The Consult Service consists of myself, Dr. Edward Cowen (Staff Clinician) and Dr. Heidi Kong (Associate Investigator). Dr. Cowen and myself see the bulk of the consult patients with Dr. Kong taking care of a half day clinic once a week. She is in training to do clinical trials. As previously stated, we participate as Associate Investigators in some protocols initiated by other branches at the same time that we are Principal Investigators on our own protocols. Dr. Maria L. Turner: Principal Investigator Phase 1 study of topical romidepsin in Cutaneous T-Cell Lymphoma (CTCL);CTCL natural history of disease;UVR/UVA phototoxicity testing . These are all open to accrual. Associate Investigator (Dermatology Branch protocols) Botox for painful leiomyomas;Imatinib for sclerotic GVHD;Melanocytic nevi and melanoma; Standard of care;Sampling skin and blood for research Associate Investigator (non-Derm Branch initiated trials): Hereditary Renal Cell Carcinoma (HLRCC);Humanized anti-TAC for Adult T-cell Lymphoma (ATL);Natural History of Chronic GVHD;Ontak for ATL;Treatment of CD25+ CTCL with LMB-2;Phase I/II Yttrium for Tac expressing malignancies;Microbiome in normal human volunteers;Microbiome in atopic dermatitis;protocols on the study of patients with autoinflammatory diseases;Rituximabindermatomyositis/polymyositis. Dr. Edward Cowen: Principal Investigator Botox for painful leiomyomas;Imatinib for sclerotic chronic GVHD Associate Investigator (Dermatology Branch protocols) same as M.L. Turner Associate Investigator (non-Dermatology Branch protocols) Natural History of GVHD;Reduced intensity transplants for malignant lymphomas/leukemias;Phase II Montelukast for bronchiolitis obliterans;Sirolimus for Cowdens;Reduced intensity transplants for hematologic malignancies. Dr. Heidi Kong: Associate Investigator (Derm Branch protocols) - Phase I study of topical romidepsin for CTCL; UVR/UVA phototoxicity testing;Associate Investigatory (Non-Derm Br. Protocols) - Microbiome in normal human volunteers;Microbiome in atopic dermatitis Dr. Heidi Kong and I finished the recruitment and tissue acquisition for one part of protocol 06-C0198. This part of the protocol had for its aim to determine the transcriptional profile of the epidermal response to solar-simulated UVR exposure in normal subjects with doxycycline-induced phototoxicity and relating their reactions to their CYP450 profiles. The microarrays from these samples have been done and results remain to be analyzed. Dr. Kong and I have started recruiting patients with early cutaneous T-cell lymphoma (CTCL)/mycosis fungoides to a new protocol testing the safety of topical depsipeptide (a histone deacetylase inhibitor) for the treatment of early CTCL. This is a toxicity protocol and we are currently at dose level 3, with no evidence of toxicity nor benefit. We are in the process of submitting an amendment to allow us to try increasing concentrations over 25 sq cm of skin until we get to the concentration that cause mild irritation. Once the maximal tolerated dose is determined, we will proceed to applications over larger areas. Dr. Heidi Kong is now an associate investigator and is spearheading both trials under my supervision. Dr. Kong and I continue to collaborate with Dr. Julie Segre (NHGRI and Sequencing Center) on projects exploring the human cutaneous microbiome. Dr. Kong and I provide the clinical expertise for patient selection while Dr. Segre is responsible for the molecular biology arm. The results of a pilot study of the cutaneous microbiome in 5 normal subjects has already been published (see list of publications). Our biggest achievement this year was a publication in Science of the microbiome at 20 different sites in 10 normal human volunteers. We are well into recruitment of patients with atopic dermatitis, Jobs syndrome and methicillin resistant staphylococcus aureus (MRSA) infection. There are strong clinical indications that atopic dermatitis is exacerbated and perpetuated by the presence of staphylococcus aureus on the skin. It also is calmed by the administration of antibiotics. How this interrelationship works and how it can be altered without the need for long-term antibiotic therapy are just some of the questions that we intend to pursue. In the future, we plan to explore why patients with late CTCL are subject to skin staphylococcal infections such that it is a very common if not the most common cause their death. The chronic graft versus host disease (GVHD) collaborative effort continues with Dr. Edward Cowen concentrating on the cutaneous aspects. He is spearheading 3 trials on chronic cutaneous graft versus host disease (GVHD)which will be described in the project section of this report. Dr. Stratton, a gynecologist, and I continue to evaluate and treat women with vulvo-vaginal complications of chronic GVHD. These activities have resulted in several publications that will be listed separately. Dr. Cowen has become recognized as an expert on the cutaneous manifestations of GVHD publishing and giving presentations on cutaneous GVHD to various groups around the country (Harvard, Tufts, U. of Pennsylvania, the American Academy of Dermatology, regional dermatologic societies, and the World Congress of Dermatology.) Collaborative clinical research is extremely active by virtue of the busy consultation service. Dr. Cowen has become increasingly involved in these collaborative efforts, now that he shares in the coverage of the Consultation Service. Collaborative projects can be seen by looking at the list of protocols that each of us are involved in. The newly discovered mutations in pyrin genes in patients with several periodic fever syndromes, and the availability of biologic therapies that have efficacy in the resulting autoinflammatory diseases have introduced a new group of patients to the clinic. We are now systematically characterizing cutaneous manifestations and assessing responses to treatment in patients with PAPA syndrome, Behcets and DIRA. We are also evaluating the relationship between panniculitis and calcium deposition in patients with juvenile dermatomyosistis and assessing the benefit of Rituximab in this disease. Dr. Cowen and I are actively involved in the continuing operation of the multidisciplinary chronic graft versus host disease (GVHD) consortium not only within NCI but nationally. He is the Principal Investigator on a new protocol investigating the usefulness of Imatinib in the treatment of sclerotic skin disease associated with chronic GVHD. Only lately has it been recognized that chronic GVHD results in significant involvement in the female genital tract. My expertise in vulvovaginal diseases has enabled me to study the manifestations and treatment of vulvovginal GVHD. Since Dr. Hwang left, I have taken over the Natural History of CTCL protocol. My cooperative efforts with Dr. Susan Bates, who was the PI on the use of systemic depsipeptide for late CTCL/PTCL has resulted in the approval of Depsipeptide for this indication by the Food and Drug Administration
