Citations 12
Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report
Ahn, Kwang Woo , Hu, Zhen‐Huan , Volpe, Virginia O. , Antin, Joseph H. , Sorror, Mohamed L. , Press, Oliver W. , Pidala, Joseph, Negrin, Robert S., Uberti, Joseph P., Agura, Edward, Nash, Richard A. , Mehta, Jayesh, Forman, Stephen J. , Langston, Amelia , Hale, Gregory A., Marks, David I. , Ganguly, Sid, Reshef, Ran , Hildebrandt, Gerhard , Inamoto, Yoshihiro , Cahn, Jean‐Yves, Solh, Melhem , Kharfan‐Dabaja, Mohamed A. , Saad, Ayman , Aljurf, Mahmoud , Schouten, Harry C. , Hill, Brian T. , Pawarode, Attaphol , Kindwall‐Keller, Tamila L. , Saba, Nakhle S. , Copelan, Edward A. , Nathan, Sunita , Beitinjaneh, Amer , Černý, Jan , Wirk, Baldeep , Olsson, Richard F. , Bashey, Asad, Sobecks, Ronald , Alyea, Edwin P. , Saber, Wael , Brown, Jennifer R. , Hogan, William, Kharfan-Dabaja, Mohamed A., Saad, Ayman , Press, Oliver , Olsson, Richard F , Reshef, Ran , Kim, Haesook T. , Davids, Matthew S. , Shadman, Mazyar , Hogan, William J. , Devine, Steven M. , McGuirk, Joseph P. , Giralt, Sergio , Perales, Miguel‐Angel , Battiwalla, Minoo , Gale, Robert Peter , Hamadani, Mehdi , Bacher, Ulrike , Lazarus, Hillard M. , Cahn, Jean‐Yves , Ghosh, Nilanjan , Savani, Bipin N. , Grunwald, Michael R. , Yared, Jean A. , Nishihori, Taiga , Chhabra, Saurabh , Gergis, Usama , Popat, Uday R , Sorror, Mohamed
Clinical Cancer Research | June 28, 2019 | Volume: 25 | Issue: 16 | Pages: 5143-5155
Abstract Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years). Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
Wang, Eunice S. , Baer, Maria R. , Perl, Alexander E. , Coutré, Steven , Stuart, Robert K. , Baccarani, Michele , Cripe, Larry D., Tallman, Martin S. , Meloni, Giovanna, Godley, Lucy A. , Langston, Amelia , Amadori, Sergio , Lewis, Ian D., Nagler, Arnon , Stone, Richard M. , Yee, Karen , Douer, Dan , Wiktor-Jędrzejczak, W , Juliusson, Gunnar , Litzow, Mark R. , Petersdorf, Stephen H., Sanz, Miguel Á. , Kantarjian, Hagop M. , Tremmel, Lothar, Bensen-Kennedy, Debra M., Small, Donald , Levis, Mark J. , Ravandi, Farhad , Wang, Eunice S. , Erba, Harry Paul , Advani, Anjali S. , Sato, Takashi , Smith, B. Douglas , Godley, Lucy A , Kantarjian, Hagop
Blood | January 26, 2011 | Volume: 117 | Issue: 12 | Pages: 3294-3301
Abstract In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.