BCR (BCR Activator Of RhoGEF And GTPase)

Fever and pallor at initial diagnosis are the main symptoms of ALL recurrence, but they are not specific. The recurrence time is very early, and the prognosis of early recurrence is poor. The main site of recurrence is bone marrow, and the prognosis of combined recurrence is poor. BCR-ABL+ children are common and prone to occur very early recurrence and bone marrow recurrence.

Routine TDM was most frequently used for classical agents (methotrexate, cyclosporin A), antifungals, and antibiotics, but substantial interest was reported for targeted therapies, including BCL-2 inhibitors, BCR-ABL tyrosine kinase inhibitors, FLT3 inhibitors, and Bruton tyrosine kinase inhibitors. While firmly established for classical agents and anti-infectives, clinicians express growing interest in extending TDM to targeted therapies. Optimizing turnaround times, expanding assay availability, and integrating pharmacokinetics-informed dosing into clinical trials may further clarify the role of TDM within precision medicine approaches in hematology.

P1, N=30, Recruiting, Andrew E. Place, MD | Active, not recruiting --> Recruiting | N=13 --> 30 | Trial completion date: Jul 2028 --> Jul 2030 | Trial primary completion date: Jul 2026 --> Jul 2028

P3, N=406, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2028 --> Jan 2031

In the event of molecular relapse, carefully considered use of imatinib or nilotinib at the lowest effective dose may be employed exclusively in the second or third trimester following multidisciplinary counseling, whereas dasatinib should be avoided throughout gestation. We emphasize structured algorithms, explicit intervention thresholds, and monthly BCR-ABL1 (IS) testing, as well as collaboration with obstetrics, neonatology, and reproductive medicine, including assisted reproductive technologies. Finally, we discuss practical pathways applicable to resource-limited settings to balance maternal-fetal safety with patient values and to support informed, preference-concordant decision-making.

P2, N=53, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jan 2027

P2, N=97, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Jan 2027

P1, N=60, Not yet recruiting, M.D. Anderson Cancer Center

P2, N=20, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P3, N=310, Suspended, Alliance for Clinical Trials in Oncology | Trial completion date: Aug 2026 --> Aug 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

VEGF inhibitors, such as bevacizumab and VEGFR-TKIs (e.g., sorafenib, sunitinib), significantly elevate the risk of ATEs, with hypertension and proteinuria as common comorbidities. BCR-ABL-TKIs, especially nilotinib and ponatinib, are linked to rapid-onset PAD, even in patients without prior cardiovascular risk factors...Hormonal therapies, including tamoxifen and androgen deprivation therapy, also contribute to ATEs through metabolic and vascular mechanisms...Monitoring and prevention strategies, such as regular cardiovascular risk assessments, lipid management, and arterial ultrasound surveillance, are critical for high risk patients. Multidisciplinary onco-vascular teams are essential to mitigate these risks and optimize patient outcomes.

P2, N=126, Not yet recruiting, National Cancer Institute (NCI)