Citations 2
Prognostic impact of RAS mutations in patients with myelodysplastic syndrome
Al‐Kali, Aref , Luthra, Raja, Bueso‐Ramos, Carlos E. , Kadia, Tapan M. , Faderl, Stefan, Cortes, Jörge E. , Tefferi, Ayalew , Kantarjian, Hagop M. , Garcia‐Manero, Guillermo , Quintás‐Cardama, Alfonso , Pierce, Sherry A. , Borthakur, Gautam , Estrov, Zeev E. , Jabbour, Elias , Ravandi, Farhad , Cortes, Jorge , Kantarjian, Hagop
American Journal of Hematology | February 8, 2013 | Volume: 88 | Issue: 5 | Pages: 365-369
RAS is an oncogene frequently mutated in human cancer. RAS mutations have been reported in 10–15% of cases of acute myeloid leukemia (AML) but they appear to be less frequent among patients with myelodysplastic syndrome (MDS). The impact of RAS mutations in patients with MDS is unclear. We conducted a retrospective study in 1,067 patients with newly diagnosed MDS for whom RAS mutational analysis was available. Overall, 4% of patients carried mutant RAS alleles. Notably, FLT3 mutations, which were found in 2% of patients, were mutually exclusive with RAS mutations. Patients with RAS mutations had a higher white blood cell count as well as bone marrow blasts compared with patients carrying wild‐type RAS. However, no differences were observed between both groups regarding the risk of AML transformation (9% vs. 7%) and overall survival (395 days vs. 500 days, P = 0.057). In summary, RAS mutations are infrequent in patients with MDS and do not appear to negatively impact their outcome. Am. J. Hematol. 88:365–369, 2013. © 2013 Wiley Periodicals, Inc.
Alemtuzumab Therapy for Hypereosinophilic Syndrome and Chronic Eosinophilic Leukemia
Verstovšek, Srđan , Tefferi, Ayalew , Kantarjian, Hagop M. , Manshouri, Taghi, Luthra, Raja, Pardanani, Animesh , Quintás‐Cardama, Alfonso , Ault, Pat, Bueso‐Ramos, Carlos E. , Cortes, Jörge E. , Ravandi, Farhad , Cortes, Jorge , Verstovsek, Srdan , Kantarjian, Hagop
Clinical Cancer Research | December 31, 2008 | Volume: 15 | Issue: 1 | Pages: 368-373
Abstract Purpose: Patients with hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (CEL) that are refractory to standard therapies are difficult to manage and have significantly shortened life expectancy. Experimental Design: CD52 is a surface glycoprotein highly expressed on eosinophils. We treated 11 patients with advanced HES/CEL with alemtuzumab, a humanized anti-CD52 monoclonal antibody. Alemtuzumab was administered, in general, first in escalating doses (5, 10, 30 mg i.v. on days 1-3), then at the tolerated dose thrice per week for a total of 12 doses. Patients with complete hematologic response (CHR; normal percent and absolute eosinophil count) were allowed to continue therapy once weekly as maintenance. Results: Ten patients (91%) achieved CHR after a median of 2 weeks (0.5-5 weeks) of therapy. Bone marrow eosinophilia resolved in four of seven evaluable patients. The median duration of CHR was 3 months (1.5-17+ months). Seven of the 10 CHR patients relapsed, five while off-therapy. Two patients achieved second CHR upon alemtuzumab rechallenge. Three patients experienced mild infusion-related symptoms, two developed cytomegalovirus reactivation requiring therapy, and one developed orbital lymphoma that was successfully treated. Conclusions: Our limited experience suggests alemtuzumab to be a valuable therapy for advanced HES or CEL, refractory to standard therapies, and supports the clinical evaluation of alemtuzumab in a larger trial.