Comprehensive Molecular and Clinical Evaluation of Pediatric and Adult MDS

Background: Myelodysplastic syndromes (MDS) occur when the cells that make blood cells are abnormal. There are limited treatment options for MDS. Researchers want to learn more through this natural history study so they can develop better treatments. Objective: To study the natural course of MDS and MDS/myeloproliferative neoplasms (MPN) and collect biological samples that can help researchers understand the disease. Eligibility: People with suspected or confirmed MDS or MDS/MPN. Healthy donors are also needed. They can be people who are scheduled to donate bone marrow at NIH for a relative, or they may be providing bone marrow in another study. Design: Participants will be screened with a medical history. Participants will have a physical exam. They will give blood and urine samples. They will discuss their symptoms, medications, and ability to perform their normal activities. They will complete surveys about how they are feeling. Participants will have a bone marrow biopsy. A needle will be inserted through a small cut. Bone marrow will be removed. A small piece of bone may be removed. Participants may have an optional skin biopsy. Participants may give optional saliva and stool samples. They may collect these samples at home and mail them to NIH. Participants may undergo optional apheresis. One or two needles or intravenous (IV) lines will be placed in their arm, neck, or groin veins. Blood will be removed. A machine will separate out the white cells. The rest of the blood will be returned to the participant. Participants will be contacted for follow-up once a year for up to 20 years. Healthy donors will have marrow collected for this study during their scheduled procedure with no follow-up.

Background: * Myelodysplastic syndromes (MDS) are heterogenous stem cell disorders characterized by ineffective hematopoiesis resulting in cellular dysplasia, peripheral cytopenias, and increased risk for transformation to acute myeloid leukemia (AML). * There are limited treatments options, all of which have unimpressive response rates and limited response durations, with the only potential cure being hematopoietic stem cell transplant (HSCT). Unfortunately, as a disease of the elderly (average age of diagnosis \>65 years), most participants are not eligible for HSCT due to advanced age and other comorbidities. * It is critical we further elucidate the processes that lead to disease manifestation in an effort to develop novel therapeutic strategies and to alter the natural history of the disease. * Chronic inflammation is central to disease pathology, as evidenced by pro-inflammatory cytokines in the bone marrow milieu, transcriptional upregulation of inflammatory genes, and dysregulation of innate immune signaling pathways. * We hypothesize the chronic inflammation drives MDS pathogenesis and may be exploited therapeutically. Further, we anticipate the correlatives proposed here to be used not only to uncover critical disease driving pathways, but also to potentially reveal disease and treatment response biomarkers, as well to better refine both diagnosis and prognosis. Objectives: \- To characterize the natural history of myelodysplastic syndromes (MDS) and to assess overall and progression free survival Eligibility: Participants with MDS * Either sex, any age * Histologically or cytologically suspected or confirmed MDS, MDS/MPN, (MDS/MPN- RS-T, MDS/MPN-U, CMML, aCML) or sAML with antecedent MDS or MDS/MPN OR * diagnosis with a precursor condition that is associated with a risk of progression to MDS. * Any amount of prior therapy and may be currently receiving MDS-directed therapy. * Must have an identified primary oncologist, hematologist or generalist outside NIH who agrees to manage care and any diagnostic findings provided by this study. Controls * Either sex and must be eligible for marrow donation per clinical center requirements. * No history of hematological malignancies listed as inclusion criteria for the group of participants with MDS or current autoimmune disease * Control marrow volunteers must be scheduled for bone marrow harvest for clinical application, or if evaluated for malignancy, have a bone marrow aspirate scheduled to rule out bone marrow involvement at which time additional samples will be taken as controls for the research purposes of this study. Design: * This is a natural history and biospecimen acquisition protocol for participants with Myelodysplastic Syndromes (MDS). * In addition, we will perform a comprehensive research analysis based on the hypothesis that chronic inflammation in MDS arising from a variety of contributors results in hematopoietic differentiation and maturation blocks leading to dysplasia, cytopenias, and disease progression, and that these may be exploited for novel therapeutic targeting strategies. * This is a single site (Clinical Center) study that will accrue 1000 MDS participants and 100 marrow controls (transplant donor or non-involved malignancy) volunteers over a 20-year study accrual duration. * Diagnostic testing will be performed as is routine for these participants in addition to planned research correlative analyses. Follow-up will occur approximately annually to assess status and survival.