Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy in Patients With Richter's Syndrome or Fludarabine-Refractory Chronic Lymphocytic Leukemia

Tsimberidou, Apostolia M.; Wierda, William G.; Plunkett, William; Kurzrock, Razelle; O’Brien, Susan; Wen, Sijin; Ferrajoli, Alessandra; Ravandi‐Kashani, Farhad; Garcia‐Manero, Guillermo; Estrov, Zeev; Kipps, Thomas J.; Brown, Jennifer R.; Fiorentino, Albert; Lerner, Susan; Kantarjian, Hagop M.; Keating, Michael J.

doi:10.1200/jco.2007.11.8513

Cited by 143 publications

(113 citation statements)

References 36 publications

(6 reference statements)

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“…This principle has been clinically validated, as relapse-free survival is extended with combinations of cyclophosphamide and fludarabine (Eichhorst et al, 2006;Catovsky et al, 2007;Flinn et al, 2007). New combinations of nucleoside analogs and platinum derivatives with complementary mechanisms of action and non-overlapping side effect profiles may further increase activity (Tsimberidou et al, 2008). These studies validate strategies that target DNA repair mechanisms and suggest that this may be an important step in the development of novel approaches for overcoming drug resistance to DNAtargeting chemotherapeutics.…”

Section: Targeting Dna Repair In Quiescent Cellsmentioning

confidence: 90%

Nucleoside analogs: molecular mechanisms signaling cell death

2008

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Nucleoside analogs are structurally similar antimetabolites that have a broad range of action and are clinically active in both solid tumors and hematological malignancies. Many of these agents are incorporated into DNA by polymerases during normal DNA synthesis, an action that blocks further extension of the nascent strand and causes stalling of replication forks. The molecular mechanisms that sense stalled replication forks activate cell cycle checkpoints and DNA repair processes, which may contribute to drug resistance. When replication forks are not stabilized by these molecules or when subsequent DNA repair processes are overwhelmed, apoptosis is initiated either by these same DNA damage sensors or by alternative mechanisms. Recently, strategies aimed at targeting DNA damage checkpoints or DNA repair processes have demonstrated effectiveness in sensitizing cells to nucleoside analogs, thus offering a means to elude drug resistance. In addition to their DNA synthesisdirected actions many nucleoside analogs trigger apoptosis by unique mechanisms, such as causing epigenetic modifications or by direct activation of the apoptosome. A review of the cellular and molecular responses to clinically relevant agents provides an understanding of the mechanisms that cause apoptosis and may provide rationale for the development of novel therapeutic strategies.

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Section: Targeting Dna Repair In Quiescent Cellsmentioning

confidence: 90%

Nucleoside analogs: molecular mechanisms signaling cell death

2008

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“…Rituximab has been successfully applied in the clinic in combination with Fludarabine, or Fludarabine and Dexamethasone, and Mitoxantrone. 1,2 We sought to investigate the mechanisms of Rituximab-induced apoptosis in chronic lymphocytic leukemia cells through the upregulation of AU-rich binding proteins that can target certain mRNAs for degradation. 3,4 We found that 20 mg/ml of Rituximab induced apoptosis when crosslinked with an anti-human Fcg-specific antibody (referred to as XRituximab), especially at 48 h post-stimulation as measured by either propidium iodide alone or Annexin V-propidium iodide methods, which is in agreement with earlier work.…”

mentioning

confidence: 99%

Involvement of Tis11b, an AU-rich binding protein, in induction of apoptosis by rituximab in B cell chronic lymphocytic leukemia cells

et al. 2008

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“…Rapidly enlarging lymph nodes, increasing LDH level, new onset of B symptoms (fever, night sweats, and weight loss greater than 10%), and poor response to usual CLL therapies support the diagnosis of RT (6). Unfortunately, the clinical features of RT are non-specific, and suggestive laboratory findings can also frequently be seen in patients without RT.…”

Section: Discussionmentioning

confidence: 99%

A Case of Hodgkin Transformation of Chronic Lymphocytic Leukemia

Sincan¹,

Kıkı²,

Bilen³

2016

Haseki

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Case Report / Olgu SunumuRichter's transformation is a serious complication of chronic lymphocytic leukemia. We present a patient with Hodgkin transformation of chronic lymphocytic leukemia. This patient was admitted to our clinic with the complaints of weakness and fatigue. She had palpable axillary and cervical lymphadenomegaly. Positron emission tomography/ computed tomography scans with fluorodeoxyglucose revealed multiple cervical axillary lymph nodes in the right axilla and the right side of the neck with minimally increased fluorodeoxyglucose uptake and paraaortic, pancreaticoduodenal, aortocaval lymph nodes with intense fluorodeoxyglucose uptake (SUV max : 10.86). Excisional biopsy of the intraabdominal lymph node was performed which revealed classical Hodgkin disease. Combined chemotherapy was started. She died because of pneumonia after two cycles of the therapy.

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Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine, and Rituximab Combination Therapy in Patients With Richter's Syndrome or Fludarabine-Refractory Chronic Lymphocytic Leukemia

Abstract: The OFAR regimen is highly active in RS and has activity in fludarabine-refractory patients with CLL. This regimen warrants further investigation in the treatment of these disorders.

Cited by 143 publications

References 36 publications

Nucleoside analogs: molecular mechanisms signaling cell death

Nucleoside analogs: molecular mechanisms signaling cell death

Involvement of Tis11b, an AU-rich binding protein, in induction of apoptosis by rituximab in B cell chronic lymphocytic leukemia cells

A Case of Hodgkin Transformation of Chronic Lymphocytic Leukemia

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