Veidlapa Nr. M-3 (8)
Study Course Description
Chronic Lymphocytic Leukaemia and Lymphoproliferative Leukaemias
Course Code
RHE_058
Branch of Science
Clinical medicine
ECTS
7.00
Target Audience
Medicine
LQF
Level 8
Study Course Implementer
Course Supervisor
Sandra Lejniece
Residency Speciality
Speciality
Hematologist
Supervisor of Medical Speciality
Sandra Lejniece
Contacts
-
About Study Course
Objective
To ensure acquisition and improvement of theoretical knowledge and practical skills in chronic lymphocytic leukaemia and other lymphoproliferative leukaemias in accordance with the requirements of the haematology specialty in order to prepare the doctor for certification in the haematology specialty.
Learning Outcomes
Knowledge
1.- Will know about chronic lymphocytic leukaemia, its causes, pathogenesis, clinical picture, laboratory changes, complications, treatment, prognosis; - Will know about chronic prolymphocytic leukaemia, hairy cell leukaemia, Richter’s syndrome. - Will know about monoclonal B-cell lymphocytosis.
Skills
1.- Will know how to diagnose and treat patients with chronic lymphocytic leukaemia and lymphoproliferative leukaemia.
Competences
1.Diagnosis and treatment of patients with chronic lymphocytic leukaemia and lymphoproliferative leukaemia.
Assessment
Individual work
|
Title
|
% from total grade
|
Grade
|
|---|---|---|
|
1.
Individual work |
-
|
-
|
|
1. Independently studies the literature related to the course topics;
2. Independently prepares for seminars;
3. Independently collects disease anamnesis data, objectively examines the patient, formulates a preliminary diagnosis, which is discussed with the lecturer;
4. Gets acquainted with and analyses medical documentation;
5. Completes medical documentation;
6. Independently follows the instructions of the certified specialist.
|
||
Examination
|
Title
|
% from total grade
|
Grade
|
|---|---|---|
|
1.
Examination |
-
|
-
|
|
Mandatory attendance of seminars (100%) and performance of practical work (100%) in each study course.
|
||
Study Course Theme Plan
FULL-TIME
Part 1
-
Seminar
|
Modality
|
Location
|
|
|---|---|---|
|
-
|
-
|
Topics
|
Chronic lymphocytic leukaemia - causes, pathogenesis, clinical picture, laboratory changes, complications, treatment, prognosis.
|
-
Seminar
|
Modality
|
Location
|
|
|---|---|---|
|
-
|
-
|
Topics
|
Chronic prolymphocytic leukaemia. Hairy cell leukaemia. Transformation into Richter’s syndrome. Monoclonal B-cell lymphocytosis.
|
Total ECTS (Creditpoints):
7.00
Number of Residency Seminars:
2
Length (weeks):
5
Final Examination:
Residency exam (Theory and practice)
Bibliography
Required Reading
1.
Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343:1910-1916, 2000. PMID:11136261
2.
Goldin LR, Landgren O, Marti GE et al.: Familial aspects of chronic lymphocytic leukemia, monoclonal B-cell lymphocytosis (MBL) and related lymphomas. Eur J Clin Med Oncol 2:119-216, 2010. PMID:21191471
3.
Binet JL, Auquier A, Dighiero G et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer 48:198-204, 1981. PMID:7237385
4.
Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood 46:219-234, 1975. PMID:1139039
5.
Allegra A, Musolino C, Tonacci A, Pioggia G, Casciaro M, Gangemi S. Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role. Cancers (Basel). 2020 Feb 24;12(2):524. doi: 10.3390/cancers12020524. PMID: 32102441; PMCID: PMC7072434.
6.
Delgado J, Nadeu F, Colomer D, Campo E. Chronic lymphocytic leukemia: from molecular pathogenesis to novel therapeutic strategies. Haematologica. 2020 Sep 1;105(9):2205-2217. doi: 10.3324/haematol.2019.236000. PMID: 33054046; PMCID: PMC7556519.
7.
Ten Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in Chronic Lymphocytic Leukemia: Implications for disease pathogenesis and treatment. Biochim Biophys Acta. 2016 Mar;1863(3):401-413. doi: 10.1016/j.bbamcr.2015.07.009. Epub 2015 Jul 17. PMID: 26193078; PMCID: PMC4715999.
8.
Kipps TJ, Stevenson FK, Wu CJ, Croce CM, Packham G, Wierda WG, O'Brien S, Gribben J, Rai K. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017 Jan 19;3:16096. doi: 10.1038/nrdp.2016.96. PMID: 28102226; PMCID: PMC5336551.
9.
Campo E, Cymbalista F, Ghia P, Jäger U, Pospisilova S, Rosenquist R, Schuh A, Stilgenbauer S. TP53 aberrations in chronic lymphocytic leukemia: an overview of the clinical implications of improved diagnostics. Haematologica. 2018 Dec;103(12):1956-1968. doi: 10.3324/haematol.2018.187583. Epub 2018 Nov 15. PMID: 30442727; PMCID: PMC6269313.
10.
Rassenti LZ, Jain S, Keating MJ, Wierda WG, Grever MR, Byrd JC, Kay NE, Brown JR, Gribben JG, Neuberg DS, He F, Greaves AW, Rai KR, Kipps TJ. Relative value of ZAP-70, CD38, and immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic leukemia. Blood. 2008 Sep 1;112(5):1923-30. doi: 10.1182/blood-2007-05-092882. Epub 2008 Jun 24. PMID: 18577710; PMCID: PMC2518894.
11.
Emile JF, Abla O, Fraitag S, et al. Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages. Blood 2016; 127:2672.
12.
Dreger P, Schetelig J, Andersen N et al: Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: Stem cell transplantation or novel agents. A position statement of the European Research Initiative on CLL (ERIC) and the European Society for Blood and Marrow Transplantation (EBMT). Submitted.
Other Information Sources
1.
Fischer K, Cramer P, Busch R, et al: Bendamustine combined with rituximab in patients with relapsed and/ or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 29:3559-3666, 2011. DOI:10.1200/JCO.2010.33.8061
2.
Dreger P, Döhner H, Ritgen M et al: Allogeneic stem transplantation provides durable disease control in patients with chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood 116:2438-2447, 2010. DOI:10.1182/blood-2010-03-275420
3.
Raanani P, Gafter-Gvili A, Paul M et al.: Immunoglobulin prophylaxis in hematologic malignancies and hematopoietic stem cell transplantation. Cochrane Database Syst Rev CD006501, 2008. DOI:10.1002/14651858.CD006501.pub2
4.
Byrd JC, Furman RR, Coutre SE, at al: Ibrutinib Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32-42, 2013. DOI:10.1056/NEJMoa1215637
5.
Hodgson K, Ferrer G, Pereira A et al.: Autoimmune cytopenia in chronic lymphocytic leukemia: diagnosis and treatment. Brit J Haematol 154:14-22, 2011. DOI:10.1111/j.1365-2141.2011.08707.x
6.
Dores GM, Anderson WF, Curtis RE, et al. Chronic lymphocytic leukaemia and small lymphocytic lymphoma: overview of the descriptive epidemiology. Br J Haematol 139:809-819, 2007. DOI:10.1111/j.1365-2141.2007.06856.x
7.
Oscier D, Else M, Matutes E, Morilla R, Strefford JC, Catovsky D The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial Br J Haematol. 2016 Sep; 174(5): 767–775. Published online 2016 May 6. doi: 10.1111/bjh.14132
8.
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127:2391-2405. https://doi.org/10.1182/blood-2016-03-643544
9.
Eichhorst BF, Busch R, Stilgenbauer S, et al. No clinical benefit for frontline therapy with fludarabine in comparison to chlorambucil in elderly patients with advanced chronic lymphocytic leukemia. Blood 114:3382-3391, 2009. DOI:10.1182/blood-2009-02-206185
10.
Goede V, Fischer K, Busch R, et al: Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 370:1101-1110, 2014. DOI:10.1056/NEJMoa1313984
11.
Fischer K, Cramer P, Busch R, et al: Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 30:3209-3216, 2012. DOI:10.1200/JCO.2011.39.2688
12.
Knauf WU, Lissichkov, Aldaoud A, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 27:4378-4384, 2009. DOI:10.1200/JCO.2008.20.8389
13.
Hallek M, Fingerle-Rowson G, Fink A-M, et al. First-Line Treatment with Fludarabine (F), cyclophosphamide (C), and Rituximab (R) (FCR) Improves Overall Survival (OS) in Previously Untreated Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Randomized Phase III Trial On Behalf of An International Group of Investigators and the German CLL Study Group. Lancet 376:1164-1174, 2010. DOI:10.1016/S0140-6736(10)61381-5
14.
Hallek 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 111:5446-5456, 2008. DOI:10.1182/blood-2007-06-093906
15.
Rawstron AC, Bennett FL, O’Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia (CLL). N Engl J Med 359:575-583, 2008. DOI:10.1056/NEJMoa075290
16.
Burger JA, Gribben JG: The microenvironment in chronic lymphocytic leukemia and other B cell malignancies: insight into disease biology and targeted therapies. Semin Cancer Biol 24:71-81, 2014. DOI:10.1016/j.semcancer.2013.08.011
17.
Schetelig J, van Biezen A, Brand R, et al: Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol 26:5094-5100, 2008. DOI:10.1200/JCO.2008.16.2982
18.
Stilgenbauer S, Zenz T, Winkler D, et al: Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 27:3994-4001, 2009. DOI:10.1200/JCO.2008.21.1128
19.
Byrd JC, Brown JR, O’Brien S, et al: Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 371:213-223, 2014. DOI: 10.1056/NEJMoa1400376
20.
Furman RR, Sharman JP, Coutre SE, et al: Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 370:997-1007, 2014. DOI:10.1056/NEJMoa1315226