Leukemia Without a Death Sentence
Advances in Treatment Come Not Only From Laboratories but Also From Hospital Wards

Just two decades ago, acute myeloid leukemia was almost a verdict. Today, more patients are living longer, although not always due to the latest drugs. Hematologic oncologic medicine is increasingly turning to precision-targeted therapies, but older treatments have not yet said their last word.
A new European study from the HARMONY database reveals that intensive chemotherapy, combined with modern supportive care and a personalized approach tailored to each patient, can still save lives, even in the era of molecularly targeted therapies.
Older Therapies, New Outcomes
For years, breakthroughs have been the focus of hemato-oncology. Although today, immunotherapies, genetically targeted drugs, and precision medicine make the headlines, we must not overlook classic intensive chemotherapy dating back to the 1970s.
A new study conducted by the HARMONY group - a pan-European consortium comprising over 140 institutions and the most extensive clinical data repository on blood cancers in Europe - analyzed data from more than 5,300 European patients treated between 1997 and 2016. It showed that five-year survival in patients with acute myeloid leukemia increased from 15 to nearly 38 months, even before modern targeted therapies came into widespread use.

Chemotherapy: a Second Look
On the surface, little has changed. Since the 1970s, the standard treatment for acute myeloid leukemia has been the "7+3" regimen - a combination of cytarabine and anthracyclines - a straightforward, very aggressive chemotherapy. However, what has happened around the therapy itself has undergone a profound transformation.
Prof. Marta Sobas, together with Dr. Amin Turki from University Hospital Essen and other members of the research team, demonstrated in an analysis published in Haematologica that the survival of patients treated with intensive chemotherapy significantly improved—even before targeted therapies became widely implemented. The median overall survival more than doubled, and the 60-day mortality rate dropped from 13% to 4.7%.
“Our study showed that improvements in supportive care played a key role in reducing early mortality,” comments Prof. Marta Sobas, the first author of the publication. “This trend was driven by factors including treatment in specialized hematology centers, better patient preparation for intensive chemotherapy, and prompt admission to intensive care when severe complications arose.”
Although the 7+3 regimen itself has not changed, virtually every element surrounding it has improved — from more accurate diagnostics to better management of complications. Today, patients increasingly undergo detailed molecular testing before therapy, which helps assess genetic risk and tailor treatment to their individual needs. Support during therapy is also enhanced: patients receive antibiotics and antifungals at the first signs of infection, and physicians are better equipped to manage severe complications, such as tumor lysis syndrome and profound immunosuppression (neutropenia).

Intensive Chemotherapy: A Personalized Approach
Thanks to new standards of supportive care, intensive chemotherapy is no longer reserved only for younger, fitter patients. The HARMONY analysis also shows improved outcomes in patients over 60 years old. This demonstrates that "older" treatment, under the right conditions, can still be effective — and sometimes even indispensable.
“Intensive therapy can be beneficial for carefully selected patients,” says Prof. Sobas. “Survival rates in patients over 60 have improved considerably in recent years, although this effect was less evident in patients over 70.”
Older patients also benefit from allogeneic hematopoietic stem cell transplantation (alloHCT), although careful and individualized eligibility is crucial. Age alone should not determine the choice of therapy. International guidelines, including those from the European LeukemiaNet (ELN) and the NCCN, do not rule out intensive chemotherapy for patients over 75, as long as their overall health status and comorbidities permit.
New Tools: Data and Molecular Sensors
So, what has changed? Physicians now have new diagnostic tools at their disposal. Next-generation sequencing (NGS) enables the detection of genetic mutations that can enhance the success of targeted therapies, for example, in patients with FLT3 or IDH1/2 mutations.
Even more revolutionary is the use of measurable residual disease (MRD) analysis. MRD can be assessed by immunophenotyping, and genetic MRD testing is currently being developed.
"MRD is now a key prognostic factor that supports decisions about eligibility for alloHCT and/or maintenance therapy,” explains Prof. Sobas. “This is not about choosing one approach over another, but strategically integrating intensive and targeted therapies, based on risk and molecular response.”
In practice, MRD not only allows real-time monitoring of treatment effectiveness but also dynamic assessment at the immunophenotypic and molecular levels. This represents a significant departure from past standards, which primarily relied on morphological and cytogenetic testing. Today, MRD can help decide whether a patient requires a transplant or can continue on maintenance therapy, whether therapy can be safely stopped, or if further treatment is needed.
Together with NGS, this enables an entirely new level of personalized care. Physicians no longer have to rely solely on statistics; they can make decisions based on each patient’s molecular profile and the actual response of their body to treatment.

From Lower Silesia to the Heart of Europe
The HARMONY publication is also a success story for Polish hematology. Wrocław Medical University, where Prof. Marta Sobas conducted her research, played a significant role in the project as both a data contributor and analyst.
“Contributing to the HARMONY database provides access to Europe’s largest clinical data repository on acute myeloid leukemia,” emphasizes Dr. Sobas. “Our experience in this international project feeds into updated treatment protocols in Wrocław, Lower Silesia, across Poland, and even abroad.”
More than just a data repository, HARMONY is a platform that tracks the course of thousands of European patients across different treatment regimens and clinical settings. This not only enables comparisons of therapeutic efficacy but also helps identify gaps in care and early risk factors for treatment failure.
Participation in this major consortium enables Wrocław researchers to access AI-based analytical tools and continually unlock new therapeutic pathways. It also translates directly into patient benefits - from participation in clinical trials to access to modern therapies that may not yet be routinely available under national guidelines.
At a time when leukemia remains a high-relapse, high-risk disease with a limited arsenal of treatments, each new opportunity can be life-changing. For Lower Silesia, this is not only a testament to its growing scientific capacity but, most importantly, a real improvement in patients’ quality of life and overall survival.

Relay Race Against Cancer
The fight against leukemia is like a relay race: one drug passes the baton to the next. Intensive chemotherapy, which once ran the course alone, now shares the track with precision therapies, immunotherapies, CAR-T treatments, and new molecular diagnostics - but it has not left the race. Its role on the podium may shift, but it remains a key player, especially when a rapid, forceful attack on cancer cells is needed.
HARMONY showed that with better-organized care, improved safety protocols, and advanced molecular tools, we can now make much more precise decisions about when to use chemotherapy and when to use molecular therapies. Modern medicine no longer needs to follow a single path - it can create flexible, personalized treatment strategies tailored to the patient’s disease profile.
This is not merely a shift in tactics but an entirely new way of thinking about treatment as a dynamic process continuously guided by real-time data. For patients, this is more than a story of the past and future of therapy. It is a story with room for a new beginning, even for those who might once have been considered unlikely candidates for intensive treatment. Today, care is guided not only by what is written in textbooks but also by what the patient's own body reveals.
FAQ: Intensive Treatment of Acute Myeloid Leukemia (AML)
What is acute myeloid leukemia (AML), and what is the standard induction therapy?
Acute myeloid leukemia (AML) is a hematologic cancer. Since 1973, the standard intensive induction chemotherapy, known as the "7+3" protocol, has been based on cytarabine (cytosine arabinoside) in combination with anthracyclines such as daunorubicin or idarubicin. These drugs still form the backbone of today's intensive induction therapies.
What is the main reason for the improvement in AML treatment outcomes?
The primary reason for these improvements is the significant decrease in early mortality. For example, 60-day mortality dropped from 13.0% in the earliest period (1997–2001) to 4.7% in the most recent period (2012–2016). Similarly, 30-day mortality fell from 6.3% to 2.5%, and 14-day mortality from 3.0% to 0.8%. This suggests improved management of patients during the early phases of induction therapy, likely reflecting advancements in supportive care options. Advances in healthcare structure, including treatment at specialized hematology centers and earlier admission to intensive care, also contributed to fewer complications.
What role does age play in AML prognosis, and how does it affect alloHCT?
Age is a significant risk factor for reduced overall survival. Although prognosis in older AML patients remains poor, patients aged ≥60 who received alloHCT had a 20% increase in five-year survival. A significantly better overall survival (OS) was observed in patients aged 60 years or older who underwent alloHCT. The benefit of alloHCT was observed across all European LeukemiaNet (ELN) risk groups for older patients, which may be linked to age-related biological differences that result in higher relapse rates. AlloHCT is also safer for older patients today due to improved HLA matching, reduced-intensity conditioning, and enhanced supportive care. However, it's worth noting that patients aged ≥70 derived less benefit from alloHCT than those aged 60–70, based on a minimal subgroup.
Have there been any changes in the genetic landscape of AML during the study period?
No, the molecular and cytogenetic landscape of AML remained stable across the two decades of the study.
ho conducted this study, and what are its limitations?
The study was conducted by the HARMONY Alliance — a pan-European public-private partnership utilizing an extensive, multicenter database from over 100 European centers. It included 5,359 AML patients treated between 1997 and 2016. Study limitations include its retrospective design, heterogeneity across centers, lack of detailed information on supportive care and comorbidities, limited follow-up in some cases, and a relatively small proportion of patients with an ECOG performance status (PS)>2 and patients aged ≥70.
Have AML treatment outcomes improved in recent decades?
Yes, outcomes with intensive chemotherapy have greatly improved over the past two decades (1997–2016), even before targeted therapies became available. Five-year overall survival increased substantially across this period, including in different genetic risk groups. Median overall survival (OS) rose from 15.5 to 37.8 months.
Did these improvements apply to all age groups?
Yes, progress was observed both in patients under 60 and those aged 60 and above. Overall survival (OS) improved across all periods regardless of whether patients received consolidation with allogeneic hematopoietic stem cell transplantation (alloHCT).
Has the rate of allogeneic hematopoietic stem cell transplantation (alloHCT) changed over time?
Yes, the proportion of patients receiving alloHCT in first complete remission (CR1) increased from 24.1% in 1997–2001 to 39.0% in 2007–2011, then decreased to 27.1% in 2012–2016. The median age of patients undergoing alloHCT also increased, indicating that transplants are now more commonly performed in older patients.
What is the relationship between ELN genetic risk groups and alloHCT?
The distribution of ELN 2017 risk categories was comparable across all four calendar periods. In intermediate- and adverse-risk groups, patients who received consolidation with alloHCT had significantly better outcomes than those who did not. For patients with favorable-risk AML, alloHCT is only recommended if minimal residual disease (MRD) is not adequately cleared or in the case of relapse.
Were new targeted therapies included in this study?
No. Since the study concluded in 2016, the cohort did not include patients who had received new targeted agents (e.g., midostaurin), which began to improve AML outcomes from 2017 onward. Future progress in AML treatment will likely come from targeted therapeutic approaches. Less intensive options, such as hypomethylating agents combined with the BCL-2 inhibitor venetoclax, also offer promise.

This material is based on the article
Outcomes with intensive treatment for acute myeloid leukemia: an analysis of two decades of data from the HARMONY Alliance
Marta Anna Sobas, Amin T. Turki, Angela Villaverde Ramiro, Alberto Hernández-Sánchez, Javier Martinez Elicegui, Teresa González, Raúl Azibeiro Melchor, María Abáigar, Laura Tur, Daniele Dall'Olio, Eric Sträng, Jesse M. Tettero, Gastone Castellani, Axel Benner, Konstanze Döhner, Christian Thiede, Klaus H. Metzeler, Torsten Haferlach, Frederik Damm, Rosa Ayala, Joaquín Martínez-López, Ken I Mills, Jorge Sierra, Sören Lehmann, Matteo G. Della Porta, Jiri Mayer, Dirk Reinhardt, Rubén Villoria Medina, Renate Schulze-Rath, Martje Barbus, Jesús María Hernández-Rivas, Brian J.P Huntly, Gert Ossenkoppele, Hartmut Döhner, Lars Bullinger
Haematologica
DOI: DOI:10.3324/haematol.2024.285805
Web. A. Maj
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