There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method. Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL.

Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.

No abstract

The Dana-Farber Cancer Institute (DFCI) ALL Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20–30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985–2000, 1457 children aged 0–18 years were treated on four consecutive protocols: 85-01 (1985–7), 87-01 (1987–91), 91-01 (1991–5) and 95-01 (1996–2000). The 10-year event-free survival (EFS) ± standard error by protocol was 77.9 ± 2.8% (85-01), 74.2± 2.3 (87-01), 80.8 ± 2.1% (91-01) and 80.5 ± 1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (p=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79–85% for T-ALL patients and 75–78% for adolescents (age 10–18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely impacting EFS or OS in high-risk patients and frequently-dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new “basket” clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography or bidimensional tumor measurements on computerized tomography scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single-dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47 828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18–50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18–50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56–78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56–76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph−) was 71% (95% CI 58–81%), and for all 74 Ph− patients the 4-year OS was 70% (95% CI 58–79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.

These inconsistencies preclude a definitive conclusion as to the effect of chemotherapy on antioxidant status in patients undergoing anticancer therapy. However, our review suggests that total antioxidant status (measured by total radical antioxidant parameter) declines during cancer treatment. Adequately powered trials or observational studies among patients with a specific cancer diagnosis receiving a specific treatment regimen are needed to address patients' and physicians' concerns regarding these associations.

Medical Sciences. In the article "t(11;22)(q23;q11.2) in acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes" by Maureen D. Megonigal, Eric F. Rappaport, Douglas H. Jones, Terrence M. Williams, Brian D. Lovett, Kara M. Kelly, Paul H. Lerou, Thomas Moulton, Marcia L. Budarf, and Carolyn A. Felix, which appeared in number 11, May 26, 1998, of Proc. Natl. Acad. Sci. USA (95, pp. 6413-6418), the authors wish to note the following corrections. On page 6414, column 2, line 4, the text should read: "The 24-l ligation reaction mixture contained 0.5 g" not "0.05 g" as printed. Also, on page 6415, column 1, line 56, the text should read: "AmpliTaq DNA polymerase, all four dNTPs (each at 200 M)" not "(each at 250 M)" as printed.Medical Sciences. In the article "Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody" by Lingxun Duan, Omar Bagasra, Mark A. Laughlin, Joseph W. Oakes, and Roger J. Pomerantz, which appeared in number 11, May 24, 1994, of Proc. Natl. Acad. Sci. USA (91, 5075-5079), the undersigned authors wish to note the following: "The sequence of the heavy chain of the D8 anti-Rev single chain variable fragment (SFv) has been reanalyzed and found to be not what was reported in the article. It is likely that the coding DNA was derived from the fusion partner cell line used to make the original D8 hybridoma, and not from the heavy chain gene expressed by the B cell precursor to this hybridoma. There is a deletion in the framework region 3 (FR3) leading to a framehsift in CDR3 and downstream regions of the heavy chain gene. Individual nucleotide differences make this sequence very close to that described [Thammana, P. (1994)