BACKGROUND: Treatment of fludarabine-refractory disease in patients with chronic lymphocytic leukemia (CLL) remains a challenge. Because a recent genome-wide methylation analysis of CLL cells suggested that demethylation therapy might be beneficial in CLL, we conducted a phase II trial with the hypomethylating agent azacitidine in patients with recurrent fludarabine-refractory CLL. PATIENTS AND METHODS: Nine patients with recurrent fludarabine-refractory Rai stage IV CLL (median age, 74 years; range, 49-81 years) were enrolled. Azacitidine (75 mg/m(2)) was administered by subcutaneous injection daily for 7 consecutive days every 3 to 8 weeks, and the data were analyzed at a median follow-up of 9 months (range 3-47 months). RESULTS: The trial was prematurely discontinued because of lack of response and slow accrual. The number of cycles administered ranged from 1 to 6. Three patients received 1 cycle, 3 patients received 2 cycles, and the remaining 3 patients received 4, 5, or 6 cycles. Side effects included grade 2 or 3 infectious episodes (resulting from immunosuppression and drug-induced neutropenia), diarrhea, rash, vomiting, anemia, and thrombocytopenia. One patient experienced reduction of hepatosplenomegaly and a substantial increase in platelet count after 4 cycles of therapy. However this response did not qualify as a partial response according to the National Cancer Institute International Workshop on CLL (NCI-IWCLL) criteria. At a median follow-up of 9 months after the start of azacitidine treatment, 3 patients (33%) who went on to receive other treatments were alive. CONCLUSIONS: Although no partial or complete responses occurred in these heavily pretreated patients, the encouraging response in 1 of these patients may warrant further studies to investigate the effects of azacitidine in CLL.
BACKGROUND: Treatment of fludarabine-refractory disease in patients with chronic lymphocytic leukemia (CLL) remains a challenge. Because a recent genome-wide methylation analysis of CLL cells suggested that demethylation therapy might be beneficial in CLL, we conducted a phase II trial with the hypomethylating agent azacitidine in patients with recurrent fludarabine-refractory CLL. PATIENTS AND METHODS: Nine patients with recurrent fludarabine-refractory Rai stage IV CLL (median age, 74 years; range, 49-81 years) were enrolled. Azacitidine (75 mg/m(2)) was administered by subcutaneous injection daily for 7 consecutive days every 3 to 8 weeks, and the data were analyzed at a median follow-up of 9 months (range 3-47 months). RESULTS: The trial was prematurely discontinued because of lack of response and slow accrual. The number of cycles administered ranged from 1 to 6. Three patients received 1 cycle, 3 patients received 2 cycles, and the remaining 3 patients received 4, 5, or 6 cycles. Side effects included grade 2 or 3 infectious episodes (resulting from immunosuppression and drug-induced neutropenia), diarrhea, rash, vomiting, anemia, and thrombocytopenia. One patient experienced reduction of hepatosplenomegaly and a substantial increase in platelet count after 4 cycles of therapy. However this response did not qualify as a partial response according to the National Cancer Institute International Workshop on CLL (NCI-IWCLL) criteria. At a median follow-up of 9 months after the start of azacitidine treatment, 3 patients (33%) who went on to receive other treatments were alive. CONCLUSIONS: Although no partial or complete responses occurred in these heavily pretreated patients, the encouraging response in 1 of these patients may warrant further studies to investigate the effects of azacitidine in CLL.
Authors: Kristie A Blum; Zhongfa Liu; David M Lucas; Ping Chen; Zhiliang Xie; Robert Baiocchi; Donald M Benson; Steven M Devine; Jeffrey Jones; Leslie Andritsos; Joseph Flynn; Christoph Plass; Guido Marcucci; Kenneth K Chan; Michael R Grever; John C Byrd Journal: Br J Haematol Date: 2010-04-29 Impact factor: 6.998
Authors: M Hallek; K Fischer; G Fingerle-Rowson; A M Fink; R Busch; J Mayer; M Hensel; G Hopfinger; G Hess; U von Grünhagen; M Bergmann; J Catalano; P L Zinzani; F Caligaris-Cappio; J F Seymour; A Berrebi; U Jäger; B Cazin; M Trneny; A Westermann; C M Wendtner; B F Eichhorst; P Staib; A Bühler; D Winkler; T Zenz; S Böttcher; M Ritgen; M Mendila; M Kneba; H Döhner; S Stilgenbauer Journal: Lancet Date: 2010-10-02 Impact factor: 79.321
Authors: Xavier C Badoux; Michael J Keating; Xuemei Wang; Susan M O'Brien; Alessandra Ferrajoli; Stefan Faderl; Jan Burger; Charles Koller; Susan Lerner; Hagop Kantarjian; William G Wierda Journal: Blood Date: 2011-06-13 Impact factor: 22.113
Authors: Guillermo Garcia-Manero; Steven D Gore; Christopher Cogle; Renee Ward; Tao Shi; Kyle J Macbeth; Eric Laille; Heidi Giordano; Sarah Sakoian; Elias Jabbour; Hagop Kantarjian; Barry Skikne Journal: J Clin Oncol Date: 2011-05-16 Impact factor: 44.544
Authors: William G Wierda; Swaminathan Padmanabhan; Geoffrey W Chan; Ira V Gupta; Steen Lisby; Anders Osterborg Journal: Blood Date: 2011-08-19 Impact factor: 22.113
Authors: Fadi Braiteh; Andres O Soriano; Guillermo Garcia-Manero; David Hong; Marcella M Johnson; Leandro De Padua Silva; Hui Yang; Stefanie Alexander; Johannes Wolff; Razelle Kurzrock Journal: Clin Cancer Res Date: 2008-10-01 Impact factor: 12.531
Authors: Roger M Lyons; Thomas M Cosgriff; Sanjiv S Modi; Robert H Gersh; John D Hainsworth; Allen L Cohn; Heidi J McIntyre; Indra J Fernando; Jay T Backstrom; C L Beach Journal: J Clin Oncol Date: 2009-03-02 Impact factor: 44.544
Authors: Davendra Sohal; Smitha Krishnamurthi; Rita Tohme; Xiaorong Gu; Daniel Lindner; Terry H Landowski; John Pink; Tomas Radivoyevitch; Sherry Fada; Zhenghong Lee; Dale Shepard; Alok Khorana; Yogen Saunthararajah Journal: Am J Cancer Res Date: 2020-09-01 Impact factor: 6.166
Authors: Min Shen; Yaqin Zhang; Nakhle Saba; Christopher P Austin; Adrian Wiestner; Douglas S Auld Journal: PLoS One Date: 2013-09-20 Impact factor: 3.240