“[LMWH] could even be disadvantageous within the older sufferers above 40 years with out [pegaspargase] within the first induction cycle. This requires a necessity for future and presumably randomized trials on VTE prevention in ALL,” in keeping with Mandy N. Lauw, MD, PhD.
Sufferers with newly identified acute lymphoblastic leukemia (ALL) who have been handled with low-molecular weight heparin (LMWH) by way of an intermediate-dose routine didn’t expertise a discount in venous thromboembolism (VTE) in contrast with those that didn’t obtain thromboprophylaxis, in keeping with findings from a sub-study of the HOVON-100 trial (NTR2004).1 The info have been offered on the 2024 European Hematology Affiliation (EHA) Congress.
Outcomes confirmed that after the primary 60 days of remedy, thrombosis occurred in 17% (n = 44) of sufferers who acquired LMWH in contrast with 11% of sufferers who didn’t obtain thromboprophylaxis (n = 13; adjusted subdistribution hazard ratio [SHR], 1.52; 95% CI, 0.79-2.90). The SHR was break up per age group and was 0.88 for sufferers aged between 18 and 40 years (95% CI, 0.37-2.08) vs 2.47 (95% CI, 0.92-6.63) in these between 41 years and 70 years.
In sufferers with and with out LMWH, the thrombosis occasions have been comprised of deep vein thrombosis (9% vs 0%, respectively), pulmonary embolism (7% vs 8%), cerebral vein thrombosis (25% vs 38%), arm vein plus central venous catheter–associated thrombosis (52% vs 31%), arterial thrombosis (2% vs 0%), and different occasions (5% vs 23%).
“We nonetheless noticed a cumulative incidence of 15% VTE after the primary 60 days of ALL remedy, and total, throughout your entire follow-up, it was 29.8%,” lead examine creator Mandy N. Lauw, MD, PhD, of the Division of Hematology at Erasmus College Medical Heart (MC), Erasmus MC Most cancers Institute in Rotterdam, The Netherlands, stated in an oral presentation of the information. “[LMWH] could even be disadvantageous within the older sufferers above 40 years with out [pegaspargase] within the first induction cycle. This requires a necessity for future and presumably randomized trials on VTE prevention in ALL.”
The remedy of sufferers with ALL has advanced in recent times as a result of addition of pediatric-inspired regimens, Lauw defined. Nonetheless, she famous that the advance in survival outcomes additionally got here with a rise in cardiac toxicities, particularly symptomatic VTE occurring between 10% and 40% of pediatric and grownup sufferers. This adversarial impact not solely causes morbidity, however speaks to an unmet want for therapeutic anticoagulation, she added.
“It additionally has an impression on ALL remedies and survival charges,” Lauw stated.
Moreover, she defined there are prothrombotic adjustments in a affected person with ALL upon their prognosis, which decreases after initiation of remedy, and the impression of L-asparaginase on the coagulation system may in reality be contributing to the VTE issues. There isn’t a consensus on whether or not LMWH reduces the chance of VTE, however prior information demonstrated that pediatric sufferers have lessened VTE with out main bleeding.Worldwide Society on Thrombosis and Haemostasis Scientific and Standardization Committees steerage recommends LMWH high-prophylactic dose plus antithrombin if antithrombinlevels are lower than 0.5 to 0.6 U/ml.2
To find out whether or not an analogous impact was seen in grownup sufferers, investigators performed a potential side-study of the HOVON-100 trial, which comprised grownup sufferers with newly identified ALL aged between 18 and 70 years. Sufferers have been randomly assigned 1:1 to obtain clofarabine plus induction remedy or induction remedy alone. Thromboprophylaxis was administered with LMWH utilizing a hard and fast intermediate dose of nadroparin at 5700 anti-Xa worldwide items subcutaneously as soon as each day. There was additionally a suggestion of no measurement or supplementation of antithrombin/fibrinogen.
The trial modification began in January 2012. Of 369 sufferers, investigators used a per-protocol evaluation for sufferers who acquired LMWH (n = 253) and those that didn’t (n = 116) for the sub-study.
The first finish level was first venous or arterial thrombosis through the first 60 days of remedy for ALL. Secondary finish factors have been main bleeding, all venous or arterial thrombosis throughout remedy or HOVON-100 follow-up total, and event-free survival.
Concerning baseline traits, 40% of sufferers have been feminine, the median age was 42 years (vary, 26-55), and 51% of sufferers have been older than 40 years. Most sufferers had B-cell ALL (73%), and 20% of sufferers had a BCR–ABL mutation in t(9;22). Sixty-three p.c of sufferers have been labeled as having poor-risk illness. 5 p.c of sufferers had prior thrombosis that was venous (3%) or arterial (2%).
Extra information confirmed that through the HOVON-100 trial remedy total, which included a median follow-up of 87 months, 33% of sufferers who had LMWH had a thrombosis occasion in contrast with 22% of those that didn’t have thromboprophylaxis (adjusted SHR, 1.59; 95% CI, 1.02-2.48). When break up by age, the SHR distinction was not pronounced; SHR was 1.59 (95% CI, 0.81-3.11) in these between 18 and 40 years and 1.60 (95% CI, 0.89-2.87) in sufferers between 41 years and 70 years.
The thrombosis occasions have been comprised of deep vein thrombosis (11% of LMWH-treated sufferers vs 8% of these with out), pulmonary embolism (10% vs 15%, respectively), cerebral vein thrombosis (17% vs 19%), arm vein plus central venous catheter–associated thrombosis (54% vs 35%), arterial thrombosis (5% vs 4%), and different occasions (5% vs 19%).
Editor’s Word: Lauw famous that the analysis was supported by grants from ZonMw and GlaxoSmithKline.
References
- Lauw M, Rijneveld A, Ko A, et al. Low-molecular-weight heparin doesn’t forestall venous thromboembolism in adults with newly identified acute lymphoblastic leukemia; potential side-study of the HOVON-100 trial. Offered at: 2024 European Hematology Affiliation Congress; June 13-16, 2024; Munich, Germany. Summary S325.
- Zwicker JI, Wang T-F, DeAngelo DJ, et al. The prevention and administration of asparaginase-related venous thromboembolism in adults: steerage from the SSC on Hemostasis and Malignancy of the ISTH. J Thromb Haemost. 2020;18(2):278-284. doi:10.1111/jth.14671.
