Poster Abstracts Session: 612. Acute Lymphoblastic Leukemia: Clinical Studies with Asparaginase


Risk of Thrombosis in Adult Philadelphia-Positive ALL Treated with an Asparaginase-Free Pediatric-Inspired ALL Regimen with Imatinib

Ruiqi Chen, et al. 

Conclusion cited from the abstract: VTE was observed in more than 20% of adults with Ph+ ALL patients treated with imatinib plus a modified DFCI pediatric ALL protocol. The majority of VTE events occurred during active treatment (induction and intensification), and DVT/PE incidence was similar to that of line-related thrombosis. The high observed VTE incidence suggests that prophylactic anticoagulation should be considered for adult patients with Ph+ ALL even in ASNase-free regimens, especially if additional thromboembolic risk factors are present.



Nicole Kucine, et al.
Conclusion cited from the abstract: Our study is limited by a low response rate. Due to technical issues, we had missing data for many questions and could not obtain free-text answers for some of the prophylaxis questions, limiting full data acquisition. Despite these issues, our results provide some insights into current practices of pediatric hematologist/oncologists. This study shows that many physicians are not utilizing primary anticoagulant prophylaxis in their pediatric leukemia patients, despite the high-risk nature of these patients, possibly trying to balance bleeding risk due to thrombocytopenia. Duration of anticoagulant therapy varies, and it is likely that there are no clear definitions regarding resolution of predisposing factors. Given their unique set of risk factors, and the potential morbidity associated with VTE, further study of VTE prophylaxis is essential for development of pediatric leukemia-specific guidelines.



Melanie Degliuomini, et al. 

Conclusion cited from the abstract: The results of this survey revealed variation in practice among practitioners regarding VTE management and prevention. Despite the lack of data in this population, a number of physicians are using direct Xa inhibitors in children with leukemia for anticoagulation. Imaging is being done earlier than treatment is being discontinued, potentially implying it is being used to monitor for progression, rather than help guide duration of therapy. Our survey had some limitations, including the low response rate and missing data for questions, which may be due to electronic data collection errors or respondent choice. Recent ASH guidelines endorsed by the Children’s Oncology Group propose limited general guidelines and do not consider a cancer patient’s unique VTE risk profile. Given the variation seen, multi-center, prospective clinical trials are urgently needed for developing consensus guidelines for the management of VTE in children with leukemia.





Cindy Lynn Hickey, et al. 

Conclusion cited from the abstract: 

This retrospective single center study showed that the use of an intensified pediatric-inspired regimen including asparaginase in older patients with ALL is reasonable, resulting in an impressive CR rate and 5-year OS. The benefit, however, appears to be limited to those aged 50-59 while those over 60 years of age have dismal survival rates as reported in previous literature. Certainly, with 100% infection rates and almost half of patients requiring an ICU admission, toxicity needs to be considered and this treatment should be reserved for the fit elderly population.




Carmelo Rizzari, et al. 

Conclusion cited from the abstract: 

In the AIEOP-BFM ALL 2009 trial, the incidence of HSR was much lower with respect of historical experiences of previous AIEOP-BFM ALL protocols wherein the native E.Coli ASP product was used I.V. as first-line product. No difference in terms of HSR was found between patients belonging to the EA and SA of the RMR. As expected, due to the higher number of PEG-ASP doses administered, the cumulative incidence of HSR was much higher in the HR group. Interestingly and in keeping with the concept that continuous and prolonged exposures to PEG-ASP reduce the probability of developing an HSR, patients randomized to receive in the RHR the SA (long interval between the first and subsequent exposures) showed an incidence of HSR much higher (18.3%) than that observed in the EA control arm (6.1%).



Luke Maese, et al. 

Conclusion cited from the abstract: The primary objectives are to (1) determine the efficacy of IM RC-P administration measured by the last 72-hour nadir SAA (NSAA) level being ≥0.1 IU/mL during the first course of treatment, and (2) assess the safety and tolerability of IM RC-P in patients with ALL/LBL who are hypersensitive to E. coli–derived asparaginases. Secondary objectives include determination of the efficacy of IM RC-P measured by the last 48-hour and last 72-hour NSAA levels being ≥0.4 IU/mL during the first course, characterization of PK of IM RC-P using a population PK approach, and assessment of immunogenicity following repeat administration of RC-P. Exploratory objectives include determination of the efficacy, safety, PK, and immunogenicity of IV RC-P.



Rachael E Hough, et al. 

Conclusion cited from the abstract: Major deviations in the delivery of induction chemotherapy on UKALL2003 were significantly associated with a greater risk of further deviations in subsequent blocks of therapy and a higher risk of relapse. Further improvement in efficacy of ALL therapy in children and young people will require a greater understanding of which toxicities lead to major deviations in therapy and strategies developed to mitigate these risks.



Ryan J. Daley, et al. 

Conclusion cited from the abstract: 

PEG-ASP was incorporated into the treatment of 60 adult ALL pts age ≥40, with manageable toxicity. Seven pts discontinued PEG-ASP due to hypersensitivity reactions and 5 discontinued due to hepatotoxicity, but other reported toxicities did not lead to PEG-ASP discontinuation and the majority of the pts completed all intended doses of PEG-ASP. This study suggests that with careful monitoring, PEG-ASP can safely be administered in adults ≥40 years of age.





Tong Lin, et al. 

Conclusion cited from the abstract: 

RC-P administration in healthy adults was well tolerated and there were no unanticipated AEs, no reported SAEs, and no grade ≥3 AEs. SAA levels ≥0.1 IU/mL, a surrogate marker for asparagine depletion, were achieved in all sbj receiving IM and IV RC-P at 48 hours. SAA levels ≥0.1 IU/mL were also achieved by all sbj at 72 hours after RC-P dosing, except for 2 sbj in the 25 mg/m2 IV group. Based on the totality of PK and safety data from this study, the recommended phase 2/3 starting dose is 25 mg/m2 for the IM route of administration and 37.5 mg/m2 for the IV route of administration on a Monday/Wednesday/Friday dosing schedule.




Cecilie Utke Rank, et al. 

Conclusion cited from the abstract: adolescents and young adults tolerated asparaginase treatment as well as children; however, the risk of AAP was higher for patients older than 5.0 years of age with no difference with increasing age. Despite a low AAP-related mortality, the morbidity was considerable and most profound for patients aged 9.0–16.9 years. Since asparaginase re-exposure was associated with a high risk of a second AAP event and neither AAP development nor AAP-related asparaginase truncation was associated with increased relapse risk, asparaginase re-exposure should be attempted only in patients with a high risk of leukemic relapse. Finally, there is an unmet need for preventive strategies toward AAP.



Paul Koller, et al. 

Conclusion cited from the abstract: 

CRLF2 overexpression in ALL is associated with a high rate of progression. Allogeneic HCT is beneficial against relapse, showing a trend for improved PFS and OS. A larger sample size and longer follow up is needed to confirm these findings.