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Stage III Chronic Lymphocytic Leukemia

MedGen UID:
82977
•Concept ID:
C0278769
•
Neoplastic Process
Synonyms: Chronic Lymphocytic Leukemia Stage III; CLL Stage III; Stage III Chronic Lymphocytic Leukemia- Modified Rai Staging System; Stage III CLL

Definition

Risk: High; Findings: Lymphocytosis and hemoglobin less than 11 g/dL; Survival (months): 30. (from AJCC 8th Ed.) [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVStage III Chronic Lymphocytic Leukemia

Professional guidelines

PubMed

The evolving treatment landscape of chronic lymphocytic leukemia.
Schiattone L, Ghia P, Scarfò L
Curr Opin Oncol 2019 Nov;31(6):568-573. doi: 10.1097/CCO.0000000000000585. PMID: 31593975
iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ
Blood 2018 Jun 21;131(25):2745-2760. Epub 2018 Mar 14 doi: 10.1182/blood-2017-09-806398. PMID: 29540348
Prognostic markers and standard management of chronic lymphocytic leukemia.
Stilgenbauer S
Hematology Am Soc Hematol Educ Program 2015;2015:368-77. doi: 10.1182/asheducation-2015.1.368. PMID: 26637745

Recent clinical studies

Etiology

Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial.
Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, Walewska R, Furtado M, Preston G, Neilson JR, Pemberton N, Sidra G, Morley N, Cwynarski K, Schuh A, Forconi F, Elmusharaf N, Paneesha S, Fox CP, Howard DR, Hockaday A, Brown JM, Cairns DA, Jackson S, Greatorex N, Webster N, Shingles J, Dalal S, Patten PEM, Allsup D, Rawstron A, Munir T
Lancet Oncol 2023 May;24(5):535-552. doi: 10.1016/S1470-2045(23)00144-4. PMID: 37142374
The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia.
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Müller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M
Blood 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845. PMID: 34758069
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial.
Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K
Lancet Oncol 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5. PMID: 32888452
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Ghia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, Kaplan P, Kraychok I, Illes A, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery E, Lee JH, Liang W, Patel P, Quah C, Jurczak W
J Clin Oncol 2020 Sep 1;38(25):2849-2861. Epub 2020 May 27 doi: 10.1200/JCO.19.03355. PMID: 32459600
Genomic aberrations and survival in chronic lymphocytic leukemia.
Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P
N Engl J Med 2000 Dec 28;343(26):1910-6. doi: 10.1056/NEJM200012283432602. PMID: 11136261

Diagnosis

The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia.
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Müller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M
Blood 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845. PMID: 34758069
iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ
Blood 2018 Jun 21;131(25):2745-2760. Epub 2018 Mar 14 doi: 10.1182/blood-2017-09-806398. PMID: 29540348
Chronic lymphocytic leukemia.
Kay NE, Hamblin TJ, Jelinek DF, Dewald GW, Byrd JC, Farag S, Lucas M, Lin T
Hematology Am Soc Hematol Educ Program 2002:193-213. doi: 10.1182/asheducation-2002.1.193. PMID: 12446424
Increased serum levels of vascular endothelial growth factor predict risk of progression in early B-cell chronic lymphocytic leukaemia.
Molica S, Vitelli G, Levato D, Gandolfo GM, Liso V
Br J Haematol 1999 Dec;107(3):605-10. doi: 10.1046/j.1365-2141.1999.01752.x. PMID: 10583266
Mantle cell lymphomas: characteristics, natural history and prognostic factors of 45 cases.
Decaudin D, Bosq J, Munck JN, Bayle C, Koscielny S, Boudjemaa S, Bennaceur A, Venuat AM, Naccache P, Bendahmane B, Ribrag V, Carde P, Pico JL, Hayat M
Leuk Lymphoma 1997 Aug;26(5-6):539-50. doi: 10.3109/10428199709050890. PMID: 9389361

Therapy

The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia.
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Müller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M
Blood 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845. PMID: 34758069
Acalabrutinib in treatment-naive chronic lymphocytic leukemia.
Byrd JC, Woyach JA, Furman RR, Martin P, O'Brien S, Brown JR, Stephens DM, Barrientos JC, Devereux S, Hillmen P, Pagel JM, Hamdy A, Izumi R, Patel P, Wang MH, Jain N, Wierda WG
Blood 2021 Jun 17;137(24):3327-3338. doi: 10.1182/blood.2020009617. PMID: 33786588Free PMC Article
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial.
Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K
Lancet Oncol 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5. PMID: 32888452
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Ghia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, Kaplan P, Kraychok I, Illes A, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery E, Lee JH, Liang W, Patel P, Quah C, Jurczak W
J Clin Oncol 2020 Sep 1;38(25):2849-2861. Epub 2020 May 27 doi: 10.1200/JCO.19.03355. PMID: 32459600
iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ
Blood 2018 Jun 21;131(25):2745-2760. Epub 2018 Mar 14 doi: 10.1182/blood-2017-09-806398. PMID: 29540348

Prognosis

Acalabrutinib in treatment-naive chronic lymphocytic leukemia.
Byrd JC, Woyach JA, Furman RR, Martin P, O'Brien S, Brown JR, Stephens DM, Barrientos JC, Devereux S, Hillmen P, Pagel JM, Hamdy A, Izumi R, Patel P, Wang MH, Jain N, Wierda WG
Blood 2021 Jun 17;137(24):3327-3338. doi: 10.1182/blood.2020009617. PMID: 33786588Free PMC Article
Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial.
Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K
Lancet Oncol 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5. PMID: 32888452
iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating M, Montserrat E, Chiorazzi N, Stilgenbauer S, Rai KR, Byrd JC, Eichhorst B, O'Brien S, Robak T, Seymour JF, Kipps TJ
Blood 2018 Jun 21;131(25):2745-2760. Epub 2018 Mar 14 doi: 10.1182/blood-2017-09-806398. PMID: 29540348
First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.
Eichhorst B, Fink AM, Bahlo J, Busch R, Kovacs G, Maurer C, Lange E, Köppler H, Kiehl M, Sökler M, Schlag R, Vehling-Kaiser U, Köchling G, Plöger C, Gregor M, Plesner T, Trneny M, Fischer K, Döhner H, Kneba M, Wendtner CM, Klapper W, Kreuzer KA, Stilgenbauer S, Böttcher S, Hallek M; international group of investigators; German CLL Study Group (GCLLSG)
Lancet Oncol 2016 Jul;17(7):928-942. Epub 2016 May 20 doi: 10.1016/S1470-2045(16)30051-1. PMID: 27216274
Genomic aberrations and survival in chronic lymphocytic leukemia.
Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P
N Engl J Med 2000 Dec 28;343(26):1910-6. doi: 10.1056/NEJM200012283432602. PMID: 11136261

Clinical prediction guides

Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): interim analysis of a multicentre, open-label, randomised, phase 3 trial.
Hillmen P, Pitchford A, Bloor A, Broom A, Young M, Kennedy B, Walewska R, Furtado M, Preston G, Neilson JR, Pemberton N, Sidra G, Morley N, Cwynarski K, Schuh A, Forconi F, Elmusharaf N, Paneesha S, Fox CP, Howard DR, Hockaday A, Brown JM, Cairns DA, Jackson S, Greatorex N, Webster N, Shingles J, Dalal S, Patten PEM, Allsup D, Rawstron A, Munir T
Lancet Oncol 2023 May;24(5):535-552. doi: 10.1016/S1470-2045(23)00144-4. PMID: 37142374
The CLL12 trial: ibrutinib vs placebo in treatment-naïve, early-stage chronic lymphocytic leukemia.
Langerbeins P, Zhang C, Robrecht S, Cramer P, Fürstenau M, Al-Sawaf O, von Tresckow J, Fink AM, Kreuzer KA, Vehling-Kaiser U, Tausch E, Müller L, Eckart MJ, Schlag R, Freier W, Gaska T, Balser C, Reiser M, Stauch M, Wendtner CM, Fischer K, Stilgenbauer S, Eichhorst B, Hallek M
Blood 2022 Jan 13;139(2):177-187. doi: 10.1182/blood.2021010845. PMID: 34758069
ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia.
Ghia P, Pluta A, Wach M, Lysak D, Kozak T, Simkovic M, Kaplan P, Kraychok I, Illes A, de la Serna J, Dolan S, Campbell P, Musuraca G, Jacob A, Avery E, Lee JH, Liang W, Patel P, Quah C, Jurczak W
J Clin Oncol 2020 Sep 1;38(25):2849-2861. Epub 2020 May 27 doi: 10.1200/JCO.19.03355. PMID: 32459600
Chronic lymphocytic leukemia.
Kay NE, Hamblin TJ, Jelinek DF, Dewald GW, Byrd JC, Farag S, Lucas M, Lin T
Hematology Am Soc Hematol Educ Program 2002:193-213. doi: 10.1182/asheducation-2002.1.193. PMID: 12446424
Genomic aberrations and survival in chronic lymphocytic leukemia.
Döhner H, Stilgenbauer S, Benner A, Leupolt E, Kröber A, Bullinger L, Döhner K, Bentz M, Lichter P
N Engl J Med 2000 Dec 28;343(26):1910-6. doi: 10.1056/NEJM200012283432602. PMID: 11136261

Recent systematic reviews

Maintenance therapy for chronic lymphocytic leukaemia.
Lee CH, Wu YY, Huang TC, Lin C, Zou YF, Cheng JC, Chen PH, Jhou HJ, Ho CL
Cochrane Database Syst Rev 2024 Jan 4;1(1):CD013474. doi: 10.1002/14651858.CD013474.pub2. PMID: 38174814Free PMC Article
Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation.
Kharfan-Dabaja MA, Kumar A, Hamadani M, Stilgenbauer S, Ghia P, Anasetti C, Dreger P, Montserrat E, Perales MA, Alyea EP, Awan FT, Ayala E, Barrientos JC, Brown JR, Castro JE, Furman RR, Gribben J, Hill BT, Mohty M, Moreno C, O'Brien S, Pavletic SZ, Pinilla-Ibarz J, Reddy NM, Sorror M, Bredeson C, Carpenter P, Savani BN
Biol Blood Marrow Transplant 2016 Dec;22(12):2117-2125. Epub 2016 Sep 19 doi: 10.1016/j.bbmt.2016.09.013. PMID: 27660167Free PMC Article

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