We want to say thank you: The MLL Annual Review for 2022

Even if the corona pandemic is no longer every day’s top headline, the disease is still important in our practice, MLL MVZ, and in the MLL Munich Leukemia Laboratory. Naturally, this is especially true with regard to protecting the patients entrusted to us in our daily consultation hours, but it also applies to our employees. As in many practices and businesses, it is necessary to ensure that operations continue to function (seven days/week in the laboratory). Therefore, together with our staff, we are making every effort to improve our service again this year in the interests of the patients entrusted to us and those who send them to us as the number of requests increases.

That is why the year 2022 is of particular importance: The newly published guidelines for diagnostics, classification, prognosis assessment, and prognosis prediction change the laboratory workflow in many places – and sometimes the reporting times as well (turnaround time, TAT). The new classifications according to the WHO and ICC are of central importance, as is the newly published ELN on the diagnosis and therapy of AML and the IPSS-M for prognosis assessment in MDS, including molecular genetic markers. These publications and online versions (WHO) complement the ELN AML Guidelines for measurable residual disease (MRD) already published last year.

Not only do all these publications need to be taken into account, but they must also be harmonized. Only then are they implemented into the daily routine of our findings. As one example, we will be changing our findings to the new WHO 2022 terminology in January 2023.

This will make diagnostics more complicated – not only for every provider on the laboratory side but also for physicians and ultimately for our patients. A large amount of new therapeutic and prognostic information based on this will need to be considered. However, all of this factors into the progress of science and is now indispensable, especially in these times of precision medicine.

In addition to the introduction of new, specifically molecularly defined entities and prognosis scores, the hierarchy of the respective diagnosis also plays an important role in the diagnostic process: With the new classifications and guidelines, we are taking a big step toward genotype-based diagnostics while easing away from phenotype-based diagnostics (previously cytomorphology, histology, immunophenotyping, and immunohistology).

Today, chromosomal changes are joined by a variety of molecular genetic changes, such as fusion genes and variants/mutations. Gene expression patterns need to be considered as well. Without next-generation sequencing (NGS) – such as in the form of panel sequencing, in which many genes are examined in a patient-specific manner in a single approach – the mapping of these new guidelines in routine diagnostics would not even be possible.

From the above, it is easy to imagine just how complex the analysis and findings have now become. At the same time, the “user,” namely our submitting physicians and our common patients, must not only understand the findings but also receive the best possible diagnosis and – especially – therapy.

That is why we are continuously working on simplifying the requests using request sheets, whether this is still done with paper, a PDF file, or even via our “Order Entry” digital requests platform. For example, the new quick request option in our Order Entry Portal has reduced the number of clicks required per request by 2/3, namely from 20 to 6.

From now on – also for everyone’s convenience – we will be strictly following the new guidelines and allowing for a simple “request by guideline.”

Furthermore, the diagnoses of CHIP and CCUS according to the WHO and CCUS according to the ICC have been included in the portfolio of diseases: as precursor diseases of MDS in the sense of a continuum. This must also be taken into account in the laboratory procedure and when reporting findings. In order to make the whole thing easier for later use, we have supplemented and expanded our “integrated report” and stored the new guidelines: This is currently being made available for the primary diagnoses of AML and MDS and – in the very foreseeable future – for multiple myeloma and CLL as well.

For difficult cases, we are enabling cutting-edge technologies like whole-genome sequencing and whole-transcriptome sequencing (WGS and WTS). The study which we started, “The Exciting Case” (ClinicalTrials.gov Identifier: NCT05046444), has already recruited more than 40 cases using WGS and WTS as parallel diagnostics in addition to today’s optimal gold standard diagnostics. In one third of the cases, we were able to establish a definite diagnosis with the help of the new sequencing methods with otherwise unclear results from the gold standard diagnostics, thereby underlining their diagnostic significance.

For the past three years, we have been promoting projects where diagnostics are supported by artificial intelligence (AI). In cytogenetics, this has been part of routine practice for more than two years. In 2023, we will be able to introduce the AI algorithms into our routine diagnostics for the areas of molecular genetics, such as genome sequencing, and particularly for the daily routine of cytomorphological assessments for peripheral blood and bone marrow and for immunophenotyping. The results obtained in this way will be presented to the MLL colleagues who obtained the findings, checked, and included in the final findings.

In October 2022, the total number of submissions since MLL’s inception surpassed the one million mark. What a special experience for us all!

At the same time, we are increasing our scientific output through our own publications and by participating in global research alliances. For example, this is true of the EU-funded HARMONY, GenoMed4All, and Intercept-MDS collaborations. Many collaborations involve leading research laboratories at universities worldwide. We consider it an important mission not only to make our data and our knowledge between cytomorphology and genome sequencing optimally and quickly available to each individual patient but also to offer them in cumulative publications to other researchers, scientifically interested parties, and clinically active colleagues.

More detailed lists of MLL’s 2022 publications can be found on our website. Furthermore, we, Prof. Dr. med. Claudia Haferlach and Prof. Dr. med. Dr. phil. Torsten Haferlach, have also had the opportunity since this year to author the new WHO classification and contribute the cumulative knowledge of MLL there.

Once again, and for over 17 years now, we want to thank all of our employees for their excellent work this year. None of this would be possible without them!

We thank our submitters for their confidence in us and in our diagnostics. We owe a great debt of gratitude to all our partners who are working with us on the development of our laboratory workflows and on studies for introducing new drugs and, of course, to all the suppliers who keep us supplied, especially in times of supply bottlenecks.

More than ever, we are continuing to pursue our mutual goal of extending lives and increasing cure rates – thanks to the results of our diagnostics.

We wish you all a peaceful holiday season and especially positive and good developments for the coming year 2023. 

Best regards,

Prof. Dr. med. Claudia Haferlach

Prof. Dr. med. Dr. phil. Torsten Haferlach

Prof. Dr. med. Wolfgang Kern

»Do you have questions regarding this article or do you need further information? Please send me an e-mail.«

Prof. Dr. med. Claudia Haferlach

Executive management
Medical doctor
Department manager Diagnostics

T: +49 89 99017-400

»Do you have questions regarding this article or do you need further information? Please send me an e-mail.«

Prof. Dr. med. Dr. phil. Torsten Haferlach

Executive management
Internist, Hematologist and Oncologist
Deputy Head of Cytomorphology

T: +49 89 99017-100

»Do you have questions regarding this article or do you need further information? Please send me an e-mail.«

Prof. Dr. med. Wolfgang Kern

Executive Management
Internist, Hematologist and Oncologist
Deputy Head of Immunophenotyping

T: +49 89 99017-200