Reporting Autoimmune Diseases in Hematopoietic Stem Cell Transplantation
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1 Reporting Autoimmune Diseases in Hematopoietic Stem Cell Transplantation Marcelo C. Pasquini, MD, MSc HVD05_1.ppt Outline Review of autoimmune diseases (AID). Role of transplantation for AID Data collection: points to consider. AID when present as a comorbidity. HVD05_2.ppt Introduction AID is a heterogenous group of diseases that have a link between the immune system and specific organ damage. Spectrum of disease intensities great impact on quality of life. Treatment: Immunosuppressive agents: MMF, CSA, tacrolimus, MTX, Cy Immunomodulatory Disease Modifying Antirheumatic Drugs (DMARDs) 1
2 Classification Connective tissue diseases: Systemic Sclerosis (SSc) Systemic Lupus Erythematous (SLE) Rheumatoid Arthritis (RA) Juvenile Idiopathic Arthritis (JIA) Neurologic Multiple Sclerosis (MS) Hematologic Idiopathic Thrombocytopenic Purpura (ITP) Hemolytic Anemia (HA) Gastrointestinal Inflammatory Bowel Diseases Vasculitis Wegner Granulomatosis Poyarteritis nodosa Endocrine Diabetes type I Thyroiditis Multiple Sclerosis Neurologic AID Direct myelin destruction and secondary oligodendrocytes and axonal damage. Symptoms start in early adulthood. Variable disease course but most often progressive Estimate that 50% of patients with MS will not able to walk within 15 years of onset. MS Clinical Course 2
3 MS Clinical Evaluation Diagnosis: Dissemination of time and space Performance of activities MRI evaluation CSF: Oligoclonal banding Multiple Sclerosis Diagnosis Criteria (Poser) Two attacks and clinical evidence of two separate lesions or one lesion and other clinical sign of the disease Symptoms: Multifocal neurologic deficits Treatment: Interferon, antibodies, corticosteroids. Systemic Sclerosis (Scleroderma) Chronic multisystem disorder of unknown etiology, characterized by skin thickening and several visceral organs. Target organs: Skin, heart, lungs, GI, blood vessels, kidneys. Two subsets: Diffuse cutaneous Limited cutaneous 3
4 SSc Disease Evaluation Clinical features Skin thickness Raynaud s Sclerodactily CREST Disease markers: ANA, Scl-70, ACA Evaluation of organ involvement: Echo, PFTs, creatinine clearance, right heart cath, endoscopy Raynaud s Phenomenon 4
5 Systemic Lupus Erythematous Collagen vascular disease with organ damage by autoantibodies or immune complexes. Women are affected in 90% of cases Clinical Manifestation: Fever Skin rash Muskoskeletal (myalgias and arthritis) Kidney disease Cardiopulmonary Hematologic, Neurologic, GI, others SLE Evaluation Symptoms and signs of organ involvement Presence of autoantibodies or low complement levels: ANA, dsdna, C3, C4 Rheumatoid Arthritis (RA) Chronic multisystem disease with persistent synovitis as the main characterisitic features Women are 3 more affected than men. Symmetric joint involvement Other manifestations: Rheumatoid nodules Vasculitis Pleural effusion and lung nodules Neutropenia 5
6 RA Evaluation Number of inflammed joints Rheumatoid Factor Radiologic evaluation Transplantations for AID Objective: Halt the autoimmunity process Allogeneic Graft versus autoimmunity Patient population: severe disease and refractory to previous therapies Transplant Indications MS: Except for primary progressive Scleroderma: SCOT trial and CTN 0602 SLE: Reduced intensity auto (?) RA: Frequent post transplant relapses 6
7 Most Common Diseases Reported to the CIBMTR Multiple Sclerosis Systemic Sclerosis Systemic Lupus Erythematous Idiopathic Thromobocytopenic Purpura Rheumatoid Arthritis Juvenile idiopathic arthritis Evan s Syndrome Hemolytic Anemia Other Autoimmune Diseases Allogeneic N Autologous N Data from North and South American Centers Points in Data Collection Similar time points: Diagnosis, pre-mobilization, prestem cell infusion, post transplant follow up. Diagnostic Criteria Prior Therapies Markers of disease activity Laboratory and imaging evaluation Evaluation of organ involvement: PFT, echocardiogram. Disease specific scales Pre-TED 7
8 CIBMTR Disease Inserts Recipient Baseline data and Post-HSCT Data MS SSc SLE RA JIA 8
9 Scales and Criteria MS Expanded Disability Severity Scale (EDSS) Scripps neurological rating scale Timed 25-foot walk 9-hole peg test Paced Auditory Serial Addition Test (PASAT) SSc Modified Rodnan Skin Score HVD05_3.ppt EDSS Scale from 0-10 according to the degree of disability O no disability 3 moderate disability 5 severe disability but ambulatory 7 unable to walk beyond 5 meters 9 bedridden with little interaction 10 death due to MS Scales and Criteria American College of Rheumatology diagnostic criteria (RA, SSc and SLE) RA: EULAR Joint count SLE: SLE Disease Activity Index (SLEDAI) Quality of life and functional Assessments SF36 Health Assessment Questionnaire 9
10 SLEDAI Difficulties in Reporting Evaluations are less objective than evaluation of malignant diseases. Different diagnostic criteria Several data points for collection Disease status evaluation relies on different scales AID as a Comorbidity Patients with minimally active disease at time of transplantation. How the transplant affects the disease. 10
11 Case Reports Diseases: RA, SLE, psoriasis, myasthenia gravis, MS, ulcerative colitis, ITP, Sjogren s Sydrome Most patient received an autologous HCT The majority experience long lasting remissions. Recipient Baseline Data Reporting AID as a Coexisting diseases What is relevant collect? Patients with active disease Patients requiring active antirheumatic medications Why collect? Understand the effect of HCT in early AID Understand whether the presence of AID affects post transplant outcomes. 11
12 AID and Transplantation: summary Primary indication Transplant is the main therapy. Patients with more advanced AID Coexisting Presence as a comorbidity Donor with autoimmune diseases Adoptive transfer of autoimmunity Post transplant chimerism and AID Conclusion HCT for AID is mainly investigational. Reporting data on AID is more laborious and requires subspecialties outside the transplant unit. It is important to recognize AID when present as a comorbidity. 12
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