• Blood Cancer Prevention of Progression Clinic (BCPC)

    Although many patients are diagnosed with earlier phases (also known as "precursor conditions") of blood cancers, in most cases, there are no effective, disease-modifying therapies available. This means that most patients do not receive treatment until their cancer progresses.

    Precursor conditions include early cases of chronic lymphocytic leukemia called monoclonal B cell lymphocytosis (MBL); early cases of multiple myeloma or Waldenström's Macroglobulinemia called monoclonal gammopathy of undermined significance (MGUS); and early cases of myelodysplastic syndrome and myeloproliferative disorders.

    In order to understand why some patients with these precursor conditions go on to develop progressive disease, while others do not show progression — and to develop better targeted therapeutic agents to prevent progression, or even eliminate the disease before it leads to symptoms — the Dana-Farber Cancer Institute/Brigham and Women's Cancer Center (DF/BWCC) Blood Cancer Prevention of Progression Clinic (BCPC) has been created.

    About

    Although the last decade has seen the development of effective target therapies for patients with blood cancers, their clinical use has been hampered by drug resistance, clonal evolution, and disease progression — all of which limit the extent and duration of patients' response.

    Of note, most blood cancers — including multiple myeloma, chronic lymphocytic leukemia, and acute myeloid leukemia — are preceded by clonal disease states that then progress into disease. However, the genomic, genetic, and epigenetic factors governing the process of progression and therapeutic resistance have not been systematically characterized.

    The BCPC is a research initiative focused on understanding the progression and clonal evolution of blood cancers, with an ultimate aim to develop targeted therapeutic agents that can eliminate the early clones of disease.

     

    Conditions Studied by the Blood Cancer Prevention of Progression Clinic

    • Early Myelodysplastic Syndrome (MDS): MDS is a type of cancer in which the bone marrow does not make enough healthy blood cells. In advanced MDS, there are abnormal leukemia-like "blast" cells in the blood and/or bone marrow, and often abnormal chromosomes in the marrow, as well. These findings are less common in early MDS. MDS, especially advanced MDS, has a risk of progressing to acute myeloid leukemia (AML); AML is defined by the presence of at least 20 percent blast cells in the blood or marrow. Often patients have mild blood count abnormalities, such as unexplained anemia, that could be a result of MDS, but that do not meet established diagnostic criteria for MDS. Such patients are sometimes said to have "Idiopathic Cytopenias of Undetermined Significance" (ICUS -- idiopathic means of uncertain cause, and a cytopenia is a low blood count) and in the past these patients were just observed over time with periodic blood counts. Newer molecular testing may help identify patients with ICUS who actually have early MDS and are at higher risk of developing advanced stage MDS or AML. Learn more about MDS. 
    • Myeloprofliferative Neoplasms (MPN): MPN is a category of cancer in which the bone marrow produces excessive amounts of blood cells, often resulting in high blood counts or enlargement of the spleen. Patients with MPN have a risk of developing blood clots and of progressing to acute myeloid leukemia (AML); AML is defined by the presence of at least 20 percent blast cells in the blood or marrow. This category is composed of three major myeloid disorders: essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). ET and PV can turn into MF oover time. There are also some uncommon disorders that have features of both MPN and myelodysplastic syndrome (MDS -- see above), such as chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and refractory anemia with ring sideroblasts and thrombocytosis (RARS-T). Learn more about MPN. 
    • Asymptomatic Multiple Myeloma and Waldenström's Macroglobulinemia, including Monoclonal Gammopathy of Undermined Significance (MGUS), Smoldering Multiple Myeloma (SMM), and Smoldering Waldenström's Macroglobulinemia (SWM)
      • MGUS: In this type of plasma cell neoplasm, there are abnormal plasma cells in the bone marrow – but there is no cancer. The abnormal plasma cells produce what is called monoclonal (M) protein, which may be found during a routine blood or urine test. In most patients, the amount of M protein stays the same and there are no symptoms or problems. In some patients, MGUS may later become a more serious condition or cancer, such as multiple myeloma, lymphoma, or Waldenström's Macroglobulinemia.
      • SMM: SMM is a precursor condition in which high concentrations of abnormal plasma cells are found in the bone marrow and secrete monoclonal (M) proteins and/or free light-chains (FLCs). SMM is characterized by the absence of end organ damage; M protein concentrations of 3 g/dL or greater; 10 percent or more abnormal plasma cells in the bone marrow; or a combination of all of these factors.
      • SWM: SWM is a precursor condition in which high concentrations of abnormal lymphocytes and plasma cells are found in the bone marrow and secrete M proteins of IgM type. SWM is characterized by the absence of end organ damage; M protein concentrations of 3 g/dL or greater; 10 percent or more abnormal lymphocytes and plasma cells in the bone marrow; or a combination of all of these factors.
      Learn more about multiple myeloma and related disorders. 
    • Early-Stage, Asymptomatic Chronic Lymphocytic Leukemia (CLL), including Monoclonal B Cell Lymphocytosis (MBL): CLL is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). It is a disease that usually gets worse slowly. CLL is the second most common type of leukemia in adults, and often occurs during or after middle age; it rarely occurs in children. Learn more about CLL. 
    • Early-Stage, Asymptomatic Low-Grade Lymphomas: These are cancers of the lymphoid cells, and include follicular lymphoma, lymphoplasmacytic lymphoma, marginal zone lymphoma, and splenic marginal zone lymphoma. In many cases, these lymphomas grow very slowly and do not require treatment for many years.
    • Other precursor conditions or clonal genetic abnormalities of the blood/bone marrow that do not meet criteria for symptomatic hematological malignancy, or patients exposed to prior chemotherapies (e. g., alkylating agents, platinum derivatives, taxanes, topo-2 inhibitors, anti-metabolites, systemic radioisotopes)
     

    Blood Cancer Prevention of Progression Clinic Leadership

    Robert Soiffer, MD  

    Robert Soiffer, MD
    Co-Principal Investigator, Blood Cancer Prevention of Progression Clinic
    Chief, DF/BWCC Division of Hematologic Malignancies and Co-Chief, DF/BWCC Adult Stem Cell Transplantation Program
    Professor of Medicine, Harvard Medical School

    Dr. Soiffer graduated from New York University School of Medicine in 1983, and trained in internal medicine at Brigham and Women's Hospital, where he also was chief medical resident.

    He joined Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) in 1988, after completing a medical oncology fellowship. Dr. Soiffer has served as vice president (2006), president (2007), and immediate past president (2008) of the American Society of Blood and Marrow Transplantation.

    Irene Ghobrial, MD  

    Irene Ghobrial, MD
    Co-Principal Investigator, Blood Cancer Prevention of Progression Clinic
    Director, Michele & Stephen Kirsch Laboratory, Dana-Farber Cancer Institute
    Medical Oncologist, DF/BWCC Jerome Lipper Multiple Myeloma Center
    Associate Professor of Medicine, Harvard Medical School

    Dr. Ghobrial is a physician-scientist who specializes in early precursor conditions of multiple myeloma and Waldenström's Macroglobulinemia, specifically MGUS and smoldering diseases. Her research interests are in the area of cell trafficking and cell metastasis in B cell malignancies and the malignant bone marrow niches. She is the principal investigator of several clinical trials in both multiple myeloma and Waldenström's Macroglobulinemia.

    David Steensma, MD  

    David P. Steensma, MD
    Co-Principal Investigator, Blood Cancer Prevention of Progression Clinic
    Medical Oncologist, DF/BWCC Adult Leukemia Program
    Associate Professor of Medicine, Harvard Medical School

    Dr. Steensma's primary area of clinical activity and research focus is the myelodysplastic syndromes (MDS) and related conditions. His research activity includes development of new therapies, as well as discovery of new somatic genetic mutations important in the pathobiology of this difficult and poorly-understood group of smoldering myeloid neoplasms.

    Dr. Steensma is also involved in collaborations with several laboratory-based scientists, particularly Benjamin Ebert, MD, PhD and Mark Fleming, MD, DPhil, to try to discover new pathways disturbed in MDS and related disorders – with the goal of finding pathways that can be exploited therapeutically.

    Benjamin Ebert, MD, PhD  

    Benjamin Ebert, MD, PhD
    Co-Principal Investigator, Blood Cancer Prevention of Progression Clinic
    Medical Oncologist, DF/BWCC
    Assistant Professor of Medicine, Harvard Medical School

    Dr. Ebert's laboratory studies the biology and genetics of hematologic malignancies and other hematologic disorders. His group employs a range of genomic and proteomic technologies, as well as classical cellular and molecular biology approaches, to investigate the molecular basis of specific human diseases.

    Major focuses of the laboratory are myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Dr. Ebert identified a gene that plays a central role in the pathophysiology of MDS with deletions of chromosome 5q. These findings revealed a molecular link between del(5q) MDS and congenital bone marrow syndromes such as Diamond Blackfan anemia. The Ebert laboratory has also definied sets of mutations in MDS that are associated with various disease phenotypes, including overall survival and response to specific therapies.

    Investigators by Disease Group

    Monoclonal Gammopathy of Undermined Significance (MGUS) and Smoldering Multiple Myeloma

    Core leaders

    Irene Ghobrial, MD
    Jacob Laubach, MD
    Nikhil Munshi, MD
    Robert Schlossman, MD 

    Other team members

    Kenneth Anderson, MD
    Claudia Paba-Prada, MD
    Paul Richardson, MD 

    Immunoglobulin (Ig)M-MGUS and Smoldering Waldenström's Macroglobulinemia

    Core leaders

    Jorge Castillo, MD
    Irene Ghobrial, MD 

    Other team members

    Steven Treon, MD, PhD 

    Myelodysplastic Syndrome (MDS)

    Core leaders

    Benjamin Ebert, MD, PhD
    R. Coleman Lindsley, MD, PhD
    David Steensma, MD 

    Other team members

    Daniel DeAngelo, MD, PhD
    Richard Stone, MD 

    Myeloproliferative Neoplasms (MPN)

    Core leaders

    Ann Mullally, MD
    David Steensma, MD 

    Other team members

    Martha Wadleigh, MD 

    Monoclonal B Cell Lymphocytosis (MBL) and Early Chronic Lymphocytic Leukemia (CLL)

    Core leader

    Matthew Davids, MD 

    Other team members

    Jennifer Brown, MD, PhD
    Catherine Wu, MD 

    Low-Grade Lymphomas, including Early-Stage Follicular Lymphoma

    Core leader

    Ann LaCasce, MD 

    Other team members

    Jennifer Brown, MD, PhD
    Arnold Freedman, MD
    Catherine Wu, MD 

    Other Precursor Conditions or Clonal Genetic Abnormalities of the Bone Marrow/Blood

    Core leaders

    Benjamin Ebert, MD, PhD
    Aric Parnes, MD 

    Other team members

    Nancy Berliner, MD 

    Relevant Dana-Farber Clinical Trials

    Enrolling

    • Study of Precursor Hematological Malignancies to Assess the Relationship between Molecular Events of Progression and Clinical Outcomes (Protocol 14-174)
     

    Information for Patients Who May be Eligible to Participate

    Study of Precursor Hematological Malignancies to Assess the Relationship between Molecular Events of Progression and Clinical Outcomes

    An important note: Taking part in the Blood Cancer Prevention of Progression Clinic (BCPC) research study is voluntary. Instead of being in this research study, you may continue to obtain your clinical care without participating in the study. Your decision not to participate will not affect your clinical care in any way.

    The research study seeks to perform research tests on specimens obtained during the course of clinical care, bank the specimens and material derived from the specimens, and link the specimen data to clinical data. It also seeks to obtain blood and a buccal swab or mouthwash for germline genomic testing, bank this material and the DNA derived from it, share de-identified genomic data with other investigators or centralized repositories. Finally, it seeks to permit providers to see the results of these research tests and permit re-contact for potential treatment or clinical trial enrollment opportunities.

    The following patients are eligible to participate in this study:

    • Patients with Known or Suspected Precursor Hematological Cancer including the following subgroups of diseases:
      • Early MDS, including pathologically-confirmed MDS (IPSS Low/Int-1; IPSS-R Very Low/Low) and idiopathic cytopenias of undetermined significance (ICUS);
      • Myeloproliferative neoplasms (MPN);
      • Asymptomatic Multiple Myeloma and Waldenstrom Macroglobulinemia such as monoclonal gammopathy of undermined significance (MGUS) or Smoldering Multiple Myeloma (SMM or SWM);
      • Monoclonal B cell lymphocytosis (MBL);
      • Early stage asymptomatic low-grade lymphomas; or
      • Other precursor conditions or clonal genetic abnormalities of the blood/bone marrow that do not meet criteria for symptomatic hematological malignancy, or patients exposed to prior chemotherapies (e. g., alkylating agents, platinum derivatives, taxanes, topo-2 inhibitors, anti-metabolites, systemic radioisotopes)
       
    • Patients must be at least 18 years of age to participate in this research.
    • In accordance with NIH guidelines, women and members of minority groups and their subpopulations will be included in this protocol.
    What are the benefits of taking part in this research study?

    It is important to understand that this is not a clinical study being done to benefit you directly. Therefore, taking part in this research study may not directly benefit you. However, the information gained from your participation is likely to generate important information which will help future patients with blood and individuals at high risk of developing those diseases.

    Why is this research study taking place?

    Blood cancers occur when the molecules that control normal cell growth are damaged. Many of these changes can be detected by directly examining parts of the cancer or cells in blood. Several alterations that occur repeatedly in certain types of blood cancers have already been identified, and these discoveries have led to the development of new drugs that target those alterations. More remain to be discovered.

    The purpose of this research study is to perform these molecular analyses on your tissues (obtained from biopsies), blood, or other body fluids such as saliva or urine. Importantly, this study will use tissue specimens that have already been collected as part of your clinical care. Your tissue sample may be used to create a living tissue sample (called a "cell line") that can be grown in the laboratory. This allows researchers to have an unlimited supply of your cells in the future without asking for more samples from you.

    What kind of information could be found in this study, and will I be able to see it?

    These studies are being done to add to our knowledge of how genes and other factors affect cancer. We are gathering this knowledge by studying groups of people, and the study is not meant to test your personal medical status. For that reason we will not ordinarily give you the results of our research on your samples unless there is clear evidence of actions that could benefit your health.

     
     
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