Smart Conditioning with Venetoclax-Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies.

Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA-based sequential conditioning with venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related, or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to venetoclax was observed. On day +30, 55 patients (90%) were in complete remission. Acute GvHD II°-IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The off-label combination of sequential FLAMSA-RIC with venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial was initiated in July 2023.

Evaluating Fidelity of reporting in randomized controlled trials on childhood acute lymphocytic leukemia

Background: Randomized controlled trials (RCTs) play an integral role in childhood cancer research. Several efforts to improve the quality of reporting of clinical trials have been published in recent years, including the TIDieR checklist. Many reviews have since used TIDieR to evaluate how well RCTs are being reported, but no such study has yet been done in childhood cancer. The aim of this study is to evaluate adherence of RCTs involving acute lymphocytic leukemia (ALL) to the TIDieR checklist. Methods: The PubMed database was used to screen for RCTs involving ALL published since 2015. Of 1546 articles identified, 46 met study criteria and were then evaluated against the TIDieR 12-point checklist to measure the degree of adherence. Results: Of the 46 articles included, 9 (19.6%) met full TIDieR criteria. Seven of the 9 reported non-pharmacological interventions, and the remaining 2 reported pharmacological interventions. The average article properly reported 8.98/12 checklist items. Item 5 (intervention provider) was the most poorly reported item, properly reported in only 34.8% of articles. Conclusion: We conclude that overall TIDieR adherence is low and needs to be adhered to more fully in order to improve research in ALL as well as in all childhood cancers.