FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 345:241-247 July 26, 2001 Number 4 Next

	Full Text PDF Editorial by Schnipper, L. E. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells.

Methods RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses.

Results Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic–uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels.

Conclusions BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues.

Source Information

From the Laboratory of Molecular Biology (R.J.K., K.B., D.J.F., I.P.), the Medicine Branch (W.H.W., M.R.), and the Laboratory of Clinical Pathology (M.S.-S.), National Cancer Institute, Bethesda, Md.

Address reprint requests to Dr. Kreitman at the National Cancer Institute, Laboratory of Molecular Biology, Bldg. 37, Rm. 4B27, 37 Convent Dr., MSC 4255, Bethesda, MD 20892, or at kreitmar{at}mail.nih.gov.

Full Text of this Article

This article has been cited by other articles:

• Kreitman, R. J., Hassan, R., FitzGerald, D. J., Pastan, I. (2009). Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P. Clin. Cancer Res. 15: 5274-5279 [Abstract] [Full Text]  
• Kreitman, R. J., Stetler-Stevenson, M., Margulies, I., Noel, P., FitzGerald, D. J.P., Wilson, W. H., Pastan, I. (2009). Phase II Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With Hairy Cell Leukemia. JCO 27: 2983-2990 [Abstract] [Full Text]  
• Mahmud, H., Dalken, B., Wels, W. S. (2009). Induction of programmed cell death in ErbB2/HER2-expressing cancer cells by targeted delivery of apoptosis-inducing factor. Molecular Cancer Therapeutics 8: 1526-1535 [Abstract] [Full Text]  
• Weldon, J. E., Xiang, L., Chertov, O., Margulies, I., Kreitman, R. J., FitzGerald, D. J., Pastan, I. (2009). A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood 113: 3792-3800 [Abstract] [Full Text]  
• Dong, H. Y., Weisberger, J., Liu, Z., Tugulea, S. (2009). Immunophenotypic Analysis of CD103+ B-Lymphoproliferative Disorders: Hairy Cell Leukemia and Its Mimics. Am J Clin Pathol 131: 586-595 [Abstract] [Full Text]  
• Zhang, Y., Pastan, I. (2008). High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy. Clin. Cancer Res. 14: 7981-7986 [Abstract] [Full Text]  
• Matsushita, K., Margulies, I., Onda, M., Nagata, S., Stetler-Stevenson, M., Kreitman, R. J. (2008). Soluble CD22 as a tumor marker for hairy cell leukemia. Blood 112: 2272-2277 [Abstract] [Full Text]  
• Onda, M., Beers, R., Xiang, L., Nagata, S., Wang, Q.-c., Pastan, I. (2008). An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proc. Natl. Acad. Sci. USA 105: 11311-11316 [Abstract] [Full Text]  
• Du, X., Beers, R., FitzGerald, D. J., Pastan, I. (2008). Differential Cellular Internalization of Anti-CD19 and -CD22 Immunotoxins Results in Different Cytotoxic Activity. Cancer Res. 68: 6300-6305 [Abstract] [Full Text]  
• Golomb, H. M. (2008). Hairy Cell Leukemia: Treatment Successes in the Past 25 Years. JCO 26: 2607-2609 [Full Text]  
• Sampson, J. H., Akabani, G., Archer, G. E., Berger, M. S., Coleman, R. E., Friedman, A. H., Friedman, H. S., Greer, K., Herndon, J. E. II, Kunwar, S., McLendon, R. E., Paolino, A., Petry, N. A., Provenzale, J. M., Reardon, D. A., Wong, T. Z., Zalutsky, M. R., Pastan, I., Bigner, D. D. (2008). Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro Oncol Duke 10: 320-329 [Abstract] [Full Text]  
• Du, X., Nagata, S., Ise, T., Stetler-Stevenson, M., Pastan, I. (2008). FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins. Blood 111: 338-343 [Abstract] [Full Text]  
• Wang, T., Zhao, J., Ren, J.-L., Zhang, L., Wen, W.-H., Zhang, R., Qin, W.-W., Jia, L.-T., Yao, L.-B., Zhang, Y.-Q., Chen, S.-Y., Yang, A.-G. (2007). Recombinant Immunoproapoptotic Proteins with Furin Site Can Translocate and Kill HER2-Positive Cancer Cells. Cancer Res. 67: 11830-11839 [Abstract] [Full Text]  
• Orbach, A., Rachmilewitz, J., Parnas, M., Huang, J.-H., Tykocinski, M. L., Dranitzki-Elhalel, M. (2007). CTLA-4 {middle dot} FasL Induces Early Apoptosis of Activated T Cells by Interfering with Anti-Apoptotic Signals. J. Immunol. 179: 7287-7294 [Abstract] [Full Text]  
• Zhang, Y., Xiang, L., Hassan, R., Pastan, I. (2007). Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors. Proc. Natl. Acad. Sci. USA 104: 17099-17104 [Abstract] [Full Text]  
• Stein, R., Mattes, M. J., Cardillo, T. M., Hansen, H. J., Chang, C.-H., Burton, J., Govindan, S., Goldenberg, D. M. (2007). CD74: A New Candidate Target for the Immunotherapy of B-Cell Neoplasms. Clin. Cancer Res. 13: 5556s-5563s [Abstract] [Full Text]  
• Onda, M., Nagata, S., FitzGerald, D. J., Beers, R., Fisher, R. J., Vincent, J. J., Lee, B., Nakamura, M., Hwang, J., Kreitman, R. J., Hassan, R., Pastan, I. (2006). Characterization of the B Cell Epitopes Associated with a Truncated Form of Pseudomonas Exotoxin (PE38) Used to Make Immunotoxins for the Treatment of Cancer Patients. J. Immunol. 177: 8822-8834 [Abstract] [Full Text]  
• Li, Z., Mahesh, S. P., Shen, D. F., Liu, B., Siu, W. O., Hwang, F. S., Wang, Q.-C., Chan, C.-C., Pastan, I., Nussenblatt, R. B. (2006). Eradication of Tumor Colonization and Invasion by a B Cell-Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma. Cancer Res. 66: 10586-10593 [Abstract] [Full Text]  
• Kennedy, P. E., Bera, T. K., Wang, Q.-C., Gallo, M., Wagner, W., Lewis, M. G., Berger, E. A., Pastan, I. (2006). Anti-HIV-1 immunotoxin 3B3(Fv)-PE38: enhanced potency against clinical isolates in human PBMCs and macrophages, and negligible hepatotoxicity in macaques. J. Leukoc. Biol. 80: 1175-1182 [Abstract] [Full Text]  
• Zhang, Y., Xiang, L., Hassan, R., Paik, C. H., Carrasquillo, J. A., Jang, B.-s., Le, N., Ho, M., Pastan, I. (2006). Synergistic Antitumor Activity of Taxol and Immunotoxin SS1P in Tumor-Bearing Mice. Clin. Cancer Res. 12: 4695-4701 [Abstract] [Full Text]  
• Ho, M., Nagata, S., Pastan, I. (2006). Isolation of anti-CD22 Fv with high affinity by Fv display on human cells. Proc. Natl. Acad. Sci. USA 103: 9637-9642 [Abstract] [Full Text]  
• Arons, E., Margulies, I., Sorbara, L., Raffeld, M., Stetler-Stevenson, M., Pastan, I., Kreitman, R. J. (2006). Minimal residual disease in hairy cell leukemia patients assessed by clone-specific polymerase chain reaction.. Clin. Cancer Res. 12: 2804-2811 [Abstract] [Full Text]  
• Beum, P. V., Kennedy, A. D., Williams, M. E., Lindorfer, M. A., Taylor, R. P. (2006). The Shaving Reaction: Rituximab/CD20 Complexes Are Removed from Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Cells by THP-1 Monocytes. J. Immunol. 176: 2600-2609 [Abstract] [Full Text]  
• Gattenlohner, S., Marx, A., Markfort, B., Pscherer, S., Landmeier, S., Juergens, H., Muller-Hermelink, H.-K., Matthews, I., Beeson, D., Vincent, A., Rossig, C. (2006). Rhabdomyosarcoma Lysis by T Cells Expressing a Human Autoantibody-Based Chimeric Receptor Targeting the Fetal Acetylcholine Receptor. Cancer Res. 66: 24-28 [Abstract] [Full Text]  
• Chang, C.-H., Sapra, P., Vanama, S. S., Hansen, H. J., Horak, I. D., Goldenberg, D. M. (2005). Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin. Blood 106: 4308-4314 [Abstract] [Full Text]  
• Ravandi, F., O'Brien, S. (2005). Chronic Lymphoid Leukemias Other Than Chronic Lymphocytic Leukemia: Diagnosis and Treatment. Mayo Clin Proc. 80: 1660-1674 [Abstract]  
• Vallera, D. A., Brechbiel, M. W., Burns, L. J., Panoskaltsis-Mortari, A., Dusenbery, K. E., Clohisy, D. R., Vitetta, E. S. (2005). Radioimmunotherapy of CD22-Expressing Daudi Tumors in Nude Mice with a 90Y-Labeled Anti-CD22 Monoclonal Antibody. Clin. Cancer Res. 11: 7920-7928 [Abstract] [Full Text]  
• Kreitman, R. J., Squires, D. R., Stetler-Stevenson, M., Noel, P., FitzGerald, D. J.P., Wilson, W. H., Pastan, I. (2005). Phase I Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With B-Cell Malignancies. JCO 23: 6719-6729 [Abstract] [Full Text]  
• Onda, M., Willingham, M., Nagata, S., Bera, T. K., Beers, R., Ho, M., Hassan, R., Kreitman, R. J., Pastan, I. (2005). New Monoclonal Antibodies to Mesothelin Useful for Immunohistochemistry, Fluorescence-Activated Cell Sorting, Western Blotting, and ELISA. Clin. Cancer Res. 11: 5840-5846 [Abstract] [Full Text]  
• Chadha, P., Rademaker, A. W., Mendiratta, P., Kim, B., Evanchuk, D. M., Hakimian, D., Peterson, L. C., Tallman, M. S. (2005). Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA): long-term follow-up of the Northwestern University experience. Blood 106: 241-246 [Abstract] [Full Text]  
• Nagata, S., Ise, T., Onda, M., Nakamura, K., Ho, M., Raubitschek, A., Pastan, I. H. (2005). Cell membrane-specific epitopes on CD30: Potentially superior targets for immunotherapy. Proc. Natl. Acad. Sci. USA 102: 7946-7951 [Abstract] [Full Text]  
• Vallera, D. A., Todhunter, D. A., Kuroki, D. W., Shu, Y., Sicheneder, A., Chen, H. (2005). A Bispecific Recombinant Immunotoxin, DT2219, Targeting Human CD19 and CD22 Receptors in a Mouse Xenograft Model of B-Cell Leukemia/Lymphoma. Clin. Cancer Res. 11: 3879-3888 [Abstract] [Full Text]  
• Pastan, I. (2005). An NIH Career: from Bedside to Basic Research and Back. J. Biol. Chem. 280: 18553-18557 [Full Text]  
• Marks, A. J., Cooper, M. S., Anderson, R. J., Orchard, K. H., Hale, G., North, J. M., Ganeshaguru, K., Steele, A. J., Mehta, A. B., Lowdell, M. W., Wickremasinghe, R. G. (2005). Selective Apoptotic Killing of Malignant Hemopoietic Cells by Antibody-Targeted Delivery of an Amphipathic Peptide. Cancer Res. 65: 2373-2377 [Abstract] [Full Text]  
• Bang, S., Nagata, S., Onda, M., Kreitman, R. J., Pastan, I. (2005). HA22 (R490A) Is a Recombinant Immunotoxin with Increased Antitumor Activity without an Increase in Animal Toxicity. Clin. Cancer Res. 11: 1545-1550 [Abstract] [Full Text]  
• Ho, M., Kreitman, R. J., Onda, M., Pastan, I. (2005). In Vitro Antibody Evolution Targeting Germline Hot Spots to Increase Activity of an Anti-CD22 Immunotoxin. J. Biol. Chem. 280: 607-617 [Abstract] [Full Text]  
• Sampson, J. H., Reardon, D. A., Friedman, A. H., Friedman, H. S., Coleman, R. E., McLendon, R. E., Pastan, I., Bigner, D. D. (2005). Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: Case study. Neuro Oncol Duke 7: 90-96 [Abstract]  
• Ise, T., Maeda, H., Santora, K., Xiang, L., Kreitman, R. J., Pastan, I., Nagata, S. (2005). Immunoglobulin Superfamily Receptor Translocation Associated 2 Protein on Lymphoma Cell Lines and Hairy Cell Leukemia Cells Detected by Novel Monoclonal Antibodies. Clin. Cancer Res. 11: 87-96 [Abstract] [Full Text]  
• Shahied, L. S., Tang, Y., Alpaugh, R. K., Somer, R., Greenspon, D., Weiner, L. M. (2004). Bispecific Minibodies Targeting HER2/neu and CD16 Exhibit Improved Tumor Lysis When Placed in a Divalent Tumor Antigen Binding Format. J. Biol. Chem. 279: 53907-53914 [Abstract] [Full Text]  
• Shibata, H., Yoshioka, Y., Ikemizu, S., Kobayashi, K., Yamamoto, Y., Mukai, Y., Okamoto, T., Taniai, M., Kawamura, M., Abe, Y., Nakagawa, S., Hayakawa, T., Nagata, S., Yamagata, Y., Mayumi, T., Kamada, H., Tsutsumi, Y. (2004). Functionalization of Tumor Necrosis Factor-{alpha} Using Phage Display Technique and PEGylation Improves Its Antitumor Therapeutic Window. Clin. Cancer Res. 10: 8293-8300 [Abstract] [Full Text]  
• DiJoseph, J. F., Goad, M. E., Dougher, M. M., Boghaert, E. R., Kunz, A., Hamann, P. R., Damle, N. K. (2004). Potent and Specific Antitumor Efficacy of CMC-544, a CD22-Targeted Immunoconjugate of Calicheamicin, against Systemically Disseminated B-Cell Lymphoma. Clin. Cancer Res. 10: 8620-8629 [Abstract] [Full Text]  
• Kreitman, R. J. (2004). Confirmation and prevention of targeted toxicity by a recombinant fusion toxin. Molecular Cancer Therapeutics 3: 1691-1692 [Full Text]  
• (2004). Session 9: Cancer Therapy. Toxicol Pathol 32: 745-746  
• Decker, T., Oelsner, M., Kreitman, R. J., Salvatore, G., Wang, Q.-c., Pastan, I., Peschel, C., Licht, T. (2004). Induction of caspase-dependent programmed cell death in B-cell chronic lymphocytic leukemia by anti-CD22 immunotoxins. Blood 103: 2718-2726 [Abstract] [Full Text]  
• DiJoseph, J. F., Armellino, D. C., Boghaert, E. R., Khandke, K., Dougher, M. M., Sridharan, L., Kunz, A., Hamann, P. R., Gorovits, B., Udata, C., Moran, J. K., Popplewell, A. G., Stephens, S., Frost, P., Damle, N. K. (2004). Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood 103: 1807-1814 [Abstract] [Full Text]  
• Onda, M., Wang, Q.-c., Guo, H.-f., Cheung, N.-K. V., Pastan, I. (2004). In Vitro and in Vivo Cytotoxic Activities of Recombinant Immunotoxin 8H9(Fv)-PE38 against Breast Cancer, Osteosarcoma, and Neuroblastoma. Cancer Res. 64: 1419-1424 [Abstract] [Full Text]  
• Thomas, D. A., O'Brien, S., Bueso-Ramos, C., Faderl, S., Keating, M. J., Giles, F. J., Cortes, J., Kantarjian, H. M. (2003). Rituximab in relapsed or refractory hairy cell leukemia. Blood 102: 3906-3911 [Abstract] [Full Text]  
• Dyer, M. J.S. (2003). Bioweapons of Tumor Mass Destruction?. JCO 21: 3011-3012 [Full Text]  
• Nieva, J., Bethel, K., Saven, A. (2003). Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. Blood 102: 810-813 [Abstract] [Full Text]  
• Di Paolo, C., Willuda, J., Kubetzko, S., Lauffer, I., Tschudi, D., Waibel, R., Pluckthun, A., Stahel, R. A., Zangemeister-Wittke, U. (2003). A Recombinant Immunotoxin Derived from a Humanized Epithelial Cell Adhesion Molecule-specific Single-Chain Antibody Fragment Has Potent and Selective Antitumor Activity. Clin. Cancer Res. 9: 2837-2848 [Abstract] [Full Text]  
• Mavromatis, B., Cheson, B. D. (2003). Monoclonal Antibody Therapy of Chronic Lymphocytic Leukemia. JCO 21: 1874-1881 [Abstract] [Full Text]  
• Goodman, G. R., Burian, C., Koziol, J. A., Saven, A. (2003). Extended Follow-Up of Patients With Hairy Cell Leukemia After Treatment With Cladribine. JCO 21: 891-896 [Abstract] [Full Text]  
• Hassan, R., Lerner, M. R., Benbrook, D., Lightfoot, S. A., Brackett, D. J., Wang, Q.-C., Pastan, I. (2002). Antitumor Activity of SS(dsFv)PE38 and SS1(dsFv)PE38, Recombinant Antimesothelin Immunotoxins against Human Gynecologic Cancers Grown in Organotypic Culture in Vitro. Clin. Cancer Res. 8: 3520-3526 [Abstract] [Full Text]  
• Posey, J. A., Khazaeli, M. B., Bookman, M. A., Nowrouzi, A., Grizzle, W. E., Thornton, J., Carey, D. E., Lorenz, J. M., Sing, A. P., Siegall, C. B., LoBuglio, A. F., Saleh, M. N. (2002). A Phase I Trial of the Single-Chain Immunotoxin SGN-10 (BR96 sFv-PE40) in Patients with Advanced Solid Tumors. Clin. Cancer Res. 8: 3092-3099 [Abstract] [Full Text]  
• McHugh, L., Hu, S., Lee, B. K., Santora, K., Kennedy, P. E., Berger, E. A., Pastan, I., Hamer, D. H. (2002). Increased Affinity and Stability of an Anti-HIV-1 Envelope Immunotoxin by Structure-based Mutagenesis. J. Biol. Chem. 277: 34383-34390 [Abstract] [Full Text]  
• Jurcic, J. G., Larson, S. M., Sgouros, G., McDevitt, M. R., Finn, R. D., Divgi, C. R., Ballangrud, A. M., Hamacher, K. A., Ma, D., Humm, J. L., Brechbiel, M. W., Molinet, R., Scheinberg, D. A. (2002). Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100: 1233-1239 [Abstract] [Full Text]  
• Nagata, S., Onda, M., Numata, Y., Santora, K., Beers, R., Kreitman, R. J., Pastan, I. (2002). Novel Anti-CD30 Recombinant Immunotoxins Containing Disulfide-stabilized Fv Fragments. Clin. Cancer Res. 8: 2345-2355 [Abstract] [Full Text]  
• Pan, X. Q., Zheng, X., Shi, G., Wang, H., Ratnam, M., Lee, R. J. (2002). Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta -targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid. Blood 100: 594-602 [Abstract] [Full Text]  
• Bera, T. K., Iavarone, C., Kumar, V., Lee, S., Lee, B., Pastan, I. (2002). MRP9, an unusual truncated member of the ABC transporter superfamily, is highly expressed in breast cancer. Proc. Natl. Acad. Sci. USA 99: 6997-7002 [Abstract] [Full Text]  
• Peipp, M., Kupers, H., Saul, D., Schlierf, B., Greil, J., Zunino, S. J., Gramatzki, M., Fey, G. H. (2002). A Recombinant CD7-specific Single-Chain Immunotoxin Is a Potent Inducer of Apoptosis in Acute Leukemic T Cells. Cancer Res. 62: 2848-2855 [Abstract] [Full Text]  
• Frankel, A. E., Powell, B. L., Hall, P. D., Case, L. D., Kreitman, R. J. (2002). Phase I Trial of a Novel Diphtheria Toxin/Granulocyte Macrophage Colony-stimulating Factor Fusion Protein (DT388GMCSF) for Refractory or Relapsed Acute Myeloid Leukemia. Clin. Cancer Res. 8: 1004-1013 [Abstract] [Full Text]  
• Frankel, A. E. (2002). Increased Sophistication of Immunotoxins. Clin. Cancer Res. 8: 942-944 [Full Text]  
• Salvatore, G., Beers, R., Margulies, I., Kreitman, R. J., Pastan, I. (2002). Improved Cytotoxic Activity toward Cell Lines and Fresh Leukemia Cells of a Mutant Anti-CD22 Immunotoxin Obtained by Antibody Phage Display. Clin. Cancer Res. 8: 995-1002 [Abstract] [Full Text]  
• Bera, T. K., Williams-Gould, J., Beers, R., Chowdhury, P., Pastan, I. (2001). Bivalent Disulfide-stabilized Fragment Variable Immunotoxin Directed against Mesotheliomas and Ovarian Cancer. Molecular Cancer Therapeutics 1: 79-84 [Abstract] [Full Text]  
• Saven, A., Kreitman, R. J., Wilson, W. H., Pastan, I. (2001). Treatment of Hairy-Cell Leukemia. NEJM 345: 1500-1501 [Full Text]  
• Schnipper, L. E., Strom, T. B. (2001). A Magic Bullet for Cancer -- How Near and How Far?. NEJM 345: 283-284 [Full Text]