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SCIENTIFIC RESEARCH AND OTHER PUBLICATIONS

EDUCATION AND PATIENT WELFARE  ARE IMPORTANT ASPECTS OF THE OVERALL SCOPE OF THE LYMPHOMA FOUNDATION (Click on this link to Publications of Special Interest by Friends of the Lymphoma Foundation e.g. Savoring Life a thoughtful memoir by David M. Klein and other publications.)


THE MAJOR ROLE OF THE LYMPHOMA FOUNDATION, HOWEVER, IS TO FUND CLINICAL AND BASIC RESEARCH AT THE CUTTING EDGE OF SCIENTIFIC ADVANCEMENT
 

 

IN THE QUEST FOR A CANCER VACCINE THE FOLLOWING WAS REPORTED

TO THE LYMPHOMA FOUNDATION IN 2007

 

TO THE LYMPHOMA FOUNDATION FROMMaria Lia Palomba, MD and Alan N. Houghton, MD:  Regarding a clinical trial of anti-CD20 DNA vaccine in patients with relapsed or refractory lymphoma: “We have developed a clinical trial for patients with relapsed or refractory lymphoma, and we are in the final stages of attaining approval to begin the trial, which we anticipate will be in the early fall 2007, pending no request to changes to the protocol:The protocol was approved by the Department of Medicine Steering Committee, Research Council and passed initial IRB review at MSKCC (along with several other committees). The protocol was approved by the Recombinant DNA Advisory Committee of the NIH after public review and following minor modifications. A pre-IND teleconference with the FDA raised only minor concerns. Toxicity studies in rabbits are now completed and show no evidence of toxic effects.The CD20 vaccine to be used in the proposed study has been manufactured and vialed, and the GMP-manufactured product is being stored at MSKCC in the Pharmacy Department and ready for use following protocol approval by the FDA. An IND application was recently submitted to the FDA. The protocol is also simultaneously undergoing final reviews by the MSKCC Institutional Biosafety Committee and the Institutional Review Board. Bringing this vaccine to clinical trials has been challenging but we are delighted to report that the clinical trial should begin in the next few months.”

 

THE FOLLOWING CLINICAL AND BASIC RESEARCH WAS SUPPORTED BY LYMPHOMA FOUNDATION GRANTS IN 2005-2006 (A PARTIAL LIST)
 

JOACHIM YAHALOM, M.D. et al: MALT LYMPHOMA: In October 2006 Dr. Yahalom reported that at the Memorial Sloan Kettering Cancer Center treatment of Mucosa Associated Lymphoid Tissue (MALT) lymphoma with low-dose radiotherapy was developed. Dr. Kathryn Beal, a former Lacher Radiation Oncology Fellow worked on this project during her fellowship resulting in the following reports:

Beal K, Yeung H, Yahalom J. FDG-PET scanning for detection and staging of extranodal marginal zone lymphomas of the MALT type: A report of 42 cases. Annals of Oncology 2005 Mar;16(3):473-80 Beal, K„ Yahalom, J. Mucosa Associated Lymphoid Tissue (MALT) Lymphoma: Characteristics and Treatment Outcome of 195 Cases were initially reported as oral presentations at the 9 th International Conference of Malignant Lymphoma in June 2005 in Lugano, Switzerland. BONE LYMPHOMA: A review of patients with primary bone lymphoma was accepted for publication in the journal Cancer: Beal, K, Allen, L, Yahalom, J. Primary Bone Lymphoma: Treatment results and prognostic factors with longterm follow-up of 82 patients

RAYMOND COMENZO, M.D. et al: SYSTEMIC AL (Ig light-chain) AMYLOIDOSIS: In September

2006 Dr. Comenzo, Medical Director of the Cytotherapy Laboratory of the Memonal Sloan Kettering Cancer Center reported that the following research regarding Systemic AL (Ig light-chain) amyloidosis and multiple myeloma was published with grant support from the Lymphoma Foundation and the Lymphoma Foundation's special Werner and Elaine Dannheiser Fund for Research on the Biology of Aging: Comenzo RL, Zhou P, Fleisher M, Clark B, Teruya-Feldstein J. Seeking confidence in the diagnosis of systemic AL (Ig light-chain) amyloidosis: patients can have both monoclonal gammopathies and hereditary amyloid proteins. Blood 2006; 107:3489-91; Hassoun H, Reich L, Klimek VM, Dhodapkar M, Cohen A, Kewalramani I: Zimman R, Drake L, Riedel ER, Hedvat CV; Teruya-Feldstein J; Filippa DA,

Fleisher M, Nimer SD, Comenzo RL. MULTIPLE MYELOMA: Doxorubicin and dexamethasone followed by thalidomide and dexamethasone is an effective well tolerated initial therapy for multiple myeloma. Br J Haematol 2006; 132: 155-61; Comenzo RL, Hassoun H, Kewalramani I: Klimek V; Dhodapkar M, Reich L, Teruya- Feldstein J; Fleisher M, Filippa D, Nimer SD. Results of a phase Ill Itrial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation. Leukemia 2006;20: 345-9; Zhou P, Kalakonda N; Comenzo RL. Changes in gene expression profiles of multiple myeloma cells induced by arsenic trioxide (ATO): possible mechanisms to explain ATO resistance in vivo. Br J Haematol 2005 128:636-44; Gupta S, Zhou

P, Hassoun H, Kewalramani I: Reich L, Costello S, Drake L, Klimek V; Dhodapkar M, Teruya-Feldstein J; Hedvat C, Kalakonda N; Fleisher M, Filippa D, Qin J; Nimer SD, Comenzo RL. Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial. Bone Marrow Transplant 2005 35:441-7.

SURESH JHANWAR, Ph.D., et al: Dr. Jhanwar is the Director of the Cytogenetics Laboratory of Memonal

Sloan Kettering Cancer Center and with grant support from the Lymphoma Foundation he continues his research of NEUROFIBROMATOSIS TYPE I. In November 2006 Dr. Jhanwar reported the following: "We have recently performed molecular genetic analysis on the cell lines derived from four such tumors [NF I related cancers]. The underlying premise for such studies was based on the expectations that results generated would provide important clues relating to molecular basis of transformation and progression of the NF-1 related cancers, and possible molecular markers for therapeutic approaches."

TARUN KEWALRAMANI, M.D. et al: With the assistance of Lymphoma Foundation grants Dr. Kewalramani conducted research concerning PERIPHERAL T-CELL LYMPHOMA... AND AUTOLOGOUS STEM CELL TRANSPLANTATION THERAPY.

Autologous transplantation for relapsed or primary refractory peripheral T-cell lymphoma. Kewalramani T, Zelenetz AD, Hamlin P, Yahalom J, Horwitz S, Nimer SD, Moskowitz CH. British Journal of Haematology 2006;134:202-207.This research "...disputes the notion the patients with relapsed or primary refractory peripheral T-cell lymphoma do not benefit from autologous transplantation and establishes that the results of autologous transplantation are indeed equivalent to those for diffuse large B-cell lymphoma." And... "Since it is extremely unlikely that a randomized study of autologous transplantation in this patient population will ever be performed..." this data, along with other reports, should... "establish autologous transplantation as a standard treatment for these patients." Another important innovative clinical research observation was also published regarding a means of distinguishing infectious from non-infectious causes of fever during autologous stem cell transplantation by measuring various cytokines in the blood: Serum IL-12:1L-6 ratio reliably distinguishes infectious from non-infectious causes of fever during autologous stem cell transplantation Tuma RA, Pamer EG, Panageas K, Almyroudis N, Sohn S, Rice RD,Galinkin D, Blain M, Montefusco M, Nimer SD, Kewalramani T. Cytotherapy (2006) Vol. 8, No. 4, 327- 334 and Tuma RA, Pamer EG, Panageas K, Almyroudis N, Sohn S, Rice RD,Galinkin D, Blain M, Montefusco M, Nimer SD, Kewalramani T.  Dr. Kewalramani noted in his report to the Lymphoma Foundation that the results of this research "...proposes a unique method to assess patients with post-engraftment fever after autologous transplantation, demonstrating that serum levels of IL-12 and IL-6 [cytokines] can reliably discriminate between infectious and non-infectious causes of fever. If confirmed, these data have the potential to significantly alter the management of patients undergoing autologous transplantation."

 

PROGRESS TOWARD A CLINICAL TRIAL OF A NOVEL CD20 DNA VACCINE

IN PATIENTS WITH LYMPHOMA

 

DR. ALAN HOUGHTON and his research team at the Memorial Sloan Kettering Cancer Center (MSKCC) have developed a clinical trial for patients with lymphoma to test the heteroclitic CD20 extracellular domain vaccine. Dr. Houghton's report of September 14, 2006 to the Lymphoma Foundation stated: "The clinical trial was approved by the Memorial Sloan-Kettering Research Council and five other MSKCC committees and by the Recombinant DNA Advisory Committee of the NIH. The next step, which is currently being carried out, is safety testing the vaccine at doses equivalent to the ones that will be used in humans, using laboratory animals (rabbits). Once the safety of the vaccine is fully established (which we fully expect), the trial will undergo review by the Food & Drug Administration and finally by the MSKCC Institutional Review Board and the Biosafety Committee. We expect the study to be ready to open within 9

months. This will be the first vaccine trial for lymphoma based on a common antigen rather than patient specific proteins (idiotypes), which are currently being tested at other centers. The Lymphoma Foundation support has been central to the translation of this vaccine approach into a clinical trial."

 

MORE RESEARCH CONCERNING LEUKEMIA AND LYMPHOMA VACCINES

 

DR. DAVID SCHEINBERG stated (in August 2006) in his progress report to the Lymphoma Foundation with

regard to research supported in part by Lymphoma Foundation grants : "Work in the area of leukemia and lymphoma vaccines continues to move forward. The bcr-abl vaccine is now being tested at multiple sites in the United States and in Europe. We should know within a year whether it has significant activity against CML (Chronic Myelocytic Leukemia). We have developed a vaccine candidate for WT-1, which is found in a variety of leukemias, some solid tumors, and some lymphomas. This is expected to enter trials within the next several months. We have also recently embarked on a plan to make a vaccine for mantle cell lymphoma using cyclin DIA, which is found over expressed in mantle cell lymphoma, as our target."

 

GENETIC RESEARCH

 

KENNETH OFFIT, M.D., et al: Dr. Offit and his research group conducted cancer and lymphoma genetics research supported in part by Lymphoma Foundation grants that was reported in 2005-2006: Localization of Breast Cancer Susceptibility Loci by Genome-Wide SNP Linkage Disequilibrium Mapping Ellis NA, Kirchhoff T, Mitra N, Ye T, Chuai S, Huang H, Nafa K, Norton L, Neuhausen S, Gordon D, Streuwing JP, Naiod S Offit K. Genetic Epidemiology 2006,30(1):48-61 MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner Bond GL, Hirshfield KM, KirchhoffT, Alexe G, Bond EE, Robins H, Basrtel F, Taubert H, Wuerl P, Hait W, Toppmeyer D, Offit K, Levine AJ.. Cancer Research 2006,66(10):5104-10 Accuracy of BRCAI and BRCA2 founder mutation analysis in formalin-fixed and paraffin-embedded (FFPE) tissue Adank MA, Brogi E, Bogomolniy F, Wadsworth EA, Lafaro KJ, Yee CJ, KirchhoffT, Meijers-Heijboer EJ, KaufiNK, Boyd J, Offit K. Familial Cancer 2006 (in press) Cancer Genetic Testing and Assisted Reproduction. Offit K, Kohut K, Clagett B, Wadsworth E, Cummings S, White M, Sagi M, Bernstein D, Davis JG. Journal of Clinical Oncology 2006. Electronically published online by the Journal of Clinical Oncology in July, 2006 and was formally published in October 2006 The TP53 Mutational spectrum and frequency of CHEK2* 1100deIC in Li Fraumeni-like kindreds Siddiqui, R, Onel K, Facio F, Nafa D, Robles-Diaz R, Kauff N, Huang H, Robson M, Ellis N, Offit K. Familial Cancer 2005; 4(2):177-81 Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Kaklamani VG, Baddi L, Liu J, Rosman D, Phukan S, Bradley C, Hegarty C, McDaniel B, Rademaker A, Oddoux C, Ostrer H, Michel LS, Huang H, Chen Y, Ahsan H, Oft K, Pasche B. Cancer Research 2005; 65(8):3454-61. Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Shaag A, Walsh T, Renbaum P, Kirchhoff T, Nafa K, Shiovitz S, Mandell JB, Welcsh P, Lee MK, Ellis N, Offit K, Levy-Lahad E, King MC. Human Molecular Genetics 2005; 14:555-63.


MONOCLONAL ANTIBODY THERAPY

 

JOHN LEONARD, M.D., et al, reported: The assistance of the Lymphoma Foundation has supported the following [at the Weill Cornell Medical Center] in very meaningful ways": 1) Further assessment of novel monoclonal antibodies in B-cell malignancies. 2) Evaluation of combination regimens with rituximab and biologic agents (including IL-2, anti-CD80, revlimid and CpG immunostimulatory oligonucleotides). 3) Studies of radioimmunotherapy as part of initial therapy for lymphoma. We have reported exciting data on fludarabine + 1-131 tositumomab (JCO), and are currently evaluating CVP and CHOP in sequential combination with 1-131 tositumomab as upfront treatment. Initial results are promising. 4) Novel initial therapies for aggressive lymphoma. We continue to explore ways to improve outcomes with chemotherapy, particularly combinations of CHOP chemotherapy and rituximab along with agents such as Bcl-2 antisense, idiotype vaccines, and bortezomib (Velcade). And the following research was published: Leonard JP, Coleman M, Ketas J, Ashe M, Fiore JM, Furman R, Niesvizky R, Shore T, Chadbum A, Horne H, Kovacs J, Ding CL, Wegener WL, Horak ID, Goldenberg DM. Combination antibody therapy with epratuzumab (humanized anti-CD22 antibody) and rituximab (chimeric anti-CD20 antibody) in relapsed/refractory non-Hodgkin's lymphoma (NHL). J Clin Oncol, 2005:23(22):5044-51. Leonard JP, Coleman M, Kostakoglu L, Chadbum A, Cesarman E, Furman R, Schuster MW, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by Bexxar (tositumomab and Iodine 1 131 tositumomab) for untreated follicular lymphoma. J Clin Oncol, 2005:23(24):5696-704. Leonard JP, Furman RR, Ruan J, Coleman M. New developments in immunotherapy for non-Hodgkin's lymphoma. Curr Oncol Rep, 2005;7(5):364-71. Leonard JP. Targeting CD20 in follicular NHL: Novel anti-CD20 therapies, antibody engineering, and the use of radioimmunoconjugates, Hematology (Am Soc Hematol Educ Program), 2005;335-9. Dosik AD, Coleman M, Kostakoglu L, Furman R, Fiore JM, Kroll S, Stewart P, Vallabhajosula S, Goldsmith SJ, Leonard JP. Subsequent therapy can be administered following tositumomab and iodine-131 tositumomab treatment for non-Hodgkin's lymphoma, Cancer. 2006;106(3):616-2 . Ruan J, Coleman M, Leonard JP. Mantle cell lymphoma: current concepts in biology and treatment. Cancer Treat Res. 2006;131:141-59. Furman RR, Coleman M, Leonard JP. Monoclonal antibodies and radioimmunotherapy for lymphoma. Cancer Treat Res, 2006; 131:221-50. Leonard JP, Furman RR, Coleman M. Proteosome inhibition with bortezomib, a new therapeutic strategy for non-Hodgkin 's lymphoma. Int J. Cancer, 2006; 119(5):971-9. Siegel AB, Lachs M, Coleman M, Niesvizky R, Leonard JP. Lymphoma in the elderly: novel functional assessment techniques provide better discrimination among patients than traditional performance status measures Clin Lymphoma Myeloma, 2006 Jul;7(1):65-9.

THE FOLLOWING IS A PARTIAL LIST OF IMPORTANT RESEARCH PUBLICATIONS SUPPORTED  BY  LYMPHOMA  FOUNDATION  GRANTS IN 2004-2005

SCHEINBERG - Controlling the Errant Products of a Targeted Atomic Nanogenerator, J.S. Jaggi, B.J. Kappel, M.R. McDevitt, C.D. Flombau, C.Cabassa, D.A.  Scheinberg, Submitted for publication;  Targeted Deletion of T-Cell Clones Using Alpha-Emitting Suicide MHC Tetramers,  R.R. Yuan, P. Wong, M.R. McDevitt E. Doubrovina, I. Leiner, W. Bommann, R. O’Reilly, E.G. Pamer, D.A. Scheinberg, Blood, Vol 104, No. 8, 15 October 2004;  A Multivalent BCR-ABL Fusion Peptide Vaccination Trial in Patients with Chronic Myeoid Leukemia, K. Cathcart, J. Pinilla-Ibarz, T. Korontsvit, J. Schwartz, V. Zakhaleva, E.B. Papadopoulos, D.A. Scheinberg,  Blood, Vol. 103: 1032-1042, 1 February 2004.

SCHEINBERG/HOUGHTON -  CD8+  T-Cell-Dependent Immunity Following Xenogeneic DNA Immunization against CD20 in a Tumor Challenge Model of B-Cell Lymphoma, M.L. Palomba, W.K. Roberts, T. Dao, G. Manukian, J.A. Guevara-Patino, J.D. Wolchok. D.A. Scheinberg, A.N. Houghton, Clinical Cancer Research, Vol. 11, 370-379, January 1, 2005.

STRAUS - Results of a Prospective Randomized Clinical Trial of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Followed by Radiation Therapy (RT) Versus ABVD Alone for Stages I, II, and IIIA Nonbulky Hodgkin Disease, D.J. Straus, C.S. Portlock, J. Qin, J. Myers, A.D. Zelenetz, C. Moskowitz, A. Noy, A. Goy, J. Yahalom,  Blood 104:3483-9, 2004.

MOSKOWITZ - Outcome of patients with primary refractory HD treated with high dose combined modality therapy and ASCT, C.H. Moskowitz, S.D. Nimer, T. Kewalramani, A.D. Zelenetz, J. Yahalom, British Journal of Haematology 2004, 124: 645-652; Rituximab Significantly Increases the complete Response Rate in Patients with Relapsed or Primary Refractory DLBCL Receiving ICE as Second-Line Therapy (SLT), T. Kewalramani, A.D. Zelenetz,  J. Bertino, G. Donnelly, E. Hedrick, A. Noy, O. O’Connor, C. Portlock, D. Straus, J. Yahalom, A. Gencarelli, D. Remy, J. Qin, S.D. Nimer, C.H. Moskowitz, Blood 2004 May 15; 103(10):3684-8;  Adverse Prognostic Significance of CD 20 Positive Reed-Sternberg Cells in Classical Hodgkin’s Disease, C.S. Portlock, G.B. Donnelly, J. Qin, D. Straus, J. Yahalom, A.D. Zelenetz, A. Noy, O. O’Connor, S. Horwitz, C.H. Moskowitz, D.A. Filippa, British Journal of Hematology 2004, 125: 701-708; An update on the management of relapsed and refractory Hodgkin’s Lymphoma, C.H. Moskowitz, Seminars in Oncology 2004, 31: 54-59.

SABBATINI/AGHAJANIAN/SPRIGGS - Clinical Update: Novel Targets in Gynecologic Malignancies, C. Aghajanian, Semin Oncol 31 [suppl 16]: 22-26, 2004;  To Explore the Hypothesis that Inhibition of NF-K {3 with Bortezomib Renders Ovarian Cancer More Sensitive to Platinum Agents,  D. Dizon, P. Sabbatini, J. Raizer, D. Spriggs, J Clin Oncol 23:5943-5949, 2005.

KEWALRAMANI  - Rituximab and ICE as Second-Line Therapy Before Autologous Stem Cell Transplantation for Relapsed or Primary Refractory Diffuse Large B-Cell Lymphoma, T. Kewalramani, A.D. Zeleneetz, S.D. Nimer, C. Portlock, D. Straus, A. Noy, O.O’Connor, D.A. Filippa, J. Teruya-Feldstein, A. Gencarelli, J. Qin, A. Waxman, J. Yahalom, C.H. Moskowitz, Blood, Vol. 103, No. 10 15 May 2004.

OFFIT - The Genetics of Familial Lymphomas, R. Siddiqui, K. Onel, F. Facio, K. Offit, Current Oncology Reports 2004, 6:380-387  The TP53 Mutational spectrum and frequency of CHEK2* 1100delC in Li Fraumeni-like kindreds Siddiqui, R, Onel K, Facio F, Nafa D, Robles-Diaz R, Kauff N, Huang H, Robson M, Ellis N, Offit K  Familial Cancer 2005; 4(2):177-81 Combined genetic assessment of transforming growth factor-beta signaling pathway variants may predict breast cancer risk. Kaklamani VG, Baddi L, Liu J, Rosman D, Phukan S, Bradley C, Hegarty C, McDaniel B, Rademaker A, Oddoux C, Ostrer H, Michel LS, Huang H, Chen Y, Ahsan H, Offit K, Pasche B. Cancer Research 2005; 65(8):3454-61.  Estrogen receptor genotypes and haplotypes associated with breast cancer risk. Gold B, Kalush F, Bergeron J, Scott K, Mitra N, Wilson K, Ellis N, Huang H, Chen M, Lippert R, Halldorsson BV, Woodworth B, White T, Clark AG, Parl FF, Broder S, Dean M, Offit K.   Cancer Research 2004; 64:8891-900. Localization of cancer susceptibility genes by genome-wide single-nucleotide polymorphism linkage-disequilibrium mapping. Mitra N, Ye TZ, Smith A, Chuai S, Kirchhoff T, Peterlongo P, Nafa K, Phillips MS, Offit K, Ellis NA.  Cancer Research 2004; 64: 8116-25. Hereditary ovarian cancer in Ashkenazi Jews. Robles-Diaz L, Goldfrank D, Kauff N, Robson M, Offit K  Familial  Cancer 2004; 3:259-64  A636P testing in Ashkenazi Jews. Guillem JG, Moore HG, Palmer, C, Glogowski E, Finch R, Nafa K, Markowitz AJ, Offit K, Ellis NA.  Familial Cancer 2004; 3:223-227  Pleomorphic expression of a germline kit mutation in a large kindred with gastrointestinal stromal tumors, hyperpigmentation, and dysphagia. Robson ME, Glogowski E, Sommer G, Antonescu CR, Khedoudja N, Maki RG, Ellis N, Besmer P, Brennan M, Offit K.   Clinical Cancer Research 2004;10:1250-4.Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population. Shaag A, Walsh T, Renbaum P, Kirchhoff T, Nafa K, Shiovitz S, Mandell JB, Welcsh P, Lee MK, Ellis N, Offit K, Levy-Lahad E, King MC. Human Molecular Genetics 2005; 14:555-63

COMENZO - Systemic AL amyloidosis due to non-Hodgkin’s lymphoma: an unusual clinicopathologic association,  A.D. Cohen, P. Zhou, Q. Xiao, M. Fleisher, N. Kalakonda, T. Akhurst, C. Moskowitz, M. Dhodapkar, J. Feldstein, D. Filippa, R.L. Comenzo, British Journal of Haematology 2004; 124:309

YAHALOM - Intensity-Modulated Radiotherapy for Lymphoma Involving the Mediastinum, K.A. Goodman, S. Toner, M. Hunt, et al: Int J Radiat Oncol Biol Phys 62:198-206, 2005; Radiation Treatment Planning Techniques for Lymphoma of the Stomach,  C. Della Biancia, M. Hunt, E. Furhang, et al:  Int J Radiat Oncol Biol Phys 62:745-51, 2005; FDG-PET Scanning for Detection and Staging of Extranodal Marginal Zone Lymphomas of the MALT Type: A Report of 42 Cases, K.P. Beal, H.W. Yeung, J. Yahalom, Ann Oncol 16:473-80, 2005 

COOPER - New Approaches to Allografting in Non-Hodgkin’s Lymphoma, S. Seropian, D. Cooper,  Progress in Oncology 2004, Jones and Bartlett, Sudbury, MA.

SPANGRUDE - Lymphoid Potential of Primitive Bone Marrow Progenitors Evaluated In Vitro, H.Wang, L.J.Pierce, G.J. Spangrude,  Ann. N.Y. Acad. Sci, 1044:1-10, 2005;  L-Selectin Defines a Bone Marrow Analog to the Thymic Early T-Lineage Progenitor, S.S.Perry, H. Wang, L.J. Pierce, A.M. Yang, S. Tsai, G.J. Spangrude,  Blood, Vol. 103, No.8, 15 April 2004.

COUNTER - Loss of HPot1 Function Leads to Telomere Instability and a Cut-Like Phenotype, T. Veldman, K.T. Etheridge, C.M. Counter, Current Biology, Vol. 14, 2264-2270, December 29, 2004.

LEONARD - Abbreviated Chemotherapy with Fludarabine Followed by Tositumomab and Iodine I 131 Tositumomab for Untreated Follicular Lymphoma, J.P. Leonard, M. Coleman, et al:  in press;  Combination Antibody Therapy with Epratuzumab (Humanized Anti-CD22 Antibody) and Rituximab (Chimeric Anti-CD20 Antibody) in Relapsed/Refractory Non-Hodgkin’s Lymphoma (NHL), J.P. Leonard, M. Coleman, et al:  in press.    

O’CONNOR - Phase II Clinical Experience with the Novel Proteasome Inhibitor Bortezomib in Patients with Indolent Non-Hodgkin’s Lymphoma and Mantle Cell Lymphoma,  O.A. O’Connor, J. Wright, C. Moskowitz, J. Muzzy, B. MacGregor-Cortelli, M. Stubblefield, D. Straus, C. Portlock, P. Hamlin, E. Choi, O.Dumetrescu, J. Qin, D. Esseltine, E. Trehu, J. Adams, D. Schenkein, A.D. Zelenetz Journal of Clinical Oncology, Vol 23, No 4 (February 1), 2005: pp. 676-684 Targeting Histones and Proteasomes: New Strategies for the Treatment of Lymphoma, Owen A. O'Connor  Journal of Clinical Oncology, Vol 23, No 26 (September 10), 2005: pp. 6429-6436
 

THE FOLLOWING IS A PARTIAL LIST OF IMPORTANT RESEARCH PUBLICATIONS SUPPORTED  BY  LYMPHOMA  FOUNDATION  GRANTS IN 2003-2004

MOSKOWITZ et al: Intensive Methotrexate and Cytarabine Followed by High-Dose Chemotherapy with Autologous Stem Cell Rescue in Patients with Newly Diagnosed Primary CNS Lymphoma: Intent to Treat Analysis, L.E. Abrey, C.H. Moskowitz, W.P. Mason, M. Crump, D. Stewart, P. Forsyth, N. Paleologos, D.D. Correa, N.D. Anderson, D. Caron, A. Zelenetz, S.D. Nimer, L.M. DeAngelis, Journal of Clinical Oncology 2003, 21: 4151-4156;  Outcome of patients with primary refractory HD treated with high dose combined modality therapy and ASCT, C.H. Moskowitz, S.D. Nimer, T. Kewalramani, A.D. Zelenetz, J. Yahalom, British Journal of Haematology 2004, 124: 645-652; Rituximab Significantly Increases the complete Response Rate in Patients with Relapsed or Primary Refractory DLBCL Receiving ICE as Second-Line Therapy (SLT), T. Kewalramani, A.D. Zelenetz,  J. Bertino, G. Donnelly, E. Hedrick, A. Noy, O. O’Connor, C. Portlock, D. Straus, J. Yahalom, A. Gencarelli, D. Remy, J. Qin, S.D. Nimer, C.H. Moskowitz, Blood 2004 May 15; 103(10):3684-8;  Adverse Prognostic Significance of CD 20 Positive Reed-Sternberg Cells in Classical Hodgkin’s Disease, C.S. Portlock, G.B. Donnelly, J. Qin, D. Straus, J. Yahalom, A.D. Zelenetz, A. Noy, O. O’Connor, S. Horwitz, C.H. Moskowitz, D.A. Filippa, British Journal of Hematology 2004, 125: 701-708; An update on the management of relapsed and refractory Hodgkin’s Lymphoma, C.H. Moskowitz, Seminars in Oncology 2004, 31: 54-59.

O’CONNOR et al:  Phase II Clinical Experience with the Novel Proteasome Inhibitor Bortezomib in Patients with Indolent Non-Hodgkin’s Lymphoma and Mantle Cell Lymphoma,  O.A. O’Connor, J. Wright, C. Moskowitz, J. Muzzy, B. MacGregor-Cortelli, M. Stubblefield, D. Straus, C. Portlock, P. Hamlin, E. Choi, O.Dumetrescu, J. Qin, D. Esseltine, E. Trehu, J. Adams, D. Schenkein, A.D. Zelenetz (accepted for publication in the Journal of Clinical Oncology in 2004). 

OFFIT et al: Shared Genetic Susceptibility to Breast Cancer, Brain Tumors, and Fanconi Anemia, K. Offit, O. Levran, B. Mullaney, K. Mah, K. Nafa, S.D. Batish, R. Diotti, H. Schneider, A. Deffenbaugh, T. Scholl, V.K. Proud, M. Robson, L. Norton, N. Ellis, H. Hanenberg, A.D. Auerbach, Journal of the National Cancer Institute, Vol. 95, No. 20, October 15, 2003; The FANCD1/BRCA2*6174DELT Mutation is Rare in Sporadic Pediatric Medulloblastoma, K. Onel, T. Kirchhoff, J.C. Allen, E. Jiminez, K. Offit, (in preparation);  Localization of Breast Cancer Susceptibility Loci by Genome-Wide SNP Linkage Disequilibrium Mapping, N.A. Ellis, T. Kirchhoff, N. Mitra, T.-Z. Ye, S. Chuai, H. Huang, K. Nafa, L. Norton, S. Neuhausen, J.P. Struewing, S. Narod, K. Offit, (in preparation).The Genetics of Familial Lymphomas, R. Siddiqui, K. Onel, F. Facio, K. Offit, Current Oncology Reports 2004, 6:380-387

SABBATINI / AGHAJANIAN / SPRIGGS et al:  Clinical Update: Novel Targets in Gynecologic Malignancies (in press) Supplement to Seminars in Oncology; PS-341 in Combination with Carboplatin in Ovarian Cancer (abstract) ASCO – submitted for publication to the Journal of Clinical Oncology. 

SCHEINBERG et al:  A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia, K. Cathcart, J. Pinilla-Ibarz, T. Korontsvit, J. Schwartz, V. Zakhaleva, E.B. Papadopoulos, D.A. Scheinberg, Blood, 1 February 2004, Vol 103, 1037-1042;  Clonal deletion of CD8 T cells by use of alpha emitting suicide MHC tetramers, R.R. Yuan, D. Ekaterink, M.R. McDevitt, P. Wong, E. Pamer, R. O’Reilly, D.A. Scheinberg, Blood, (In Press); Controlling the errant products of a targeted atomic nanogenerator, J.S. Jaggi, B.J. Kappel, M.R. McDivitt, C.D. Flombaum, C. Cabassa, D.A. Scheinberg (submitted for publication);  Targeted deletion of T cell clones using alpha emitting suicide MHC tetramers, R.R. Yuan, P. Wong, M.R. McDevitt, E. Doubrovina, I. Keiner, W. Bornmann, R. O’Reilly, E.G. Pamer, D.A. Scheinberg, Blood. 2004 Oct 15;104(8):2397-402.

COOPER et al:  Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin’s lymphoma, S. Seropian, E. Bahceci, D. Cooper, Bone Marrow Transplantation, (2003) 32, 763-769 © 2003 Nature Publishing Group;  New approaches to allografting in non-Hodgkin’s  lymphoma, S. Seropian, D. Cooper, In: Progress in Oncology 2004, Jones and Bartlett, Sudbury, MA.

COUNTER et al: Loss of hPot1 function leads to telomere instability and a cut-like phenotype, T. Veldman, K. Etheridge, C.M. Counter, Accepted for publication in: Current Biology.

 

PUBLICATIONS OF SPECIAL INTEREST BY FRIENDS OF THE LYMPHOMA FOUNDATION

Savoring Life is a thoughtful memoir by David M. Klein that describes his extraordinary solo journey by bicycle across the United States, from coast to coast, after recovering from Hodgkin's disease and a myriad of complications. 

Savoring Life in Sickness and Health by David M. Klein is still available for purchase.  For further information on how to obtain a copy... write to:   Marcia Klein, 15 Roundabend Road, Tarrytown, New York 10591 or  Email: marciakle@optonline.net
 

 

Clinical Cancer Genetics: Risk Counseling and Management by Kenneth Offit, M.D., M.P.H. is a comprehensive review and guide for health professionals participating in clinical cancer genetic services. (Published by Wiley-Liss, Inc., New York, NY, 1998)
 See recent publications by Dr. Offit and his research colleagues supported in part by Lymphoma Foundation grants

Hodgkin's Disease: The Consequences of Survival by Mortimer J. Lacher, M.D. and John Redman, M.D., Editors, is a compendium of fourteen chapters outlining the potential and actual problems encountered by the long-surviving Hodgkin's patient (Published by Lea & Febiger, Philadelphia - London, 1990)

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A SELECT FEW OF THE IMPORTANT CLINICAL RESEARCH STUDIES FROM THE  AMERICAN SOCIETY OF HEMATOLOGY  MEETING (ASH)  IN DECEMBER 2003
THAT WERE SUPPORTED IN PART BY LYMPHOMA FOUNDATION GRANTS TO VARIOUS CLINICIAN SCIENTISTS AND LYMPHOMA/HEMATOLOGY FELLOWS -
ARE AS FOLLOWS:

TREATMENT OF PRIMARY REFRACTORY OR RELAPSING HODGKIN’S DISEASE

Risk-Adpated High Dose Chemoradiotherapy and ASCT for Patients with Relapsed and Primary Refractory Hodgkin's Disease: An Intent to Treat Analysis. Craig H. Moskowitz, Tarun Kewalramani, Stephen D. Nimer, Robert D. Rice, Lisa Rosenzweig, Steven Horwitz, Ariela Noy, Owen O'Connor, Carol S. Portlock, David Straus, Tanya Tripett, Andrew D. Zelenetz, Joachim Yahalom. The Departments of Medicine and Radiation Oncology,  Memorial Sloan Kettering Cancer Center, NY, NY
Unique treatment combinations were divided into three distinct complex therapy regimens using combinations of drugs including ifosfamide, carboplatin and etoposide (ICE) followed by involved field radiotherapy utilizing intensity modulated radiotherapy or total lymphoid radiation therapy and cyclophosphamide and etoposide or carmustine. It is anticipated that this approach will improve the outcome in treatment resistant Hodgkin's patients.


TREATMENT OF PRIMARY  HODGKIN’S DISEASE
Stanford V and Radiotherapy for Advanced and Locally Extensive Hodgkin's Disease (HD): The Memorial Sloan-Kettering Cancer Center (MSKCC) Experience. Joachim Yahalom, Sophia Edwards-Bennet, Jordan Jacobs, Craig H. Moskowitz, Elisa J. Wu, Michael Cotler, Steven M. Horwitz, Ariela Noy, Owen A. O'Connor, Carol S. Portlock, David J. Straus, Andrew D. Zelenetz  Lymphoma Disease Management Team, Memorial Sloan-Kettering Cancer Center, New York, NY
"... the Stanford group published excellent results with their 12-week chemotherapy program (Stanford V) followed by 36 Gy involved-field radiotherapy for sites initially (equal to or greater) than 5 cm in advanced and/or locally extensive (HD (Horning et al, Blood 2002), others reported markedly inferior outcome (Chisesi et al, Ann Oncol 2002)." In an analysis of 126 patients over a seven year period the Memorial Sloan Kettering group confirmed the excellent results reported by Stanford group.

TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA AND LOW-GRADE LYMPHOMAS
Pentostatin, Cyclophosphamide, and Rituximab (PCR Therapy): A New Active Regimen for Previously Treated Patients with Chronic Lymphocytic Leukemia (CLL). Mark A. Weiss, Lamanna Nicole, Jurcic G. Joseph, Maslak G. Peter, Melissa vonHassel, Denise Horgan, David A. Scheinberg, Alison N. Gencarelli  Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
In this study (PCR) Pentostatin 4mg/m2, Cyclophosphamide 600mg/m2, and Rituximab 375mg/m2 as treatment were combined for previously treated patients with CLL. For cycle 1, patients received only pentostatin and cyclophosphamide. For cycles 2-6 all three drugs were administered on day 1. Cycles were repeated every 3 weeks for a total of 6 treatments. Supportive measures included prophylactic administration of filgrastim, sulfamethoxazole/ trimethoprim, acyclovir, adequate hydration with each treatment, and antiemetics.  In the thirty three patients (median age 61, range 30-80) with intermediate or high risk CLL (21 patients) or other low grade B cell neoplasms (12 patients) who received this PCR therapy the preliminary results indicated that PCR therapy is active and can be safely administered to previously treated patients with CLL and low grade lymphoma. NOTE: This is an extension of the PCR study presented at ASCO in June 2003 with the addition of 11 patients.

TREATMENT OF MANTLE CELL LYMPHOMA
Initial Treatment of Mantle Cell Lymphoma with Sequential Radioimmunotherapy with Tositumoamb/Iodine I131 I-Tositumoamb followed by CHOP Chemotherapy Results in a High Complete Remission Rate. Andrew D. Zelenetz, Gerard Donnelly, Jeffery Halaas, George Sgouros, John Humm, Leslie Popplewell, Susan Reyes, Kathleen Maignan, Charlene Campbell, Craig H. Moskowitz, Stephen D. Nimer, Neeta Pandit-Taskar, Chaitanya Divgi Lymphoma Service/Medicine, Hematology Service/Medicine, Nuclear Medice Service/Radiology, Nursing, and Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 
Recognizing the clinical challenge in finding a successful treatment for Mantle cell lymphoma (MCL) a unique therapeutic approach was attempted. Radioimmunotherapy (RIT) and Chemotherapy (C) was used. This was the first report of a regimen using RIT for cytoreduction (to provide optimal crossfire) followed by Chemotherapy. It was determined that sequential RITC for Mantle Cell Lymphoma is both feasible and effective. It was also concluded that further follow-up is necessary to determine if this unique therapeutic approach represented a treatment advance for MCL and the optimal sequence, RITC versus CRIT, will only be determined by proceeding with prospective clinical trials.

TREATMENT OF MANTLE CELL LYMPHOMA AND INDOLENT NON-HODGKIN'S LYMPHOMA
Promising Activity of the Proteasome Inhibitor Bortezomib (Velcade) in the Treatment of Indolent Non-Hodgkin’s Lymphoma and Mantle Cell Lymphoma Owen O'Connor, John Wright, Craig H. Moskowitz, Jamie Muzzy, Barbara MacGregor-Cortelli, Paul Hamlin, David Straus, Elizabeth Trehu, David P.Schenkin, Andrew D. Zelenetz Memorial Sloan Kettering Cancer Center, New York, NY; Drug Development Branch, National Cancer Institute, Bethesda, MD; Millenium Pharmaceuticals, Cambridge, MA 
One patient with marginal zone lymphoma achieved a Partial Remission after 2 cycles of therapy. Major responses were also seen in three patients with refractory mantle cell lymphoma. All patients with small lymphocytic lymphoma were found to have stable disease after 2 and 4 cycles respectively. Six of the 8 evaluable patients with follicular lymphoma achieved a major response, with one patient obtaining a durable complete remission. These data continue to support the biological activity of bortezomib in patients with indolent lymphomas, and suggests that this drug's activity may be sub-type dependent.
TREATMENT OF MULTIPLE MYELOMA
Doxorubicin and Dexamethasone (AD) Followed by Thalidomide and Dexamethasone (TD) as Initial Therapy for Symptomatic Patients with Multiple Myeloma.  Raymond L. Comenzo, Hani Hassoun, Lilian Reich, Virginia Klimek, Tarun Kewalramani, Madhav Dhodapkar, Lisa Drake, Cyrus Hedvat, Julie Teruya-Feldstein, Martin Fleisher, Daniel A. Filippa, Stephen D. Nimer Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 
Because of the particular concern of the development of thromboembolic complications during thalidomide treatment for multiple myeloma this study was devised to see if that complication could be reduced or eliminated. The results indicated that temporal separation of doxorubicin and thalidomide fashion could preserve a high response rate and reduce the incidence of therapy-related thromboembolic complications.

ADDITIONAL RESEARCH PRESENTATIONS SUPPORTED IN PART BY LYMPHOMA FOUNDATION GRANTS AT THE AMERICAN SOCIETY OF HEMATOLOGY MEETING IN DECEMBER 2003 (EITHER AS ORAL PRESENTATIONS OR AS POSTER PRESENTATIONS) ARE LISTED BELOW  BY TITLE AND AUTHORS

Oblimersen (Bcl-2 Antisense) Enhances the Antitumor Activity of Bortezomib (Bor) in Multiple Myeloma (MM) and Non-Hodgkin's Lymphoma (NHL) Preclinical Models.  Owen O'Connor, Sridhar Srinivasan, Francisco Hernandez, Emily A. Smith, Lorraine E. Toner, Myron S. Czuczman, Asher Alban Chanan-Khan Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Medicine, Roswell Park Cancer Institute, Buffalo, NY

A Phase II Study of Stem Cell Mobilization with IV Melphalan (60 mg/M2) + G-CSF in Multiple Myeloma. Seema Gupta, Suzanne Costello, Ping Zhou, Reich Lilian, Hassoun Hani, Virginia Klimek, Tarun Kewalramani, Madhav Dhodapkar, Martin Fleisher, Cyrus Hedvat, Julie Teruya-Feldstein, Daniel A. Filippa, Jing Qin, Stephen D. Nimer, Raymond L. Comenzo  Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Hematology Research, Sloan-Kettering Institute, New York, NY; Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY

Doxorubicin and Dexamethasone (AD) Followed by Thalidomide and Dexamethasone (TD) as Initial Therapy for Symptomatic Patients with Multiple Myeloma. Session Type Raymond L. Comenzo, Hani Hassoun, Lilian Reich, Virginia Klimek, Tarun Kewalramani, Madhav Dhodapkar, Lisa Drake, Cyrus Hedvat, Julie Teruya-Feldstein, Martin Fleisher, Daniel A. Filippa, Stephen D. Nimer Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY

CD 20 Negative (-) Large Cell Lymphoma with Plasmablastic Features: A Heterogenous Spectrum in Both HIV + and -Patients. Julie Teruya-Feldstein, Oscar Lin, Elizabeth Chiao, Qianxun Xiao, Daniel A. Filippa, Morton Coleman, Raymond Comenzo, Carol S. Portlock, Ariela Noy Pathology and Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; Medicine, New York Presbyterian Hospital-Weill Cornell, New York

 Systemic AL Amyloidosis Due to Non-Hodgkin's Lymphoma: An Unusual Clinicopathologic Association. Adam D. Cohen, Ping Zhou, Qianxun Xiao, Martin Fleisher, Nagesh Kalakonda, Tim Akhurst, Dhananjay A. Chitale, Craig Moskowitz, Madhav V. Dhodapkar, Julie Teruya-Feldstein, Daniel A. Filippa, Raymond L. Comenzo Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY; Hematology Research, Sloan-Kettering Institute, New York, NY; Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY

Clonal Deletion of CD8+ T Cells by Alpha Emitting Suicide Peptide/MHC Tetramers.  Rui Rong Yuan, Phillip Wong, Michael R. McDevitt, Christophe Antczak, Doubrovina Ekaterink, Ingrid Leiner, Patrick Guirnalda, Christophe P. Borella, William Bornmann, Richard O'Reilly, Eric G. Pamer, David A. Scheinberg  Department of Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, NYC, NY; Medicine, Memorial Sloan-Kettering Cancer Center, NYC, NY; Pediatrics, Memorial Sloan-Kettering Cancer Center, NYC, NY; Organic Chemistry, Memorial Sloan-Kettering Cancer Center, NYC, NY

Sequential Therapy with Fludarabine, High Dose Cyclophosphamide, and Rituximab Induces a High Incidence of Complete Response in Patients with Chronic Lymphocytic Leukemia (CLL). Nicole Lamanna, Mark A. Weiss, Peter G. Maslak, Alison N. Gencarelli, David A. Scheinberg, Denise Horgan Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY

Improved Molecular Design and Immunization Route of CD20 Peptides Induce Antibody Against Human CD20 Protein. Tao Dao, Christophe Antczak, George Boutsalis, Cynthia Kou, Jaspreet Jaggi, Barry Kappel, Javier Pinilla-Ibarz, David A. Scheinberg Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY

Reducing Standard Postremission Chemotherapy in Acute Promyelocytic Leukemia (APL) with Risk-Adapted Therapy.  Deborah A. Mulford, Peter G. Maslak, Mark A. Weiss, David A. Scheinberg, Joseph G. Jurcic Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

A Heteroclitic Peptide Vaccine Induces CD8+ T-Cell Responses to CD20. Session Type: Poster Session 566-III Maria Lia Palomba, Jose A. Guevara-Patino, Gregor Manukian, Alan N. Houghton  Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY

Early Treatment with Epoetin Alfa Improves Anemia, Quality of Life (QOL), and Productivity in Patients (Pts) with Hematologic Malignancies and Mild Anemia during Chemotherapy (CT). David J. Straus, Marcia Testa, Shirley A. Riggs, Anil Tulpule, Brenda Sarokhan Lymphoma Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Biostatistics, Harvard School of Public Health, Boston, MA; Department of Hematology/Oncology, MD Anderson Cancer Center, Houston, TX; Department of Medicine-Hematology, USC Norris Cancer Hospital, Los Angeles, CA; Clinical Affairs, Ortho Biotech Products, L.P., Bridgewater, NJ

NOTE: The italicized names represent clinician/scientists who are currently receiving Lymphoma Foundation research grants or who have received research grants from the Lymphoma Foundation in the past.

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IMPORTANT CLINICAL RESEARCH STUDIES - SUPPORTED IN PART BY LYMPHOMA FOUNDATION GRANTS TO VARIOUS CLINICIAN SCIENTISTS AND LYMPHOMA/HEMATOLOGY FELLOWS -
WERE PRESENTED AT THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY MEETING
(ASCO)  - JUNE 2003

NON-HODGKIN’S LYMPHOMA
Phase II clinical experience with the proteasome inhibitor bortezomib (formerly PS-341) in patients with indolent lymphomas O. A. O'Connor, J. Wright, C. Moskowitz, B. Macgregor-Cortelli, D. Straus, D. Horse-Grant, D. Schenkein, A. Zelenetz; Memorial Sloan-Kettering Cancer Center, New York, NY; National Cancer Institute, Bethesda, MD; Millenium Pharmaceuticals, Cambridge, MA Over 33 cycles of PS-341 (average 2.4 per patient) to 14 previously treated patients with relapsed or refractory indolent lymphomas (small lymphocytic lymphoma, SLL (n=2); follicular lymphoma, FL (n=7) and mantle cell lymphoma, MCL (n=5)) were administered. All patients had received some form of [chemotherapy] treatment prior to receiving PS-341, including: CHOP; CVP; CTX/fludarabine; and/or rituximab. Of the evaluable patients with FL, there was one CR [Complete Remission], three PR [Partial Remissions] and 2 with stable disease. Major responses were also seen in 3 patients with MCL, all three of whom achieved a PR after only 2 cycles of treatment, with 1 patient having over an 80% reduction in tumor volume. These preliminary data support the biological activity of PS-341 in patients with low-grade lymphomas.

LEUKEMIA - VACCINE THERAPY
A phase II trial of patients with CML using a multivalent BCR-ABL oncogene product fusion peptide vacccine. J. Pinilla, K. Cathcart, T. Korontsvit, J. Schwartz, V. Zakhaleva, E. Papadopoulos, D. A. Scheinberg; Memorial Sloan-Kettering Cancer Ctr, New York, NY  Fourteen evaluable patients with CML (Chronic Myelocytic Leukemia) in chronic phase with any HLA type and a b3a2, bcr-abl breakpoint were vaccinated subcutaneously five times over a 10 week period using a preparation of 6 peptides mixed with the immunologic adjuvant QS-21. Patients that responded immunologically received booster vaccinations. It was concluded that a tumor-specific bcr-abl breakpoint peptide-derived vaccine could be safely administered and could elicit measurable peptide specific CD4 immune responses in patients with CML (including patients post Bone Marrow Transplant) although a causal relationship between the clinical responses and vaccination remained unclear.

LYMPHOCYTIC LEUKEMIA – RITUXIN THERAPY
Pentostatin, cyclophosphamide and rituximab (PCR therapy): A new active regimen for previously treated patients with chronic lymphocytic leukemia (CLL) M. A. Weiss, N. Lamanna, P. G. Maslak, A. N. Gencarelli, D. A. Scheinberg, J. Jurcic, D. Horgan, Leukemia Service; Memorial Sloan-Kettering Cancer Center, New York, NY  The current study combined pentostatin 4mg/m2, cyclophosphamide 600mg/m2, and rituximab 375mg/m2. Twenty patients (median age 60, range 30-80) with CLL (14 patients) or other low grade B cell neoplasms (6 patients) received PCR therapy. Response data is currently available for 13/14 patients with CLL. There were 10 responses (77%), including 4 CRs (31%) and 6 PRs(46%). For the patients with low grade lymphoma there were 2 PRs of the 5 evaluable patients. In general this regimen was well tolerated. These preliminary results indicate that PCR therapy appears active and can be safely administered to previously treated patients with CLL and low grade lymphoma.

Sequential therapy with fludarabine, high dose cyclophosphamide, and rituximab induces a high incidence of complete response in patients with chronic lymphocytic leukemia (CLL). N. Lamanna, M. A. Weiss, P. G. Maslak, A. N. Gencarelli, D. A. Scheinberg, D. Horgan, Leukemia Service; Memorial Sloan-Kettering Cancer Center, New York, NY Reported a three-stage sequential treatment program with fludarabine as induction, high dose cyclophosphamide (HDC) as first consolidation, and rituximab as a second non-cross-resistant consolidation. Twenty four previously untreated patients with intermediate (9pts) or high-risk (15 pts) CLL were included in this study. They concluded that equential therapy with fludarabine, HDC, and rituximab produces a high frequency of CR with improvements in response seen with each phase of therapy.

OVARIAN CANCER – PROTEASOME INHIBITOR THERAPY
Phase I trial of PS-341 and carboplatin in recurrent ovarian cancer C. Aghajanian, D. Dizon, X. J. Yan, J. Raizer, P. Sabbatini, S. Pezzulli, A. Philip, S. Anderson, J. Dupont, D. R. Spriggs; Memorial Sloan-Kettering Cancer Ctr, New York, NY. At present, 9 patients with recurrent ovarian cancer have been entered on to the first 3 dose levels. Dose Limiting Toxicity (DLT) has not been reached. There have been no grade 3 or 4 toxicities. No neurotoxicity has been seen. Seven of the 9 patients entered have had major responses.

BREAST CANCER
Breast cancer screening compliance in BRCA1 and BRCA2 heterozygotes H. Huang, L. M. Scheuer, N. Kauff, M. Robson, R. Baum, P. I. Borgen, C. Hudis, L. Norton, K. Offit; Memorial Sloan-Kettering Cancer Center, New York, NY This study reviewed longer term compliance with screening in a cohort of BRCA mutation carriers. Method: Baseline and follow-up screening data was obtained from 134 women with BRCA mutations and breast tissue at risk seen at Memorial Sloan-Kettering Cancer Center between 1995 and 2001.They concluded that the results provided evidence that women at hereditary risk continue to participate in breast surveillance, at least during the first several years after receiving genetic test results.

Breast cancer screening utilizing magnetic resonance imaging (MRI) in carriers of BRCA mutations M. E. Robson, E. Morris, N. Kauff, L. Scheuer, P. I. Borgen, C. Hudis, L. Norton, K. Offit; Memorial Sloan-Kettering Cancer Center, New York, NY The present study describes the outcomes of breast MRI screening specifically in women with documented BRCA mutations. Conclusions: Breast MRI screening in women with BRCA mutations appears to be sensitive, and may detect mammographically occult disease. However, specificity in the clinical setting is suboptimal, resulting in a significant number of false positive results. Further investigations are required to improve specificity and to investigate the psychological and economic impact of this screening modality in mutation carriers.

NOTE: The italicized names represent clinician/scientists who are currently receiving Lymphoma Foundation research grants or who have received research grants from the Lymphoma Foundation in the past.

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PUBLISHED RESEARCH OR RESEARCH SUBMITTED FOR PUBLICATION SUPPORTED IN PART BY LYMPHOMA FOUNDATION GRANTS 2002-2003

SCHEINBERG/HOUGHTON et al: A multivalent bcr-abl fusion peptide vaccination trial in patients with chronic myeloid leukemia, K. Cathcart, J. Pinilla-Ibarz, T. Korontsvit, J. Schwartz, V. Zakhaleva, E.B. Papadopoulos, D.A. Scheinberg, Blood, (In Press) 2003. The role of lipopolysaccharide in T-cell responses following DNA vaccination, W.G. Hawkins, J. Trcka, N. Segal, N.E. Blachere, J.S. Gold, Y. Moroi, W.B. Bowne, J.J. Lewis, J.D. Wolchok, Houghton, A.N., Vaccine  2003: 21: 1548-1553. Xenogeneic DNA Immunization Against CD20 Elicits Immune Responses and Confers Modest Tumor Protection in a Mouse Model of Lymphoma,   M.L. Palomba, W.K. Roberts, D.A. Scheinberg, A.N. Houghton, Abstract  Presented at the American Society of Hematology 44th Annual Meeting, Philadelphia, Pennsylvania, December 6-10, 2002; A Heteroclitic Peptide Vaccine Induces CD8+ T-Cell Responses to CD20, M. L. Palomba, J.A. Guevara-Patino, G. Manukian, A.N. Houghton, Presented at the American Society of Hematology 45th Annual Meeting, San Diego, California, December 6-9, 2003.

MOSKOWITZ et al: Outcome of patients with aggressive NHL and HD who fail ASCT, T. Kewalramani, S.D. Nimer, J. Donnelly, J. M. Satagopan,  A.D. Zelenetz and C.H. Moskowitz, Bone Marrow Transplantation  (In Press); Outcome of patients with primary refractory HD treated with high dose combined modality therapy and ASCT, C.H. Moskowitz, S.D. Nimer, T. Kewalramani, A.D. Zelenetz, J. Yahalom, (Submitted) British Journal of Haematology; Rituximab Significantly Increases the Complete Response Rate in Patients with Relapsed or Primary Refractory DLBCL Receiving ICE as Second Line Therapy (SLT). T. Kewalramani, A. Zelenetz, J. Bertino, G. Donnelly, E. Hedrick, A. Noy, O. O'Connor, C.S. Portlock, D. Straus, J. Yahalom, A. Gencarelli, D. Remy, J. Qin, S. Nimer, C.H. Moskowitz, (Submitted) BLOOD; An effective regimen for patients with relapsed/refractory Hodgkin’s disease who progress after autologous stem cell transplantation, P.H. Hamlin, T. Kewalramani, P. Schanslin, A.D. Zelenetz, C.H. Moskowitz,  Annals of Oncology (In Press)

OFFIT et al:  Analysis of Mismatch Repair Defects in the Familial Occurrence of Lymphoma and Colorectal Cancer, Teruya-Feldstein, J., Greene, J., Cohen, L., Popplewell, L., Ellis, N.A., Offit, K., Leukemia and Lymphoma, 2002 Vol. 43 (8), pp. 1619-1626. Similar Patterns of Genomic Alterations Characterize Primary Mediastinal Large-B-Cell Lymphoma and Diffuse Large-B-Cell Lymphoma, Palanisamy, N., Abou-Elella, A., Chaganti, S.R., Houldsworth, J. Offit, K., Louie, D.C., Terayu-Feldstein, J., Cigudosa, J.C., Rao, P.H., Sanger, W.G., Weisenburger, D.D., Chaganti, R.S.K., Genes, Chromosomes & Cancer, 33:114-122 (2002); Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients,  C. Bäumler, F. Duan, K. Onel, B. Rapaport, S. Jhanwas, K. Offit, K.B. Elkon,  Leukemia Research 27 (2003) 841-851 Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers, Scheuer, L., Kauff, N., Robson, M., Kelly, B., Barakat, R., Satagopan, J., Ellis, N., Hensley, M., Boyd, J., Borgen, P., Norton, L., Offit, K., J Clin Oncol, Vol 20, No 5 (March 1), 2002: pp 1260-1268.  Risk-reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 Mutation, Kauff, N.D., Satagopan, J.M., Robson, M.E., Scheuer, L., Hensley, M., Hudis, C.A., Ellis, N.A., Boyd, J., Borgen, P.I., Barakat, R.R., Norton, L., Offit, K., N Engl J Med, Vol. 346 , No. 21 May 23, 2002: pp 1609-1615. BLM  Heterozygosity and the Risk of Colorectal Cancer,  Gruber, S.B., Ellis, N.A., Rennert, G., Offit, K., et al.  Science, Vol 297, 20 September 2002.  The Founder Mutation MSH2*1906G®C Is an Important Cause of Herditary Nonpolyposis Colorectal Cancer in the Ashkenazi Jewish Population,  W.D. Foulkes, I. Thiffault, S.B. Gruber, M. Horwitz, N. Hamel, C. Lee, J. Shia, A. Markowitz, A. Figer, E. Friedman, D. Farber, C.M.T. Greenwood, J.D. Bonner, K. Nafa, T. Walsh, V. Marcus, L. Tomsho, J. Gebert, F.A. Macrae, C.L. Gaff, B. Bressac-de Paillerets, P.K. Gregersen, J.N. Weitzel, P.H. Gordon, E. MacNamara, M.-C. King, H. Hampel, A. de la Chapelle, J Boyd, K. Offit, G. Rennert, G. Chong, and N.A. Ellis.  Am. J. Hum. Genet. 71:1395-1412, 2002; Differential recruitment of caspase 8 to cFlip confers sensitivity or resistance to Fas-mediated apoptosis in a subset of familial lymphoma patients,  C. Bäumler, F. Duan, K. Onel, B. Rapaport, S. Jhanwas, K. Offit, K.B. Elkon,  Leukemia Research 27 (2003) 841-851 © 2003;  Rare Variants of ATM and Risk for Hodgkin’s Disease and Radiation-associated Breast Cancers,  K. Offit,, S. Gilad, S. Paglin, P. Kolachana, L.C. Roisman, K. Nafa, V. Yeugelewitz, M. Gonzales, M. Robson, D. McDermott, H.H. Pierce, N.D. Kauff, P. Einat, S. Jhanwar, J.M. Satagopan, C. Oddoux, N. Ellis, R. Skaliter, J. Yahalom,  Clinical Cancer Research, Vol. 8, 3813-3819, December 2002; Frequency of CHEK2*1100delC in New York breast cancer cases and controls, K. Offit, H. Pierce, T. Kirchhoff, P. Kolachana, B. Rapaport, P. Gregersen, S. Johnson, O. Yossepowitch, H. Huang, J. Satagopan, M. Robson, L. Scheuer,  BMC Medical Genetics, 2003, 4 BRCA1 and BRCA2 Germline Mutations in Lymphoma Patients, O. Yossepowitch, N. Olvera, J. M. Satagopan, H. Huang, S. Jhanwar, B. Rapaport, J. J. Boyd, K. Offit, Leukemia and Lymphoma, 2003 Vol. 44 (1), pp. 127-131; A636P Is Associated with Early-Onset Colon Cancer in Ashkenazi Jews,   J.G. Guillem, B.S. Rapaport, T. Kirchhoff, P. Kolachana, K. Nafa, E. Glogowski, R. Finch, H. Huang, W.D. Foulkes, A. Markowitz, N.A. Ellis, K. Offit,   J Am Coll Surg., Vol. 196, No. 2, 222-225, February 2003; Shared Genetic Susceptibility to Breast Cancer, Brain Tumors, and Fanconi Anemia,   K Offit,  O. Levran, B. Mullaney, K. Mah, K Nafa, S.D. Batish, R. Diotti, H. Schneider, A. Deffenbaugh, T. Scholl, V.K. Proud, M. Robson, L. Norton, N. Ellis, H. Hanenberg, A.D. Auerbach,  Journal of the National Cancer Institute, Vo. 95, No. 20, 2003; Potential applications for gene discovery by linkage disequilibrium mapping using the GeneChip® Mapping 10K Array,  T. Kirchhoff, N. Mitra, T. Ye, R. Mei, G.A. Marcus, H. Matsuzki, H. Loi, S. Dong, K. Nafa, K. Offit, N. Ellis
STRAUS: National protocol of the Cancer and Acute Leukemia Group B (CALGB #50203), A phase II trial of doxorubicin, vinblastine, and gemcitabine (AVG) chemotherapy for non-bulky stage I and II Hodgkin’s disease, Straus, D.J. Study Chairman.

SPANGRUDE: Characterization of Thymic Progenitors in Adult Mouse Bone Marrow,   S.S. Perry,  L.J. Pierce, W.B. Slayton, G.J. Spangrude,   The Journal of Immunology,  2003, 170:  1877-1886. Aspects of early lymphoid commitment,  H. Wang, G.J. Spangrude, Current Opinion in Hematology, 2003 10: 203-207. Early Stages of Hematopoietic Differentiation, G. J. Spangrude, S.S. Perry, W.B. Slayton, Ann. N.Y Acad. Sci.  996: (In press) 2003

COOPER: Allogeneic peripheral blood stem cell transplantation for high-risk non-Hodgkin’s lymphoma,  S. Seropian, E. Bahceci, D. Cooper,  Bone Marrow Transplantation, (2003) 32, 763-769; New approaches to allografting in non-Hodgkin’s lymphoma,  D. Cooper,  (Submitted for Publication)

COMENZO:   Systemic AL amyloidosis due to non-Hodgkin’s lymphoma: an unusual clinicopathologic association, Cohen, A., Comenzo, R.;  British Journal of Haematology,  (accepted for publication 2003)

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SELECTED RESEARCH SUPPORTED IN PART BY LYMPHOMA FOUNDATION GRANTS - 2000-2002

HOUGHTON/SCHEINBERG Tumor Therapy with Targeted Atomic Nanogenerators, McDevitt, M.R., Ma, D., Lai, L.T., Simon, J., Borchardt, P., Frank, R.K., Wu, K., Pellegrini, V., Curcio, M.J., Miederer, M., Bander, N.H., Sheinberg, D.A., Science, Vol 294 (November 16) 2001: pp 1537-1540; Vaccination with CD20 peptides induces a biologically active, specific immune response in mice, Roberts, W.K., Livingston, P.O., Agus, D.B., Pinilla-Ibarz, J., Zelenetz, A., Scheinberg, D.A., Blood, Volume 99, Number 10 (May 15) 2002: 3748-3755; The Role of Lipopolysaccharide in T-cell Responses Following DNA Vaccination, Hawkins, W.G., Trcka, J., Segal, N., Blachere, N.E., Gold, J.S., Moroi, Y., Bowne, W.B., Lewis, J.J., Wolchok, J.D., Houghton, A.N., Vaccine (In Press) 2002. KEWALRAMANI/ZELENETZ/MOSKOWITZ High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis, Kewalramani, T., Zelenetz, A.D., Hedrick, E.E., Donnelly, G.B., Hunte, S., Priovolos, A.C., Qin, J., Lyons, N.C., Yahalom, J., Nimer, S.D., Moskowitz, C.H., Blood, Vol. 96 No. 7 October 1, 2000: 2399-2404 WARRELL/SOIGNET United States Multicenter Study of Arsenic Trioxide in Relapsed Acute Promyelocytic Leukemia, Soignet, S.L., Frankel, S.R., Dauer, D., Tallman, M.S., Kantarjian, H., Calleja, E., Stone, R.M., Kalaycio, M., Scheinberg, D.A., Steinherz, P., Sievers, E.L., Coutre, S., Dahlberg, S., Ellison, R., Warrell, R.P., Jr., Journal of Clinical Oncology, Vol 19, No. 18 (September 15) 2001: pp 3852-3860  OFFIT Analysis of Mismatch Repair Defects in the Familial Occurrence of Lymphoma and Colorectal Cancer, Teruya-Feldstein, J., Greene, J., Cohen, L., Popplewell, L., Ellis, N.A., Offit, K., Leukemia and Lymphoma, 2002 Vol. 43 (8), pp. 1619-1626; Similar Patterns of Genomic Alterations Characterize Primary Mediastinal Large-B-Cell Lymphoma and Diffuse Large-B-Cell Lymphoma, Palanisamy, N., Abou-Elella, A., Chaganti, S.R., Houldsworth, J., Offit, K., Louie, D.C., Terayu-Feldstein, J., Cigudosa, J.C., Rao, P.H., Sanger, W.G., Weisenburger, D.D., Chaganti, R.S.K., Genes, Chromosomes & Cancer, 33:114-122 (2002); BRCA 1 and  BRCA2 Germline Mutations in Lymphoma Patients, Yossepowitch, O., Olvera, N., Satagopan, J. M., Huang, H., Jhanwar, S., Rapaport, B., Boyd, J., Offit, K., (submitted for publication); Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers, Scheuer, L., Kauff, N., Robson, M., Kelly, B., Barakat, R., Satagopan, J., Ellis, N., Hensley, M., Boyd, J., Borgen, P., Norton, L., Offit, K., J Clin Oncol, Vol 20, No 5 (March 1), 2002: pp 1260-1268; Risk-Reducing Salpingo-oophorectomy in Women with a BRCA1 or BRCA2 MutationRIS, Kauff, N.D., Satagopan, J.M., Robson, M.E., Scheuer, L., Hensley, M., Hudis, C.A., Ellis, N.A., Boyd, J., Borgen, P.I., Barakat, R.R., Norton, L., Offit, K., N Engl J Med, Vol. 346 , No. 21 May 23, 2002: pp 1609-1615. STRAUS Results of a Prospective Randomized Trial of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Alone vs. ABVD + Radiation Therapy for Early Stage Non Bulky Hodgkin’s Disease, Straus, D. J., Yahalom, J., Zelenetz, A.D., Qin, J., Myers, J., Moskowitz, C.H., Noy, A., Bertino, J.R., Portlock, C.S., (Abstract #3201) American Society of Hematology Meeting December 2001; STRAUS : CALGB Study Chair  A phase II trial of doxorubicin, vinblastine, and gemcitabine (AVG) chemotherapy for non-bulky stage I and II Hodgkin’s disease National protocol of the Cancer and Acute Leukemia Group B (CALGB #50203)

SPANGRUDE Phenotypic Distinction and Functional Characterization of Pro-B Cells in Adult Mouse Bone Marrow, Mojica, M.P., Perry, S.S., Searles, A.E., Elenitoba-Johnson, K.S.J., Pierce, L.J., Wiesmann, A., Slayton, W.B., Spangrude, G.J., The Journal of Immunology, 2001, 166: 3042-3051; Enrichment of long-term thymic progenitors from adult mouse bone marrow, Perry, S.S., Pierce, L.J., Slayton, W.B., Spangrude, G.J., (submitted for publication); Approaches to the isolation and characterization of hematopoietic stem and progenitor cells, Perry, S.S., Spangrude, G.J., In: Pluripotent Hematopoietic Stem Cells, Keller, J. (Ed). Georgetown: Eurekah.com, 2002 (in press); Lymphoid progenitors exhibit accelerated thymic and marrow engraftment relative to stem cells, Perry, S.S., Pierce, L.J., Searles, A.E., Mojica, M.P., Slayton, W.B., Spangrude, G.J., Exp. Hematol. 28:63, 2000 (abstract); L-selectin expression on early lymphoid progenitors separates multi-lineage and T lineage potentials, Perry, S.S., Pierce, L.J., Slayton, W.B., Marx, M. Spangrude, G.J., Blood 98:275a, 2001 (abstract).
MOSKOWITZ A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model, Moskowitz, C.H., Nimer, S.D., Zelenetz, A.D., Hedrick, E.E., Filippa, D.A., Louie, D., Gonzales, M., Walits, J. Coady-Lyons, N., Qin, J., Frank, R., Bertino, J.R., Goy, A., Noy, A., O'Brien, J.P., Straus, D., Portlock, C.S., Yahalom, J., Blood 1 February 2001, Vol. 97, No. 3 616-623. YAHALOM Rare Variants of ATM and Risk for Hodgkin’s Disease and Radiation-Associated Breast Cancers, Offit, K., Gilad, S., Paglin, S., Kolachana, P., Roisman, L.C., Nafa, K., Yeugelewitz, V., Gonzales, M., Robson, M., McDermott, D., Pierce, H.H., Kauff, N., Einat, P., Jhanwar, S., Satagopan, J., Oddoux, C., Ellis, N., Skaliter, R., Yahalom, J., Clinical Cancer Research (In Press)

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