scholarly journals MEK1/2 inhibition by binimetinib is effective as a single agent and potentiates the actions of Venetoclax and ABT-737 under conditions that mimic the chronic lymphocytic leukaemia (CLL) tumour microenvironment

2018 ◽  
Vol 182 (3) ◽  
pp. 360-372 ◽  
Author(s):  
Kyle Crassini ◽  
Yandong Shen ◽  
William S. Stevenson ◽  
Richard Christopherson ◽  
Chris Ward ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Tumour Microenvironment

scholarly journals Use of anticoagulants and antiplatelet in patients with chronic lymphocytic leukaemia treated with single-agent ibrutinib

2017 ◽  
Vol 178 (2) ◽  
pp. 286-291 ◽  
Author(s):  
Jeffrey A. Jones ◽  
Peter Hillmen ◽  
Steven Coutre ◽  
Constantine Tam ◽  
Richard R. Furman ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent

Single-agent Smac-mimetic compounds induce apoptosis in B chronic lymphocytic leukaemia (B-CLL)

2013 ◽  
Vol 37 (7) ◽  
pp. 809-815 ◽  
Author(s):  
Cinzia Scavullo ◽  
Federica Servida ◽  
Daniele Lecis ◽  
Francesco Onida ◽  
Carmelo Drago ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Smac Mimetic

The Use of Low-Dose Alemtuzumab as Single Agent in the Treatment of Complication in Advanced Chronic Lymphocytic Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4212-4212
Author(s):  
Luca Laurenti ◽  
Michela Tarnani ◽  
Idanna Innocenti ◽  
Silvia De Matteis ◽  
Simona Sica ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Peripheral Blood ◽  
Low Dose ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Previous Treatment ◽  
High Dose ◽  
End Of Treatment ◽  
Hb Concentration ◽  
Cmv Reactivation

Abstract There are some report in literature about the use of Alemtuzumab in patients affected by advanced B-cell chronic lymphocytic leukaemia who developed severe transfusion-dependent autoimmune haemolytic anaemia (AIHA) resistant to conventional therapy or cutis involvement. We report the use of low-dose Alemtuzumab in 4 AIHA patients and in 1 case of eyelid leukaemia cutis. Alemtuzumab was given subcutaneously at 10 mg three times weekly for 30 administrations (10 weeks). Treatment was stopped for progression disease, grade IV thrombocytopenia and/or infections or Cytomegalovirus (CMV) reactivation. Prophylaxis consiste on co-trimoxazole and aciclovir from the start of the treatment until 2 months after the end of treatment. Peripheral blood count, biochemical screening, antigenemia and CMV DNA analysis, reticulocyte count were conducted weekly. DAT and IAT were studied every two weeks during the treatment. Patient with eyelid leukaemia cutis underwent to histological examination before and after the end of treatment. AIHA response, was defined as the independence from RBC transfusion and a concomitant > 2.0 g/dl rise in Hb concentration. Four male patients developed DATpositive AIHA at a median of 44.5 months from the B-CLL diagnosis. Previous treatment for B-CLL, stage and haemoglobin (Hb) values at Alemtuzumab administration are shown in table 1. Three patients underwent to RBCu transfusion before Alemtuzumab treatment, and one also during the treatment (2RBCu). The median haemoglobin value at first Alemtuzumab administration was 8.25 gr/dl. (table1) Two patients showed CMV reactivation at 5th and 6th week of therapy and were treated with oral ganciclovir for 14 and 21 days respectively. AIHA response was reached at median of 7 weeks of Alemtuzumab therapy in all patients while the median duration time of response to Alemtuzumab therapy was 10 months. Two patients underwent to further treatment for DAT negative progressive disease after 9 and 10 months from the end of Alemtuzumab therapy respectively, one patients was treated after 26 months for AIHA relapse, while the last patients even if showed AIHA remission is currently at 6th week of Alemtuzumab treatment (Hb 8g/dl). At the end of Alemtuzumab administrations the median Hb concentration was 12.7 g/dl regarding clinical responses, the patient no.1 obtained SD, the other 2 PR. Patient with leukemia cutis (LC) showed a constant reduction of eyelid involvement until clinical resolution after 240 mg of Alemtuzumab. Now a day, a manteinance therapy is ongoing with Alemtuzumab 30 mg monthly maintaining complete remission of eyelid localization and partial remission of CLL 10 months after induction therapy. In All patients the therapy has been well tolerated, with mild haematological and extra-haematological side effects (grade I). No episode of febrile neutropenia or bacterial/fungal infection occurred during the treatment. Our data confirmed the literature data about the use of Alemtuzumab, even if with low-dose, as salvage treatment for transfusion-dependent and resistant AIHA in pre-treated B-CLL patients and show a new indication for LC involvement. Table 1: Patient’s clinical characteristics Age/Sex Binet/Rai Stage Months from B-CLL diagnosis and AIHA/LC Previous treatment for B-CLL (number of cycles) Biological Parameter Months between last B-CLL therapy-AIHA/LC Hb at baseline Alemtuzumab treatment (gr/dl) DAT/IAT 68/M C/IV 9 CHOP(6), CVP(3) Unmutated IgVH
 Zap-70 +
 CD38 +
 Del17p 1 9.4 DAT 4+
 (IgG 4+)
 IAT 4+ 53/M C/IV 31 Chl/Pdn(6), FC(6), Pdn(6), Ig, Splenectomy Mutated
 Zap-70 −
 Normal karyotipe 3 7.1 DAT 2+
 (IgG 1+)
 IAT 2+ 46/M C/III 58 CHOP(8), HD-CTX, aPBSCT Unmutated IgVH
 Normal Kariotype 38 10.1 DAT 4+
 (IgG 3+; C3d 1+)
 IAT − 56/M C/IV 64 FC, chl, fludarabine, RIC transplant Unmutated IgVH Zap-70 + CD38 −Del 17p, Del 13q 28 4.9 DAT 4+
 (IgG 4+)
 IAT 2+ 61/M B/II 108 Fludarabine, CHOP, INFa, chl/pdn Mutated IgVH
 Zap-70 +
 CD38 +
 Del 17p, +12 24 14.3 Negative M: male, Chl: chlorambucil, Pdn: prednisone, FC: fludarabine+cyclophosphamide, Ig: intravenous immunoglobulin, HD-CTX: high dose-cyclophosphamide, aPBSCT: autologous peripheral blood stem cell transplantation.

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 Long-term follow-up of a phase 2 trial of single agent lenalidomide in previously untreated patients with chronic lymphocytic leukaemia

2014 ◽  
Vol 165 (5) ◽  
pp. 731-733 ◽  
Author(s):  
Christine I. Chen ◽  
Harminder Paul ◽  
Trina Wang ◽  
Lisa W. Le ◽  
Nimisha Dave ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Single Agent ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Long Term Follow Up

scholarly journals A Boolean Model of the Formation of Tumour Associated Macrophages in an in-vitro Model of Chronic Lymphocytic Leukaemia

2020 ◽  
Author(s):  
Malvina Marku ◽  
Flavien Raynal ◽  
Nina Verstraete ◽  
Marcin Domagala ◽  
Miguel Madrid-Mencía ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Cancer Cells ◽  
Lymphocytic Leukaemia ◽  
Tumour Progression ◽  
Macrophage Polarization ◽  
Tumour Microenvironment ◽  
Boolean Model ◽  
Specific Receptors ◽  
Vitro Model

AbstractThe tumour microenvironment is the collection of cells in and surrounding cancer cells in a tumour including a variety of immune cells, especially neutrophils and monocyte-derived macrophages. In a tumour setting, macrophages encompass a spectrum between a tumour-suppressive (M1) or tumour-promoting (M2) state. The biology of macrophages found in tumours (Tumour Associated Macrophages) remains unclear, but understanding their impact on tumour progression is highly important. In this paper, we perform a comprehensive analysis of a macrophage polarization network, following two lines of enquiry: (i) we reconstruct the macrophage polarization network based on literature, extending it to include important stimuli in a tumour setting, and (ii) we build a dynamical model able to reproduce macrophage polarization in the presence of different stimuli, including the contact with cancer cells. Our simulations recapitulate the documented macrophage phenotypes and their dependencies on specific receptors and transcription factors, while also elucidating the formation of a special type of tumour associated macrophages in an in-vitro model of chronic lymphocytic leukaemia. This model constitutes the first step towards elucidating the cross-talk between immune and cancer cells inside tumours, with the ultimate goal of identifying new therapeutic targets that could control the formation of tumour associated macrophages in patients.

Single-agent purine analogues for the treatment of chronic lymphocytic leukaemia: A systematic review and meta-analysis

2006 ◽  
Vol 32 (5) ◽  
pp. 377-389 ◽  
Author(s):  
Michael Steurer ◽  
Georg Pall ◽  
Sue Richards ◽  
Guido Schwarzer ◽  
Julia Bohlius ◽  
...  
Keyword(s):  
Systematic Review ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Meta Analysis ◽  
Single Agent ◽  
Purine Analogues
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