Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial

Elter, Thomas; Borchmann, Peter; Schulz, H.; Reiser, Marcel; Trelle, Sven; Schnell, Roland; Jensen, Markus; Staib, Peter; Schinköthe, Timo; Stützer, H.; Rech, Jürgen; Gramatzki, Martin; Aulitzky, Walter E.; Hasan, Ibrahim; Josting, Andreas; Hallek, Michael; Engert, Andreas

doi:10.1200/jco.2005.01.9950

Cited by 194 publications

(120 citation statements)

References 35 publications

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“…The T-cell population gradually recovered to baseline levels by 36 weeks after therapy initiation [30]. Similar results on the recovery of CD4 + cells in alemtuzumab combination therapy were reported [12]. Importantly, several studies have shown that infectious events typically occur around the time of T-cell and neutrophil nadirs (Fig.…”

Section: Effect Of Alemtuzumab On Immune Cellssupporting

confidence: 79%

“…In a recent study, 36 [12]. Most infections occurred within the first 3 months of treatment, when CD4 + cells were at the lowest levels ( Table 2).…”

Section: Alemtuzumab In Combination Therapymentioning

confidence: 88%

“…Single-agent alemtuzumab is highly effective as both first-line treatment for CLL and treatment for relapsed/ fludarabine-refractory CLL, and has been approved for both indications [24,30]. Alemtuzumab is also being evaluated intensively in the settings of combination therapy [12], consolidation therapy [14,32,37,43,61], and as part of the conditioning regimen for patients undergoing autologous [37] or allogeneic stem cell transplantation (SCT) [10].…”

Section: Introductionmentioning

confidence: 99%

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Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

et al. 2008

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International audienceInfection is a significant cause of morbidity and death in patients with chronic lymphocytic leukemia (CLL). Increased infectious events may arise from the multiple courses of immunosuppressive therapy and progressive deterioration of a patient's immune system over the course of disease. The humanized, anti-CD52 monoclonal antibody alemtuzumab (Campath or Campath-1H) has shown notable activity for both untreated and fludarabine-refractory CLL. The antibody not only targets malignant cells but also affects normal, healthy immune cells. The cumulative effects of the malignancy and successive courses of treatments adversely impinge on a patient's defense response to certain bacterial, fungal, and viral infections. In this review article, we provide an overview of common infectious events associated with alemtuzumab therapy in CLL. We also discuss recommendations for effectively monitoring and managing infections in CLL patients

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Section: Effect Of Alemtuzumab On Immune Cellssupporting

confidence: 79%

“…In a recent study, 36 [12]. Most infections occurred within the first 3 months of treatment, when CD4 + cells were at the lowest levels ( Table 2).…”

Section: Alemtuzumab In Combination Therapymentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

et al. 2008

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“…Efficacy did not vary significantly between genetic subgroups, indicating that alemtuzumab treatment could overcome the adverse prognostic impact of IGHV mutation status, TP53 mutation, and genomic aberrations. The potential benefit of alemtuzumab in combination with chemotherapy was first observed in 6 patients by Kennedy et al [57]; their findings were confirmed by a phase II trial on relapsed or refractory CLL, which reported an OR of 83%, including 11 patients with CR, and resolution of disease in all affected sites [58].…”

Section: Clanahan Et Al Treatment Of Chronic Lymphocytic Leukemiasupporting

confidence: 51%

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

Clanahan¹,

Dreger

2011

Turk J Hematol

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Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL). Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs® should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL. (Turk J Hematol 2011; 28: 86-96) Key words: CLL, genetics, poor-risk, treatment, allogeneic stem cell transplantation Günümüzde bu hastalarda şifa sağlayıcı potansiyele sahip tek tedavi seçeneği allogeneik kök hücre naklidir. Bu yöntemle, geleneksel immünokemoterapinin aksine, del 17p veya diğer olumsuz biyolojik ve klinik risk faktörlerine sahip hastalarda bile hastalığın uzun süreli denetimi sağlanabilir. Bu derleyici incelemede, yüksek riskli KLL'ye odaklanarak KLL tanı ve tedavisine ilişkin güncel stratejilerin özetlenmesi amaçlanmıştır. (Turk J Hematol 2011; 28: 86-96)

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“…In a phase II trial 36 patients were included. A high overall response rate was reached with 83 % (11 CR, 19 PR), but there were remarkable adverse events: fungal pneumonia in two progressive patients and one case of death caused by E. coli sepsis at CMV reactivation [17].…”

Section: Alemtuzumabmentioning

confidence: 93%

Refractory chronic lymphocytic leukemia - new therapeutic strategies

Schnaiter

Stilgenbauer

2010

Oncotarget

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AbstrAct:Treatment outcome of chronic lymphocytic leukemia (CLL) has considerably improved since the introduction of fludarabine (F) as part of the standard therapy. Nevertheless, refractoriness to fludarabine occurs in a significant number of patients and is associated with an unfavorable prognosis. Important risk factors are 17p deletion and/or mutation of TP53. For this subgroup the CD52 antibody alemtuzumab (A) presents a new treatment approach and has already been approved. Meanwhile we have to face also refractoriness to alemtuzumab. Importantly, the monoclonal CD20 antibody ofatumumab has now shown efficacy in F and A double-refractory CLL. The next generation CD20 antibody GA-101 is currently compared to rituximab (R) and will possibly be its more potent successor. Further B-cell antigens are targeted by lumiliximab (CD23), TRU-016 (CD37) and blinatumomab (CD19). Apart from monoclonal antibody therapies, a great number of small molecules are examined for the treatment of refractory and relapsed CLL. Most of these agents aim to overcome apoptosis resistance in CLL cells or influence the microenvironment. Typical targets are regulators of the cell cycle and antiapoptotic molecules like the members of the Bcl-2 family. Up to now the most promising agents appear to be flavopiridol and lenalidomide among others.

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Fludarabine in Combination With Alemtuzumab Is Effective and Feasible in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia: Results of a Phase II Trial

Abstract: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.

Cited by 194 publications

References 35 publications

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

Management of infections in patients with chronic lymphocytic leukemia treated with alemtuzumab

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

Refractory chronic lymphocytic leukemia - new therapeutic strategies

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