Fludarabine Compared with Chlorambucil as Primary Therapy for Chronic Lymphocytic Leukemia

Kanti, R.; Peterson, Bercedis L.; Appelbaum, Frederick R.; Kolitz, Jonathan E.; Elias, Laurence; Shepherd, Lois E.; Hines, John; Threatte, Gregory A.; Larson, Richard A.; Cheson, Bruce D.; Schiffer, Charles A.

doi:10.1056/nejm200012143432402

Cited by 917 publications

(632 citation statements)

References 16 publications

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“…The median latency interval in these patients was 23 months, significantly shorter than patients who achieved complete hematological recovery after FCR. Fludarabine, a purine analog, is a potent single agent in chronic lymphocytic leukemia/small lymphocytic lymphoma treatment, 22 but is also known to cause severe cytopenia more frequently than other chemotherapy agents in chronic lymphocytic leukemia/small lymphocytic lymphoma treatment. 22,23 This side effect is largely attributed to its cytotoxicity on hematopoietic stem cells.…”

Section: Therapy-related Myeloid Neoplasm Post Fcrmentioning

confidence: 99%

“…Fludarabine, a purine analog, is a potent single agent in chronic lymphocytic leukemia/small lymphocytic lymphoma treatment, 22 but is also known to cause severe cytopenia more frequently than other chemotherapy agents in chronic lymphocytic leukemia/small lymphocytic lymphoma treatment. 22,23 This side effect is largely attributed to its cytotoxicity on hematopoietic stem cells. 24,25 Despite potent myelosuppression, therapyrelated myeloid neoplasms secondary to fludarabine single-agent treatment is extremely rare, reported 0 in 174 (0%) and 1 in 188 (0.5%) in two studies conducted on chronic lymphocytic leukemia/small lymphocytic lymphoma patients who received fludarabine as initial therapy with a long-term followup.…”

Section: Therapy-related Myeloid Neoplasm Post Fcrmentioning

confidence: 99%

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Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

et al. 2012

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This study is focused on therapy-related myeloid neoplasms after the most promising frontline FCR (fludarabine, cyclophosphamide, and rituximab) therapy in previously untreated chronic lymphocytic leukemia patients. A total of 28 therapy-related myeloid neoplasm patients were identified, including 19 patients from 3 well-controlled FCR frontline trials (n ¼ 426 patients), giving an estimated frequency of 4.5% (1.9-8.3%) in a follow-up period of 44 months (range 5-122 months). Clinically, therapy-related myeloid neoplasms could emerge directly from 'prolonged myelosuppression' after FCR (10 patients), or after achieving complete hematological recovery (n ¼ 18). The overall latency was 35 months (range 3-118 months), with the former group of 23 months and the latter 42 months (Po0.001). In all, 10 cases presented as therapy-related acute myeloid leukemia and 18 as therapy-related myelodysplastic syndromes. Abnormal cytogenetics was present in 26 of 27 (96%) patients, with frequent chromosomes 5 and 7 abnormalities. The median survival was 7 months after therapy-related myeloid neoplasms. Our results indicate that the risk of therapy-related myeloid neoplasms secondary to frontline FCR therapy may not be as high as previously reported after removing the confounding factor of previous cytotoxic exposure, but this risk increased with older age and likely growth factor co-administration. Therapy-related myeloid neoplasms after FCR therapy shares clinicopathological features with therapy-related myeloid neoplasms secondary to other alkylating agents, but has a shorter latency interval indicating possible synergetic effects of the nucleotide analog fludarabine. The fact that therapy-related myeloid neoplasms can directly emerge from 'prolonged myelosuppression' warrants a bone marrow examination to rule out therapy-related myeloid neoplasms in this clinical setting.

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Section: Therapy-related Myeloid Neoplasm Post Fcrmentioning

confidence: 99%

Section: Therapy-related Myeloid Neoplasm Post Fcrmentioning

confidence: 99%

Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

et al. 2012

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“…Fludarabine as a single agent was shown to have remarkable activity in a range of indolent lymphoid malignancies refractory to other treatments, including up to a 100% complete remission rate in relapsed CLL [27]. Fludarabine was shown to be superior to chlorambucil in a major intergroup study, with a higher response rate and longer disease-free interval [28]. Single-agent fludarabine also has response rates superior to those of several combination regimens, such as cyclophosphamide, doxorubicin (Adriamycin ® ; Bedford Laboratories, Bedford, OH, http://www.bedfordlabs.com), vincristine, and prednisone (CHOP) and CVP, in previously untreated CLL [29].…”

Section: Purine Nucleoside Analoguesmentioning

confidence: 99%

Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment

Abbott

2006

The Oncologist

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“…In first line monotherapy, there have been response rates of 63 to 80 % [3,4]. Nevertheless not all the patients respond.…”

Section: Fludarabine Refractoriness and Relapsementioning

confidence: 99%

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 Compared with Chlorambucil as Primary Therapy for Chronic Lymphocytic Leukemia

Abstract: When used as the initial treatment for chronic lymphocytic leukemia, fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil.

Cited by 917 publications

References 16 publications

Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

Chronic Lymphocytic Leukemia: Recent Advances in Diagnosis and Treatment

Refractory chronic lymphocytic leukemia - new therapeutic strategies

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