Blood Podcast Episode Summary:

Title: VTE Recurrence Risk Factors and Poor-Response AML Transplant Outcome Indicators
Date: January 1, 2026
Host: Dr. Laurie Sen, Blood Podcast Editor
Guests: Dr. Johannes Schedelig (University Hospital TU Dresden, Germany) and Dr. Gael Munch (Bordeaux Population Health Research Center, France)

Episode Overview

This episode of the Blood Podcast features two conversations highlighting recent, high-impact research in hematology as published in Blood.

• Part 1: Dr. Johannes Schedelig discusses data from the ASAP trial, focusing on transplant outcomes in AML and the influence of disease risk versus remission status pre-transplant.
• Part 2: Dr. Gael Munch presents findings on molecular determinants of venous thromboembolism (VTE) recurrence across different subtypes, from the largest genomic study of its kind.

PART 1: Acute Myeloid Leukemia (AML) Transplant Outcomes — Disease Risk vs Remission Status

Guest: Dr. Johannes Schedelig
Paper: "Disease Risk but not Remission Status determines Transplant Outcomes in AML: Long Term Outcomes of the ASAP Trial"
Timestamps: 00:31–07:36

Key Discussion Points

Background and Current Practice (01:01–01:16)

• Standard care before allogeneic transplant in AML typically involves inducing remission—especially for first treatment or after relapse.
• For primary refractory disease, some centers, notably in Germany, proceed directly to transplant without remission induction.

"Most centers think of inducing a remission prior to referring the patient to transplantation... In Germany we have a long tradition of offering transplantation for patients with active disease and this prompted the research question which we addressed with the ASAP trial."
– Dr. Johannes Schedelig (01:16)

Study Design and Methodology (02:01–03:30)

• The ASAP trial tested whether immediate transplantation is non-inferior to sequential therapy (i.e., salvage chemotherapy to induce remission, then transplant).
• Patients: Those with active disease (failed first induction, untreated first relapse), with at least intermediate risk AML.
• Randomization: Immediate transplant vs. standard salvage chemotherapy prior to transplant.

Initial and Long-Term Findings (03:36–04:34)

• Initial data: No difference in the rate of complete remission post-transplant (day 56) between arms.
• Long-term results: Overall survival from randomization (intention-to-treat) also showed no advantage of pre-transplant salvage therapy.

"With respect to this analysis, we do not see a difference between either options which in a way shows that there is no advantage of adding another course of treatment prior to transplantation."
– Dr. Johannes Schedelig (04:04)

Genetics vs. Pretreatment Therapy (04:34–06:09)

• A key commentary by Dr. John Levine underscored that AML genetics, rather than pre-transplant therapy, drive outcomes.
• Open question remains: Would novel therapies pre-transplant (vs. standard options) shift these findings? Need for future randomized trials.

"We should attempt to demonstrate an advantage of inducing remission with new agents prior to transplantation and we should address this question in a very open way... Randomized trials need to demonstrate that with pretreatment we gain a benefit for the patient."
– Dr. Johannes Schedelig (05:05)

Implications for Clinical Practice (06:09–07:36)

• The study shifts focus from intensive pre-transplant therapy to genetic risk assessment and post-transplant care.
• Suggested post-transplant approaches: modulation of immunosuppression, donor lymphocyte infusions, pharmacotherapies (e.g., Gilteritinib, Sorafenib, menin inhibitors) to prevent relapse.

"We should improve post-transplant care for patients at the highest risk of relapse and we can identify those patients... In the past 10 to maybe 20 years we focused on trying to induce deeper remissions and our interpretation of the data is that we failed."
– Dr. Johannes Schedelig (06:20)

PART 2: Molecular Determinants of VTE Recurrence Risk

Guest: Dr. Gael Munch
Paper: "Molecular Determinants of Thrombosis Recurrence Risk across Venous Thromboembolism Subtypes"
Timestamps: 07:36–13:56

Key Discussion Points

Background and Study Rationale (08:34–09:34)

• VTE has a high recurrence risk (approx. 20% at 5 years).
• Anticoagulation is standard but increases bleeding risk.
• Previous genomic data existed for first VTE risk but not for recurrence.

"There was no previous work on genomics of venous thrombosis recurrence... We conducted this international effort on this topic."
– Dr. Gael Munch (08:47)

Study Design and Cohorts (09:34–10:19)

• Included data from 8 cohorts (France, Netherlands, US, Canada).

• 6,000 VTE patients, ~1,800 with recurrent events.

• Prospective follow-up for VTE recurrence.

Key Results and Insights (10:24–11:22)

• Identified molecular biomarkers associated with risk of VTE recurrence.
• Some biomarkers were universal; others were subgroup-specific (by sex, location and type of first VTE—DVT vs. PE, provoked vs unprovoked).
• Genetic factors for VTE recurrence are distinct from those for first VTE.

"Genetics of VTE recurrence tend to differ from that of the first VTE, which reflects the multifactorial and heterogeneous nature of VTE..."
– Dr. Gael Munch (10:24)

Clinical Implications and the Future (11:22–12:56)

• Validation for certain known associations (e.g., von Willebrand factor, coagulation factors).
• Findings may inform the development and repositioning of drugs, and creation of personalized risk tools (e.g., in the European Morpheus Project).
• Plan to develop predictive tools for recurrence, integrated into clinical workflows.
• Limitation: All participants were of European ancestry, questioning global generalizability. Ongoing collaborations with non-European cohorts (e.g., China) to address this.

"Our findings... provide a novel insight into the genomic architecture of VTE recurrence and we highlight potential targets for developing or repositioning drugs."
– Dr. Gael Munch (11:29)

Next Directions (13:21–13:56)

• Desire to study cancer-associated thrombosis, which was excluded from this analysis.
• Further investigation into identified molecular targets.

"I would really like to investigate this topic [VTE recurrence] in [patients with cancer] and also to follow up the potential targets we identified."
– Dr. Gael Munch (13:25)

Notable Quotes & Memorable Moments

• On challenging tradition:
  "In the past 10 to maybe 20 years we focused on trying to induce deeper remissions and our interpretation of the data is that we failed."
  – Dr. Johannes Schedelig (06:20)

• On shifting the paradigm in VTE research:
  "Genetics of VTE recurrence tend to differ from that of the first VTE, which reflects the multifactorial and heterogeneous nature of VTE, which becomes more pronounced with VT recurrence."
  – Dr. Gael Munch (10:24)

Important Timestamps

• 00:31: Introduction of Dr. Johannes Schedelig and background to the ASAP trial.
• 02:01: Explanation of the trial design and patient randomization.
• 03:36: Review of initial and long-term results.
• 04:34: Discussion of AML genetics vs. pre-transplant therapies and external commentary.
• 06:09: Clinical implications and future directions for AML transplantation.
• 07:36: Introduction of Dr. Gael Munch and transition to VTE topic.
• 09:34: Cohort description and study methodology.
• 10:24: Key discovered biomarkers and their stratified impact.
• 11:29: Clinical implications and development of risk tools.
• 12:56: Limitations and generalizability across ancestries.
• 13:25: Next research questions and future studies.

Episode Takeaway

This episode highlights a paradigm shift in the management of two hematologic conditions:

• For AML, it refocuses attention from aggressive pre-transplant therapies to genetic risk and post-transplant management.
• For VTE, it lays the groundwork for precision medicine in recurrence prediction, with ongoing efforts to validate and extend genetic insights across diverse populations.

For in-depth reading, both featured articles are available at bloodjournal.org.