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 MRD in predicting survival. Relapse remains a leading cause of death in pediatric AML, despite recent trials achieving overall survival (OS) rates of approximately 80%. It’s relevant for specialists to understand how the AML behaves during therapy after the first relapse, and MRD negativity is identified as a key predictor of higher OS.

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 in t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) showed an OS of 85%, while non-CBF AML had an OS of 37%.

• Relapse timing impact in OS: Late relapses (>12 months) had significantly higher overall survival (62%) compared to early relapses (31%).

• Stem cell transplant before vs chemotherapy OS: 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 reinduction therapy showed improved OS (68%) compared to MRD-positive patients (34%). Similar trends were observed 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 MRD negativity after reinduction, were associated with significantly higher OS.

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

This ASH conference session compiled six research abstracts with important findings for the AML pediatric community, where there are limitations in research protocols. 

The AML treatments mentioned in the abstracts are the following: 

• Gemtuzumab Ozogamicin, a treatment that targets CD33 on AML cells, was featured in two abstracts within the session. 

• One abstract (967) compared a combination of gemtuzumab ozogamicin with standard therapy with gemtuzumab ozogamicin alone. The study was stopped early because it became clear that continuing it would not provide the desired results.

• The second abstract (968) 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. 

• Venetoclax + Azacitidine: This combination was given to newly diagnosed young AML patients (969). The resulting outcomes were comparable to intensive chemotherapy but with reduced hospital stays, transfusions, and infections, supporting this new combination as a less toxic alternative for high-risk AML patients.

• Venetoclax and decitabine (971) compared with standard idarubicin plus cytarabine as induction therapy in newly diagnosed AML patients, the results showed that VEN+DEC was equally effective and safer overall, with fewer severe infections, though certain subgroups responded better to the standard treatment.

• Standard Induction therapies DAC/DA-90: A prospective international randomized multicenter clinical trial in Poland (970) compared the efficacy of two standard induction therapies: (daunorubicin 90 mg/m² and cytarabine) and DAC (daunorubicin 60 mg/m², cytarabine, and cladribine) in AML patients ≤ 60 Years Old. The trial ended early due to slow recruitment and lack of superiority in outcomes, confirming both therapies as comparable options. 

• Comparing high-dose cytarabine with idarubicin to high-dose cytarabine alone as consolidation therapy for AML patients in their first remission (972), the results showed that high-dose cytarabine with idarubicine led to deeper remissions, lower relapse rates, and improved disease-free survival while being well-tolerated. This could also potentially reduce the need for stem cell transplantation. 

Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia: Results of the AML BFM Study Group

Advances in allogeneic hematopoietic stem cell transplantation (allo-HSCT) have significantly improved outcomes for pediatric AML, with survival rates reaching up to 85% for patients transplanted in first complete remission. 

A population-based analysis from 2004 to 2019 demonstrated superior survival and disease-free survival in patients transplanted in the first complete remission compared to those in subsequent remissions or with refractory disease. The findings highlight the importance of optimizing risk stratification, pre-transplant treatment, and the inclusion of pediatric AML patients in clinical trials to refine transplant indications, integrate novel therapies, and achieve better outcomes.

Conclusions

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 conferences, overcoming these challenges has led to critical advances that pave 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 prognostication, and adapting therapies like venetoclax-based regimens to reduce toxicity. 

While challenges remain, particularly in enrolling underrepresented groups and refining risk-based therapies, the progress showcased during the conference is an example of the dedication of the AML research community. 

If you’re interested in learning more about AML treatment updates, conferences and comprehensive articles, you can bookmark our HealthTree News landing page. 

Keep Reading More News

References:

• 116: Near Universal National Uptake of Dexrazoxane in the Real-World Setting Associated with Reduced Cardiac ICU Care Requirements in Pediatric Acute Myeloid Leukemia

• 323: Measurable Residual Disease Monitoring during Treatment for Pediatric Acute Myeloid Leukemia in First Relapse Predicts Outcome

• 531: Real-World Generalizability of Clinical Trial Cytomolecular Features By Race and Ethnicity in Pediatric Acute Myeloid Leukemia (AML)
• 617: Acute Myeloid Leukemias: Commercially Available Therapies: Optimizing Regimens in Children/Young Adults and Around the World

• 3548: Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia: Results of the AML BFM Study Group