Leucocyte doubling time is a useful predictor of progression-free survival in chronic lymphocytic leukaemia

1995 ◽  
Vol 237 (2) ◽  
pp. 205-209
Author(s):  
U. AXDORPH ◽  
B. I. NILSSON ◽  
B. R. NILSSON ◽  
M. BJÖRKHOLM
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Doubling Time ◽  
Lymphocytic Leukaemia ◽  
Progression Free Survival ◽  
Free Survival

High Dose Methylprednisolone and Rituximab Is an Effective Therapy in Advanced Refractory Chronic Lymphocytic Leukaemia Resistant to Fludarabine Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3125-3125
Author(s):  
Moez Dungarwalla ◽  
Pamala Kanagasabapathy ◽  
Samar Kulkarni ◽  
Steve O. Evans ◽  
Unell Riley ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Viral Infections ◽  
Lymphocytic Leukaemia ◽  
Fungal Infections ◽  
Single Agent ◽  
Progression Free Survival ◽  
High Dose ◽  
Fish Analysis ◽  
Free Survival ◽  
High Dose Methylprednisolone

Abstract The management of refractory advanced chronic lymphocytic leukaemia (CLL) continues to pose a considerable challenge to the clinician. CLL patients who are refractory or become resistant to fludarabine containing regimens currently have a poor prognosis. High dose methylprednisolone (HDMP) has been shown to be an effective therapeutic option in patients who are resistant to fludarabine particularly those with bulky lymphadenopathy or refractory cytopenias who are unsuitable for alemtuzumab therapy. We have used HDMP in combination with the anti-CD20 monoclonal antibody, Rituximab, to treat 14 patients with advanced refractory CLL. Eight of fourteen patients were male. The median age was 62.5 years (range 30–71). Twelve patients had bulky lymphadenopathy with nodal masses greater than 5 centimetres in diameter. Nine patients had Binet stage C and the remainder were stage B. Autoimmune manifestations were present in five of the patients, and in one of them fludarabine therapy was contraindicated due to active autoimmune haemolysis. FISH analysis was performed to detect 17p, 11q and 13q deletions and showed 11q23 deletions in five patients. The overall response rate was 93% with a median progression free survival (PFS) of seven months. Two patients achieved a CR, another a nodular PR and 10 patients had a PR. Responses were seen in all 4 patients who had not responded to alemtuzumab as a single agent. Only one patient failed to respond. The median survival was 20 months. All five patients with 11q23 deletions responded, and the mean progression free survival in this subgroup was 10.5 months. These results compare extremely favourably with our own previous study (Thornton et al, 1998) that used HDMP alone in the management of advanced/refractory CLL where only 43% of patients responded and no patients achieved a CR. We have demonstrated that the combination of HDMP with rituximab is more effective than HDMP alone (p<0.01) in advanced refractory CLL. Although HDMP in combination with rituximab causes little or no myelosuppression, 6/14 patients (43%) developed opportunistic fungal or viral infections and this included fungal mould infections, fungal yeast infections and opportunistic viral infections. Three patients died of pulmonary fungal infections, although 2 of these patients had been retreated with alternative regimens. While the immunosuppressive effects of high dose steroids are well recognised, it appears that the addition of rituximab has made these patients more prone to opportunistic infections. In summary, HDMP in combination with rituximab is an effective rescue regime in purine analogue refractory CLL particularly in patients with bulky lymphadenopathy who are unsuitable for alemtuzumab, and in patients with 11q23 deletions.

scholarly journals Protocol description of the HOVON 141/VISION trial: a prospective, multicentre, randomised phase II trial of ibrutinib plus venetoclax in patients with creatinine clearance ≥30 mL/min who have relapsed or refractory chronic lymphocytic leukaemia (RR-CLL) with or without TP53 aberrations

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039168
Author(s):  
Mark-David Levin ◽  
Arnon Kater ◽  
Mattias Mattsson ◽  
Sabina Kersting ◽  
Juha Ranti ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Residual Disease ◽  
Medical Center ◽  
Progression Free Survival ◽  
Inclusion Criteria ◽  
Exclusion Criteria ◽  
Free Survival ◽  
Informed Consent Form ◽  
Registration Number

IntroductionLiterature is scarce on the combination treatment of ibrutinib and venetoclax (IV) is scarce in relapsed or refractory chronic lymphocytic leukaemia (RR-CLL). Especially, the possibility of stopping ibrutinib in RR-CLL patients in deep remission is unclear.Methods and analysisIn the HOVON 141/VISION trial, patients with RR-CLL are treated with 12 cycles of IV after a short induction with ibrutinib. Patients reaching undetectable minimal residual disease (uMRD) after 12 cycles of IV are randomised 1:2 to continue ibrutinib or stop treatment. The persistence of uMRD after stopping IV is studied. In addition, in patients who become positive for MRD again after stopping, IV treatment is reinitiated. The efficacy of this approach with regard to progression-free survival 12 months after randomisation is the primary endpoint of the study.Ethics and disseminationThis protocol respects the Helsinki declaration and has been approved by the ethical committee of the Amsterdam Medical Center. Study findings will be disseminated through peer-reviewed papers. All patients who fulfil the inclusion criteria and no-exclusion criteria, and have signed the informed consent form are included in the study.Trial registration numberClinicalTrials.gov Registry (NCT03226301).

Lymphocyte doubling time in chronic lymphocytic leukaemia: analysis of its prognostic significance

1986 ◽  
Vol 62 (3) ◽  
pp. 567-575 ◽  
Author(s):  
Emilio Montserrat ◽  
Juan Sanchez-Bisono ◽  
Nuria Viñolas ◽  
Ciril Rozman
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Doubling Time ◽  
Lymphocytic Leukaemia ◽  
Prognostic Significance

scholarly journals Will New Drugs Replace Transplants for Chronic Lymphocytic Leukaemia?

2021 ◽  
Vol 10 (11) ◽  
pp. 2516
Author(s):  
Shenmiao Yang ◽  
Xiaojun Huang ◽  
Robert Peter Gale
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Lymphocytic Leukemia ◽  
New Drugs ◽  
Free Survival ◽  
Immune Mediated ◽  
Ionizing Radiations

Transplants have been used to treat chronic lymphocytic leukemia (CLL) for more than 35 years. Use has been restricted to <1 percent of highly selected persons typically failing concurrent conventional therapies. As therapies of CLL have evolved, so have indications for transplantation and transplant techniques. The data that we review indicate that transplants can result in long-term leukemia-free survival in some persons but are associated with substantial transplant-related morbidity and mortality. We discuss the mechanisms underlying the anti-leukemia effects of transplants including drugs, ionizing radiations, immune-mediated mechanisms and/or a combination. We discuss prognostic and predicative covariates for transplant outcomes. Importantly, we consider whether there is presently a role of transplants in CLL and who, if anyone, is an appropriate candidate in the context of new drugs.

Use of Bendamustine in Chronic Lymphocytic Leukaemia Patients with Co-morbidities

2012 ◽  
Vol 08 (01) ◽  
pp. 52 ◽  
Author(s):  
Véronique Leblond ◽  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Response Rate ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Best Supportive Care ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Study

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia and mainly affects older patients. First-line treatments for 'fit' (go go) and 'unfit' (no go) CLL patients are well defined, in the form of fludarabine–cyclophosphamide–rituximab (FCR) combination chemoimmunotherapy and best supportive care, respectively. However, the majority of CLL patients fall between these two extremes (slow go patients), nevertheless the standard of care for these patients is not well defined. Recent data suggest that bendamustine chemotherapy may be a good option in this group. In a recent Phase III study, significant improvements in overall response rate, complete response and progression-free survival were reported with bendamustine compared with chlorambucil. Chlorambucil plus rituximab has been shown to induce high responses in elderly CLL patients with a relatively low complete response rate. Bendamustine plus rituximab, and reduced-dose fludarabine plus cyclophosphamide plus high-dose rituximab have demonstrated promising efficacy, but have not been evaluated in elderly CLL patients. Several trials are also ongoing evaluating novel cytostatic agents, combination chemotherapy and chemoimmunotherapy regimens in elderly patients.

Mcl-1 Promoter Insertions as an Independent Prognostic Factor for Treatment Free Survival in Chronic Lymphocytic Leukaemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4930-4930
Author(s):  
Laura Hooper ◽  
Julio Delgado ◽  
Jane Starczynski ◽  
Jason Evans ◽  
Chris Pepper ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Myeloid Cell ◽  
Cell Leukaemia ◽  
Similar Frequency ◽  
Mutation Status ◽  
Free Survival ◽  
Protein Levels ◽  
Cd38 Expression ◽  
Number Of Patients

Abstract Mcl-1 (Myeloid cell leukaemia 1) is an anti-apoptotic member of the Bcl-2 family of proteins and is known to be important in the biology of Chronic Lymphocytic Leukaemia (CLL). A study by Moshynska et al demonstrated that a 6 or 18 nucleotide promoter insertion within the Mcl-1 promoter region influenced clinical outcome in CLL. In this study the presence of the insertion was also associated with high Mcl-1 mRNA and Mcl-1 protein levels. Subsequently there have been a number of published reports showing that these insertions have no impact at all on survival or any role in the pathogenesis of CLL. Using PCR and WAVE analysis, we analysed both the 6–18bp Mcl-1 promoter insertions in a cohort of a 100 CLL patients and 100 normal controls. Mcl-1 promoter insertions occurred at a similar frequency in the control and CLL groups. Mcl-1 promoter insertions did not correlate with any of the established prognostic factors in CLL (CD38 expression, VH mutation status, LDT, Zap 70 and stage), did not correlate with Mcl-1 protein levels and did not influence overall survival (P values &gt;0.05). However Mcl-1 promoter insertions significantly affected treatment free survival (P= 0.002). This result needs confirming in a larger number of patients as it suggests that promoter insertions identify patients that are more likely to require therapy and again raises the question of its role, if any, in CLL pathology.

Kinetics of HE4 and CA125 markers in metastatic ovarian cancer: The META4 study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17059-e17059 ◽  
Author(s):  
Pierre-Jean Lamy ◽  
Célia Touraine ◽  
Caroline Mollevi ◽  
Sylvie Roques ◽  
Catherine Viglianti ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Median Time ◽  
Half Life ◽  
Doubling Time ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Free Survival ◽  
Secondary Endpoints ◽  
Kinetics Of

e17059 Background: HE4 is a new marker that could improve the detection of ovarian cancer (OC). The objective of the present study was to compare the prognostic value of the HE4 and CA125 markers in patients (pts) with metastatic epithelial OC, considering the progression-free survival (PFS). Methods: 101 pts, treated with 2nd/3rd line of chemotherapy, were included in 3 cancer centers between 2010 and 2014. Serums were prospectively collected before the 1stchemotherapy cycle, during chemotherapy and every 3 months until disease progression. The primary endpoint was HE4 and CA125 marker level evolution under treatment. Secondary endpoints were the markers’ main kinetic parameters: initial concentration, nadir, time to nadir, time to normalisation, half-life, doubling time and time to exceed the clinical threshold (CA125≥35UI/L; HE4≥75pM) (NCT01768156). Results: 89 pts were included in the final analysis. Median age was 65 (34-83). Histological sub-types were mainly serous (88%). The median PFS was 45 weeks (95%CI: 33.4-52). At baseline, median CA125 and HE4 levels were 210UI/L (7-10310) and 184pM (31-4836), respectively. Among 12 pts (13%) CA125- (with CA125 < 35UI/L), 8 were HE4+ (with HE4≥75pM) and among 16 pts (18%) HE4-, 12 were CA125+. The median nadir was 31UI/L (3-8744) for CA125 and 75pM (20-4836) for HE4. Median time to nadir was 14 (0-130) and 12 weeks (0-52) for CA125 and HE4, respectively. The median time to normalization was 17 (3-247) and 17 weeks (2-203) for CA125 and HE4, and the median half-life was 8 (1-193) and 12 weeks (2-166), respectively. The median doubling time and the time to exceed the clinical threshold were respectively of 13.5 and 40.2 weeks for CA125, and 23 and 23.6 weeks for HE4. In multivariate analysis, the CA125 nadir ( < 35 vs ≥35: HR = 3.13; 95%CI: 1.75-5.58), CA125 time to nadir ( < 14 vs ≥14: HR = 0.46, 95%CI: 0.28-0.76), HE4 nadir ( < 75 vs ≥75: HR = 1.95; 95%CI 1.16-3.27), and HE4 time to nadir ( < 12 vs≥12: HR = 0.39; 95%CI: 0.23-0.67) were found significant prognostic factors for PFS. Conclusions: Nadir and time to nadir were significant for both HE4 and CA125 markers in multivariate analysis. Further investigations on HE4 kinetic could be helpful for monitoring pts presenting no variation of CA125. Clinical trial information: NCT01768156.

Sign in / Sign up

Export Citation Format

Share Document