ABSTRACT
ABSTRACT: We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation). All patients were eligible for allogeneic stem cell transplant (SCT), whereas those in MMR could receive autologous SCT, followed by 2-year imatinib maintenance in both cases. After the enrollment of 156 of 265 planed patients, the data and safety monitoring board decided to hold the randomization because of an excess of relapse in the investigational arm. Among the 155 evaluable patients, 76 received Ara-C during consolidation (arm A) and 79 did not (arm B). Overall, 133 patients (85%) underwent SCT, 93 allogeneic and 40 autologous. The noninferiority end point regarding MMR was reached with 71.1% (arm A) and 77.2% (arm B) of patients reaching MMR. However, the 4-year cumulative incidence of relapse was higher in arm B compared with arm A (31.3% [95% confidence interval {CI}, 21.1%-41.9%] vs 13.2% [95% CI, 6.7%-21.9%]; P = .017), which translated to a lower relapse-free survival. With a median follow-up of 3.8 years, 4-year overall survival was 79.0% (95% CI, 70.6%-89.3%) in arm A vs 73.4% (95% CI, 63.9%-84.4%) in arm B (P = .35). Despite a noninferior rate of MMR, more relapses were observed when ARA-C was omitted without impact on survival. ClinicalTrials.gov ID, NCT02611492.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Cytarabine , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Pyrimidines , Humans , Cytarabine/administration & dosage , Cytarabine/therapeutic use , Female , Male , Adult , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Pyrimidines/therapeutic use , Pyrimidines/administration & dosage , Aged , Young Adult , Adolescent , Fusion Proteins, bcr-abl/genetics , Hematopoietic Stem Cell TransplantationABSTRACT
KMT2A-rearranged (KMT2A-r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is widely recognized as a high-risk leukemia in both children and adults. However, there is a paucity of data on adults treated in recent protocols, and the optimal treatment strategy for these patients is still a matter of debate. In this study, we set out to refine the prognosis of adult KMT2A-r BCP-ALL treated with modern chemotherapy regimen and investigate the prognostic impact of comutations and minimal residual disease (MRD). Of 1091 adult patients with Philadelphia-negative BCP-ALL enrolled in 3 consecutive trials from the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), 141 (12.9%) had KMT2A-r, with 5-year cumulative incidence of relapse (CIR) and overall survival (OS) rates of 40.7% and 53.3%, respectively. Molecular profiling highlighted a low mutational burden in this subtype, reminiscent of infant BCP-ALL. However, the presence of TP53 and/or IKZF1 alterations defined a subset of patients with significantly poorer CIR (69.3% vs 36.2%; P = .001) and OS (28.1% vs 60.7%; P = .006) rates. Next, we analyzed the prognostic implication of MRD measured after induction and first consolidation, using both immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements and KMT2A genomic fusion as markers. In approximately one-third of patients, IG/TR rearrangements were absent or displayed clonal evolution during the disease course, compromising MRD monitoring. In contrast, KMT2A-based MRD was highly reliable and strongly associated with outcome, with early good responders having an excellent outcome (3-year CIR, 7.1%; OS, 92.9%). Altogether, our study reveals striking heterogeneity in outcomes within adults with KMT2A-r BCP-ALL and provides new biomarkers to guide risk-based therapeutic stratification.
Subject(s)
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Adult , Neoplasm, Residual/genetics , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Immunoglobulins , Risk AssessmentABSTRACT
Genetic testing plays a central role in myelodysplastic neoplasms (MDS) diagnosis, prognosis, and therapeutic decisions. The widely applied cytogenetic revised international prognostic scoring system (IPSS-R) was based on chromosome banding analysis (CBA). However, subsequently developed genetic methodologies, such as single nucleotide polymorphism (SNP) array, demonstrated to be a valid alternative test for MDS. SNP array is, in fact, able to detect the majority of MDS-associated cytogenetic aberrations, by providing further genomic information due to its higher resolution. In this study, 290 samples from individuals with a confirmed or suspected diagnosis of MDS were tested by both CBA and SNP array, in order to evaluate and compare their cytogenetic IPSS-R score in the largest MDS cohort reported so far. A concordant or better refined cytogenetic IPSS-R array-based score was obtained for 95% of cases (277). Therefore, this study confirms the effective applicability of SNP array toward the cytogenetic IPSS-R evaluation and consequently, toward the molecular international prognostic scoring system for MDS (IPSS-M) assessment, which ensures an improved MDS risk stratification refinement. Considering the advent of additional genetic technologies interrogating the whole genome with increased resolutions, counting cytogenetic abnormalities based on their size may result in a simplistic approach. On the contrary, assessing overall genomic complexity may provide additional crucial information. Independently of the technology used, genetic results should indeed aim at ensuring a highly refined stratification for MDS patients.
Subject(s)
Chromosome Aberrations , Myelodysplastic Syndromes , Humans , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Chromosome BandingABSTRACT
Aplastic anemia is a rare disease with a large differential diagnosis, including neoplastic origin as well as congenital bone marrow failure syndromes. Investigations must be quick and precise. Treatment depends on the patient's age and consists of immunosuppression treatment or allogeneic bone marrow transplantation. Because of the risk of progression to other hematological diseases, a close specialized follow-up is recommended.
L'anémie aplasique est une maladie rare avec un diagnostic différentiel large, comprenant des maladies d'origine néoplasique ainsi que les syndromes d'insuffisance médullaire congénitale. Les investigations doivent être rapides et précises. Le traitement dépend de l'âge du patient et consiste en une immunosuppression plus ou moins sévère ou une allogreffe de moelle osseuse. En raison du risque d'évolution vers d'autres maladies hématologiques, un suivi spécialisé rapproché est préconisé.
Subject(s)
Anemia, Aplastic , Humans , Anemia, Aplastic/diagnosis , Anemia, Aplastic/therapy , Diagnosis, Differential , Bone Marrow Transplantation/methods , Immunosuppressive Agents/therapeutic useABSTRACT
Myelodysplasic syndromes (MDS) are diseases occurring mainly in the elderly population. Although hematopoietic stem cell transplantation is the only hope for cure, a majority of the patients suffering from MDS are too old or frail for intensive treatment regimens such as intensive chemotherapy and transplantation. The gold standard for those patients is currently treatment with hypomethylating agents, although real-life data could not reproduce the overall survival rates reported for the pivotal azacitidine phase III study. MDS treatment is often inspired by treatment for acute myeloid leukemia (AML). The new gold standard for elderly and frail patients not able to undergo intensive treatment regimens in AML is the combination of hypomethylating agents with venetoclax, a BCL-2 inhibitor that also showed excellent treatment outcomes in other hematological malignancies. In this review, we explain the rationale for the use of venetoclax in hematological malignancies, study outcomes available so far and the current knowledge of its use in MDS.
Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/pathology , Azacitidine/therapeutic use , Hematologic Neoplasms/chemically induced , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathology , Proto-Oncogene Proteins c-bcl-2ABSTRACT
Bone marrow (BM) cellularity assessment is a crucial step in the evaluation of BM trephine biopsies for hematologic and nonhematologic disorders. Clinical assessment is based on a semiquantitative visual estimation of the hematopoietic and adipocytic components by hematopathologists, which does not provide quantitative information on other stromal compartments. In this study, we developed and validated MarrowQuant 2.0, an efficient, user-friendly digital hematopathology workflow integrated within QuPath software, which serves as BM quantifier for 5 mutually exclusive compartments (bone, hematopoietic, adipocytic, and interstitial/microvasculature areas and other) and derives the cellularity of human BM trephine biopsies. Instance segmentation of individual adipocytes is realized through the adaptation of the machine-learning-based algorithm StarDist. We calculated BM compartments and adipocyte size distributions of hematoxylin and eosin images obtained from 250 bone specimens, from control subjects and patients with acute myeloid leukemia or myelodysplastic syndrome, at diagnosis and follow-up, and measured the agreement of cellularity estimates by MarrowQuant 2.0 against visual scores from 4 hematopathologists. The algorithm was capable of robust BM compartment segmentation with an average mask accuracy of 86%, maximal for bone (99%), hematopoietic (92%), and adipocyte (98%) areas. MarrowQuant 2.0 cellularity score and hematopathologist estimations were highly correlated (R2 = 0.92-0.98, intraclass correlation coefficient [ICC] = 0.98; interobserver ICC = 0.96). BM compartment segmentation quantitatively confirmed the reciprocity of the hematopoietic and adipocytic compartments. MarrowQuant 2.0 performance was additionally tested for cellularity assessment of specimens prospectively collected from clinical routine diagnosis. After special consideration for the choice of the cellularity equation in specimens with expanded stroma, performance was similar in this setting (R2 = 0.86, n = 42). Thus, we conclude that these validation experiments establish MarrowQuant 2.0 as a reliable tool for BM cellularity assessment. We expect this workflow will serve as a clinical research tool to explore novel biomarkers related to BM stromal components and may contribute to further validation of future digitalized diagnostic hematopathology workstreams.
Subject(s)
Bone Marrow , Hematology , Humans , Bone Marrow/pathology , Workflow , Bone Marrow Cells/pathology , Bone Marrow ExaminationABSTRACT
The gene encoding for transcription factor ETV6 presents recurrent lesions in hematologic neoplasms, most notably the ETV6-RUNX1 rearrangement in childhood B-ALL. The role of ETV6 for normal hematopoiesis is unknown, but loss of its function probably participates in oncogenic procedures. In myeloid neoplasms, ETV6-locus (12p13) deletions are rare but recurrent; ETV6 translocations are even rarer, but those reported seem to have phenotype-defining consequences. We herein describe the genetic and hematologic profile of myeloid neoplasms with ETV6 deletions (10 cases), or translocations (4 cases) diagnosed in the last 10 years in our institution. We find complex caryotype to be the most prevalent cytogenetics among patients with 12p13 deletion (8/10 patients), with most frequent coexisting anomalies being monosomy 7 or deletion 7q32 (5/10), monosomy 5 or del5q14-15 (5/10), and deletion/inversion of chromosome 20 (5/10), and most frequent point mutation being TP53 mutation (6/10 patients). Mechanisms of synergy of these lesions are unknown. We describe the entire genetic profile and hematologic phenotype of cases with extremely rare ETV6 translocations, confirming the biphenotypic T/myeloid nature of acute leukemia associated to ETV6-NCOA2 rearrangement, the association of t (1;12) (p36; p13) and of the CHIC2-ETV6 fusion with MDS/AML, and the association of the ETV6-ACSL6 rearrangement with myeloproliferative neoplasm with eosinophilia. Mutation of the intact ETV6 allele was present in two cases and seems to be subclonal to the chromosomal lesions. Decoding the mechanisms of disease related to ETV6 haploinsufficiency or rearrangements is important for the understanding of pathogenesis of myeloid neoplasms and fundamental research must be guided by observational cues.
Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Myeloproliferative Disorders , Humans , In Situ Hybridization, Fluorescence , Proto-Oncogene Proteins c-ets/genetics , Translocation, Genetic , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Hematologic Neoplasms/geneticsABSTRACT
Tyrosine kinase inhibitors (TKI) have emerged as a paradigm-shifting therapeutic approach for the treatment of chronic myeloid leukemia (CML) following their regulatory approval in 2001. These agents have revolutionized the management of CML by significantly improving patient outcomes and enabling them to achieve near-normal life expectancies. Consequently, the utilization of TKI has become increasingly prevalent, accompanied by the recognition and management of their associated adverse effects. Given the expanding patient population receiving TKI therapy, it is imperative that hematologists, as well as general practitioners, assume the responsibility of closely and meticulously monitoring patients' treatment progress while effectively addressing the occurrence of any untoward effects.
Les inhibiteurs de tyrosine kinase (ITK) ont révolutionné la prise en charge de la leucémie myéloïde chronique (LMC) depuis leur autorisation de mise sur le marché en 2001, permettant aux patients d'obtenir une survie comparable à celle de la population générale. À ce jour, plusieurs générations d'ITK sont apparues, avec leurs effets secondaires respectifs. Leur prescription nécessite donc un suivi rapproché et pluridisciplinaire entre l'hématologue et l'interniste hospitalier, mais également le médecin généraliste, qui peut aussi être confronté à ces effets indésirables.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Protein Kinase Inhibitors/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Molecular Targeted Therapy , PersonalityABSTRACT
Short telomere syndrome (STS) is a group of rare, often underrecognized, diseases caused by defects in telomere-maintenance genes, leading to abnormal telomere shortening and associated with diverse multi-organ manifestations. In pediatric patients, STS typically presents with mucocutaneous or gastrointestinal lesions, bone marrow failure and neoplasia. In adulthood, aplastic bone marrow disease, liver disease and pulmonary fibrosis are classic clinical manifestations. At present, medical treatment options for STS remain limited. Danazol, a synthetic androgenic hormone, can slow down telomere shortening and thus limit the progression of the disease. Finally, hematopoietic, hepatic and pulmonary transplantation, sometimes combined, may be discussed in a multidisciplinary setting in certain situations.
Le syndrome des télomères courts (STC) est un groupe de maladies rares dues à un défaut dans les gènes de maintenance des télomères, provoquant leur raccourcissement anormal et des manifestations cliniques multiorganiques. Dans l'enfance, le STC se présente par des lésions mucocutanées et gastro-intestinales, une insuffisance médullaire et des néoplasies. À l'âge adulte, une atteinte médullaire aplasiante, hépatique, et une fibrose pulmonaire sont des manifestations cliniques classiques. Les options thérapeutiques pour le STC restent limitées. Le danazol, une hormone androgène synthétique, permet, parfois, de freiner le raccourcissement télomérique et de limiter la progression de la maladie. Finalement, les transplantations hématopoïétique, hépatique et pulmonaire sont discutées dans certaines situations de manière multidisciplinaire.
Subject(s)
Bone Marrow Diseases , Nephrocalcinosis , Adult , Bone Marrow Diseases/genetics , Bone Marrow Diseases/pathology , Child , Growth Disorders , Humans , Hypercalcemia , Metabolic Diseases , Syndrome , Telomere/genetics , Telomere/pathologyABSTRACT
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases, with a variable probability of transformation into acute leukemia, which is, in the vast majority of cases, of myeloid lineage. Nevertheless, rare cases of acute lymphoblastic leukemia in patients with previously diagnosed MDS have been reported. We describe a series of 3 cases of MDS/CMML marked with evolution to acute lymphoblastic leukemia (ALL) and provide a comprehensive review of the 49 cases documented in the literature so far. These sporadic events have only been published as single-case reports or small series to date. Such atypical cases emphasize the possibility of major phenotypic switches arising at the leukemic stem cell (LSC) and/or early progenitor levels, as a consequence of epigenetic and genomic events driving these changes in the bone marrow niche.
Subject(s)
Disease Progression , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Aged, 80 and over , Female , Humans , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/geneticsABSTRACT
BACKGROUND: About 1%-5% of acquired haemophilia A cases affect mothers in the postpartum setting. AIMS: This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies. METHODS: Report of two cases and literature study (1946-2019), yielding 73 articles describing 174 cases (total 176 cases). RESULTS: Patients were aged 29.9 years (17-41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0-308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was <1% (range 0%-8%). FVIII inhibitor was documented in 75.4% cases (median titre of 20 BU/ml, range 1-621). Haemostatic treatment was necessary in 57.1% using fresh frozen plasma (16%), factor concentrate (27.6%) and/or bypassing agents (37.4%). Immunosuppressive treatment was administered in 90.8%, mostly steroids (85.3%), alone or combined with immunosuppressants (27%). Rituximab was used mostly as a second line treatment. Only 24 patients (13.6%) had documented subsequent pregnancies and 6 (22.2%) suffered haemophilia recurrence during pregnancy. CONCLUSION: This study allows better definition of: (1) clinical and laboratory characteristics of postpartum acquired haemophilia, (2) response to therapy, and (3) the risk of relapse for subsequent pregnancies.
Subject(s)
Hemophilia A , Hemostatics , Factor VIII , Female , Hemophilia A/diagnosis , Hemophilia A/drug therapy , Hemophilia A/epidemiology , Humans , Postpartum Period , Pregnancy , RecurrenceABSTRACT
The COVID-19 pandemic impacts the hematology practice. Intensive chemotherapies for high-grade lymphomas and acute leukemias, multiple myeloma treatments and most hematopoietic stem cell transplantations should be performed as usual. Low-grade lymphomas should only be treated when strictly indicated, maintenance can be postponed. Other myeloid neoplasia and their therapies cause imunosupression; dose adjustment is recommended but no brisk stopping. Sickle cell anemia patients are highly succeptible to severe COVID-19 course. Thrombocytopenia and procoagulant state are associated with severe courses of COVID-19, requiring an individualized therapy. No data indicate a risk of SARS-CoV-2 transmission through blood product transfusion.
La pandémie de COVID-19 affecte la prise en charge hématologique. Les chimiothérapies intensives pour les lymphomes agressifs et les leucémies aiguës, les traitements du myélome multiple, ainsi que la plupart des greffes de cellules souches hématopoïétiques doivent continuer à être pratiquées. Les lymphomes de bas grade seront traités uniquement avec des indications clairesâ ; et la maintenance repoussée. Les autres néoplasies myéloïdes et leurs traitements causent une immunosuppressionâ ; on recommande une adaptation des doses, mais pas d'arrêt brusque. La drépanocytose rend les patients très vulnérables au COVID-19. La thrombopénie signe un état procoagulant et la sévérité du COVID-19, nécessitant un traitement individualisé. Aucune donnée n'indique de risque d'une transmission du SARS-CoV-2 par transfusion de produits sanguins.
Subject(s)
Betacoronavirus , Coronavirus Infections , Hematologic Diseases/complications , Pandemics , Pneumonia, Viral , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Hematologic Diseases/diagnosis , Hematologic Diseases/therapy , Hematology/trends , Humans , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2ABSTRACT
Acute leukaemia is a life-threatening disease that needs treatment without delay. Fertility preservation is recommended, but often not possible because of the necessity to start treatment as soon as possible. The present study is a retrospective single-centre analysis of 459 patients diagnosed with acute leukaemia between 2002 and 2012. Sperm or oocyte preservation was successfully performed in only 29 (6%) patients. Of the 150 children, no paediatric patient sample was taken. The collected samples enabled the conception of 2 children by in vitro fertilisation; in addition, 3 spontaneous, non-assisted births in partners of male patients were observed. Fertility preservation is important but difficult to accomplish in patients with acute leukaemia; more efforts are clearly needed to preserve fertility in long-term survivors of acute leukaemia.
Subject(s)
Fertility Preservation/methods , Leukemia/complications , Acute Disease , Child , Cryopreservation , Female , Humans , Male , Oocytes/cytology , Retrospective Studies , Spermatozoa/cytology , Treatment OutcomeSubject(s)
Central Nervous System Neoplasms , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Incidence , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Adult , Central Nervous System Neoplasms/therapy , Female , Middle Aged , Adolescent , Europe/epidemiology , Recurrence , Young Adult , Treatment Outcome , AgedABSTRACT
Intensive chemotherapy (IC) used to be a common treatment approach for patients with higher-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia after MDS (sAML). We conducted a retrospective analysis of 299 patients, including a matched pair analysis comparing 96 patients receiving IC with 96 patients not undergoing IC, in order to evaluate the impact of IC on overall survival (OS) and to identify factors that influence remission rates and OS. Complete remission (CR) after first induction chemotherapy was reached in 50% of patients. Parameters influencing the probability of achieving CR were blast count in the bone marrow (< 30%), age < 65 years, presence of Auer rods, duration of antecedent MDS shorter than 6 months, and timing of IC in relation to first diagnosis. The difference in survival time was not significantly better for patients receiving IC (median OS 12.7 months vs. 7 months). Parameters favorably influencing survival were the presence of Auer rods, age below 60 years, blast count below 30%, IC given shortly after first diagnosis, and achievement of CR. On multivariate analysis, achieving CR, presence of Auer rods, and percentage of blasts below or above 30% significantly influenced median survival. Relapse occurred in 63% of patients after a median of 9.9 months with a median survival of 7.6 months. Considering the high relapse rate and short survival, we conclude that intensive chemotherapy is not promising for high-risk MDS or sAML.
Subject(s)
Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Adult , Age Factors , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate , Time FactorsABSTRACT
PURPOSE OF REVIEW: Adverse karyotype acute myeloid leukemia is a disease particularly of older patients, but also observed in younger patients. Despite all efforts, standard chemotherapy is still generally applied in fit patients, as already for decades, and for nearly all different subtypes of acute myeloid leukemia. Lack of more specifically targeted therapy and the often older age of the patients are complicating treatment, and in the subgroup of patients achieving a complete remission, the strikingly high frequency of relapse is a characteristic of this disease. This review aims to give an overview of current treatment approaches as well as emerging therapies. RECENT FINDINGS: Currently, the approach of a targeted therapy specific to the genetic and/or epigenetic aberrations detected in the individual patient is still not possible, and a 'one treatment fits all' course of action is still used, with allografting as curative consolidation. However, first immunotherapeutic approaches are emerging as treatment options and first phase 1 and 2 studies are described. SUMMARY: Treatment of acute myeloid leukemia with adverse karyotype is still not individualized, most treatment options currently not being curative. This can change in the near future, but recent findings will have to be implemented into larger phase 3 studies before being standard of care.