scholarly journals New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Piotr Smolewski ◽  
Magdalena Witkowska ◽  
Anna Korycka-Wołowiec
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Biologically Relevant ◽  
Clonal Proliferation ◽  
Apoptosis Inhibition ◽  
Risk Patients ◽  
New Treatment ◽  
Anti Cd20

Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values seem to be the most biologically relevant. During the last decades, the treatment of CLL has been significantly changed. Different strategies such as monotherapy with chlorambucil and purine nucleoside analogues (PNA) used alone or in combination with cyclophosphamide have been introduced. Most recently, immunochemotherapy with anti-CD20 monoclonal antibody, rituximab, combined with fludarabine and cyclophosphamide, became a gold standard of first-line treatment in eligible CLL patients. Currently, new treatment strategies including new monoclonal antibodies, bendamustine, lenalidomide, or inhibitors of several cell signaling pathways are under clinical studies in resistant/relapsed CLL patients. Moreover, allogeneic stem cell transplantation has to be considered, especially in younger high risk patients, for example, those who are resistant to PNA or those with 17p deletion. In this paper, we present the most important recent advances in CLL biology and treatment.

scholarly journals The Difficult-to-Treat del 17 p Patient—A Case Report in Chronic Lymphocytic Leukemia

Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 33
Author(s):  
Ana-Maria Moldovianu ◽  
Ana Manuela Crisan ◽  
Zsofia Varady ◽  
Daniel Coriu
Keyword(s):  
High Risk ◽  
Chronic Lymphocytic Leukemia ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Risk Patients ◽  
Potential Benefits

Chronic lymphocytic leukemia (CLL) treatment strategies have evolved to include mechanism-driven drugs but now raise new questions regarding their optimum timing and sequencing. In high-risk patients, switching from pathway inhibitors to allogeneic stem cell transplantation (allo-HCT) is still a matter of intense debate. We report the case of a CLL patient with 17 p deletion treated with ibrutinib as a bridge to allo-HCT. Early relapse after allo-HCT urged the initiation of salvage therapy, including donor lymphocytes infusions, ibrutinib, and venetoclax. We aim to outline and discuss the potential benefits of novel therapies, the current role of allo-HCT in CLL, drug timing and sequencing, and the unmet need to improve the long-term outcome of high-risk CLL patients.

scholarly journals Current and future treatment strategies in chronic lymphocytic leukemia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Krish Patel ◽  
John M. Pagel
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Emerging Therapies ◽  
B Cell Leukemia ◽  
Anti Cd20 ◽  
Insight Into

AbstractTreatment decisions for patients with chronic lymphocytic leukemia (CLL) are dependent on symptoms and classification into high-, medium-, or low-risk categories. The prognosis for CLL hinges, in part, on the presence or absence of less-favorable genetic aberrations, including del(17p), del(11q), TP53 dysfunction, and IGHV mutations, as these markers are associated with worse treatment response. Promising results from multiple clinical trials show emerging therapies targeting Burton tyrosine kinase, B-cell leukemia/lymphoma 2, and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta result in better outcomes and prolonged progression-free survival for patients both with and without certain high-risk aberrations. Favorable outcomes using these novel oral targeted therapies, either alone or in combination with other treatments such as anti-CD20 antibodies, has led to their use almost entirely supplanting chemoimmunotherapy in the treatment of CLL. In this narrative review, we summarize the current clinical evidence for the use of targeted mono- and combination therapies for CLL, discuss new and next-generation treatment approaches currently in development, and provide insight into areas of unmet need for the treatment of patients with CLL.

Relationship between p53 dysfunction, CD38 expression, andIgVH mutation in chronic lymphocytic leukemia

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1404-1409 ◽  
Author(s):  
Ke Lin ◽  
Paul D. Sherrington ◽  
Michael Dennis ◽  
Zoltan Matrai ◽  
John C. Cawley ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Survival Data ◽  
Lymphocytic Leukemia ◽  
Relative Lack ◽  
Cd38 Expression ◽  
Genes Encoding ◽  
Risk Patients ◽  
The Relationship ◽  
Simple Screening

Established adverse prognostic factors in chronic lymphocytic leukemia (CLL) include CD38 expression, relative lack ofIgVH mutation, and defects of theTP53 gene. However, disruption of the p53 pathway can occur through mechanisms other than TP53 mutation, and we have recently developed a simple screening test that detects p53 dysfunction due to mutation of the genes encoding either p53 or ATM, a kinase that regulates p53. The present study was conducted to examine the predictive value of this test and to establish the relationship between p53 dysfunction, CD38 expression, and IgVHmutation. CLL cells from 71 patients were examined forIgVH mutation, CD38 expression, and p53 dysfunction (detected as an impaired p53/p21 response to ionizing radiation). Survival data obtained from 69 patients were analyzed according to each of these parameters. Relative lack ofIgVH mutation (less than 5%; n = 45), CD38 positivity (antigen expressed on more than 20% of malignant cells; n = 19), and p53 dysfunction (n = 19) were independently confirmed as adverse prognostic factors. Intriguingly, all p53-dysfunctional patients and all but one of the CD38+ patients had greater than 5% IgVH mutation. Moreover, patients with p53 dysfunction and/or CD38 positivity (n = 31) accounted for the short survival of the less mutated group. These findings indicate that the poor outcome associated with having less than 5%IgVH mutation may be due to the overrepresentation of high-risk patients with p53 dysfunction and/or CD38 positivity within this group, and that CD38− patients with functionally intact p53 may have a prolonged survival regardless of the extent of IgVH mutation.

scholarly journals Treatment Options for Elderly/Unfit Patients with Chronic Lymphocytic Leukemia in the Era of Targeted Drugs: A Comprehensive Review

2021 ◽  
Vol 10 (21) ◽  
pp. 5104
Author(s):  
Alberto Fresa ◽  
Francesco Autore ◽  
Eugenio Galli ◽  
Annamaria Tomasso ◽  
Luca Stirparo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Lymphocytic Leukemia ◽  
Geriatric Syndromes ◽  
Safety Issues ◽  
Unfit Patients ◽  
Individualize Treatment ◽  
Anti Cd20

Chronic lymphocytic leukemia (CLL) incidence increases with age reaching 37.9/100,000 in patients over 85 years. Although there is no standardized geriatric tool specifically validated for CLL, a correct framing of the fitness status is of critical importance to individualize treatment strategies. Based on the evidence available to date, frontline chemoimmunotherapy has an increasingly narrowing application, being eligible for candidacy only in elderly fit patients without or with minimal geriatric syndromes. On the other hand, treatment with BCR inhibitors, monotherapy, or in combination with anti-CD20 antibodies (e.g., obinutuzumab), must be preferred both for frontline and relapsed CLL not only in unfit patients, but also in fit patients with unmutated IGHV or harboring del(17p) and/or TP53 mutations/deletions. Second-generation inhibitors (e.g., acalabrutinib, zanubrutinib, pirtobrutinib) are novel compounds that, due to their better safety profile and different specificity, will help physicians overcome some of the safety issues and treatment resistances. In the era of targeted therapies, treatment decisions in elderly and/or unfit patients with CLL must be a balance between efficacy and safety, carefully evaluating comorbidities and geriatric syndromes to ensure the best approach to improve both quality of life and life expectancy.

Complex analysis of prognostic factors in chronic lymphocytic leukemia

2007 ◽  
Vol 148 (16) ◽  
pp. 737-743
Author(s):  
Béla Kajtár ◽  
Pál Jáksó ◽  
László Kereskai ◽  
Ágnes Lacza ◽  
Gábor Méhes ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Complex Analysis ◽  
Lymphocytic Leukemia

Bevezetés: Az utóbbi években felfedezett számos új prognosztikai faktor segítséget nyújthat a várható túlélés meghatározásához krónikus lymphocytás leukémia esetében. Célok: Jelen tanulmány célja e prognosztikai faktorok gyakoriságának, valamint egymással való összefüggésének meghatározása volt 419 beteg mintáin. Módszerek: 160 esetben végezték el az immunglobulin-nehézláncgén mutációs vizsgálatát. Eredmények: Az esetek 62%-ában nem mutált immunglobulin gént találtak, a nehézlánc géncsaládok használata különbözött a mutációs státusz függvényében. A CD38 expresszió 78%-os konkordanciát mutatott a mutációs státusszal, a ZAP-70-expresszió tekintetében korrelációt nem figyeltek meg. Citogenetikai abnormalitást 76%-ban láttak, a leggyakoribb eltérések a del(13q) (57%), a 12-es triszómia (15%), a del(11q) (12%) és a del(17p) (6%) voltak. A del(11q)-t hordozó esetek 95%-a nem mutált, az egyedül del(13q)-t hordozó esetek 74%-a mutált IgH-gént tartalmazott. Következtetések: A vizsgált paraméterek nem függetlenek egymástól, ezért alkalmazásuk a klinikai gyakorlatban gondos tervezést igényel.

Survival and prognostic factors in chronic lymphocytic leukemia

2009 ◽  
Vol 38 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Amos Pines ◽  
Isaac Ben-Bassat ◽  
Michaela Modan ◽  
Tzvia Blumstein ◽  
Bracha Ramot
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia

scholarly journals Multivariable Model for Time to First Treatment in Patients With Chronic Lymphocytic Leukemia

2011 ◽  
Vol 29 (31) ◽  
pp. 4088-4095 ◽  
Author(s):  
William G. Wierda ◽  
Susan O'Brien ◽  
Xuemei Wang ◽  
Stefan Faderl ◽  
Alessandra Ferrajoli ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Multivariable Analysis ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Serum Lactate Dehydrogenase ◽  
Multivariable Model ◽  
Cervical Lymph Nodes ◽  
Mutation Status ◽  
Time To First Treatment

Purpose The clinical course for patients with chronic lymphocytic leukemia (CLL) is diverse; some patients have indolent disease, never needing treatment, whereas others have aggressive disease requiring early treatment. We continue to use criteria for active disease to initiate therapy. Multivariable analysis was performed to identify prognostic factors independently associated with time to first treatment for patients with CLL. Patients and Methods Traditional laboratory, clinical prognostic, and newer prognostic factors such as fluorescent in situ hybridization (FISH), IGHV mutation status, and ZAP-70 expression evaluated at first patient visit to MD Anderson Cancer Center were correlated by multivariable analysis with time to first treatment. This multivariable model was used to develop a nomogram—a weighted tool to calculate 2- and 4-year probability of treatment and estimate median time to first treatment. Results There were 930 previously untreated patients who had traditional and new prognostic factors evaluated; they did not have active CLL requiring initiation of treatment within 3 months of first visit and were observed for time to first treatment. The following were independently associated with shorter time to first treatment: three involved lymph node sites, increased size of cervical lymph nodes, presence of 17p deletion or 11q deletion by FISH, increased serum lactate dehydrogenase, and unmutated IGHV mutation status. Conclusion We developed a multivariable model that incorporates traditional and newer prognostic factors to identify patients at high risk for progression to treatment. This model may be useful to identify patients for early interventional trials.

scholarly journals Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 405-411 ◽  
Author(s):  
Neil E. Kay ◽  
Susan M. Geyer ◽  
Timothy G. Call ◽  
Tait D. Shanafelt ◽  
Clive S. Zent ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphocytic Leukemia ◽  
Clinical Activity ◽  
Hematologic Toxicity ◽  
Color Flow ◽  
Significant Clinical Activity ◽  
Minimal Residual

Abstract Building on the prior work of use of pentostatin in chronic lymphocytic leukemia (CLL), we initiated a trial of combined pentostatin (2 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) for 65 symptomatic, previously untreated patients. Of 64 evaluable patients, 34 (53%) were high Rai risk, 71% were nonmutated for the immunoglobulin heavy-chain variable region gene, 34% were CD38+, and 34% were ZAP-70+. Thirty patients (52%) had one anomaly detected by fluorescence in situ (FISH) hybridization, and 21 (36%) had complex FISH defects. Thirty-eight patients (58%) had grade 3+ hematologic toxicity but minimal transfusion needs and no major infections. Responses occurred in 58 patients (91%), with 26 (41%) complete responses (CRs), 14 (22%) nodular partial responses (nodular PRs), and 18 (28%) partial responses (PRs). Many patients with a CR also lacked evidence of minimal residual disease by 2-color flow cytometry. Examination of prognostic factors demonstrated poor response in the 3 patients with del(17p). In contrast, we found this regimen was equally effective in young versus older (> 70 years) patients and in del(11q22.3) versus other favorable prognostic factors. Thus, this novel regimen of pentostatin, cyclophosphamide, and rituximab for previously untreated patients with CLL demonstrated significant clinical activity despite poor risk-based prognoses, achievement of minimal residual disease in some, and modest toxicity.

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