Prospective validation of predictive value of abdominal computed tomography scan on time to first treatment in Rai 0 chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study
Corresponding Author
Massimo Gentile
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy
Correspondence Massimo Gentile, MD and Fortunato Morabito, MD, UOC Ematologia, Azienda Ospedaliera di Cosenza, viale della Repubblica snc, 87100 Cosenza, Italy. Tel: +39 0984 681329; Fax: +39-0984-681329; e-mails: [email protected]; [email protected]Search for more papers by this authorGiovanna Cutrona
SS Molecular Diagnostics IRCCS S. Martino-IST, Genova, Italy
Search for more papers by this authorStefano Molica
Department of Oncology and Haematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy
Search for more papers by this authorFiorella Ilariucci
Division of Haematology, A.O. S. Maria Nuova, Reggio Emilia, Italy
Search for more papers by this authorFrancesca R. Mauro
Divisione di Ematologia, Università La Sapienza, Rome, Italy
Search for more papers by this authorNicola Di Renzo
Hematology Unit, Ospedale Vito Fazzi, Lecce, Italy
Search for more papers by this authorFrancesco Di Raimondo
Division of Haematology, Department of Biomedical Sciences, University of Catania and Ferrarotto Hospital, Catania, Italy
Search for more papers by this authorIolanda Vincelli
Hematology Unit, A.O. of Reggio Calabria, Reggio, Italy
Search for more papers by this authorKatia Todoerti
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorSerena Matis
Direzione Scientifica IRCCS, San Martino IST, Genova, Italy
Search for more papers by this authorCaterina Musolino
Division of Haematology, University of Messina, Messina, Italy
Search for more papers by this authorSonia Fabris
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorMarta Lionetti
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorLuciano Levato
Department of Oncology and Haematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy
Search for more papers by this authorSimona Zupo
SS Molecular Diagnostics IRCCS S. Martino-IST, Genova, Italy
Search for more papers by this authorFrancesco Angrilli
Department of Hematology, Ospedale Santo Spirito, Pescara, Italy
Search for more papers by this authorUgo Consoli
U.O.S. di Emato-Oncologia, Ospedale Garibaldi-Nesima, Catania, Italy
Search for more papers by this authorGianluca Festini
Centro di Riferimento Ematologico-Seconda Medicina, Azienda Ospedaliero-Universitaria, Ospedali Riuniti, Trieste, Italy
Search for more papers by this authorGiuseppe Longo
Unità di Ematologia, Ospedale San Vincenzo, Taormina, Italy
Search for more papers by this authorAgostino Cortelezzi
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorPellegrino Musto
Scientific Direction, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorMassimo Federico
Department of Onco-hematology, Università di Modena Centro Oncologico Modenese, Policlinico Modena, Italy
Search for more papers by this authorAntonino Neri
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorManlio Ferrarini
Direzione Scientifica IRCCS, San Martino IST, Genova, Italy
Search for more papers by this authorCorresponding Author
Fortunato Morabito
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy
Correspondence Massimo Gentile, MD and Fortunato Morabito, MD, UOC Ematologia, Azienda Ospedaliera di Cosenza, viale della Repubblica snc, 87100 Cosenza, Italy. Tel: +39 0984 681329; Fax: +39-0984-681329; e-mails: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Massimo Gentile
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy
Correspondence Massimo Gentile, MD and Fortunato Morabito, MD, UOC Ematologia, Azienda Ospedaliera di Cosenza, viale della Repubblica snc, 87100 Cosenza, Italy. Tel: +39 0984 681329; Fax: +39-0984-681329; e-mails: [email protected]; [email protected]Search for more papers by this authorGiovanna Cutrona
SS Molecular Diagnostics IRCCS S. Martino-IST, Genova, Italy
Search for more papers by this authorStefano Molica
Department of Oncology and Haematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy
Search for more papers by this authorFiorella Ilariucci
Division of Haematology, A.O. S. Maria Nuova, Reggio Emilia, Italy
Search for more papers by this authorFrancesca R. Mauro
Divisione di Ematologia, Università La Sapienza, Rome, Italy
Search for more papers by this authorNicola Di Renzo
Hematology Unit, Ospedale Vito Fazzi, Lecce, Italy
Search for more papers by this authorFrancesco Di Raimondo
Division of Haematology, Department of Biomedical Sciences, University of Catania and Ferrarotto Hospital, Catania, Italy
Search for more papers by this authorIolanda Vincelli
Hematology Unit, A.O. of Reggio Calabria, Reggio, Italy
Search for more papers by this authorKatia Todoerti
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorSerena Matis
Direzione Scientifica IRCCS, San Martino IST, Genova, Italy
Search for more papers by this authorCaterina Musolino
Division of Haematology, University of Messina, Messina, Italy
Search for more papers by this authorSonia Fabris
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorMarta Lionetti
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorLuciano Levato
Department of Oncology and Haematology, Pugliese-Ciaccio Hospital, Catanzaro, Italy
Search for more papers by this authorSimona Zupo
SS Molecular Diagnostics IRCCS S. Martino-IST, Genova, Italy
Search for more papers by this authorFrancesco Angrilli
Department of Hematology, Ospedale Santo Spirito, Pescara, Italy
Search for more papers by this authorUgo Consoli
U.O.S. di Emato-Oncologia, Ospedale Garibaldi-Nesima, Catania, Italy
Search for more papers by this authorGianluca Festini
Centro di Riferimento Ematologico-Seconda Medicina, Azienda Ospedaliero-Universitaria, Ospedali Riuniti, Trieste, Italy
Search for more papers by this authorGiuseppe Longo
Unità di Ematologia, Ospedale San Vincenzo, Taormina, Italy
Search for more papers by this authorAgostino Cortelezzi
Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorPellegrino Musto
Scientific Direction, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture (Pz), Italy
Search for more papers by this authorMassimo Federico
Department of Onco-hematology, Università di Modena Centro Oncologico Modenese, Policlinico Modena, Italy
Search for more papers by this authorAntonino Neri
Department of Clinical Sciences and Community Health, University of Milano and Hematology CTMO, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Search for more papers by this authorManlio Ferrarini
Direzione Scientifica IRCCS, San Martino IST, Genova, Italy
Search for more papers by this authorCorresponding Author
Fortunato Morabito
Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy
Correspondence Massimo Gentile, MD and Fortunato Morabito, MD, UOC Ematologia, Azienda Ospedaliera di Cosenza, viale della Repubblica snc, 87100 Cosenza, Italy. Tel: +39 0984 681329; Fax: +39-0984-681329; e-mails: [email protected]; [email protected]Search for more papers by this authorAbstract
Objective
We performed an external and multicentric validation of the predictive value of abdominal computed tomography (aCT) on time to first treatment (TTFT) in early stage chronic lymphocytic leukemia (CLL) patients.
Methods
aCT was performed at diagnosis in 181 Rai 0 patients enrolled in the O-CLL1-GISL trial (clinicaltrial.gov ID:NCT00917549).
Results
Fifty-five patients showed an abnormal aCT. Patients with an abnormal aCT showed a significantly shorter TTFT than those with normal aCT (P < 0.0001). At multivariate analysis, aCT (P = 0.011), β-2 microglobulin (P = 0.019), and CD38 expression (P = 0.047) correlated with TTFT. Following IWCLL 2008 criteria, 112 (61.9%) cases remained at Rai 0, while 69 (38.1%) satisfied the criteria of clinical monoclonal B-cell lymphocytosis (cMBL). Reclassified Rai 0 patients with an abnormal aCT showed a significantly shorter TTFT than those with a normal aCT (P < 0.0001). At multivariate analysis, only aCT (P = 0.011) correlated with TTFT. Eleven cMBL cases (15.9%) showed an abnormal aCT and were reclassified as small lymphocytic lymphomas (SLL); nonetheless, TTFT was similar for cMBLs and SLLs.
Conclusion
Our results confirm the ability of the abnormal aCT to predict progression in early stage cases.
Supporting Information
| Filename | Description |
|---|---|
| ejh12545-sup-0001-Tables.docxWord document, 81.4 KB |
Table S1. Comparison of main clinical and biological patient features according to the availability of abdominal CT scan at baseline. Table S2. Comparison of clinical features between Rai 0 cases with abnormal abdominal CT scan and Rai I cases on clinical grounds. Table S3. Clinical features and correlations with abnormal abdominal CT scan in cMBL patients. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804–15.
- 2Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 1975; 46: 219–34.
- 3Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 1981; 48: 198–206.
10.1002/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V CAS PubMed Web of Science® Google Scholar
- 4Call T, Phyilky R, Noel P, et al. Incidence of chronic lymphocytic leukemia in Olmsted County, Minnesota, 1935 through 1989, with emphasis on changes in initial stage at diagnosis. Mayo Clin Proc 1994; 69: 323–8.
- 5Molica S, Levato D, Dattilo A. Natural history of early chronic lymphocytic leukemia. A single institution study with emphasis on the impact of disease-progression on overall survival. Haematologica 1999; 84: 1094–9.
- 6Rozman C, Bosch F, Montserrat E. Chronic lymphocytic leukemia: a changing natural history? Leukemia 1997; 11: 775–8.
- 7Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000; 343: 1910–6.
- 8Hamblin TJ, Davis Z, Gardiner A, et al. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94: 1848–54.
- 9Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840–7.
- 10Gentile M, Cutrona G, Mosca L, et al. Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study. Am J Hematol 2014; 89: 743–50.
- 11Shanafelt TD, Geyer SM, Bone ND, et al. CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol 2008; 140: 537–46.
- 12Gentile M, Cutrona G, Neri A, et al. Predictive value of beta2-microglobulin (beta2-m) levels in chronic lymphocytic leukemia since Binet A stages. Haematologica 2009; 94: 887–8.
- 13Morabito F, De Filippi R, Laurenti L, et al. The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. Blood 2011; 118: 6353–61.
- 14Wierda WG, O'Brien S, Wang X, et al. Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood 2007; 109: 4679–85.
- 15Pflug N, Bahlo J, Shanafelt TD, et al. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood 2014; 124: 49–62.
- 16Mavromatis BH, Cheson BD. Pre- and post-treatment evaluation of non-Hodgkin's lymphoma. Best Pract Res Clin Haematol 2002; 15: 429–47.
- 17Cheson BD, Bennett JM, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–7.
- 18Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446–56.
- 19Muntanola A, Bosch F, Arguis P, et al. Abdominal computed tomography predicts progression in patients with Rai stage 0 chronic lymphocytic leukaemia. J Clin Oncol 2007; 25: 1576–80.
- 20Gentile M, Cutrona G, Fabris S, et al. Total body computed tomography scan in the initial work-up of Binet stage A chronic lymphocytic leukemia patients: results of the prospective, multicenter O-CLL1-GISL study. Am J Hematol 2013; 88: 539–44.
- 21Dorfman RE, Alpern MB, Gross BH, et al. Upper abdominal lymph nodes: criteria for normal size determined with CT. Radiology 1991; 180: 319–22.
- 22Vinnicombe SJ, Reznek RH. Computerised tomography in the staging of Hodgkin's disease and non-Hodgkin's lymphoma. Eur J Nucl Med Mol Imaging 2003; 30(Suppl 1): S42–55.
- 23Sutinen E, Jyrkkio S, Varpula M, et al. Nodal staging of lymphoma with whole-body PET: comparison of. J Nucl Med 2000; 41: 1980–8.
- 24Geraghty EM, Boone JM, McGahan JP, Jain K. Normal organ volume assessment from abdominal CT. Abdom Imaging 2004; 29: 482–90.
- 25Morabito F, Cutrona G, Gentile M, et al. Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia. Br J Haematol 2009; 146: 44–53.
- 26Morabito F, Cutrona G, Gentile M, et al. Is ZAP70 still a key prognostic factor in early stage chronic lymphocytic leukaemia? Results of the analysis from a prospective multicentre observational study. Br J Haematol 2015; 168: 455–9.
- 27Cutrona G, Colombo M, Matis S, et al. Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells. Haematologica 2008; 93: 413–22.
- 28Lionetti M, Fabris S, Cutrona G, et al. High-throughput sequencing for the identification of NOTCH1 mutations in early stage chronic lymphocytic leukemia: biological and clinical implications. Br J Haematol 2014; 165: 629–39.
- 29Brenner DJ, Hall EJ. Computed tomography–an increasing source of radiation exposure. N Engl J Med 2007; 357: 2277–84.
- 30Tsimberidou AM, Wen S, McLaughlin P, et al. Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 2009; 27: 904–10.
- 31Eichhorst BF, Fischer K, Fink AM, et al. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis. Blood 2011; 117: 1817–21.
- 32Armitage JO. Staging non-Hodgkin lymphoma. CA Cancer J Clin 2005; 55: 368–76.
Citing Literature
