Patients (pts) with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) have been reported Vu k et al Cancer Medicine. 2015;4(1):27-35. doi:10.1002/cam4.332.to have a higher incidence of venous thromboembolism (VTE). It has been suggested that the incidence of VTE in ALL pts is affected by the use of L-Asparaginase (ASNase) which is an integral part of many chemotherapy regimens. Consistent with this we previously reported a high VTE rate (22%) in pts with Philadelphia chromosome negative (Ph - ALL) that were treated with a modified Dana Farber Cancer Institute (DFCI) chemotherapy regimen containing high dose ASNase as part of the intensification phase. In 2001 imatinib was added to our modified DFCI chemotherapy regimen for Ph+ ALL which included 30 weeks of high dose of ASNase during intensification. However, due to a relative intolerance to the combination of ASNase and imatinib, the ASNase was omitted from the protocol in 2008. In this abstract we compare the incidence of VTE in Ph+ALL pts pre and post 2008 and Ph-ALL patients.
We conducted a retrospective chart review of 130 adult pts with Ph + ALL treated at Princess Margaret Cancer Center between 2001-2015. All Ph+ pts were treated first line with imatinib mesylate in addition to our modified version of the DFCI chemotherapy protocol. As noted, before Feb 1, 2008 the intensification phase included ASNase, while after that date ASNase was omitted. In addition to the Ph+ patients we assessed the incidence of VTE in Ph- ALL patients. From July-2001 to May-2009 no VTE prophylaxis (prx) was given. For the Ph- cases, enoxaparin 0.62 mg/kg was given during intensification from June2009 to Dec2014; following that the dose was increased to 0.90 mg/kg of enoxaparin. VTE was diagnosed by ultrasound or CT pulmonary embolism study. VTEs were further classified as line related or unrelated.
Twenty eight thrombotic events were detected in 25/130 (19.2%) pts with Ph + ALL. VTE with pts received minim one dose ASNase Pre Feb 1, 2008: 8/47 17% post Feb 1, 2008 without ASNase: 17/83 :20.4% One third (7/25)of the VTE were associated with a venous access device. Documented pulmonary embolism occurred in five patients. Almost all events occurred while on therapy with the largest proportion (9/25:36%) occurring while on the intensification phase; 3/19 events and 5/44 during the intensification phase. Three pts developed VTE after receiving and allogeneic SCT (allo SCT). There was no association with age, gender, weight, and allo SCT and the development of VTE.
For the Ph- ALL group receiving prophylaxis the incidence of VTE during intensification was 18.9% (low dose) vs 13.3% (high dose).
We have previously identified an incidence of 21.7% VTE in Ph - ALL patients treated with a modified DFCI chemotherapy that occurred during intensification. The current series describes a similar rate (19.2%) of VTE in Ph + ALL patients despite over 2/3rd of these patients never receiving ASNase. This rate is similar to that reported in other series regardless of whether or not ASNase was given. When we compare the Ph+ ALL group that never received VTE prophylaxis to the Ph- ALL patients who received prophylaxis after 2009 there was no significant difference in the incidence of VTE.
This information indicates that the pathogenesis of VTE in Ph + ALL patients may be more complex than previously thought and it is not related to the use of ASNase as the incidence of VTE was the same before and after the use of ASNase in the imatinib treated group. Further evaluation of Ph + ALL and its treatment as an inherently prothrombotic state, using proteomic and advanced genomic analysis, may identify risk factors that can be addressed so as to ameliorate the morbidity caused by VTE events.
Gupta: Incyte: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Schuh: Amgen: Consultancy, Honoraria. Yee: Astex: Research Funding; Novartis Canada: Honoraria; Karyopharm: Research Funding; Oncoethix: Research Funding; Celgene Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Asterisk with author names denotes non-ASH members.