Fludarabine in Resistant or Relapsing B-Cell Chronic Lymphocytic Leukemia<i>The Spanish Group</i>Experience

Montserrat, Emilio; Jl, Lopez-Lorenzo; Manso, Félix; Martin, Andrew St.; E, Prieto; Arias-Sampedro, J; Mn, Fernández; Fj, Oyarzabal; Odriozola, J; Alcalá, Antonio; Garcı́a-Conde, J; Guàrdia, Ramón; Bosch, Francesc

doi:10.3109/10428199609093445

Cited by 48 publications

(23 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The prognosis of patients with refractory CLL is very poor, their median survival being measured in months. 16,17 Refractory disease should be separated from progressing disease, the prognosis of the latter situation being much better. Unfortunately, in some studies these 2 situations are not separated, making it difficult to interpret the results obtained with salvage regimens.…”

Section: What Is Refractory Cll?mentioning

confidence: 99%

“…41 In other studies, the response rate to fludarabine or fludarabine-based treatment in patients refractory to alkylating agents has been between 20% and 40%. 6,13,16,[42][43][44][45] As previously discussed, this emphasizes that treatment refractoriness is a concept that should only be applied to patients not responding to purine analogs.When purine analogs were first introduced in the treatment of patients with CLL, the issue of whether or not these agents showed cross-resistance was a matter of extensive debate. The current notion is that cross-resistance does exist.…”

mentioning

confidence: 97%

See 1 more Smart Citation

How I treat refractory CLL

Montserrat

Moreno

Esteve

et al. 2006

Blood

View full text Add to dashboard Cite

Therapy for patients with chronic lymphocytic leukemia (CLL) has greatly changed over the past few years. After years of stagnation, with treatment revolving around the use of rather ineffective drugs such as alkylators, many patients are now being treated with more effective agents such as purine analogs either alone or combined with other drugs and/or monoclonal antibodies. Treatment of patients refractory to these treatments is particularly challenging and should be decided only upon a careful evaluation of the disease, patient characteristics, and prognostic factors. Refractory disease should be clearly separated from relapsing disease. The only curative therapy for patients with CLL, including those with refractory disease, is allogeneic stem cell transplantation. However, the use of allogeneic transplantation is limited because of the advanced age of most patients and the high transplant-related mortality (TRM). Transplants with nonmyeloablative regimens may reduce TRM and allow more patients to receive transplants more safely. For patients in whom an allogeneic transplantation is not feasible or in whom it is deemed inappropriate, participation in phase 2 trials should be encouraged. Finally, to investigate mechanisms to overcome resistance to therapy in CLL and to identify patients that might gain benefit from early, intensive therapies (eg, based on biologic markers) constitute a challenge that needs active investigation. IntroductionChronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of monoclonal peripheral (mature) CD5 ϩ B cells in lymphoid tissues, bone marrow, and peripheral blood. [1][2][3] The basic physiopathologic defect in CLL is the resistance of neoplastic cells to programmed cell death or apoptosis. CLL is the most frequent form of leukemia in Western countries and predominates in older people, the median age of patients at diagnosis being around 65 years. 4 Median survival is about 10 years but it largely varies from one patient to another, from less than 3 years to a normal life expectancy. Treatment should therefore be individualized on the basis of the risk to each patient. 5,6 For many decades, treatment of patients with CLL was based on the use of chlorambucil and other alkylating agents, which resulted in a complete response (CR) rate of less than 10% along with palliation of symptoms and only a modest, if any, impact on survival. Over the last few years, the management of CLL has greatly improved. The introduction of purine analogs and monoclonal antibodies has made possible combined treatments that result in CR rates of up to 60% to 70%; this translates into a longer progression-free interval. [5][6][7] It is important to emphasize that no matter how exciting the results with new, experimental combination chemotherapy and other innovative treatment approaches are, the advantages of these strategies in terms of survival have not yet been demonstrated. In this regard, it is important to keep in mind that the ultimate goal of therapy is to prolong surv...

show abstract

Section: What Is Refractory Cll?mentioning

confidence: 99%

mentioning

confidence: 97%

How I treat refractory CLL

Montserrat

Moreno

Esteve

et al. 2006

Blood

View full text Add to dashboard Cite

show abstract

“…Much progress has been made over the past years in our understanding of therapy of CLL, particularly after the introduction of purine analogues. [5][6][7][8][9][10][11][12][13][14][15][16] Despite the fact that CLL is an incurable hematologic malignancy, complete remission can be achieved with conventional chemotherapy. [14][15][16][17][18][19] In 1996, The National Cancer Institute-sponsored Working Group (NCI-WG) on CLL defined patients with complete remission (CR) and persistent bone marrow nodules as nPR.…”

Section: Introductionmentioning

confidence: 99%

Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission

et al. 2002

View full text Add to dashboard Cite

Patients with chronic lymphocytic leukemia (CLL) are considered in nodular partial remission (nPR) when they are in remission but bone marrow biopsies show rare nodules. The significance of the level of residual disease in nPR is not known. We studied 91 previously untreated CLL patients who were treated with fludarabine alone, fludarabine with prednisone, or fludarabine with cyclophosphamide and achieved nPR at the end of six courses. We compared bone marrow lymphoid infiltration before therapy and at the end of three and six courses of therapy as evaluated by a pathologist in retrospective fashion with that of the routine evaluation at the time of performing bone marrow biopsy. We then compared these results with those obtained by computer-aided histomorphometry in 28 patients in nPR. There was significant correlation (P Ͻ 0.05) between pathologists as well as between pathologists and histomorphometry. Upon correlation with clinical characteristics, there was significant correlation (P Ͻ 0.01) between marrow involvement before therapy and white blood cell counts (WBC), hemoglobin (Hgb), absolute lymphocyte counts, and ␤2-microglobulin (␤2-M) but none of these parameters correlated with the lymphoid infiltrate at the end of three or six courses of therapy. More importantly, lymphoid infiltration after three and six courses did not correlate with time to progression (TTP) or overall survival (OS). However, patients with Ͼ70% marrow involvement before therapy had a significantly shorter TTP (P = 0.02). All 91 patients showed similar results. However, we found reverse correlation between marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01). Leukemia (2002) 16, 632-635.

show abstract

“…Two studies were RCTs 23, 24 and seven were case-series (six prospective and one retrospective). [25][26][27][28][29][30][31] Number and type of studies excluded, with reasons for specific exclusions Of the potentially included 38 studies, 29 were excluded. Most were excluded either because the patient population was < 50 or because the study was restricted to untreated patients.…”

Section: Number and Type Of Studies Includedmentioning

confidence: 99%

Fludarabine as second-line therapy for B cell chronic lymphocytic leukaemia: a technology assessment

Hyde

Wake

Bryan

et al. 2002

Health Technol Assess

View full text Add to dashboard Cite

Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30-40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email. Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK.We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA Programme and lists the membership of the various committees. HTA NHS R&D HTA ProgrammeT he NHS R&D Health Technology Assessment (HTA) Programme was set up in 1993 to ensure that high-quality research information on the costs, effectiveness and broader impact of health technologies is produced in the most efficient way for those who use, manage and provide care in the NHS.The research reported in this monograph was commissioned by the HTA Programme on behalf of the National Institute for Clinical Excellence (NICE). Rapid reviews are completed in a limited time to inform the appraisal and guideline development processes managed by NICE. The review brings together evidence on key aspects of the use of the technology concerned. However, appraisals and guidelines produced by NICE are informed by a wide range of sources.The research reported in this monograph was funded as project number 00/12/01.The views expressed in this publication are those of the authors and not necessarily those of the HTA Programme, NICE or the Department of Health. The editors wish to emphasise that funding and publication of this research by the NHS should not be taken as implicit support for any recommendations made by the authors.Criteria for inclusion in the HTA monograph series Reports are pub...

show abstract

Fludarabine in Resistant or Relapsing B-Cell Chronic Lymphocytic LeukemiaThe Spanish GroupExperience

Cited by 48 publications

References 28 publications

How I treat refractory CLL

How I treat refractory CLL

Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission

Fludarabine as second-line therapy for B cell chronic lymphocytic leukaemia: a technology assessment

Contact Info

Product

Resources

About