological response to preoperative ICI combination chemotherapy is considered a predictor of postoperative prognosis [10]. ...

Association between pathologic response and survival after neoadjuvant therapy in lung cancer

Nature Medicine

... In recent years, there had been numerous attempts to tackle these challenges and to improve patient selection. One approach aims at combining multiple biomarkers to enhance performance compared to individual biomarkers ( 15 ). TMB and a T cell inflamed gene expression profile, when jointly assessed, had a superior ability to identify responders to PD-1 inhibition compared to individual biomarkers ( 16 ). ...

Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma

Cell Reports Medicine

... Four minutes of meeting [10][11][12][13] and one article [14] were included after the completion of bibliographic retrieval for more information. The trials named as AEGEAN [15][16][17][18], CheckMate 77T [11], CheckMate 816 [19][20][21][22][23][24][25][26][27][28][29], KEYNOTE-671 [12,30,31], NADIM II [32][33][34], Neotorch [14,35,36], RATIONALE-315 [10,13] and TD-FOREKNOW [37,38]. ...

LBA50 Analysis of pathological features and efficacy outcomes with neoadjuvant nivolumab (N) plus platinum-doublet chemotherapy (C) for resectable non-small cell lung cancer (NSCLC) in CheckMate 816
  • Citing Article
  • September 2022

Annals of Oncology

... In a review by Horna et al. of the 79 reported cases, 22% (17) were associated with underlying hematological malignancy including six cases of chronic myelomonocytic leukemia (CMML), three cases of acute myeloid leukemia (AML), and four cases of follicular lymphoma [5]. Lie et al. have reported an association with low-grade B-cell neoplasms in 31% of the cases, but the patient numbers were small [13]. In our case, there was no coexisting diagnosis of myeloid malignancy or MDS but clonal hematopoeisis was detected supporting an association between myeloid malignancies and IDCN. ...

Generalized Indeterminate Cell Histiocytosis Successfully Treated with Methotrexate

JAAD Case Reports

... Most of these are grade 1-2 and easily manageable. However, calciphylaxis is very rare and only a few cases are reported, especially for pemigatinib (8,9). Calciphylaxis is defined by the deposition of calcium hydroxyapatite in the skin and soft tissues. ...

Calciphylaxis Cutis Associated With Fibroblast Growth Factor Receptor (FGFR) Inhibitor Therapy: A New Challenge

Cureus

... This implies that treating patients with diabetic wounds with an MDP hydrogel would be a desirable option. Furthermore, two topical treatments involving the reformulation of valsartan into a self-assembling filament hydrogel by Nidadavolu et al. enabled the treatment to release over a prolonged period of time and functioned as a scaffold in the wound bed of diabetic rats [115]. In comparison to one wound that healed in the placebo group on day 23, peptide-based hydrogel treatments on fullthickness wounds in Zucker Diabetic Fatty (ZDF) rats produced faster rates of wound closure, and all val-filament treated wounds were completely closed. ...

Valsartan nano-filaments alter mitochondrial energetics and promote faster healing in diabetic rat wounds

Wound Repair and Regeneration

... The authors propose generalized differences between ancestries (6,8) exist in the molecular pathology underlying AD symptoms using primary citations which exclusively rely on racial categorization. For example, the authors claim to have "confirmed" a patient's ancestry in a clinic visit (8) (10)(11)(12)(13)(14), the aim is not to deride specific manuscripts but to dissect them for a teachable moment of how entrenched claims of racialized biologic determinism are unintentionally perpetuated in the scientific literature due to an uncritical assessment of the underlying evidence. ...

Transcriptomic analysis of atopic dermatitis in African Americans is characterized by Th2/Th17-centered cutaneous immune activation

... To identify immune cell composition and immunopathogenic populations in the index patient, functional immunophenotyping via high-parameter flow cytometry was performed and compared with erythrodermic controls (PRP and SS) as well as healthy controls with no known history of inflammatory or pruritic dermatologic conditions (n = 3) (Fig. 1A). Flow cytometric analysis was performed on peripheral blood mononuclear cells (PBMCs) stimulated with a pan-T stimulation (phorbol 12-myristate 13-acetate [PMA]-ionomycin) to characterize T cell differentiation, and on PBMCs stained with antigen-presenting cell (APC)-focused markers to characterize macrophages, monocytes, and dendritic cells (DCs) 13 . To further examine the granulocytic population, flow cytometric analysis was performed on the patients' whole blood. ...

Prurigo Nodularis is Characterized by Systemic and Cutaneous Th22 Immune Polarization
  • Citing Article
  • March 2021

Journal of Investigative Dermatology

... 2,3 While no phenotype-genotype correlation has been observed in most series, rare fusion partners (DCTN1, AP3D1, CO-L1A, LRRFIP2, and others) have been reported in cases lacking the classic EFH morphology. 16,17 ALK+ histiocytosis represents another recently recognized entity that may variably mimic our current cases. This rare disease frequently affects infants and small children and presents with skin and generalized manifestations. ...

Spindle cell variant of epithelioid cell histiocytoma (spindle cell histiocytoma) with ALK gene fusions: Cases series and review of the literature
  • Citing Article
  • November 2020

Journal of Cutaneous Pathology