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336 Treatment and Disease Characteristics of Chronic Myeloid Leukemia in Blast Crisis: The European Leukemianet Blast Crisis Registry

Program: Oral and Poster Abstracts
Type: Oral
Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Molecular Predictors and Advanced Phase Disease
Hematology Disease Topics & Pathways:
Research, adult, Clinical Practice (Health Services and Quality), Clinical Research, CML, Combination therapy, Chronic Myeloid Malignancies, Diseases, Therapies, registries, Myeloid Malignancies, Study Population, Human
Saturday, December 10, 2022: 5:15 PM

Annamaria Brioli, MD, PhD1*, Elza Lomaia, MD, PhD2*, Christian Fabisch, PhD3*, Tomasz Sacha, MD, PhD4*, Hana Klamová, MD, PhD5*, Elena Morozova, MD, PhD6*, Aleksandra Golos, MD, PhD7*, Philipp Ernst, MD3*, Ulla Olsson-Strömberg, MD, PhD8*, Jiri Mayer, Prof, MD9*, Franck E. Nicolini, MD, PhD10, Han Bao11*, Fausto Castagnetti, MD, PhD12, Elzbieta Patkowska, MD, PhD13*, Klaus Hirschbühl, MD14*, Edyta Paczkowska, MD, PhD15*, Anne Parry, MD16*, Astghik Voskanyan, MD17*, Susanne Saussele, MD 18, Georg-Nikolaus Franke, MD19*, Alexander Kiani, MD20*, Edgar Faber, MD, PhD, prof21*, Krzysztof Lewandowski, MD PhD22*, Stefan W. Krause, MD23*, Elke Dammann24*, Peter Anhut, MD25*, Justyna Gil, MD26*, Thomas Südhoff, MD27*, Sonja Heibl, MD28*, Markus Pfirrmann, PhD29*, Andreas Hochhaus, MD3 and Michael Lauseker, PhD11*

1Klinik für Innere Medizin C, Universitätsmedizin Greifswald, Greisfwald, Germany
2Almazov National Medical Research Centre, St. Petersburg, Russian Federation
3Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany
4Department of Hematology, Jagiellonian University Medical College, Krakow, Poland
5Institute of Clinical and Experimental Hematology of the First Faculty of Medicine, Charles University and Institute of Hematology and Blood Transfusion, Prague, Czech Republic
6RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation
7Hemato-oncology Department, Copernicus Memorial Hospital, Lodz, Poland
8Department of Hematology, University Hospital Uppsala, Uppsala, Sweden
9Hematology and Oncology, University Hospital Brno, Czech Republic, Brno, Czech Republic
10Centre Hospitalier Lyon Sud, LYON Cedex 03, France
11Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig-Maximillians-University, Munich, Germany
12Istituto di Ematologia “Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy
13Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
14Section for Stem Cell Transplantation, University Hospital Augsburg, Augsburg, Germany
15Department of General Pathology, Pomeranian Medical University, Szczecin, Poland
16Centre Hospitalier Annecy Genevois, Annecy, France
17Hematology Center after Prof. R.Yeolyan, Yerevan, Armenia
18III. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg, Mannheim, Germany
19Department for Hematology, Cell Therapy and Hemostaseology, University of Leipzig Medical Center, Leipzig, Germany
20Department of Medicine IV, Klinikum Bayreuth GmbH, Bayreuth, Germany
21Department of Hemato-oncology, Faculty Hospital and Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
22Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland
23Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany
24Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
25Onkologische Schwerpunktpraxis Anhut, Kronach, Germany
26Department of Hematooncology, Oncology Centre of the Podkarpackie Province, Brzozow, Poland
27Department Hematology and Oncology, Klinikum Passau, Passau, Germany
284th Medical Dept. of Internal Medicine, Hematology, Internistic Oncology and Palliative Medicine, Klinikum Wels-Grieskirchen GmbH, Wels, Austria
29Institute for Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University, München, Germany


Despite improvements in the treatment of chronic myeloid leukemia (CML), an important minority of patients (pts) will still develop blast crisis (BC). BC is highly aggressive, and if not treated promptly, will inevitably lead to patient’s death. Due to its rarity and heterogeneous clinical presentation, no standard treatment is available for BC, and specifically addressed clinical trials are difficult to perform. Furthermore, it is unclear if the biology of BC has changed since the advent of tyrosine kinase inhibitors (TKI). To better understand BC and its treatment we sought to collect clinical and biological data of pts diagnosed with BC and started an international registry within the European LeukemiaNet (ELN) in 2018.

Materials and methods

The European Blast Crisis Registry with participants in 9 countries (Germany, Poland, Czech Republic, France, Italy, Sweden, Austria, Russia, and Armenia) gathers routinely collected clinical data in an online database. Pts are eligible for the registry if they had a diagnosis of BCR::ABL1 positive BC after January 1st, 2015 and were at least 18 years old at the time of BC. Both de novo BC and BC developing from a precedent CML in chronic phase are included. The Mann-Whitney and exact Fisher tests were used to compare variables. Overall survival (OS) was calculated according to Kaplan Meier. Significance was set at p<.05.


At the cutoff date of July 2nd, 2022, 200 patients (60% male) with confirmed BC were recruited. Median age at diagnosis of CML and at diagnosis of BC was 45 years (yrs, range, 13-86) and 48 yrs (range, 18-86), respectively. BC occurred de novo in 37% of pts. At the time of CML diagnosis 47 pts had at least one additional cytogenetic abnormality (ACA) beside the t(9;22)(q34;q11), with 5 pts having 3 different ACAs. The most frequent ACA was +8 (10 pts) followed by +der(22) (6 pts). For pts diagnosed with a previous history of CML, median time between CML and BC was 31.3 months (range, 1-378 months). Before BC, 76% of patients were treated with TKI, most frequently with imatinib (78%). Median number of TKI treatments for chronic phase CML were 2 (range, 1-5). At the time of BC, mutations of BCR::ABL1 occurred in 25% of pts. The most frequent mutations were E255K and T315I, seen in 9 pts each. Mutations occurred more frequently in pts with evolution to BC after chronic phase (25% vs 8%, p<.001). The morphology of BC was myeloid (mBC) in 58% of the pts and lymphoid (lyBC) in 35%; 7% had a mixed or megakaryoblastic phenotype. Thirty-five and 16 pts had extramedullary manifestations (EMM) and central nervous system (CNS) involvement, respectively. Treatment data of BC are available for 191 pts and show the expected heterogeneity. Median lines of therapy for BC were 3. Most common was TKI+chemotherapy (Ctx)+allogeneic stem cell transplantation (alloTx) (49%), 19% received TKI+Ctx, 10% TKI alone, 5% TKI+alloTX, 1% Ctx+alloTx, 6% Ctx alone and 1 pt each alloTx upfront or no treatment. Pts receiving dasatinib (p=.004), Ctx (p=.005) and alloTx (p<.001) were younger. Imatinib was more used in de novo BC (p<.001), whilst ponatinib in pts with a previous CML (p=.016). Shorter time between CML and BC correlated significantly with a higher use of Ctx (p=.005). The type of therapy was not significantly associated with EMM/CNS involvement or BC phenotype, although slightly more pts with lyBC received Ctx (93% vs 82% p=.054).

Best responses within the first 6 months of treatment are available in 82 pts (4 received an alloTx) and are: 18% MR5, 6% in MR4.5, 2% MR4 and 10% MMR; 24% had no response.

With a median follow up of 27.0 months from diagnosis of BC, median OS was 23.7 months. Pts with EMM and CNS involvement had a similar outcome compared with pts with no EMM/CNS (median OS 46.0 vs 60.0 months for EMM/CNS vs none respectively, p=.56). The morphology of BC had a significant influence on survival. LyBC had a 2-yrs survival of 62% (95%-confidence interval (CI): 46-72%), mBC had a 2-yrs survival of 39% (95%-CI: 28-50%), p=.01). Sex had no influence on survival, morphology of BC or treatment received.


This analysis on a large cohort of CML pts in BC demonstrates a high degree of heterogeneity with regard to presentation and treatments. The outcome of lyBC is more favorable as compared to mBC, whilst the presence of CNS involvement and EMM had no significant impact on survival. Focused trials are warranted to identify the best treatment option for this still difficult disease.

Disclosures: Brioli: GlaxoSmithKline GmbH: Honoraria, Other: Advisory board; Janssen Cilag: Honoraria, Other: Advisory board; Sanofi: Other: Advisory board; BMS: Honoraria, Other: Advisory board, Travel support; AstraZeneca: Honoraria; Takeda: Honoraria; Bioclinica: Honoraria; Amgen: Honoraria; Novartis: Honoraria; MedConcept: Honoraria; Teamworx mediamanagement GmbH: Honoraria. Lomaia: Pfizer: Other: Travel, Accommodation, Expenses , Speakers Bureau; Bristol Myers Squibb: Other: Travel, Accommodation, Expenses ; Fusion Pharma: Speakers Bureau; Novartis: Other: Travel, Accommodation, Expenses , Speakers Bureau. Sacha: Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Adamed: Consultancy, Honoraria; Angelini: Honoraria, Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Honoraria, Speakers Bureau; BMs-Celgene: Honoraria, Speakers Bureau. Morozova: AMGen: Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Novartis: Speakers Bureau. Mayer: Sierra Oncology: Research Funding; Celgene: Research Funding. Nicolini: Incyte biosciences: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis Services, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; KARTOS: Consultancy; Sun Pharma Ltd: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Patkowska: Novartis: Honoraria. Saussele: Incyte: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Roche: Honoraria; Pfizer: Honoraria. Franke: Takeda: Other: Travel support; Gilead: Other: Travel support; Incyte: Honoraria; BMS: Honoraria; Jazz Pharmaceuticals: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Kiani: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Krause: Art-tempi: Honoraria; Kosmas: Honoraria; Abbvie: Other: Expenses. Heibl: BMS: Honoraria; Janssen Cilag: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria; Roche: Honoraria; AOP: Honoraria; AbbVie: Honoraria. Hochhaus: Incyte: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Research Funding. Lauseker: Novartis: Research Funding.

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