Sujet(s)
Leucémie myélomonocytaire chronique , Protéine p53 suppresseur de tumeur , Humains , Protéine p53 suppresseur de tumeur/génétique , Protéine p53 suppresseur de tumeur/métabolisme , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/thérapie , Leucémie myélomonocytaire chronique/diagnostic , Leucémie myélomonocytaire chronique/métabolisme , Pronostic , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Sujet âgé de 80 ans ou plusRÉSUMÉ
Traditionally, skin involvement in chronic myelomonocytic leukemia (CMML) has been considered to be either specific (leukemia cutis) or non-specific, with granulomatous dermatitis included in the latter group. More recently, the true nature of the myeloid cells present in the cutaneous infiltrates of this theoretically reactive dermatitis is being clarified with the use of new molecular techniques such as next-generation sequencing. The same mutations in bone marrow (BM) myeloid neoplastic cells and in the cells of cutaneous infiltrates have been found. We present the case of a 77-year-old man who presented with spread and treatment-resistant skin granulomatous lesions previous to the diagnosis of CMML. The same clonal mutations in SRSF2, IDH1, and RUNX1 were found in both skin and BM with resolution of the lesions after the initiation of azacytidine. In conclusion, we report an exceptional case in which specific granulomatous cutaneous lesions have preceded and allowed the earlier diagnosis of an underlying CMML and a review of all previous similar cases in the literature, including molecular alterations.
Sujet(s)
Dermatite , Leucémie myélomonocytaire chronique , Humains , Mâle , Leucémie myélomonocytaire chronique/anatomopathologie , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/complications , Sujet âgé , Dermatite/anatomopathologie , Granulome/anatomopathologie , Facteurs d'épissage riches en sérine-arginine/génétique , Mutation , Azacitidine/usage thérapeutique , Isocitrate dehydrogenases , Sous-unité alpha 2 du facteur CBFRÉSUMÉ
RAS pathway mutations, which are present in 30% of patients with chronic myelomonocytic leukemia (CMML) at diagnosis, confer a high risk of resistance to and progression after hypomethylating agent (HMA) therapy, the current standard of care for the disease. Here, using single-cell, multi-omics technologies, we seek to dissect the biological mechanisms underlying the initiation and progression of RAS pathway-mutated CMML. We identify that RAS pathway mutations induce transcriptional reprogramming of hematopoietic stem and progenitor cells (HSPCs) and downstream monocytic populations in response to cell-intrinsic and -extrinsic inflammatory signaling that also impair the functions of immune cells. HSPCs expand at disease progression after therapy with HMA or the BCL2 inhibitor venetoclax and rely on the NF-κB pathway effector MCL1 to maintain survival. Our study has implications for the development of therapies to improve the survival of patients with RAS pathway-mutated CMML.
Sujet(s)
Apoptose , Leucémie myélomonocytaire chronique , Mutation , Protéine Mcl-1 , Leucémie myélomonocytaire chronique/traitement médicamenteux , Leucémie myélomonocytaire chronique/anatomopathologie , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/métabolisme , Protéine Mcl-1/métabolisme , Protéine Mcl-1/génétique , Protéine Mcl-1/antagonistes et inhibiteurs , Humains , Apoptose/effets des médicaments et des substances chimiques , Animaux , Mutation/génétique , Souris , Transduction du signal/effets des médicaments et des substances chimiques , Cellules souches hématopoïétiques/métabolisme , Cellules souches hématopoïétiques/effets des médicaments et des substances chimiques , Évolution de la maladie , Sulfonamides/pharmacologie , Sulfonamides/usage thérapeutique , Facteur de transcription NF-kappa B/métabolisme , Méthylation de l'ADN/effets des médicaments et des substances chimiques , Méthylation de l'ADN/génétique , Composés hétérocycliques bicycliques/pharmacologie , Composés hétérocycliques bicycliques/usage thérapeutique , Crise blastique/anatomopathologie , Crise blastique/traitement médicamenteux , Crise blastique/génétique , Crise blastique/métabolismeRÉSUMÉ
Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.
Sujet(s)
Transplantation de cellules souches hématopoïétiques , Leucémie myélomonocytaire chronique , Syndromes myélodysplasiques , Humains , Femelle , Mâle , Leucémie myélomonocytaire chronique/mortalité , Leucémie myélomonocytaire chronique/thérapie , Syndromes myélodysplasiques/thérapie , Syndromes myélodysplasiques/mortalité , Syndromes myélodysplasiques/complications , Adulte d'âge moyen , Transplantation de cellules souches hématopoïétiques/effets indésirables , Études rétrospectives , Facteurs de risque , Adulte , Sujet âgé , Maladies auto-immunes/mortalité , Maladies auto-immunes/thérapie , Transplantation homologue/effets indésirables , Allogreffes , Taux de survieRÉSUMÉ
DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms, characterized by prominent monocytosis and an inherent risk for leukemic transformation (~15%-20% over 3-5 years). DIAGNOSIS: Newly revised diagnostic criteria include sustained (>3 months) peripheral blood (PB) monocytosis (≥0.5 × 109/L; monocytes ≥10% of leukocyte count), consistent bone marrow (BM) morphology, <20% BM or PB blasts (including promonocytes), and cytogenetic or molecular evidence of clonality. Cytogenetic abnormalities occur in ~30% of patients, while >95% harbor somatic mutations: TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), RAS pathway (~30%), and others. The presence of ASXL1 and DNMT3A mutations and absence of TET2 mutations negatively impact overall survival (ASXL1WT/TET2MT genotype being favorable). RISK STRATIFICATION: Several risk models serve similar purposes in identifying high-risk patients that are considered for allogeneic stem cell transplant (ASCT) earlier than later. Risk factors in the Mayo Molecular Model (MMM) include presence of truncating ASXL1 mutations, absolute monocyte count >10 × 109/L, hemoglobin <10 g/dL, platelet count <100 × 109/L, and the presence of circulating immature myeloid cells; the resulting 4-tiered risk categorization includes high (≥3 risk factors), intermediate-2 (2 risk factors), intermediate-1 (1 risk factor), and low (no risk factors); the corresponding median survivals were 16, 31, 59, and 97 months. CMML is also classified as being "myeloproliferative (MP-CMML)" or "myelodysplastic (MD-CMML)," based on the presence or absence of leukocyte count of ≥13 × 109/L. TREATMENT: ASCT is the only treatment modality that secures cure or long-term survival and is appropriate for MMM high/intermediate-2 risk disease. Drug therapy is currently not disease-modifying and includes hydroxyurea and hypomethylating agents; a recent phase-3 study (DACOTA) comparing hydroxyurea and decitabine, in high-risk MP-CMML, showed similar overall survival at 23.1 versus 18.4 months, respectively, despite response rates being higher for decitabine (56% vs. 31%). UNIQUE DISEASE ASSOCIATIONS: These include systemic inflammatory autoimmune diseases, leukemia cutis and lysozyme-induced nephropathy; the latter requires close monitoring of renal function during leukocytosis and is a potential indication for cytoreductive therapy.
Sujet(s)
Leucémie myélomonocytaire chronique , Humains , Leucémie myélomonocytaire chronique/thérapie , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/diagnostic , Appréciation des risques , Mutation , Transplantation de cellules souches hématopoïétiquesRÉSUMÉ
ABSTRACT: Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease presenting with either myeloproliferative or myelodysplastic features. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative option, but the inherent toxicity of this procedure makes the decision to proceed to allo-HCT challenging, particularly because patients with CMML are mostly older and comorbid. Therefore, the decision between a nonintensive treatment approach and allo-HCT represents a delicate balance, especially because prospective randomized studies are lacking and retrospective data in the literature are conflicting. International consensus on the selection of patients and the ideal timing of allo-HCT, specifically in CMML, could not be reached in international recommendations published 6 years ago. Since then, new, CMML-specific data have been published. The European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee assembled a panel of experts in the field to provide the first best practice recommendations on the role of allo-HCT specifically in CMML. Recommendations were based on the results of an international survey, a comprehensive review of the literature, and expert opinions on the subject, after structured discussion and circulation of recommendations. Algorithms for patient selection, timing of allo-HCT during the course of the disease, pretransplant strategies, allo-HCT modality, as well as posttransplant management for patients with CMML were outlined. The keynote message is, that once a patient has been identified as a transplant candidate, upfront transplantation without prior disease-modifying treatment is preferred to maximize chances of reaching allo-HCT whenever possible, irrespective of bone marrow blast counts.
Sujet(s)
Transplantation de cellules souches hématopoïétiques , Leucémie myélomonocytaire chronique , Transplantation homologue , Adulte , Humains , Prise en charge de la maladie , Transplantation de cellules souches hématopoïétiques/méthodes , Leucémie myélomonocytaire chronique/thérapie , Sociétés médicales/normesRÉSUMÉ
ABSTRACT: Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome-7 abnormalities (4% vs 13%; P = .005) but not complex karyotype (3% vs 7%; P = .15), were more frequent in tCMML. tCMML was characterized by higher TP53 mutation frequency (4% vs 12%; P = .04) and lower NRAS (6% vs 22%, P = .007) and CBL (4% vs 12%, P = .04) mutation frequency. Prior therapy with antimetabolites (odd ratio [OR], 1.22; 95% confidence interval [CI], 1.05-1.42; P = .01) and mitotic inhibitors (OR, 1.24; 95% CI, 1.06-1.44; P = .009) was associated with NF1 and SETBP1 mutations whereas prior mitotic inhibitor therapy was associated with lower TET2 mutation frequency (OR, 0.71; 95% CI, 0.55-0.92; P = .01). Although no differences in median overall survival (OS) were observed among tCMML and dnCMML (34.7 months vs 35.9 months, P = .26), multivariate analysis for OS revealed that prior chemotherapy was associated with increased risk of death (hazard ratio, 1.76; 95% CI, 1.07-2.89; P = .026). Compared with a cohort of therapy-related myelodysplastic syndrome, tCMML had lower TP53 mutation frequency (12% vs 44.4%, P < .001) and less unfavorable outcomes. In summary, tCMML does not exhibit the high-risk features and poor outcomes of t-MNs.
Sujet(s)
Leucémie myélomonocytaire chronique , Humains , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/mortalité , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Seconde tumeur primitive/étiologie , Mutation , Sujet âgé de 80 ans ou plus , Adulte , Facteurs de risqueRÉSUMÉ
Chronic myelomonocytic leukemia (CMML) is a clonal disease derived from bone marrow hematopoietic stem cells, with a poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo- HSCT) is one of the curable methods for CMML. The outcome of patient transplantation is influenced by various factors such as disease characteristics and comorbidities. Based on the existing prognostic stratification system, screening suitable CMML patients for transplantation and early transplantation is beneficial for their long-term survival. Doctors can evaluate the survival status of CMML patients after transplantation based on the newly developed transplant prognosis model and make targeted medical decisions.
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Transplantation de cellules souches hématopoïétiques , Leucémie myélomonocytaire chronique , Humains , Leucémie myélomonocytaire chronique/thérapie , Transplantation homologue , Études rétrospectives , PronosticRÉSUMÉ
BACKGROUND: Hypomethylating agents are approved in higher-riskmyelodysplastic syndromes. The combination of a hypomethylating agent with venetoclax is standard of care in acute myeloid leukaemia. We investigated the safety and activity of the first totally oral combination of decitabine plus cedazuridine and venetoclax in patients with higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia. METHODS: We did a single-centre, dose-escalation and dose-expansion, phase 1/2, clinical trial. Patients with treatment-naive higher-risk-myelodysplastic syndromes or chronic myelomonocytic leukaemia (risk level categorised as intermediate-2 or higher by the International Prognostic Scoring System) with excess blasts (>5%). Treatment consisted of oral decitabine 35 mg plus cedazuridine 100 mg on days 1-5 and venetoclax (variable doses of 100-400 mg, day 1 to 14, 28-day cycle). The primary outcomes were safety for the phase 1 part and the overall response for the phase 2 part of the study. The trial is ongoing and this analysis was not prespecified. This study is registered with ClinicalTrials.gov, NCT04655755, and is currently enrolling participants. FINDINGS: Between Jan 21, 2021, and Jan 20, 2023, we enrolled 39 patients (nine in phase 1 and 30 in phase 2). The median age was 71 years (range 27-94), 28 (72%) patients were male, and 11 (28%) were female. The maximum tolerated dose was not reached, and the recommended phase 2 dose was established as oral decitabine 35 mg plus cedazuridine 100 mg for 5 days and venetoclax (400 mg) for 14 days. The most common grade 3-4 adverse events were thrombocytopenia (33 [85%] of 39), neutropenia (29 [74%]), and febrile neutropenia (eight [21%]). Four non-treatment-related deaths occurred on the study drugs due to sepsis (n=2), lung infection (n=1), and undetermined cause (n=1). The median follow-up time was 10·8 months (IQR 5·6-16·4). The overall response rate was 95% (95% CI 83-99; 37/39). 19 (49%) patients proceeded to hematopoietic stem-cell transplantation. INTERPRETATION: This early analysis suggests that the combination of oral decitabine plus cedazuridine with venetoclax for higher-risk-myelodysplastic syndromes and chronic myelomonocytic leukaemia is safe in most patients, with encouraging activity. Longer follow-up will be needed to confirm these data. FUNDING: MD Anderson Cancer Center, MDS/AML Moon Shot, Genentech/AbbVie, and Astex Pharmaceuticals.
Sujet(s)
Composés hétérocycliques bicycliques , Leucémie aigüe myéloïde , Leucémie myélomonocytaire chronique , Syndromes myélodysplasiques , Sulfonamides , Uridine/analogues et dérivés , Humains , Mâle , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Décitabine , Résultat thérapeutique , Leucémie myélomonocytaire chronique/traitement médicamenteux , Leucémie aigüe myéloïde/traitement médicamenteux , Syndromes myélodysplasiques/traitement médicamenteuxSujet(s)
Composés hétérocycliques bicycliques , Leucémie myélomonocytaire chronique , Syndromes myélodysplasiques , Sulfonamides , Uridine/analogues et dérivés , Humains , Leucémie myélomonocytaire chronique/traitement médicamenteux , Décitabine/usage thérapeutique , Syndromes myélodysplasiques/traitement médicamenteuxRÉSUMÉ
Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.
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Transplantation de cellules souches de sang du cordon , Leucémie myélomonocytaire chronique , Humains , Transplantation de cellules souches de sang du cordon/méthodes , Leucémie myélomonocytaire chronique/thérapie , Leucémie myélomonocytaire chronique/mortalité , Mâle , Adulte d'âge moyen , Femelle , Adulte , Études rétrospectives , Sujet âgé , Taux de survieRÉSUMÉ
Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS-MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS-MDS accurately predicted overall survival (OS) and leukaemia-free survival (LFS), outperforming the Revised-IPSS score. Similarly, in the Taiwanese cohort, the AIPSS-MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS-MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision-making in CMML enables clinicians to identify high-risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS-MDS to further refine risk stratification in CMML and improve patient outcomes.
Sujet(s)
Leucémie myélomonocytaire chronique , Leucémies , Syndromes myélodysplasiques , Humains , Leucémie myélomonocytaire chronique/diagnostic , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/traitement médicamenteux , Pronostic , Intelligence artificielle , Syndromes myélodysplasiques/thérapie , Syndromes myélodysplasiques/traitement médicamenteux , Appréciation des risquesRÉSUMÉ
OBJECTIVE: To observe the clinical efficacy and safety of hypomethylating agent therapy in chronic myelomonocytic leukemia (CMML). METHODS: From February 2014 to June 2021, the clinical data, efficacy, survival time and safety of CMML patients diagnosed in the Second Hospital of Hebei Medical University and treated with hypomethylating agent therapy were retrospectively analyzed. RESULTS: A total of 25 CMML patients received hypomethylating agent therapy, including 18 cases treated with decitabine (DEC) and 7 cases treated with azacytidine (AZA) as the basic treatment. Among them, 20 patients responded, and 7 patients got complete remission (CR). All patients with CR were treated with DEC as the basic treatment. Five cases of CR occurred in the first 4 courses of treatment. After a median follow-up of 16.4 (9.4-20.5) months, 4 patients with CR progressed to acute myeloid leukemia (AML). The median overall survival (OS) time of 25 CMML patients was 17.4 months (95%CI: 12.437-22.363). According to MD Anderson prognostic scoring system (MDAPS), CMML-specific prognostic scoring system (CPSS), CPSS molecular (CPSS-mol), Mayo molecular model (MMM), risk stratification of patients was performed, and the difference only between different risk stratification of MDAPS and survival time was statistically significant. Common adverse reactions of hypomethylating agent therapy in CMML patients included infection, gastrointestinal reaction, hematological toxicity, skin allergy and liver function damage. All patients' symptoms were improved after corresponding treatment. CONCLUSION: Hypomethylating agent therapy is effective and safe for CMML patients. CR mostly occurs in the first 4 courses of treatment, and hypomethylating agent therapy combined with low-dose chemotherapy can be used for patients who do not respond. Hypomethylating agent therapy can delay the disease, but can't prevent progression.
Sujet(s)
Leucémie aigüe myéloïde , Leucémie myélomonocytaire chronique , Humains , Leucémie myélomonocytaire chronique/traitement médicamenteux , Études rétrospectives , Résultat thérapeutique , Azacitidine/usage thérapeutique , Leucémie aigüe myéloïde/traitement médicamenteuxRÉSUMÉ
Ten-eleven translocation 2 (TET2) plays a pivotal role in epigenetic regulation, cell differentiation, and the inflammatory response. It also mediates the transcriptional regulation for inflammatory cytokines, particularly interleukin-6. While loss-of-function mutation in TET2 has been associated with hematological malignancies, it has been increasingly recognized to cause atherosclerotic disease. The increased atherogenicity is thought to be the result of increased production of pro-inflammatory interleukin-1ß cytokines following activation of NLRP3 inflammasomes. We present a unique case of recurrent atherothrombosis in an elderly man who was diagnosed with chronic myelomonocytic leukemia in the setting of TET2 mutation.
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Dioxygenases , Embolie , Leucémie myélomonocytaire chronique , Thromboembolie , Thrombose , Mâle , Humains , Sujet âgé , Leucémie myélomonocytaire chronique/complications , Leucémie myélomonocytaire chronique/génétique , Leucémie myélomonocytaire chronique/anatomopathologie , Épigenèse génétique , Mutation , Cytokines/génétique , Protéines de liaison à l'ADN/génétique , Dioxygenases/génétiqueRÉSUMÉ
Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.
Sujet(s)
Antinéoplasiques , Leucémie aigüe myéloïde , Leucémie myélomonocytaire chronique , Syndromes myélodysplasiques , Syndromes myéloprolifératifs , Humains , Syndromes myélodysplasiques/diagnostic , Syndromes myélodysplasiques/traitement médicamenteux , Syndromes myélodysplasiques/génétique , Syndromes myéloprolifératifs/traitement médicamenteux , Leucémie myélomonocytaire chronique/traitement médicamenteux , Leucémie aigüe myéloïde/diagnostic , Leucémie aigüe myéloïde/traitement médicamenteux , Leucémie aigüe myéloïde/génétique , Antinéoplasiques/usage thérapeutique , Comprimés/usage thérapeutiqueRÉSUMÉ
Recent developments in high-risk Myelodysplastic Neoplasms (HR MDS) treatment are confronted with challenges in study design due to evolving drug combinations with Hypomethylating Agents (HMAs). The shift from the International Prognostic Scoring System (IPSS) to its molecular revision (IPSS-M) has notably influenced research and clinical practice. Introducing concepts like the MDS/AML overlap complicate classifications and including chronic myelomonocytic leukemia (CMML) in MDS studies introduces another layer of complexity. The International Consortium for MDS emphasizes aligning HR MDS criteria with the 2022 ELN criteria for AML. Differences in advancements between AML and MDS treatments and hematological toxicity in HR MDS underline the importance of detailed trial designs. Effective therapeutic strategies require accurate reporting of adverse events, highlighting the need for clarity in criteria like the Common Terminology Criteria for Adverse Events (CTCAE). We provide an overview on negative clinical trials in HR MDS, analyze possible reasons and explore possibilities to optimize future clinical trials in this challenging patient population.