Minimal residual disease in chronic lymphocytic leukaemia: Is it ready for primetime?

British Journal of Haematology

Volumn 136, Issue 3, 2007, Pages 379-392

  Nabhan, Chadi ^a,d   Coutré, Steven ^b   Hillmen, Peter ^c  

^a ADVOCATE LUTHERAN GENERAL HOSPITAL   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c LEEDS GENERAL INFIRMARY   (United Kingdom)

^d Division of Hematology and Oncology   (United States)

Author keywords

Alemtuzumab; Chronic lymphocytic leukaemia; Immunotherapy; Minimal residual disease

Indexed keywords

ALEMTUZUMAB; CYCLOPHOSPHAMIDE; FLUDARABINE; IMATINIB; IMMUNOGLOBULIN HEAVY CHAIN; MITOXANTRONE; PROTEIN KINASE ZAP 70; PROTEIN P53; RITUXIMAB;

ACUTE LYMPHOCYTIC LEUKEMIA; AUTOLOGOUS STEM CELL TRANSPLANTATION; BLOOD ANALYSIS; BONE MARROW EXAMINATION; CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RESISTANCE; CANCER SURVIVAL; CHROMOSOME 11Q; CHROMOSOME 17P; CHROMOSOME ANALYSIS; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; DRUG CYTOTOXICITY; DRUG DOSE ESCALATION; EARLY DIAGNOSIS; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENOME ANALYSIS; HEMATOLOGIC MALIGNANCY; HUMAN; IMMUNOGLOBULIN VARIABLE REGION; LEUKEMIA RELAPSE; LEUKEMIA REMISSION; MINIMAL RESIDUAL DISEASE; MULTIPLE CYCLE TREATMENT; MYELODYSPLASIA; OVERALL SURVIVAL; PATIENT ASSESSMENT; PATIENT MONITORING; POLYMERASE CHAIN REACTION; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROMYELOCYTIC LEUKEMIA; RECURRENT CANCER; REVIEW; RISK ASSESSMENT; SURVIVAL RATE; SURVIVAL TIME; THERAPY EFFECT; TREATMENT RESPONSE; TRISOMY 12;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE-FREE SURVIVAL; HUMANS; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC; NEOPLASM, RESIDUAL; PATIENT SELECTION; PROGNOSIS; REMISSION INDUCTION; STEM CELL TRANSPLANTATION;

EID: 33845980558     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2006.06428.x     Document Type: Review

References (70)

1. Austen, B., Powell, J.E., Alvi, A., Edwards, I., Hooper, L., Starczynski, J., Taylor, A.M., Fegan, C., Moss, P. & Stankovic, T. (2005) Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood, 106, 3175-3182.
2. Binet, J.L., Lepoprier, M., Dighiero, G., Charron, D., d'Athis, P., Vaugier, G., Beral, H.M., Natali, J.C., Raphael, M., Nizet, B. & Follezou, J.Y. (1977) A clinical staging system for chronic lymphocytic leukemia: prognostic significance. Cancer, 40, 855-864.
3. Bosch, F., Ferrer, A., Lopez-Guillermo, A., Gine, E., Bellosillo, B., Villamor, N., Colomer, D., Cobo, F., Perales, M., Esteve, J., Altes, A., Besalduch, J., Ribera, J. M. & Montserrat, E. (2002) Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. British Journal of Haematology, 119, 976-984.
4. Bosch, F., Ferrer, A., Villamor, N., Gine, E., Abella, M.A., Gardella, S., Besalduch, J., Gonzalez, M., Altes, A., Escoda, L., Ferrer, S., Gonzalez-Barca, E., Perez-Ceballos, E., Asensi, A. & Montserrat, E. (2005) Combination chemotherapy with fludarabine, cyclophosphamide and mitoxantrone (FCM) induces a high response rate in previously untreated CLL [abstract 718]. Blood, 106, 213a.
5. Breccia, M., Diverio, D., Noguera, N.I., Visani, G., Santoro, A., Locatelli, F., Damiani, D., Marmont, F., Vignetti, M., Petti, M.C. & Lo, C.F. (2004) Clinico-biological features and outcome of acute promyelocytic leukemia patients with persistent polymerase chain reaction-detectable disease after the AIDA front-line induction and consolidation therapy. Haematologica, 89, 29-33.
6. Byrd, J.C., Gribben, J.G., Peterson, B.L., Grever, M.R., Lozanski, G., Lucas, D.M., Lampson, B., Larson, R.A., Caligiuri, M.A. & Heerema, N.A. (2005) Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. Journal of Clinical Oncology, 24, 437-443.
7. Caballero, D., Garcia-Marco, J.A., Martino, R., Mateos, V., Ribera, J.M., Sarra, J., Leon, A., Sanz, G., de la, S.J., Cabrera, R., Gonzalez, M., Sierra, J. & San, M.J. (2005) Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene and chromosomal abnormalities (11q- and 17p-). Clinical Cancer Research, 11, 7757-7763.
8. Cheson, B.D., Bennett, J.M., Grever, M., Kay, N., Keating, M.J., O'Brien, S. & Rai, K.R. (1996) National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood, 87, 4990-4997.
9. Damle, R.N., Wasil, T., Fais, F., Ghiotto, F., Valetto, A., Allen, S.L., Buchbinder, A., Budman, D., Dittmar, K., Kolitz, J., Lichtman, S.M., Schulman, P., Vinciguerra, V.P., Rai, K.R., Ferrarini, M. & Chiorazzi, N. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, 94, 1840-1847.
10. Del Poeta, G., Maurillo, L., Venditti, A., Buccisano, F., Epiceno, A.M., Capelli, G., Tamburini, A., Suppo, G., Battaglia, A., Del Principe, M.I., Del, M.B., Masi, M. & Amadori, S. (2001) Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood, 98, 2633-2639.
11. Del Poeta, G., Del Principe, M.I., Consalvo, M.A., Maurillo, L., Buccisano, F., Venditti, A., Mazzone, C., Bruno, A., Gianni, L., Capelli, G., Lo, C.F., Cantonetti, M., Gattei, V. & Amadori, S. (2005) The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. Cancer, 104, 2743-2752.
12. Dewald, G.W., Brockman, S.R., Paternoster, S.F., Bone, N.D., O'Fallon, J.R., Allmer, C., James, C.D., Jelinek, D.F., Tschumper, R.C., Hanson, C.A., Pruthi, R.K., Witzig, T.E., Call, T.G. & Kay, N.E. (2003) Chromosome anomalies detected by interphase fluorescence in situ hybridization: correlation with significant biological features of B-cell chronic lymphocytic leukaemia. British Journal of Haematology, 121, 287-295.
13. Dighiero, G., Maloum, K., Desablens, B., Cazin, B., Navarro, M., Leblay, R., Leporrier, M., Jaubert, J., Lepeu, G., Dreyfus, B., Binet, J.L. & Travade, P. (1998) Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia. New England Journal of Medicine, 338, 1506-1514.
14. Diverio, D., Rossi, V., Avvisati, G., De, S.S., Pistilli, A., Pane, F., Saglio, G., Martinelli, G., Petti, M.C., Santoro, A., Pelicci, P.G., Mandelli, F., Biondi, A. & Lo, C.F. (1998) Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RARalpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter "AIDA" trial. GIMEMA-AIEOP Multicenter "AIDA" Trial. Blood, 92, 784-789.
15. Dohner, H., Fischer, K., Bentz, M., Hansen, K., Benner, A., Cabot, G., Diehl, D., Schlenk, R., Coy, J., Stilgenbauer, S., Volkman, M., Galle, P.R., Poustka, A., Hunstein, W. & Lichter, P. (1995) p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood, 85, 1580-1589.
16. Dohner, H., Stilgenbauer, S., Benner, A., Leupolt, E., Krober, A., Bullinger, L., Dohner, K., Bentz, M. & Lichter, P. (2000) Genomic aberrations and survival in chronic lymphocytic leukemia. New England Journal of Medicine, 343, 1910-1916.
17. Dreger, P., Ritgen, M., Bottcher, S., Schmitz, N. & Kneba, M. (2005) The prognostic impact of minimal residual disease assessment after stem cell transplantation for chronic lymphocytic leukemia: is achievement of molecular remission worthwhile? Leukemia, 19, 1135-1138.
18. Elter, T., Borchmann, P., Schulz, H., Reiser, M., Trelle, S., Schnell, R., Jensen, M., Staib, P., Schinkothe, T., Stutzer, H., Rech, J., Gramatzki, M., Aulitzky, W., Hasan, I., Josting, A., Hallek, M. & Engert, A. (2005) Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial. Journal of Clinical Oncology, 23, 7024-7031.
19. Engert, A., Elter, T., Borchmann, P., Schulz, H., Reiser, M., Trelle, S., Staib, P., Schinkoethe, T. & Hallek, M. (2005) Concomitant treatment of patients with relapsed/refractory CLL using a combination of flludarabine and alemtuzumab is highly effective: final results of a phase II study [abstract 6558]. Journal of Clinical Oncology, 23(Suppl. 16), 574s.
20. Esteve, J., Villamor, N., Colomer, D., Cervantes, F., Campo, E., Carreras, E. & Montserrat, E. (2001) Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia, 15, 445-451.
21. Esteve, J., Villamor, N., Colomer, D. & Montserrat, E. (2002) Different clinical value of minimal residual disease after autologous and allogenic stem cell transplantation for chronic lymphocytic leukemia. Blood, 99, 1873-1874.
22. Grever, M.R., Lucas, D.M., Dewald, G.W., Neuberg, D.S., Flinn, I.W., Appelbaum, F.R., Larson, R.A., Tallman, M.S., Gribben, J.G. & Byrd, J.C. (2004) Outcome of treatment with fludarabine versus fludarabine and cyclophosphamide in chronic lymphocytic leukemia (CLL) is adversely impacted by high-risk genetic features: results from ECOG 2997 [abstract 3487]. Blood, 104, 950a. (abstract).
23. Gribben, J.G., Zahrieh, D., Stephans, K., Bartlett-Pandite, L., Alyea, E.P., Fisher, D.C., Freedman, A.S., Mauch, P., Schlossman, R., Sequist, L.V., Soiffer, R.J., Marshall, B., Neuberg, D., Ritz, J. & Nadler, L.M. (2005) Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia. Blood, 106, 4389-4396.
24. Hallek, M., Wanders, L., Ostwald, M., Busch, R., Senekowitsch, R., Stern, S., Schick, H.D., Kuhn-Hallek, I. & Emmerich, B. (1996) Serum beta(2)-microglobulin and serum thymidine kinase are independent predictors of progression-free survival in chronic lymphocytic leukemia and immunocytoma. Leukemia & Lymphoma, 22, 439-447.
25. Hamblin, T.J., Davis, Z., Gardiner, A., Oscier, D.G. & Stevenson, F.K. (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94, 1848-1854.
26. Heintel, D., Kienle, D., Shehata, M., Krober, A., Kroemer, E., Schwarzinger, I., Mitteregger, D., Le, T., Gleiss, A., Mannhalter, C., Chott, A., Schwarzmeier, J., Fonatsch, C., Gaiger, A., Dohner, H., Stilgenbauer, S. & Jager, U. (2005) High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic leukemia. Leukemia, 19, 1216-1223.
27. Hess, G., Bunjes, D., Siegert, W., Schwerdtfeger, R., Ledderose, G., Wassmann, B., Kobbe, G., Bornhauser, M., Hochhaus, A., Ullmann, A.J., Kindler, T., Haus, U., Gschaidmeier, H., Huber, C. & Fischer, T. (2005) Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study. Journal of Clinical Oncology, 23, 7583-7593.
28. Hochhaus, A., Reiter, A., Saussele, S., Reichert, A., Emig, M., Kaeda, J., Schultheis, B., Berger, U., Shepherd, P.C., Allan, N.C., Hehlmann, R., Goldman, J.M. & Cross, N.C. (2000) Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group. Blood, 95, 62-66.
29. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Smigal, C. & Thun, M.J. (2006) Cancer statistics, 2006. CA: A Cancer Journal for Clinicians, 56, 106-130.
30. Juliusson, G., Oscier, D.G., Fitchett, M., Ross, F.M., Stockdill, G., Mackie, M.J., Parker, A.C., Castoldi, G.L., Guneo, A., Knuutila, S., Elonen, E. & Gahrton, G. (1990) Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. New England Journal of Medicine, 323, 720-724.
31. Keating, M.J., Flinn, I., Jain, V., Binet, J.L., Hillmen, P., Byrd, J., Albitar, M., Brettman, L., Santabarbara, P., Wacker, B. & Rai, K.R. (2002) Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood, 99, 3554-3561.
32. Keating, M.J., O'Brien, S., Albitar, M., Lerner, S., Plunkett, W., Giles, F., Andreeff, M., Cortes, J., Faderl, S., Thomas, D., Koller, C., Wierda, W., Detry, M.A., Lynn, A. & Kantarjian, H. (2005a) Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. Journal of Clinical Oncology, 23, 4079-4088.
33. Keating, M.J., O'Brien, S., Albitar, M., Lerner, S., Wierda, W. & Kantarjian, H. (2005b) Extended follow-up of a chemo-immunotherapy regimen FCR (fludarabine, F; cyclophosphamide, C; and rituximab, R) as initial therapy for chronic lymphocytic leukemia (CLL) [abstract 2118]. Blood, 106, 599a.
34. Kennedy, B., Rawstron, A., Carter, C., Ryan, M., Speed, K., Lucas, G. & Hillmen, P. (2002) Campath-1H and fludarabine in combination are highly active in refractory chronic lymphocytic leukemia. Blood, 99, 2245-2247.
35. Krober, A., Seiler, T., Benner, A., Bullinger, L., Bruckle, E., Lichter, P., Dohner, H. & Stilgenbauer, S. (2002) V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood, 100, 1410-1416.
36. Lo Coco, F., Diverio, D., Avvisati, G., Petti, M.C., Meloni, G., Pogliani, E.M., Biondi, A., Rossi, G., Carlo-Stella, C., Selleri, C., Martino, B., Specchia, G. & Mandelli, F. (1999) Therapy of molecular relapse in acute promyelocytic leukemia. Blood, 94, 2225-2229.
37. Lozanski, G., Heerema, N.A., Flinn, I.W., Smith, L., Harbison, J., Webb, J., Moran, M., Lucas, M., Lin, T., Hackbarth, M.L., Proffitt, J.H., Lucas, D., Grever, M.R. & Byrd, J.C. (2004) Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood, 103, 3278-3281.
38. Lundin, J., Kimby, E., Bjorkholm, M., Broliden, P.A., Celsing, F., Hjalmar, V., Mollgard, L., Rebello, P., Hale, G., Waldmann, H., Mellstedt, H. & Osterborg, A. (2002) Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood, 100, 768-773.
39. Mauro, F.R., Foa, R., Giannarelli, D., Cordone, I., Crescenzi, S., Pescarmona, E., Sala, R., Cerretti, R. & Mandelli, F. (1999) Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood, 94, 448-454.
40. Milligan, D.W., Kochethu, G., Dearden, C., Matutes, E., MacConkey, C. & Catovsky, D. (2006) High incidence of myelodysplasia and secondary leukaemia in the UK Medical Research Council Pilot of autografting in chronic lymphocytic leukaemia. British Journal of Haematology, 133, 173-175.
41. Montillo, M., Tedeschi, A., Miqueleiz, S., Veronese, S., Cairoli, R., Intropido, L., Ricci, F., Colosimo, A., Scarpati, B., Montagna, M., Nichelatti, M., Regazzi, M. & Morra, E. (2006) Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia. Journal of Clinical Oncology, 24, 2337-2342.
42. Montserrat, E., Sanchez-Bisono, J., Vinolas, N. & Rozman, C. (1986) Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance. British Journal of Haematology, 62, 567-575.
43. Moreno, C., Villamor, N., Colomer, D., Esteve, J., Martino, R., Nomdedeu, J., Bosch, F., Lopez-Guillermo, A., Campo, E., Sierra, J. & Montserrat, E. (2005) Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. Journal of Clinical Oncology, 23, 3433-3438.
44. Moreno, C., Villamor, N., Colomer, D., Esteve, J., Gine, E., Muntanola, A., Campo, E., Bosch, F. & Montserrat, E. (2006) Clinical significance of minimal residual disease, as assessed by different techniques, after stem-cell transplantation for chronic lymphocytic leukemia. Blood, 107, 4563-4569.
45. Moreton, P., Kennedy, B., Lucas, G., Leach, M., Rassam, S.M., Haynes, A., Tighe, J., Oscier, D., Fegan, C., Rawstron, A. & Hillmen, P. (2005) Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. Journal of Clinical Oncology, 23, 2971-2979.
46. National Cancer Institute (2006) Cancer Stat Fact Sheets: Chronic Lymphocytic Leukemia. Available at: http://seer.cancer.gov/statfacts/html/ clyl.html (last accessed 18 September 2006).
47. O'Brien, S.M., Kantarjian, H.M., Thomas, D.A., Cortes, J., Giles, F.J., Wierda, W.G., Koller, C.A., Ferrajoli, A., Browning, M., Lerner, S., Albitar, M. & Keating, M.J. (2003a) Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia. Cancer, 98, 2657-2663.
48. O'Brien, S.M., Gribben, J.G., Thomas, D.A., Albitar, M., Wierda, W., Ferrajoli, A., Lerner, S., Kantarjian, H.M., Kipps, T. & Keating, M.J. (2003b) Alemtuzumab for minimal residual disease in CLL [abstract 371]. Blood, 102, 109a.
49. Oscier, D.G., Gardiner, A.C., Mould, S.J., Glide, S., Davis, Z.A., Ibbotson, R.E., Corcoran, M.M., Chapman, R.M., Thomas, P.W., Copplestone, J.A., Orchard, J.A. & Hamblin, T.J. (2002) Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood, 100, 1177-1184.
50. Oscier, D.G., Richards, S., Orchard, J., Davis, Z., Best, G., Morilla, A., Brito-Bapapulle, V., Matutes, E., Pettitt, A. & Catovsky, D. (2005) Prognostic factors in the UK LRF CLL4 trial [abstract 2099]. Blood, 106, 549a.
51. Osterborg, A., Dyer, M.J., Bunjes, D., Pangalis, G.A., Bastion, Y., Catovsky, D. & Mellstedt, H. (1997) Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia. Journal of Clinical Oncology, 15, 1567-1574.
52. Osuji, N., Del Giudice, I., Matutes, E., Dearden, C. & Catovsky, D. (2004) Alemtuzumab for chronic lymphocytic leukemia with and without p53 deletions [abstract 2510]. Blood, 104, 688a.
53. Rai, K.R., Sawitsky, A., Cronkite, E.P., Chanana, A.D., Levy, R.N. & Pasternack, B.S. (1975) Clinical staging of chronic lymphocytic leukemia. Blood, 46, 219-234.
54. Rassenti, L.Z., Huynh, L., Toy, T.L., Chen, L., Keating, M.J., Gribben, J.G., Neuberg, D.S., Flinn, I.W., Rai, K.R., Byrd, J.C., Kay, N.E., Greaves, A., Weiss, A. & Kipps, T.J. (2004) ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. New England Journal of Medicine, 351, 893-901.
55. Rawstron, A.C., Kennedy, B., Evans, P.A., Davies, F.E., Richards, S.J., Haynes, A.P., Russell, N.H., Hale, G., Morgan, G.J., Jack, A.S. & Hillmen, P. (2001) Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood, 98, 29-35.
56. Rawstron, A.C., Kennedy, B., Moreton, P., Dickinson, A.J., Cullen, M.J., Richards, S.J., Jack, A.S. & Hillmen, P. (2004) Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia. Blood, 103, 2027-2031.
57. Ritgen, M., Stilgenbauer, S., von, N.N., Humpe, A., Bruggemann, M., Pott, C., Raff, T., Krober, A., Bunjes, D., Schlenk, R., Schmitz, N., Dohner, H., Kneba, M. & Dreger, P. (2004) Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood, 104, 2600-2602.
58. Robak, T., Blonski, J.Z., Kasznicki, M., Gora-Tybor, J., Dwilewicz-Trojaczek, J., Stella-Holowiecka, B. & Wolowiec, D. (2002) Cladribine combined with cyclophosphamide is highly effective in the treatment of chronic lymphocytic leukemia. Hematology Journal, 3, 244-250.
59. Rosenwald, A., Chuang, E.Y., Davis, R.E., Wiestner, A., Alizadeh, A.A., Arthur, D.C., Mitchell, J.B., Marti, G.E., Fowler, D.H., Wilson, W.H. & Staudt, L.M. (2004) Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response. Blood, 104, 1428-1434.
60. Sampath, D., Du, M., Keating, M.J. & Plunkett, W. (2006) Fludarabine resistance in CLL is associated with non-functional p53 [abstract 3760]. Proceedings of the American Association for Cancer Research, 47, 884.
61. Sanz, M.A., Tallman, M.S. & Lo-Coco, F. (2005) Practice points, consensus, and controversial issues in the management of patients with newly diagnosed acute promyelocytic leukemia. The Oncologist, 10, 806-814.
62. Sayala, H., Moreton, P., Richard, J.A., Rawstron, C.A., O'Conner, S., Evans, P., Carter, A., Dearden, C., Matutes, E., Pettitt, R.A., Kennedy, B.D. & Hillmen, P. (2005) Interim report of the UKCLL02 trial: a phase II study of subcutaneous alemtuzumab plus fludarabine in patients with flduarabine-refractory CLL (on behalf of the NCRI CLL Trials Subgroup) [abstract 2120]. Blood, 106, 599a-600a.
63. Sorror, M.L., Maris, M.B., Sandmaier, B.M., Storer, B.E., Stuart, M.J., Hegenbart, U., Agura, E., Chauncey, T.R., Leis, J., Pulsipher, M., McSweeney, P., Radich, J.P., Bredeson, C., Bruno, B., Langston, A., Loken, M.R., Al-Ali, H., Blume, K.G., Storb, R. & Maloney, D.G. (2005) Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. Journal of Clinical Oncology, 23, 3819-3829.
64. Stilgenbauer, S., Krober, A., Busch, R., Eichhorst, B., Kienle, D., Winkler, D., Hopfinger, G., Lichter, P., Emmerich, B., Hallek, M. & Dohner, H. (2005a) 17p deletion predicts for inferior overall survival after fludarabine-based first line therapy in chronic lymphocytic leukemia: first analysis of genetics in the CLL4 trial of the GCLLSG [abstract 715]. Blood, 106, 212a.
65. Stilgenbauer, S., Krober, A., Winkler, D., Kienle, D., Busch, R., Hallek, M., Hensel, M., Lengfelder, E., Trumper, L., Dreger, P., Jager, U. & Dohner, H. (2005b) Efficacy of subcutaneous alemtuzumab (Campath-1H) in genetic high-risk, fludarabine-refractory CLL: CLL2H study of the German CLL Study Group (GCLLSG) [abstract 041]. Annals of Oncology, 2005, v43.
66. Tothova, E., Kafkova, A., Fricova, M., Guman, T. & Stecova, N. (2003) Fludarabine combined with cyclophosphamid is highly effective in the treatment of chronic lymphocytic leukemia. Neoplasma, 50, 433-437.
67. Wendtner, C.M., Ritgen, M., Schweighofer, C.D., Fingerle-Rowson, G., Campe, H., Jager, G., Eichhorst, B., Busch, R., Diem, H., Engert, A., Stilgenbauer, S., Dohner, H., Kneba, M., Emmerich, B. & Hallek, M. (2004) Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission - experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia, 18, 1093-1101.
68. Wierda, W., Wang, X., O'Brien, S., Faderl, S., Ferrajoli, A., Thomas, D., Ravandi, F., Cortes, J., Giles, F., Koller, C., Kantarjian, H., Lerner, S. & Keating, M. (2005a) Serum beta-2 microglobulin: the universal independent prognostic factor for patients with CLL [abstract 5018]. Blood, 106, 336b.
69. Wierda, W., O'Brien, S., Wen, S., Faderl, S., Garcia-Manero, G., Thomas, D., Do, K.A., Cortes, J., Koller, C., Beran, M., Ferrajoli, A., Giles, F., Lerner, S., Albitar, M., Kantarjian, H. & Keating, M. (2005b) Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. Journal of Clinical Oncology, 23, 4070-4078.
70. Wiestner, A., Rosenwald, A., Barry, T.S., Wright, G., Davis, R.E., Henrickson, S.E., Zhao, H., Ibbotson, R.E., Orchard, J.A., Davis, Z., Stetler-Stevenson, M., Raffeld, M., Arthur, D.C., Marti, G.E., Wilson, W.H., Hamblin, T.J., Oscier, D.G. & Staudt, L.M. (2003) ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood, 101, 4944-4951.