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Research at Mass General
The Hematologic Malignancies Program encompasses research regarding leukemia, lymphoma and multiple myeloma, incorporating a substantial commitment to the understanding and use of stem cells in these diseases. It is closely integrated with the Bone Marrow Transplant Program, sharing commitment, faculty and research efforts.
The Hematological Malignancy Program is an integral part of the Massachusetts General Hospital Cancer Center. Our mission is to provide state of the art cutting edge treatments with the goal of improving patient care and survival. The Centers program focuses on innovative patient-based clinical research providing a critical interface between basic laboratory research and the delivery of novel therapeutics to our patients. Our program includes the centers for myeloma, lymphoma, leukemia and stem cell transplantation. We are committed to the development of novel treatment strategies informed by laboratory-based science. We focus on several areas of laboratory research including stem cell biology and the interactions of stem cells with the niche. We study the myeloma tumor cell in the context of the bone marrow microenvironment with a specific focus on the bone compartment. These studies allow us to identify and validate novel targets and clinical grade compounds and translate them rapidly into clinical trials in the treatment of multiple myeloma and the associated bone disease. These studies are largely informed by our understanding of the biology of multiple myeloma. Those tumor cell microenvironment interactions that can be translated into application are prioritized and several clinical trials with novel targeted agents either alone or in combination are currently underway. These clinical trials are accompanied by specific translational endpoints allowing us to validate and confirm the biologic sequelae of interfering with specific targets in our patients with myeloma.
The Center for Leukemia provides outstanding, compassionate medical and nursing care to patients with acute and chronic leukemias and myelodysplasia. The program has grown approximately 400% in the past four years, and treats about 70 new acute leukemia patients each year. Patients are cared for by a multidisciplinary team that includes hematology amd oncology physicians, consulting physicians from infectious disease and other medical subspecialties, radiology, and pathology, and specially trained nursing staff. Weekly meetings are held with the clinical team and the clinical research office to coordinate care. The focus of our research efforts is novel treatments to improve survival.
A linked clinical database and tissue bank is available for basic science and clinical investigators. The clinical database is a joint effort with the Dana-Farber Cancer Center. All patients with acute leukemia are offered participation and may elect to bank tissue (bone marrow) samples and/or clinical information. The goals of the bank and database are to provide:
Our program is an active member of the Cancer and Leukemia Group B (CALGB) and the Bone Marrow Transplant Program Clinical Trials Network (CTN). Acute Myelogenous Leukemia patients with AML under the age of 60 are induced on a Phase III CALGB protocol utilizing standard chemotherapy with and without Mylotarg®. Patients over the age of 60 traditionally do poorly, with higher rates of induction failure and relapse after standard induction chemotherapy. We have recently completed a Phase I study of induction chemotherapy with daunorubicin and ARA-C combined with the proteasome inhibitor, Velcade® (Drs. Amrein and Attar) Patients over the age of 60 who are not optimal induction therapy candidates may be treated on multicenter study of the drug Clofarabine. Patients with high risk leukemia or who have relapsed are candidates for stem cell transplantation. Allogeneic stem cell transplantation is an option, and the Massachusetts General Hospital (MGH) Leukemia and Bone Marrow Transplant programs are closely intertwined. Only 30% of patients have a matched donor in their family. Our area of interest is in alternative donor transplants and we have two active protocols for umbilical cord blood transplantation. Over 50 adult patients have been treated with double cord blood transplants and a reduced intensity conditioning regimen in the Harvard Cancer Center. Our current reduced intensity protocol utilizes a novel GVHD prophylaxis regimen (PI: Karen Ballen). Lineage specific chimerism and immune reconstitution are also being studied as part of this trial. An additional multicenter NIH funded study (PI: Karen Ballen) study investigates parathyroid hormone after double cord blood transplantation using a myeloablative regimen. Parathyroid hormone, through its activity on the stem cell niche, has been shown in a murine model to improve engraftment and survival. Haploidentical transplants from a mismatched family member using a T cell depletion strategy are another option for patients without matched donors (PI: Thomas Spitzer).
Patients under the age of 50 are treated on the DFCI Adult ALL Consortium Study utilizing a pediatric type regimen for these patients. A study is under development for patients over the age of 50.
Patients with CML are offered participation in the CML upfront study of Imatinib or Dasatinib, both given orally.
CLL patients, previously treated with fludarabine may participate in an MGH Investigator initiated study of Dasatinib (PI: Phil Amrein).
The myelodysplastic syndromes have traditionally been treated with supportive care. Recently, drugs used for multiple myeloma, such as thalidomide and revlimid, have been shown to have efficacy. We have just received IRB approval for a Phase I study of Revlimid® and Velcade® for patients with MDS.
Patients with relapsed or refractory leukemia pose a difficult management problem. For advanced leukemia patients who are not eligible for intensive transplant strategies, a study of cellular immune therapy is available (PI: Bimal Dey) Preliminary data suggests that very low doses of total body irradiation (100cGy TBI) followed by donor lymphocyte infusion can lead to donor chimerism and tumor response in heavily pretreated hematologic malignancy patients. This approach has now been extended to haploidentical transplants.
The Center for Lymphoma conducts a robust and innovative research effort focused around clinical trials of promising new cancer therapies. Our program is comprised of physician-scientists from the Divisions of Hematology and Oncology; Surgical Oncology and Infectious Disease; and the Departments of Radiation Oncology; Pathology and Dermatology. We also have a strong laboratory research program working to identify novel targets for therapies at the cellular and molecular levels, and to understand what pathologic features may predict a response to one novel treatment versus another.
We are both motivated and informed by the people we care for every day, and are committed to improving treatment options for the future. As a founding member of the DF/HCC, we provide access to many clinical trials that are only available at our center, as well as those that are offered nationwide and internationally. We offer clinical trials ranging from early trials (phase I) of new cancer drugs to later phase II and phase III studies of promising drugs and drug combinations in all subtypes of lymphoma.
We offer clinical trial opportunities for people with both newly diagnosed and previously treated lymphomas across a broad range of subtypes, including:
The Center for Multiple Myeloma is committed to providing comprehensive clinical care in a compassionate environment. Our patients receive the most updated treatments and have access to cutting edge research and novel targeted agents. Our multidisciplinary approach provides access to the Bone Marrow Transplant Program where autologous and allogeneic stem cell transplants are performed. Depending on the needs of our patient, we involve radiation oncology, orthopedic surgery, spine surgery, and interventional radiology for procedures and treatments such as radiation therapy including proton beam therapy, spine stabilization and vertebral augmentation procedures.
A clinical database and tissue bank is a part of our research endeavors. All patients with multiple myeloma and other related plasma cell dyscrasias are offered participation and may elect to bank tissue (bone marrow and blood) samples and/or clinical information. The goals of the bank and database are to provide:
Our program is an active member of the Dana-Farber Harvard Cancer Center and offers patients access to a wide range of clinical trials for the treatment of active symptomatic multiple myeloma, maintenance strategies and options for supportive care therapies.
Novel agents have been incorporated in the treatment of multiple myeloma. We have several studies using combinations of these novel agents in the upfront newly diagnosed patients with the goal of achieving durable and prolonged remissions. Our studies combine the current most active agents for myeloma including bortezomib (Velcade®) and lenalidomide (Revlimid®).
We have several exciting combination studies with novel targeted agents such as mTOR inhibitors, cell cyle inhibitors, heat shock protein inhibitors and histone deacytalase inhibitors. These are being studied either alone or in combination with some of the backbone agents such as Lenalidomide and Bortezomib. All of these clinical trials have been informed by strong preclinical rational with the goal of finding the most active combination for the treatment of myeloma.
Autologous transplantation is considered standard of care for younger myeloma patients. Our bone marrow transplant center offers high dose therapy with stem cell rescue with either autologous or allogeneic stem cells for the treatment of myeloma. We have several studies in the post transplant phase looking at immunological approaches such as vaccination strategies (dendritic cell/myeloma cell fusion vaccine) and maintenance approaches with agents such as Lenalidomide with the view to treating minimal residual disease and prolonging remissions.
Bone disease is a morbidity associated with the majority of myeloma patients. The standard of care for myeloma patients with bone disease is the use of intravenous aminobisphosphonates. The new ASCO guidelines recommend the use of these agents for 2 years followed by re-evaluation for the need to continue these agents. This stems largely from concerns of long-term toxicities of aminobisphosphonates such as osteonecrosis of the jaw. We have several studies evaluating alternate aminobisphosphonate use in myeloma patients as well as use of other novel agents in the treatment of bone disease.
1 Ballen KK, Gilliland DG, Guinan EC, Hsieh CC, Parsons SK, Rimm IJ, Ferrara JL, Bierer BE, Weinstein HJ, Antin JH Bone marrow transplantation for therapy-related myelodysplasia: comparison with primary myelodysplasia. Bone Marrow Transplant. 12/30/1997; 9(9); 737-43.
2 Ballen KK, Ford PA, Waitkus H, Emmons RV, Levy W, Doyle P, Stewart FM, Quesenberry PJ, Becker PS Successful autologous bone marrow transplant without the use of blood product support. Bone Marrow Transplant. 11/03/2000; 2(2); 227-9.
3 Ballen KK New trends in umbilical cord blood transplantation. Blood. 05/03/2005; 10(10); 3786-92.
4 Noronha V, Berliner N, Ballen KK, Lacy J, Kracher J, Baehring J, Henson JW Treatment-related myelodysplasia/AML in a patient with a history of breast cancer and an oligodendroglioma treated with temozolomide: case study and review of the literature. Neuro Oncol. 07/06/2006; 3(3); 280-3.
5 Ballen KK, Spitzer TR, Yeap BY, McAfee S, Dey BR, Attar E, Haspel R, Kao G, Liney D, Alyea E, Lee S, Cutler C, Ho V, Soiffer R, Antin JH Double unrelated reduced-intensity umbilical cord blood transplantation in adults. Biol Blood Marrow Transplant. 01/15/2007; 1(1); 82-9.
6 Ballen KK, Shpall EJ, Avigan D, Yeap BY, Fisher DC, McDermott K, Dey BR, Attar E, McAfee S, Konopleva M, Antin JH, Spitzer TR Phase I trial of parathyroid hormone to facilitate stem cell mobilization. Biol Blood Marrow Transplant. 06/20/2007; 7(7); 838-43.
7 Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg. 06/19/2007; 65(7); 1328-31.
8 Duda DG, Cohen KS, Kozin SV, Perentes JY, Fukumura D, Scadden DT, Jain RK Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood. 03/23/2006; 107(7); 2774-6.
9 Kim WJ, Okimoto RA, Purton LE, Goodwin M, Haserlat SM, Dayyani F, Sweetser DA, McClatchey AI, Bernard OA, Look AT, Bell DW, Scadden DT, Haber DA Mutations in the neutral sphingomyelinase gene SMPD3 implicate the ceramide pathway in human leukemias. Blood. 02/26/2008;
10 Spitzer TR, Ambinder RF, Lee JY, Kaplan LD, Wachsman W, Straus DJ, Aboulafia DM, Scadden DT Dose-reduced busulfan, cyclophosphamide, and autologous stem cell transplantation for human immunodeficiency virus-associated lymphoma: AIDS Malignancy Consortium study 020. Biol Blood Marrow Transplant. 12/26/2007; 14(1); 59-66.
11 Shaffer J, Villard J, Means TK, Alexander S, Dombkowski D, Dey BR, McAfee S, Ballen KK, Saidman S, Preffer FI, Sachs DH, Spitzer TR, Sykes M Regulatory T-cell recovery in recipients of haploidentical nonmyeloablative hematopoietic cell transplantation with a humanized anti-CD2 mAb, MEDI-507, with or without fludarabine. Exp Hematol. 06/25/2007; 35(7); 1140-52.
12 Dey BR, Shaffer J, Yee AJ, McAfee S, Caron M, Power K, Ting DT, Colby C, Preffer F, Ballen K, Attar E, Saidman S, Tarbell N, Sachs D, Sykes M, Spitzer TR Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. Bone Marrow Transplant. 06/20/2007; 40(1); 19-27.
13 Cina RA, Wikiel KJ, Lee PW, Cameron AM, Hettiarachy S, Rowland H, Goodrich J, Colby C, Spitzer TR, Neville DM, Huang CA Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation. Transplantation. 06/23/2006; 81(12); 1677-85.
14 Ballen KK, Colvin G, Dey BR, Porter D, Westervelt P, Spitzer TR, Quesenberry PJ Cellular immune therapy for refractory cancers: novel therapeutic strategies. Exp Hematol. 12/12/2005; 33(12); 1427-35.
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