{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:59:16Z","timestamp":1789970356297,"version":"4.0.1"},"reference-count":50,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"27","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,9,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>To conduct a phase I trial of recombinant immunotoxin BL22, an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Forty-six pretreated patients with CD22+ non-Hodgkin's lymphoma (NHL; n = 4), chronic lymphocytic leukemia (CLL; n = 11), and hairy cell leukemia (HCL; n = 31) received 265 cycles at 3 to 50 \u03bcg\/Kg every other day \u00d7 3 doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BL22 was active in HCL, with 19 complete remissions (CRs; 61%) and six partial responses (PRs; 19%) in 31 patients. Of 19 CRs, 11 were achieved after one cycle and eight after two to 14 cycles. All 25 responders benefited clinically with one cycle. The CR rate was 86% in patients enrolled at \u2265 40 \u03bcg\/Kg every other day \u00d7 3, and 41% at lower doses (P = .011). The median duration for CR was 36 months (range, 5 to 66 months), and eight patients remain in CR at 45 months (range, 29 to 66 months). Lower but significant activity occurred in CLL. Neutralizing antibodies occurred in 11 (24%) of 46 patients (all HCL). A reversible hemolytic uremic syndrome requiring plasmapheresis was observed in one patient with NHL during cycle 1 and in four patients with HCL during cycle 2 or 3. The maximum-tolerated dose (MTD) evaluated at cycle 1 was 40 \u03bcg\/Kg IV. QOD \u00d7 3. The most common toxicities at 30 to 50 \u03bcg\/Kg every other day \u00d7 3 included hypoalbuminemia, transaminase elevations, fatigue, and edema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BL22 was well tolerated and highly effective in HCL, even after one cycle. Phase II testing is underway to define the efficacy with one cycle and to study safety when additional cycles are needed for optimal response.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.11.437","type":"journal-article","created":{"date-parts":[[2005,8,2]],"date-time":"2005-08-02T00:26:23Z","timestamp":1122942383000},"page":"6719-6729","source":"Crossref","is-referenced-by-count":223,"title":["Phase I Trial of Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) in Patients With B-Cell Malignancies"],"prefix":"10.1200","volume":"23","author":[{"given":"Robert J.","family":"Kreitman","sequence":"first","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Squires","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryalice","family":"Stetler-Stevenson","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Noel","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.P.","family":"FitzGerald","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyndham H.","family":"Wilson","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ira","family":"Pastan","sequence":"additional","affiliation":[{"name":"From the Laboratory of Molecular Biology, Laboratory of Clinical Pathology, and Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Christiansen J, Rajasekaran AK: Biological impediments to monoclonal antibody-based cancer immunotherapy. Mol Cancer Ther 3:1493,2004-1501,","DOI":"10.1158\/1535-7163.1493.3.11"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(04)51010-4"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(04)51006-2"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.4.4.455"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1023\/B:DRUG.0000036684.67675.fe"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(04)51008-6"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1793"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403598"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1028"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00302"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0093-7754(03)00241-0"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2004.22.14_suppl.4095"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S1521-6926(03)00003-3"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V82.9.2624.2624"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3457.bloodjournal85123457"},{"key":"R16","unstructured":"Vitetta ES, Stone M, Amlot P, et al: Phase I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 51:4052,1991-4058,"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Clark EA: CD22, a B cell-specific receptor, mediates adhesion and signal transduction. J Immunol 150:4715,1993-4718,","DOI":"10.4049\/jimmunol.150.11.4715"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.5.2020"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1021\/bi00184a014"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910580123"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.5.1320"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1021\/bi971447w"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Chiron MF, Fryling CM, FitzGerald DJ: Cleavage of Pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. J Biol Chem 269:18167,1994-18176,","DOI":"10.1016\/S0021-9258(17)32431-6"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Ogata M, Fryling CM, Pastan I, et al: Cell-mediated cleavage of exotoxin between Arg and Gly generates the enzymatically active fragment which translocates to the cytosol. J Biol Chem 267:25396,1992-25401,Pseudomonas279280","DOI":"10.1016\/S0021-9258(19)74054-X"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1042\/bj3070029"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1021\/bi00185a029"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.16.7774"},{"key":"R28","unstructured":"Kreitman RJ, Margulies I, Stetler-Stevenson M, et al: Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) towards fresh malignant cells from patients with B-cell leukemias. Clin Cancer Res 6:1476,2000-1487,"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990331)81:1<148::AID-IJC24>3.0.CO;2-L"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107263450402"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.05.093"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.4.1244"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.4.888.888"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.3.1138"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.3109\/10428199709114177"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2401999"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020528"},{"key":"R38","unstructured":"Tallman MS, Hakimian D, Kopecky KJ, et al: Minimal residual disease in patients with hairy cell leukemia in complete remission treated with 2-chlorodeoxyadenosine or 2- deoxycoformycin and prediction of early relapse. Clin Cancer Res 5:1665,1999-1670,"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.4.1556.bloodjournal8741556"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.2273044.x"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.14712\/18059694.2019.148"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Sausville JE, Salloum R, Sorbara L, et al: Minimal residual disease detection in hairy cell leukemia: Comparison of flow cytometric immunophenotyping with clonal analysis using consensus primer polymerase chain reaction for the heavy chain gene. Am J Clin Pathol 119:213,2002-217,","DOI":"10.1309\/G6299513NGLCUB1K"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.10.2906.2906"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400513"},{"key":"R45","unstructured":"Filleul B, Delannoy A, Ferrant A, et al: A single course of 2-chloro-deoxyadenosine does not eradicate leukemic cells in hairy cell leukemia patients in complete remission. Leukemia 8:1153,1994-1156,"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.03143.x"},{"key":"R48","unstructured":"Lauria F, Lenoci M, Annino L, et al: Efficacy of anti-CD20 monoclonal antibodies (Mabthera) in patients with progressed hairy cell leukemia. Haematologica 86:1046,2001-1050,"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0014"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0630"},{"key":"R51","unstructured":"Salvatore G, Beers R, Margulies I, et al: Improved Cytotoxic activity towards cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. Clin Cancer Res 8:995,2002-1002,"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.11.437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T23:16:35Z","timestamp":1683155795000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.11.437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9,20]]},"references-count":50,"journal-issue":{"issue":"27","published-print":{"date-parts":[[2005,9,20]]}},"alternative-id":["10.1200\/JCO.2005.11.437"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.11.437","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,9,20]]}}}