Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen.

Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper-CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper-CVAD. The 5-year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5-year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long-term outcomes on both ABFM and hyper-CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression-associated complications were most significant with hyper-CVAD. In summary, ABFM and hyper-CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase-related with ABFM and myelosuppression-related with hyper-CVAD. Am. J. Hematol. 91:819-823, 2016. © 2016 Wiley Periodicals, Inc.

Rytting ME ，Jabbour EJ ，Jorgensen JL ，Ravandi F ，Franklin AR ，Kadia TM ，Pemmaraju N ，Daver NG ，Ferrajoli A ，Garcia-Manero G ，Konopleva MY ，Borthakur G ，Garris R ，Wang S ，Pierce S ，Schroeder K ，Kornblau SM ，Thomas DA ，Cortes JE ，O'Brien SM ，Kantarjian HM ... -  《-》

Augmented Berlin-Frankfurt-Münster therapy in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).

Various trials have reported improved outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) who received treatment with pediatric-based regimens. Those reports prompted the current investigation of the pediatric augmented Berlin-Frankfurt-Münster (ABFM) regimen in AYA patients. The results were compared with those from a similar population that received the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen. Eighty-five patients ages 12 to 40 years who had Philadelphia chromosome (Ph)-negative ALL received the ABFM regimen from October 2006 through April 2012. Their outcome was compared with outcomes in 71 historic AYA patients who received hyper-CVAD from the authors' institution. Patient and disease characteristics, as well as minimal residual disease status, were analyzed for their impact on outcomes. The complete response rate with ABFM was 94%. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 70% and 74%, respectively. For patients aged ≤21 years, the 3-year CRD and OS rates were 72% and 85%, respectively; and, for patients ages 21 to 40 years, the respective rates were 69% and 60%. The initial white blood cell count was an independent predictive factor of OS and CRD. The minimal residual disease status on days 29 and 84 of therapy also were predictive of long-term outcomes. Severe regimen toxicities included transient hepatotoxicity in 35% to 39% of patients, pancreatitis in 11% of patients, osteonecrosis in 11% of patients, and thrombosis in 22% of patients. The 3-year OS rate was 74% in the ABFM group versus 71% in the hyper-CVAD group, and the corresponding 3-year CRD rate was 70% versus 66%, respectively. ABFM was tolerable in AYA patients with ALL but was not associated with significant improvements in CRD and OS compared with hyper-CVAD.

Rytting ME ，Thomas DA ，O'Brien SM ，Ravandi-Kashani F ，Jabbour EJ ，Franklin AR ，Kadia TM ，Pemmaraju N ，Daver NG ，Ferrajoli A ，Garcia-Manero G ，Konopleva MY ，Cortes JE ，Borthakur G ，Garris R ，Cardenas-Turanzas M ，Schroeder K ，Jorgensen JL ，Kornblau SM ，Kantarjian HM ... -  《-》

Hyper-CVAD Compared With BFM-like Chemotherapy for the Treatment of Adult Acute Lymphoblastic Leukemia. A Retrospective Single-Center Analysis.

Several induction regimens have been developed for treatment of adult patients with acute lymphoblastic leukemia (ALL). However, only a few prospective randomized trials have directly compared these regimens. In this report, we retrospectively evaluated the outcome of 62 adult ALL patients treated with either hyper-CVAD (hyper fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone; n = 38) or a BFM (Berlin-Frankfurt-Munster)-like regimen (n = 24) between November 2000 and January 2016 at the American university of Beirut Medical Center in Lebanon. The feasibility of allogeneic stem cell transplantation (allo-SCT) for those patients was also evaluated. The median follow-up time was 29 (range, 1-129) months. Fifteen (39%) and 10 (42%) patients underwent allo-SCT in the hyper-CVAD and BFM-like group, respectively. At the time of the last follow-up, 28 patients (74%) were in complete remission in the hyper-CVAD group versus 18 patients (75%) in the BFM-like group. Of those, 20 patients (53%) versus 11 patients (46%) were minimal residual disease-negative at the last follow-up, respectively. The 3-year overall survival rate (71.9% vs. 76.9%; P = .808) and 3-year disease-free survival (54.7% vs. 76.4%; P = .435) were similar in hyper-CVAD group compared with the BFM-like group, respectively. Both chemotherapies were relatively well tolerated. Overall, despite the older age and a greater number of patients with high-risk category (including Philadelphia chromosome-positive) in the hyper-CVAD group, this did not translate into a difference in survival outcome between the 2 groups. The hyper-CVAD regimen appears to be feasible for adult patients with ALL in terms of tolerability and efficacy.

El-Cheikh J ，El Dika I ，Massoud R ，Charafeddine M ，Mahfouz R ，Kharfan-Dabaja MA ，Bazarbachi A ... -  《-》

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Salama H ，Eldadah S ，Omer MH ，Alhejazi A ，Bin Dayil L ，Almozaini A ，Khalil RR ，Mugairi AA ，Snnallah M ，Damlaj M ，Alaskar A ，Alsaeed A ，Bakkar MM ，Alahmari B ，Alzahrani M ，Elhemaidi I ，Alahmadi M ，Alamoudi S ，Rajkhan W ，Khalil M ，Kanfar SS ，Saleh ASA ，Raizah AA ，Ibrahim A ，Absi A ... -  《-》

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia.

Kantarjian H ，Thomas D ，O'Brien S ，Cortes J ，Giles F ，Jeha S ，Bueso-Ramos CE ，Pierce S ，Shan J ，Koller C ，Beran M ，Keating M ，Freireich EJ ... -  《CANCER》