The Latest in Pediatric AML Research and Innovations

The 66th annual ASH conference hosted various AML experts and specialists who shared recent advances and treatment breakthroughs for acute myeloid leukemia (AML) in children and young adults. We will summarize the most important findings on this subject in this article.

Widespread Use of Dexrazoxane Results in Reduced ICU Care Requirements

Dr. Daniel J. Zheng presented findings from the real world showing that dexrazoxane, a medication used to prevent or decrease the thickening of the heart muscles, can reduce heart complications that require intensive care unit (ICU) care. 

Heart damage is due to the accumulation of chemotherapy, particularly anthracyclines (such as daunorubicin, doxorubicin, and idarubicin), and it remains a critical concern in pediatric AML treatment. The Children’s Oncology Group (COG) mandated dexrazoxane use in pediatric AML trials starting in 2020. 

A study using data from the Pediatric Health Information System (PHIS) analyzed trends and outcomes associated with dexrazoxane use from 2010 to 2021. Here are some of the study’s key findings:

• Increased use after 2015: Significantly more children with AML received dexrazoxane, from 11% in 2010-2015 to 92% in 2019-2021. 

• Improved cardiac outcomes: Dexrazoxane was associated with reduced cardiac ICU care (33% to 18%) and ACE-inhibitor use (treatments used to manage hypertension) (20% to 12%).

• Mortality outcomes: Six-month mortality rates improved for children who received dexrazoxane (6.9%) compared to those who didn’t (8.8%), but the difference was not statistically significant.

Understanding Treatment Differences and Survival Disparities in Pediatric AML Among Racial and Ethnic Groups

Dr. Daniel J. Zheng also presented a retrospective study that analyzed cytomolecular risk profiles and outcomes in 654 pediatric AML patients treated between 2011 and 2023 at 10 US institutions. 

The study identified several important key points, including:

• Hispanic and non-Hispanic Black patients were less likely to be enrolled in clinical trials compared to other groups
• Molecular features did not vary significantly by race/ethnicity or trial enrollment status, indicating comparable disease biology
• Survival differences among underrepresented groups might be influenced more by external factors in society rather than just the biology of the diseases themselves

The study highlights the potential impact of social determinants, including healthcare access and structural inequities, on outcomes like minimal residual disease (MRD) and treatment timelines. Thanks to research like this, health professionals can identify gaps in attention and inclusion to improve outcomes for all patients. You can read this comprehensive article on How Social and Economic Factors Limit Access to AML Transplants to learn more about how social factors influence patient outcomes.

MRD Monitoring During Treatment in First Relapse May Help Predict Survival 

This research, presented by Camilla Poulsen, aims to understand the role of genetic factors, relapse timing, and Minimal Residual Disease (MRD) in predicting survival. 

Researchers and AML specialists are focused on understanding how minimal residual disease (MRD) changes during treatment in the relapsed setting. This knowledge is essential because achieving MRD negativity after treatment can greatly impact the chances of living longer for patients facing relapsed AML. By studying these changes, specialists aim to identify patterns and factors that contribute to longer overall survival (OS), helping to inform more effective treatment strategies. 

How can the overall survival (OS) improve? 

According to the findings there are certain factors that help improve the OS, while others make no difference.  

• Core-binding factor (CBF) mutations influence overall survival (OS): Mutations in the core-binding factor (CBF) can help predict OS. Patients with these mutations present showed an OS of 85%, while non-CBF AML had an OS of 37%.

• Relapse timing impact in OS: Those patients who relapsed 12 months after therapy had significantly higher overall survival (62%) compared to those who relapsed earlier (31%).

• What’s the best treatment to start with? Stem cell transplant vs chemotherapy: Patients who were treated with chemotherapy alone (48%) did better than those who had a stem cell transplant 

• MRD negativity: MRD-negative patients after the first treatment at relapse showed improved OS (68%) compared to MRD-positive patients (34%). Similar trends were observed with those who were MRD-negative before SCT (75% vs. 36%).

The findings in this study conclude that core-binding factor mutations, late relapse, the use of chemotherapy instead of transplant, and achieving MRD negativity after receiving a second induction therapy were associated with significantly higher OS.

The Available Therapies for Pediatric AML: Optimizing Regimens in Children and Young Adults Around the World

This ASH conference session compiled six research studies with important findings for the AML pediatric community.

• CPX-351: this study tested CPX-351 with standard therapy vs CPX-351 with gemtuzumab ozogamicin. The study was terminated early because it didn’t show the expected results, as there was no significant difference in the overall survival and progression rate between the two groups. Moreover, the group receiving CPX-351 experienced more side effects. 
• Gemtuzumab Ozogamicin, a treatment that targets CD33 on AML cells, was featured in the abstract 968, which reported that using at least one dose of gemtuzumab ozogamicin combined with mitoxantrone and cytarabine during the initial treatment phase, followed by therapy tailored to the patient’s risk level, has shown excellent results. This study also analyzed which doses were safe to administer and concluded that 3 doses of 3 mg/m² were safe for children older than 12 months. The overall survival rate considering all 512 patients was 88%, and 94% achieved complete remission. 
• Venetoclax + Azacitidine: This combination was given to newly diagnosed young AML patients. The resulting outcomes were comparable to intensive chemotherapy, and 46% received an allogeneic transplant after the study treatment but with reduced hospital stays, transfusions, and infections, supporting this new combination as a less toxic alternative for high-risk AML patients.
• When combining venetoclax and decitabine as induction therapy in newly diagnosed AML, most patients had similar outcomes than when treated with idarubicin plus cytarabine but with fewer severe infections. However, specific subgroups still benefit the most from the standard chemotherapy.
• High-dose cytarabine alone: This consolidation regimen reduced the need for stem cell transplantation. 

Study Shows that Early Bone Marrow Transplants Give Children with Leukemia Their Best Chance

When children receive an allogeneic transplant after their first successful round of chemotherapy, up to 85% survive AML. This is a remarkable improvement from past outcomes.

The researchers studied cases from 2004 to 2019 and found that timing matters significantly. Children who received transplants early in their treatment did much better than those who waited until later stages or when the disease was not responding to treatment.

These findings help doctors make better decisions about when to recommend transplants, but they also show how important it is to:

• Identify which patients need transplants early on
• Continue improving pre-transplant care
• Include more children in research studies to better understand the role of transplant with novel therapies

Key Takeaways

Research on pediatric and young adult AML has unique challenges, mainly due to smaller patient populations and the complexity of conducting trials in these age groups. However, as highlighted during the conference, overcoming these challenges has led to critical advances that paved the way for improved outcomes.

The studies presented show the importance of addressing the factors that influence survival, such as integrating dexrazoxane to mitigate cardiac complications, monitoring MRD for relapse prediction, and adapting therapies like venetoclax-based regimens to reduce toxicity. 

While challenges remain, particularly in enrolling underrepresented groups and refining personalized treatment strategies, the progress showcased during the conference is an example of the dedication of the AML research community. 

If you want to learn more about AML treatment updates, conferences, and comprehensive articles, you can bookmark our HealthTree News landing page.

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References:

• Near Universal National Uptake of Dexrazoxane in the Real-World Setting Associated with Reduced Cardiac ICU Care Requirements in Pediatric Acute Myeloid Leukemia
• Measurable Residual Disease Monitoring during Treatment for Pediatric Acute Myeloid Leukemia in First Relapse Predicts Outcome
• Real-World Generalizability of Clinical Trial Cytomolecular Features By Race and Ethnicity in Pediatric Acute Myeloid Leukemia (AML)
• Acute Myeloid Leukemias: Commercially Available Therapies: Optimizing Regimens in Children/Young Adults and Around the World
• Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia: Results of the AML BFM Study Group