About

Alain H. Rook, M.D., is a Professor of Dermatology at the University of Pennsylvania's Perelman School of Medicine. He is affiliated with the Department of Dermatology and practices at the Perelman Center for Advanced Medicine in Philadelphia, PA. Dr. Rook's educational background includes a B.A. in Biology from Brandeis University, obtained in 1971, and an M.D. in Medicine from the University of Michigan, completed in 1975. His professional focus is on dermatology, with particular expertise in cutaneous T-cell lymphomas, including mycosis fungoides and Sézary syndrome. He has contributed to research on the usage and safety of topical tacrolimus, epigenetic regulation of apoptosis in cutaneous T-cell lymphoma, and combination therapies for these conditions. Dr. Rook has authored numerous publications in the field, advancing understanding and treatment of dermatological lymphomas.

Research topics

• Medicine
• Dermatology
• Internal medicine
• Immunology
• Pathology
• Surgery
• Oncology
• Urology
• Gastroenterology

Selected publications

• Outcomes in octo- and nonagenarians treated with mogamulizumab-based regimens for cutaneous T-cell lymphoma

  Blood · 2025-11-03

  article

  Abstract Introduction: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL), with a median age at diagnosis of 55 years old. However, many patients (pts) are older, and its incidence is four-fold increased among pts over 70. As life expectancy rises, octogenarians will comprise an increasing proportion of the CTCL population; however, there are currently no consensus guidelines for managing this older demographic. Mogamulizumab (moga), a monoclonal antibody targeting C-C chemokine receptor 4 (CCR4),demonstrated remarkable efficacy in CTCL in the phase 3 MAVORIC trial. We sought to evaluate the effiacy and tolerability of moga-based regiments in patients aged 80 and older that were under-represented within this trial cohort. Methods: This single-center retrospective observational study included CTCL pts aged ≥80 who initiated moga therapy between December 2017 and December 2024, with at least 6 months of follow-up.Global treatment response was assessed by 2022 consensus criteria, and toxicity per CTCAE v5.0. Baseline characteristics were analyzed using independent t-tests, Fisher's exact tests, or Pearson's chi-square tests. Overall survival (OS) and progression-free survival (PFS) were co-primary endpoints analyzed via Kaplan-Meier log-rank and Cox proportional hazards models. Results: Nineteen pts were identified (13 SS [68%], 6 MF [32%]); median age was 82 (range:80–94). Ten (53%) were male and 16 (84%) were White. Thirteen (68%) had ECOG 0-1 and 15 (79%) had advanced stage disease. LDH was elevated in 15 pts (79%) and 8 (42%) had a history of large cell transformation. Median lines of treatment prior to moga was 3 (range:1-8). All pts received moga at 1 mg/kg on days 1, 8, 15, and 22 of cycle 1, then biweekly; 8 pts (42%) later transitioned to 3–4-week intervals. Combination therapy was used based on institutional practice in 13 pts (68%) including interferon alpha (6/13,46%), bexarotene (6/13,46%), interferon gamma (7/13,54%) and extracorporeal photopheresis (8/13, 62%). Two pts (11%) received total skin electron beam therapy during their treatment course. Median duration of moga treatment was 9 months (range 2-51 months). Seventeen pts (89%) achieved a global response (6/17 [35%] complete, 11/17 [65%] partial), while two (11%) had stable disease. Compartmental responses were highest in blood (15/16, 94%), followed by skin (17/19,89%) and nodes (2/3,67%). No pts exhibited visceral disease. Median length of follow up was 14.4 months (range: 6-72 months). Median duration of response was 10 months (range 3-49 months). Median PFS was 12.6 months (95% CI 6.8-32.3 months). Thirteen pts (68%) were alive at last follow-up; and median OS was not reached. Cause of death was attributable to CTCL in only one patient (5%) and there were no treatment-related deaths. Six pts (32%) experienced grade 1-2 infusion reactions, all manageable with subsequent additional premedication. Cytopenias were observed in 15 pts (79%) with 7/15 ( 46%) having grade 3 or 4 cytopenias. Biopsy confirmed moga-associated rash (MAR) was observed in 9 pts (47%) all of which resolved with topical corticosteroids (7/9, 78%) and/or oral methotrexate (2/9, 22%). Other notable non-hematologic adverse events included grade 2 thyroiditis in one patient (5%) and Grade 1-2 diarrhea in two pts (10.5%). Reasons for cessation of moga therapy included MAR (4,21%), progression of disease (5/19,26%) or patient preference (4/19, 21%). Six pts (32%) remained on therapy at last follow-up. Discussion: To our knowledge, this is the first real-world study to evaluate moga-based regimens in patients 80 or older with MF/SS. Notably, this patient population was largely not represented within the MAVORIC trial which led to moga approval for MF/SS. Our results suggest that moga-based treatment regimens have a significant therapeutic role in elderly pts with MF/SS, with an observed response rate of 89%, in line with our previously reported institutional experience. Given its safety and efficacy profile, moga -based regimens can play an important role in CTCL in elderly pts. However further investigation in prospective clinical trials is warranted to more clearly delineate efficacy in this patient population.

  PublisherDOI

• Harnessing the CD2 axis to broaden and enhance the efficacy of CAR T cell therapies

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-26

  preprintOpen access

  ABSTRACT Patients with T-cell lymphomas and leukemias have overall poor outcomes due to the lack of targeted and effective treatments, particularly in the relapsed and refractory settings. Development of chimeric antigen receptor (CAR) T-cells against T-cell neoplasms is limited by a lack of discriminating T-cell antigens that allow for effective anti-tumor responses while preventing CAR T-cell fratricide. We hypothesized that targeting CD2, a pan-T-cell antigen, using anti-CD2 CAR T-cells engineered without CD2 expression (CART2), would support CAR T-cell manufacturability and preclinical efficacy. Optimized CD2-knockout CART2, generated using CRISPR-Cas9, eradicated primary patient-derived CD2+ hematological neoplasms in vitro and in vivo, secreted effector cytokines, and exhibited adequate proliferative capacity. Nevertheless, CD2 has a key costimulatory function, and its deletion could lead to CAR T-cell dysfunction. Therefore, we tested the role of the CD2:CD58 axis in CAR T-cells, using the anti-CD19 CART models. We demonstrate that CD2 loss attenuates CART19 efficacy by reducing avidity for tumor antigen, co-stimulation, and ultimately in vivo activity. Analogously, we show that tumor CD58 loss reduces CART19 efficacy. To overcome this issue, we developed a novel PD-1:CD2 switch receptor that rescues intracellular CD2 signaling, particularly when PD-L1 is engaged, resulting in improved in vivo outcomes. Collectively, we studied the role of CD2 both as a target for CAR T cell therapy and as a critical costimulatory protein, whose signaling can be rescued using the PD-1:CD2 switch receptor. This receptor can be incorporated into CAR T-cells and provides an effective strategy to overcome CD2-signaling deficiencies.

  PublisherOA PDFDOI

• Leveraging Radiation and Graft Versus Lymphoma Effect for the Management of Relapsed/Refractory Cutaneous T-Cell Lymphoma

  Transplantation and Cellular Therapy · 2025-02-01

  article
  PublisherDOI

• Cutaneous T-Cell Lymphoma: Yin-Yang Effects of Transcription Factors HLF and NFIL3 in Regulation of Malignant T-Cell Markers in the Context of HDAC Inhibitor Romidepsin Treatment

  Cancers · 2025-07-17

  articleOpen access

  BACKGROUND/OBJECTIVES: We examined the in vivo effects of successive treatments with the histone deacetylase (HDAC) inhibitor romidepsin in patients with cutaneous T-cell lymphoma (CTCL), using changes in gene expression in peripheral blood mononuclear cells (PBMCs). METHODS: Exploiting data from a highly responsive CTCL patient through 12 months of treatment, we identified a malignant cell predictor (MCP), a gene signature associated with the diminishing numbers of circulating malignant cells. RESULTS: The MCP was successfully validated in the patient's relapse sample 9 months after treatment was terminated and via an independent set of CTCL patient samples. CONCLUSIONS: The MCP set of genes contained novel CTCL markers, including membrane-associated proteins not normally expressed in lymphocytes. A subclass of those markers was also detectable in residual malignant cells undetected by flow cytometry in remission samples from a patient who relapsed 10 months later. We identified a subset of transcriptional regulators, miRNAs and methylation patterns associated with the effect of progressive treatments revealing potential mechanisms of transcriptional dysregulation and functional effects in the malignant cells. We demonstrate a role for transcriptional activator HLF, over-expressed in malignant cells, and downregulated transcriptional-suppressor and immune-modulator NFIL3, as regulators of CTCL-specific genes.

  PublisherOA PDFDOI

• Pembrolizumab in Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome

  JAMA Dermatology · 2025-04-02 · 4 citations

  articleOpen access

  This case series reported survival, response, and safety outcomes for patients with mycosis fungoides or Sézary syndrome who received pembrolizumab at a single institution.

  PublisherOA PDFDOI

• From Mechanism to Marker: Single-cell insights reveal predictive immune signatures of response to ECP in Sézary syndrome

  European Journal of Cancer · 2025-10-01

  articleSenior author
  PublisherDOI

• Preliminary evaluation of the safety and feasibility of toll-like receptor ligand CB101 combined with hypofractionated radiation therapy in canine head and neck cancer: a pilot study

  Veterinary oncology. · 2025-08-03 · 1 citations

  articleOpen access

  Radiation therapy (RT) is a common treatment modality for dogs with locally advanced head and neck tumors. Most dogs experience a clinical benefit secondary to RT, however, long term remissions are rare. This study evaluates the feasibility and safety profile of intratumoral CBC101 (a proprietary hydrogel-based injectable resiquimod formulation), a toll-like receptor (TLR) 7/8 agonist with immunomodulatory properties, when used in combination with radiation therapy. Three dogs with histologically confirmed head/neck cancers were prospectively enrolled. A baseline CT scan was performed. Dogs received palliative radiation therapy (8 Gy × 4) in conjunction with intratumoral CB101. A follow-up CT scan was performed at week 12 to assess tumor response and to evaluate for metastatic disease. Intratumoral CB101 was well-tolerated, feasible, and produced minimal adverse effects. Only one grade 1 adverse event was attributable to CB101; all other adverse events were expected radiation therapy side effects. The data obtained from this preliminary study will be used for further investigation into appropriate dosing and timing of intratumoral resiquimod or other TLRs, with eventual escalation into phase II and III clinical trials.

  PublisherOA PDFDOI

• High Throughput Sequencing May Predict Relapse Risk in Patients With Sézary Syndrome

  immuneACCESS · 2025-07-29

  datasetSenior author

  We retrospectively evaluated relapse risk in eight Sézary syndrome patients over a median 19.1-year follow-up using high-throughput T-cell receptor sequencing to detect minimal residual disease (MRD) at remission. Among five MRD-positive patients, three relapsed, whereas none of three MRD-negative relapsed.

  PublisherDOI

• Clinical Features and Outcomes of Patients with Non-Erythrodermic Mycosis Fungoides with High Blood Tumor Burden

  Blood Neoplasia · 2025-11-03

  articleOpen access

  Abstract Introduction: Sézary Syndrome (SS) is an aggressive variant of cutaneous T-cell lymphoma involving diffuse erythroderma (T4) and leukemic disease (B2). Prognosis is poor, with 5-year overall survival ranging from 30-50%. A unique cohort of patients diagnosed with B2 (high blood tumor burden) leukemic disease without erythroderma has previously been described. However, little is known about these patients' clinical features and prognosis. Methods: A retrospective study of SS patients diagnosed after 1/1/2010 was conducted at the University of Pennsylvania. Patients with B2 disease with or without T4 disease at diagnosis were identified. B2 disease was defined as positive blood T-cell receptor clonality and Sézary cell count ≥1,000 cells/µl by flow cytometry (CD4+/CD7- or CD4+/CD26-). T4 was defined as erythroderma involving ≥80% body surface area (BSA). Fisher's exact test and Wilcoxon rank-sum test were used for statistical significance. Patients with HTLV-I/II and B2 disease utilizing only percentages of lymphocytes/elevated CD4:CD8 ratio criteria were excluded as per modified ISCLC/USCLC/EORTC criteria. T0/B2 patients were diagnosed based on Sézary immunophenotype and were ruled out for other diagnoses (e.g. T-PLL, T-LGLL, ATLL). Results: Two cohorts of patients with B2 disease were identified: 21 patients without erythroderma (non-erythrodermic SS, neSS) and 79 classic SS patients (T4/B2 stage at diagnosis, cSS). There were no significant differences in age (70 and 71.5 years), race (76% and 74% white, 24% and 25% black) or absolute Sézary cell count at diagnosis (2,225 vs 2,812 cells/µl) for neSS versus cSS, respectively. A significantly greater proportion of neSS patients were female (76.2% vs 44.3%, p = 0.0034), but significantly fewer had N2/3 nodal disease (4.8% vs 43.4%, p=0.0002). One neSS patient had visceral disease pathologically confirmed in the liver (M1) at diagnosis. This did not occur in the cSS patient cohort. Of the neSS patients, 3 had no skin involvement (T0), 6 had patch/plaque disease <10% BSA (T1a/b), and 13 had patch/plaque disease >10% BSA (T2a/b). Pruritus was reported in 55% (11/20) of patients at diagnosis. With a median follow-up of 5 years, 3 patients later developed erythroderma (T4). Among these patients, the median time to T4 disease was 1.9 years after B2 diagnosis. Median follow-up for the 18 patients who never developed erythroderma was 4.5 years. Interrogation of 9 neSS patient samples for cancer-associated mutations showed known disease-associated variants in TP53 (n=3), PTEN (n=1), DNMT3A (n=1) and EGR2 (n=1). The median number of systemic treatments for neSS patients was similar to cSS patients (3.5 vs 3). Among the neSS patient cohort, systemic treatments included extracorporeal photopheresis (ECP)(n=16), bexarotene (n=11), interferon (IFN)(n=8), mogamulizumab (n=8), romidepsin (n=4), brentuximab vedotin (BV)(n=3), pembrolizumab (n=3), chemotherapy (n=1), methotrexate (n=1) and clinical trial (n=1). None underwent hematopoietic stem cell transplant. Four underwent surveillance/topical-only treatment without systemic therapy. Radiation was commonly used, with 4 patients receiving localized radiation, 4 receiving total skin electron beam therapy, and 4 receiving narrow-band UV phototherapy. ECP was the most common first-line therapy. Of the 3 patients who later developed erythroderma, treatments prior to developing T4 disease included ECP (n=3), IFN (n=3), bexarotene (n=3), BV (n=2) and mogamulizumab (n=1). When compared to the cSS patients, outcomes were significantly better for neSS patients. 2-year overall survival (OS) for neSS vs cSS was 100% (18/18) versus 74% (54/73) (p = 0.0275). 5-year OS was 100% (11/11) versus 34.5% (19/55) (p<0.0001). Conclusions: Non-erythrodermic patients with B2 disease (T0-2/B2, neSS) had a significantly better prognosis compared to classic SS patients with erythroderma (T4/B2, cSS). neSS patients received multiple systemic treatments; however, 4 patients with minimal skin disease were managed with surveillance or skin-directed therapy alone. Only 3 neSS patients (9.6%) later developed erythroderma. Although neSS patients were more often women and less likely to have nodal disease at diagnosis, other clinical characteristics including age, race and Sézary cell count at diagnosis were similar to cSS patients. Further exploration into mechanisms driving these clinical differences and the optimal management of this unique cohort of patients is needed.

  PublisherDOI

• Immunobiology and treatment of cutaneous T-cell lymphoma

  Expert Review of Clinical Immunology · 2024-03-04

  reviewSenior authorCorresponding

  INTRODUCTION: Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders. AREAS COVERED: In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome. EXPERT OPINION: Recent advances in immunology have provided new insights into the biology of malignant T cells. This in turn has led to the development of new therapies that modulate the immune system to facilitate tumor clearance or target specific aspects of tumor biology.

  PublisherDOI

Recent grants

• CD164 as a novel biomarker for malignant CD4 T cells in cutaneous T cell lymphoma

  NIH · $378k · 2013–2015

• NIH Grant R01CA100499

  NIH · $1.7M · 2009

• NIH Grant R01CA089442

  NIH · $3.7M · 2007

• NIH Grant R01CA058841

  NIH · $695k · 1997

• Reversing immune evasion and enhancing immune detection with topical resiquimod

  NIH · $1.9M · 2018–2023

Frequent coauthors

• Ellen J. Kim

  University of Pennsylvania

  86 shared

• Stuart R. Lessin

  74 shared

• Carmela C. Vittorio

  Hospital of the University of Pennsylvania

  68 shared

• Gerald V. Quinnan

  Emmes (United States)

  61 shared

• Eric C. Vonderheid

  Sidney Kimmel Cancer Center

  59 shared

• Maria Wysocka

  49 shared

• Henry Masur

  48 shared

• Louise C. Showe

  48 shared

Labs

• Alain H. Rook LabPI

Education

• B.A., Biology

  Brandeis University

  1971

• M.D., Medicine

  University of Michigan

  1975