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International audience; BackgroundAllogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome . We retrospectively compared patient outcomes after allo-HSCT according to the intensity of the conditioning regimen.Patients and MethodsThree conditioning regimens were compared in 427 patients allografted for high-risk myelodysplastic syndrome: reduced-intensity conditioning (RIC), fludarabine (150-160 mg/m2) and busulfan (6.4 mg/kg); sequential FLAMSA-RIC, fludarabine, amsacrine, and aracytine followed by RIC; and myeloablative with reduced toxicity (RTC), fludarabine and busulfan (9.6 mg/kg or 12.8 mg/kg).ResultsThe patients in the 3 conditioning groups were different in regards to the number of treatment lines (P< .001), percentage of blasts in bone marrow (P< .001), and disease status at transplantation (P< .001). No significant differences in outcomes (overall survival, progression-free survival, nonrelapse mortality, relapse incidence, and graft versus host disease relapse-free survival) were observed between the 3 groups. Using propensity score analysis to overcome baseline imbalances, we compared 70 patients receiving FLAMSA-RIC to 260 patients receiving RIC, and compared 83 patients receiving RTC to 252 patients receiving RIC. The only factor influencing overall and progression-free survival was cytogenetic risk at transplantation. After the covariate adjustment using propensity score to reduce baseline imbalances, the only factor influencing overall and progression-free survival was still cytogenetic risk at transplantation.ConclusionOverall survival appears to be similar with the 3 conditioning regimens. The only factor influencing survival is cytogenetic risk at transplantation, suggesting that new promising drugs in the conditioning and/or early interventions after transplantation are needed to improve outcomes in these patients.

Iron chelation therapy (ICT) is an important tool in the treatment of transfusion-dependent lower-risk myelodysplastic syndrome (MDS) patients. ICT is effective in decreasing iron overload and consequently in limiting its detrimental effects on several organs, such as the heart, liver, and endocrine glands. Besides this effect, ICT also proved to be effective in improving peripheral cytopenia in a significant number of MDS patients, thus further increasing the clinical interest of this therapeutic tool. In the first part of the review, we will analyze the toxic effect of iron overload and its mechanism. Subsequently, we will revise the clinical role of ICT in various subsets of MDS patients (low, intermediate, and high risk MDS, patients who are candidates for allogeneic stem cell transplantation).

Background/purpose Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but advanced age with multiple comorbidities limits the eligibility for allo-HSCT. We conducted a retrospective study to investigate the comorbidities assessments and prognostic factors that predict outcomes for these patients. Methods Clinical data of patients older than 50 years who had received diagnoses of AML or MDS and underwent allo-HSCT were obtained. Information on patient characteristics, including age, gender, allogeneic transplant type, conditioning regimens, Charlson comorbidity index (CCI), and presence of acute graft-versus-host disease (GVHD) or chronic GVHD, were collected and analyzed. Results Two hundred fifty-five elderly patients with a median age at allo-HSCT of 57 years were included. The significant prognostic factors associated with worse overall survival (OS) were CCI ≥3 (hazard ratio: 1.88) and grade III–IV acute GVHD (3.18). Similar findings were noted in the non-relapse mortality analysis. To investigate the effects of chronic GVHD on patient outcomes, OS analysis was performed for those with survival >100 days after transplantation. The results revealed CCI ≥3 (1.88) and grade III–IV acute GVHD (2.73) remained poor prognostic factors for OS, whereas mild chronic GVHD (0.43) was associated with better OS. Conclusion This cohort study suggests that CCI ≥3 predicts poor outcomes, primarily due to a higher NRM risk. Careful management of GVHD after transplantation could improve outcomes in elderly patients with AML or MDS after allo-HSCT.

Haematopoietic insufficiency is the treatment target of lower-risk myelodysplastic syndrome (MDS). Although erythropoiesis-stimulating agents (ESAs) are generally effective for treating anaemia, resistance can develop. Hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) improves renal anaemia by promoting endogenous erythropoietin production and normalizing iron metabolism. HIF-PH inhibitors could be used to treat MDS, but their efficacy and safety have not been studied. A 78-year-old female patient with essential thrombocythemia gradually developed anaemia and was diagnosed with therapy-related MDS 4 years later. The anaemia temporarily improved with ESAs, but the patient became transfusion dependent. At the same time, anaemia and chronic renal failure due to nephrosclerosis progressed, and the patient was diagnosed with MDS with renal anaemia. After switching from ESAs to roxadustat, an HIF-PH inhibitor, anaemia improved, and the patient was no longer transfusion dependent. No progression of the underlying disease or any adverse events was observed 4 months after initiating roxadustat.

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders with heterogeneous presentation, ranging from indolent disease courses to aggressive diseases similar to acute myeloid leukemia (AML). Approximately 90% of MDS patients harbor recurrent mutations , which - with the exception of mutated SF3B1 -have not (yet) been included into the diagnostic criteria or risk stratification for MDS. Accumulating evidence suggests their utility for diagnostic workup, treatment indication and prognosis. Subsequently, in patients with unexplained cytopenia or dysplasia identification of these mutations may lead to earlier diagnosis. The acquisition and expansion of additional driver mutations usually antecedes further disease progression to higher risk MDS or secondary AML and thus, can be clinically helpful to detect individuals that may benefit from aggressive treatment approaches. Here, we review our current understanding of somatic gene mutations, gene expression patterns and flow cytometry regarding their relevance for disease evolution from pre-neoplastic states to MDS and potentially AML.

Objectives TP53 mutation is found frequently in therapy related acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS), AML and MDS patients with monosomy or complex karyotype. However, the prevalence and treatment outcome in TP53 mutated AML/MDS patients in Asian population are scarce. We therefore conducted this study to analyze the prevalence and the treatment outcomes of TP53 mutation in AML and MDS-EB patients. Methods Patients with newly diagnosed AML and MDS-EB were recruited, extraction of deoxyribonucleic acid from bone marrow samples were done and then performing TP53 mutation analysis, using MassArray® System (Agena Bioscience, CA, USA). Results A total of 132 AML/MDS patients were recruited, patients with de novo AML, secondary AML, MDS-EB1, MDS-EB2 and T-AML/MDS were seen in 66, 13, 9, 9 and 3%, respectively. TP53 mutation was found in 14 patients (10.6%), and prevalence of TP53 mutation in T-AML/MDS, secondary AML, de novo AML and MDS-EB patients were 50, 17.6, 9.2 and 8%, respectively. Three patients had double heterozygous TP53 mutation. Mutated TP53 was significantly detected in patients with monosomy and complex chromosome. Common TP53 mutation were R290C, T220C, A249S and V31I which V31I mutation was reported only in Taiwanese patients. Most variant allele frequency (VAF) of TP53 mutation in the study were greater than 40%. Three year-overall survival (OS) in the whole population was 22%, 3y-OS in AML and MDS-EB patients were 22 and 27%, respectively. The 1y-OS in patients with TP53-mutant AML/MDS were shorter than that in TP53 wild-type patients, 14% versus 50%, P = 0.001. In multivariate analysis, factors affecting OS in 132 AML/MDS patients was mutant TP53 (P = 0.023, HR = 1.20–7.02), whereas, WBC count> 100,000/μL (P = 0.004, HR = 1.32–4.16) and complex karyotype (P = 0.038, HR = 1.07–9.78) were associated with shorter OS in AML patients. Discussion In this study, the prevalence of TP53 mutation in de novo AML and MDS-EB patients were low but it had impact on survival. Patients with monosomy or complex karyotype had more frequent TP53 mutation.

International audience; Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.

Despite all knowledge acquired regarding the mutational profile of pediatric myelodysplastic syndrome (MDS), the somatic genomic landscape underlying that disease remains unclear. We evaluated the presence of somatic variants in 37 genes related to myeloid malignancies through targeted NGS in 20 Brazilian patients with refractory cytopenia of childhood (RCC). Only 15% (3/20) of patients showed at least one somatic driver mutation – all in genes coding to regulators of cell signaling (TP53 and CBLB) or epigenetics (ASXL1 and DNMT3A). Interestingly, those variants were identified in patients with no detected clonal chromosomal abnormalities.

Background Central diabetes insipidus (CDI) is a rare complication of myelodysplastic syndrome (MDS). Although the cytogenetic features of patients with MDS and CDI are not clear, CDI in patients with acute myeloid leukemia (AML) is associated with chromosome 7 and/or 3 anomalies. Case presentation In this report, we describe two patients with MDS and concurrent CDI, and in one of them, CDI was the first manifestation. One patient had monosomy 7 on metaphase cytogenetics (MC). Monosomy 7 and numerous cytogenetic abnormalities were found in the other patient using single-nucleotide polymorphism array (SNP-A) karyotyping, while the MC did not uncover monosomy 7. In this manuscript we also reviewed reported cases of MDS with diabetes insipidus (DI-MDS) to summarize the relationship between DI-MDS and karyotype, and explore the best treatment strategy for DI-MDS. Conclusions DI-MDS is closely related to monosomy 7. Allogeneic hematopoietic stem cell transplantation may be the only effective treatment for DI-MDS. The SNP-A-based karyotyping is helpful to reveal subtle cytogenetic abnormalities and unveil their roles in the clinical features of MDS.

Purpose Myelofibrosis (MF) may serve as a poor prognostic factor in myelodysplastic syndromes (MDS). This study explored the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of MDS patients with MF. Patients and Methods Three hundred and sixteen MDS patients were enrolled in this retrospective study. Based on the degree of MF, we divided the patients into 2 groups: grade 0–1 (MF-0/1) and grade 2–3 (MF-2/3) groups. The clinical features, treatments, and prognosis in MDS patients with MF were analyzed. Results Forty-three (13.6%) patients were diagnosed as MF-2/3. Complex karyotypes were more common in the MF-2/3 compared to MF-0/1 groups (P = 0.002). The overall response rate (ORR) of cytoreduction was 49.0%, along with 53.3% in the MF-0/1 and 16.7% in MF-2/3 groups (P = 0.017). In total, 141 patients underwent allo-HSCT, including 121 in the MF-0/1 and 20 in MF-2/3 groups. The median time to neutrophil reconstruction was 12 (range: 7–34) and 14 (range: 10–45) days (P = 0.005), and platelet reconstruction was 14 (range: 8–68) and 18 (range: 8–65) days (P = 0.045) in the MF-0/1 and MF-2/3 groups, respectively. However, the cumulative incidence of neutrophil and platelet engraftment achieved at day + 30 was not different between the two groups (P = 0.107, P = 0.303, respectively). Non-relapse mortality, relapse, and acute and chronic graft-versus-host disease were similar between the two groups (all P > 0.05). Among patients with allo-HSCT, the 2-year overall survival (OS) was 68.5% (95% CI: 60.1–76.9%) and 68.4% (95% CI: 47.4–89.4%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.636). Among patients without allo-HSCT, the 2-year OS was 49.9% (95% CI: 40.7–59.1%) and 19.2% (95% CI: 0–39.6%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.002). In multivariate cox analysis, complex karyotype was an unfavorable factor for relapse (HR, 4.16; P = 0.006), disease-free survival (DFS) (HR, 2.16; P = 0.020), and OS (HR, 2.47; P = 0.009) post-transplantation. Conclusion Patients with MF-2/3 have more complex karyotypes and lower ORR of cytoreduction in MDS. Among patients without allo-HSCT, patients with MF-2/3 have a worse prognosis than those with MF-0/1. However, the adverse impact of MF on prognosis may be overcome by allo-HSCT.

The myelodysplastic syndrome (MDS) holds a special place among blood cancers, as it represents a whole spectrum of hematological disorders with impaired differentiation of hematopoietic precursors, bone marrow dysplasia, genetic instability and is noted for an increased risk of acute myeloid leukemia. Both genetic and epigenetic factors, including microRNAs (miRNAs), are involved in MDS development. MicroRNAs are short non-coding RNAs that are important regulators of normal hematopoiesis, and abnormal changes in their expression levels can contribute to hematological tumor development. To assess the prognosis of the disease, an international assessment system taking into account a karyotype, the number of blast cells, and the degree of deficiency of different blood cell types is used. However, the overall survival and effectiveness of the therapy offered are not always consistent with predictions. The search for new biomarkers, followed by their integration into the existing prognostic system, will allow for personalized treatment to be performed with more precision. Additionally, this paper explains how miRNA expression levels correlate with the prognosis of overall survival and response to the therapy offered.

The post-transplant scoring system (PTSS), developed by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, is based on three independent post-transplant risk factors: grade of acute graft-versus-host disease, lack of platelet recovery before day 100, and relapse before day 100; discriminating low- (0), intermediate- (1–3), and high-risk (4–8) patients. We investigated the prognostic value of the PTSS in a cohort of patients with MDS who underwent myeloablative CD34-selected TCD transplants. From 2008 to 2018, 109 patients underwent a first TCD-HCT for MDS at our center. We used Cox proportional hazards models and different landmark analyses to evaluate the association of categorized PTSS score risk groups with overall survival (OS). Patients with an intermediate/ high risk PTSS score had decreased OS at day 180 (univariate HR 3.25 [95% CI 1.60, 6.60], p = 0.001) and at day 365 (univariate HR 5.42 [95% CI 2.21, 13.3], p

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by dysplasias, ineffective hematopoiesis and risk of acute myeloid leukemia transformation. Approximately 90% of MDS patients present mutations in genes involved in various cell signaling pathways. Specialized DNA polymerases, such as POLN, POLI, POLK, POLQ, POLH, POLL and REV3L, insert a nucleotide opposite replication–blocking DNA lesions in an error-prone manner and, in this way, sometimes can actively promote the generation of mutation. For the best of our knowledge, has not been described the mutations of these genes in MDS. DNA target sequencing CDS regions of the REV3L gene was performed in a 58-year-old man diagnosed as High Risk Myelodysplastic Syndrome. The patient presented very low hemoglobin, increased number of blasts, karyotype:47,XY,+8[6]/47,XY,del(7)(q32),+8[7], no response to hypomethylating therapy (decitabine), all markers of poor prognosis. Target sequencing identified a mutation c.9253-6T>C REV3L (Substitution - intronic) with VAF (variant allele frequency) = 16% considered pathogenic according to Functional Analysis through. Hidden Markov Models (FATHMM). This is the first evidence of REV3L mutation in MDS and, of utmost importance, associated with poor prognosis.

Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2–3/MF2 − 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 − 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 − 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

Cardiovascular disease (CVD) involves the second cause of death in low-risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all-cause mortality in transfusion dependent low-risk MDS patients. Thirty-one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow-up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT-proBNP ≥ 486pg/ml (HR 96·7; 95%-CI 1·135–8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%-CI 1·235–1623; P = 0·038) and higher left ventricular global longitudinal strain (LV-GLS) (HR 0·4; 95%-CI 0·196–0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low-risk MDS patients frequently suffer CVD. NT-proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high-risk patients who could benefit from a cardiac treatment and follow-up., This work was funded by aGerencia Regional de Salud de Castilla y León grant(GRS1203/A/15) and a Rıo Hortega contract (CM19/00055),supported by the Instituto de Salud Carlos III in Spain (co-funded by the European Social Fund ‘Investing in yourfuture’).

TERC variant telomere biology disorders (TBDs) are a rare, heterogenous group of disorders that arise from germline variants in TERC , a gene that encodes for the RNA component of telomerase. Variants in TERC lead to accelerated telomere attrition and can manifest as many different phenotypes. In this case series, we aimed to add to the literature describing TERC variant TBDs by reporting cases from two unrelated families from Atlantic Canada. The first case, a previously described germline TERC variant, n.107G>T (NR_001566.1), was identified in a young woman with myelodysplastic syndrome (MDS) and found to segregate with cytopenias in the family. This case represents a unique phenotypic presentation: this variant has not previously been described in patients with MDS and adds important segregation data to the literature. The second case, a novel TERC n.437T>G variant, was identified in a patient with both aplastic anemia and pulmonary fibrosis manifesting in his early 30s. We report these novel cases of germline TERC variants in order to help clinicians recognize TBDs, as well as to add important supporting information for the pathogenicity of these variants. J Hematol. 2021;10(3):130-135 doi: https://doi.org/10.14740/jh826

Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our preclinical study included n = 49 xenografts generated from n = 9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification and clonal bone marrow evolution was reconstructed by serial whole-exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient–individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients’ clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.

International audience; Systemic auto-inflammatory or autoimmune diseases (SIADs) develop in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). With or without the occurrence of SIADs, the distribution of MDS subtypes and the international or CMML-specific prognostic scoring systems have been similar between MDS/CMML patients. Moreover, various SIADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities including systemic vasculitis, connective tissue diseases, inflammatory arthritis and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can also be seen. Although the presence of SIADs does not impact the overall survival nor disease progression to acute myeloid leukemia, they can help with avoiding steroid dependence and make associated adverse events of immunosuppressive drugs challenging. While therapies using steroids and immunosuppressive treatment remain the backbone of first-line treatment, increasing evidence suggests that MDS specific therapy (hypomethylating agents) and sparing steroids may be effective in treating such complications based on their immunomodulatory effect. The aim of this review was to analyze the epidemiological, pathophysiological, clinical and therapeutic factors of systemic inflammatory and immune disorders associated with MDS.

Objectives SF3B1 mutations are the most common mutations in myelodysplastic syndromes (MDS). The International Working Group for the Prognosis of MDS (IWG-PM) recently proposed SF3B1-mutant MDS (SF3B1-mut-MDS) as a distinct disease subtype. We evaluated the spectrum and molecular landscape of SF3B1-mutated myeloid disorders and assessed the prognostication in MDS harboring SF3B1 mutations (MDS-SF3B1). Methods Cases were selected by retrospective review. Clinical course and laboratory and clinical findings were collected by chart review. SF3B1-mut-MDS was classified following IWG-PM criteria. Results SF3B1 mutations were identified in 75 of 955 patients, encompassing a full spectrum of myeloid disorders. In MDS-SF3B1, Revised International Prognostic Scoring System (IPSS-R) score greater than 3 and transcription factor (TF) comutations were adverse prognostic markers by both univariate and multivariate analyses. We confirmed the favorable outcome of IWG-PM-defined SF3B1-mut-MDS. Interestingly, it did not show sharp prognostic differentiation within MDS-SF3B1. Conclusions SF3B1 mutations occur in the full spectrum of myeloid disorders. We independently validated the favorable prognostication of IWG-PM-defined SF3B1-mut-MDS. However it may not provide sharp prognostication within MDS-SF3B1 where IPSS-R and TF comutations were prognostic-informative. Larger cohort studies are warranted to verify these findings and refine MDS-SF3B1 prognostication.

Natural killer cells (NK cells) are cytotoxic lymphocytes that play a pivotal role in maintaining immunological surveillance and in developing an innate immune response. Since the discovery of NK cells in 1973, the mechanisms of their functioning have been studied in details, and there is currently no doubt that they play a special role in the process of recognition and destruction of transformed and malignant cells. Understanding the role of NK cells in antitumor immunity, on the one hand, leads to emergence of new immunotherapeutic strategies and, on the other hand, allows to adjust the existing treatment regimens for tumor diseases, in accordance with the principle of primum non nocere. Optimization of cancer therapy protocols executed in order to protect immune cells from death and functional impairment is an important problem that cannot be successfully resolved without regular aggregation of the results from disparate studies and critical analysis of the all accumulated data.The objective of this review is to create a relevant and holistic picture of changes in the phenotypic and functional characteristics of NK cells in patients with two related hematological diseases – myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). For the treatment of both illnesses, drugs from the group of hypomethylating agents are used, the acting mechanism of which, unlike classical cytostatic agents, is based on modulation of the tumor cell genes expression. All the cells of the body are being affected, including NK cells, since these drugs act nonspecifically. Such an interaction leads to a hypomethylation of NK cell DNA and changes the expression of functional receptors, which, in turn, provide the development of antitumor NK cell immune response.Of course, just the fact of changing gene expression in certain cells does not allow us to fully judge the drug’s impact on the state of immune system. Meanwhile, the origin of this change and its role are important in the context of the disease pathogenesis. Ultimately, a simple description of an increase or decrease in a single receptor expression is not illustrative, since it can lead to uncertain consequences. For this reason, the current review, in addition to describing the existing data on the changes of NK cell receptors expression under the influence of hypomethylating drugs, gives a special attention to critical analysis of functional characteristics of NK cells, including their cytotoxic activity aimed at malignant blast cells, being a determinant of clinical course in the described diseases.

Aberrant DNA methylation plays a pivotal role in tumor development and progression. DNA hypomethylating agents (HMA) constitute a class of drugs which are able to reverse DNA methylation, thereby triggering the re-programming of tumor cells. The first-generation HMA azacitidine and decitabine have now been in standard clinical use for some time, offering a valuable alternative to previous treatments in acute myeloid leukemia and myelodysplastic syndromes, so far particularly in older, medically non-fit patients. However, the longer we use these drugs, the more we are confronted with the (almost inevitable) development of resistance. This review provides insights into the mode of action of HMA, mechanisms of resistance to this treatment, and strategies to overcome HMA resistance including next-generation HMA and HMA-based combination therapies.

Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.

Myelodysplastic syndrome (MDS) refers to a heterogeneous group of clonal blood disorders characterized by ineffective hematopoiesis, cytopenia, dysplasia, and an increased risk of acute myeloid leukemia (AML). A growing number of inherited genetic loci that contribute to MDS/AML development are rapidly being identified. As genetic sequencing has become increasingly integrated into clinical practice, clearly defined syndromes have emerged, known as the MDS/AML predisposition syndrome. With more patients and families being identified with predisposing conditions, knowledge of the approach of evaluating and managing MDS with genetic predisposition is increasingly essential. This article reviews MDS with genetic predisposition and the practical aspects of management in patients with predisposition syndrome.

The rapidity of glioblastoma progression can be exacerbated by impaired systemic immune surveillance. We describe an elderly woman with advanced 5q– myelodysplastic syndrome (MDS) associated with trilineage dysfunction in hematopoiesis. She also developed multiple solid tumor malignancies including ER/PR-positive and HER2-negative breast cancer, probable lung cancer without histologic confirmation, and primary glioblastoma with a high proliferation index of 80%. Because of low platelet counts of 20,000–30,000/µL that required periodic transfusion and a reduced white cell count of 600–900/µL, she was deemed unsafe to take concomitant daily temozolomide during radiation and her glioblastoma was treated with a shortened course of radiotherapy alone. Her baseline absolute neutrophil count was 110–390/µL, and CD4+ and CD8+ lymphocyte counts were 235/µL and 113/µL, respectively. During the last week of radiation, the patient developed a nonfluent aphasia, increased fatigue, and aspiration pneumonia. A gadolinium-enhanced head MRI, obtained 2 days after completion of radiation and 39 days after biopsy, demonstrated near tripling of the size of the left frontal tumor with a significant amount of adjacent cerebral edema. This case raises the possibility that advanced MDS is a negative immunomodulatory condition that can accelerate glioblastoma progression.

In this large single-centre study, we report high prevalence (25%) of, small (p = 0.04). PNH clone, irrespective of size, was a good predictor of response to immunosuppressive therapy (IST) and to stem cell transplant (HSCT) (in MDS: 84% if PNH+ vs. 44.7% if PNH−, p = 0.01 for IST, and 71% if PNH+ vs. 56.6% if PNH− for HSCT; in AA: 78 vs. 50% for IST, p p = 0.01 for HSCT). PNH positivity had a favorable impact on disease progression (0.6% vs. 4.9% IPSS-progression in MDS, p p = 0.01), leukemic evolution (6.8 vs. 12.7%, p = 0.01 in MDS), and overall survival [73% (95% CI 68–77) vs. 51% (48–54), p p

Introduction Myelodysplastic syndrome (MDS) is a group of heterogeneous hematological diseases characterized by ineffective hematopoiesis and dysplastic morphology. Single nucleotide polymorphism array (SNP‐A)‐based whole genome analysis has a much higher resolution for chromosomal alterations when compared with conventional cytogenetic tools. In the present study, we evaluated the diagnostic value and prognostic significance of SNP‐A in MDS patients with normal karyotypes. Methods A total of 127 patients with MDS and myeloproliferative neoplasms or acute myeloid leukemia with myelodysplasia‐related changes were included in our study. The advantages and disadvantages of SNP‐A were compared with those of traditional metaphase cytogenetic analysis (MC). The Kaplan‐Meier analysis and COX regression analysis were used to investigate the prognostic value of SNP‐A and uniparental disomy (UPD) in MDS patients with normal karyotype. Furthermore, the chromosomal abnormalities detected by SNP‐A in patients with specific gene mutations were explored. Results SNP‐A was more sensitive toward meaningful chromosomal aberrations (58.2% vs 36.9%; P

Background Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and life-threatening cytopenias. Survival is poor, and management is pivotal on rapid identification of the disease. HLH is associated with hematologic malignancies, however correlation with myelodysplastic syndromes (MDS) is exceedingly unusual. Although minimizing overwhelming hyperinflammation by treating hemophagocytosis are central for HLH outcome, there is urgent necessity to identify potential initiating mechanisms that could assist in therapy design. Case description Here, we describe an elderly African American patient who developed rapid onset of cytopenias and coagulopathy associated with hepatic and bone marrow hemophagocytosis. We analyze four additional similar cases to isolate clinical, laboratory and cytogenetic findings expected in patients exhibiting concurrent HLH and MDS. HLH linked with MDS retains common HLH features associated with systemic hyperinflammation such as fever, hypotension, hepatosplenomegaly, hyperferritinemia, coagulopathy and rapidly evolving cytopenias. Typical MDS chromosomic abnormality such as trisomy 8 was frequently observed in our studied cases. Conclusion Our case describes difficulties while managing HLH in MDS patients. Diagnosis should be based on identifying HLH appropriate criteria and if possible karyotypic abnormalities normally observed in MDS.

Background/Aims: In this study, we tested whether mutations in the methylation pathway genes ten-eleven-translocation 2 (TET2) and DNA methyltransferase gene 3A (DNMT3A) improve the responses of patients with myelodysplastic syndrome (MDS) to decitabine. Methods: We retrospectively sequenced the TET2 and DNMT3A genes from 70 patients diagnosed with de novo MDS between June 2008 and December 2011 and treated with a 5-day regimen of decitabine (290 cycles). We then analyzed treat ment outcomes. Results: Patients with hematological improvement survived longer than those without hematological improvement (22.9 months vs. 10.9 months, p = 0.006). Among the 70 patients, 12 (17.1%) carried TET2 or DNMT3A mutations. The base line characteristics of patients with wild type or mutated genes were similar. Pa tients with mutations in TET2 or DNMT3A had a higher overall response rate than those with the wild type genes (82.3% vs. 46.6%, p = 0.023). Multivariate analysis demonstrated that the TET2 or DMNT3A mutation status was associated with im proved treatment responses and better overall survival among patients receiving decitabine. Conclusions: These results demonstrate that TET2 mutations enhance the treat ment response of MDS patients to hypomethylating agents like decitabine.

Introduction Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) – including chronic myeloid leukemia (CML) – and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. Methods We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes “myeloid malignancies.” Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. Results Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML – and not for MDS or MPN – but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. Conclusions Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing “myeloid malignancies,” the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc – where appropriate – always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

Background The treatment strategies for Myelodysplastic Syndromes (MDS) are usually based on the risk stratification system. However, few risk signatures which integrate the revised international prognostic scoring system (IPSS-R) with gene mutations can be easily applied in the real world. Methods The training cohort of 63 MDS patients was conducted at Zhongda Hospital of Southeast University from January 2013 to April 2020. The validation cohort of 141 MDS patients was obtained from GSE129828. The mutation scoring system was based on the number of mutations and a unique favorable prognostic factor, which is SF3B1 mutation. Univariate Cox, multivariate Cox, and LASSO regression analyses were used to determine the significant factors that influenced the overall survival. The receiver operating characteristic curve (ROC) was used to evaluate the efficiency of the prognostic model. Results A novel risk scoring system we named “mutation combined with revised international prognostic scoring system (MIPSS-R)” was developed based on the results derived from multivariate analysis which assigned points to the IPSS-R and the mutation scores according to their relative statistical weight. Based on the quintile of the new scores, patients were divided into five risk levels. The Kaplan-Meier curves showed the superiority of MIPSS-R in separating patients from different groups, comparing with IPSS-R both in the training cohort (p = 1.71e-08 vs. p = 1.363e-04) and validation cohort (p = 1.788e-04 vs. p = 2.757e-03). The area under the ROC of MIPSS-R was 0.79 in the training cohort and 0.62 in the validation cohort. The retrospective analysis of our house patients showed that the risk levels of 57.41% of patients would adjust according to MIPSS-R. After changing risk levels, 38.71% of patients would benefit from treatment strategies that MIPSS-R recommends. Conclusion A mutation scoring system was conducted based on the number of mutations and a unique favorable prognostic factor. MIPSS-R, the novel integral risk stratification system was developed by integrating IPSS-R and the mutation scores, which is more effective on prognosis and treatment guidance for MDS patients.

Background The role of pre‐hematopoietic stem cell transplantation (HSCT) cytoreduction with either induction chemotherapy (IC) or hypomethylating agents (HMAs) in treating advanced myelodysplastic syndrome (MDS) remains debatable. We aimed to evaluate pre‐HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre‐HSCT cytoreduction and those with best supportive care. Methods We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor (HID, n = 162) or matched related donor (MSD, n = 66) with uniform myeloablative conditioning regimens between January 2015 and December 2018. Of these 228 patients, 131 (57.5%) were treated exclusively with pre‐HSCT best supportive care (BSC), 49 (22.5%) were given HMA, and 48 (21.1%) received both IC and HMA. Propensity score‐matching analysis, multivariate analyses, and subgroup analyses were performed to elucidate the impact of pre‐HSCT strategies on transplant outcomes. Results The 3‐year relapse‐free survival (RFS) rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts (P = 0.189) and were 78.2%, 66.7%, and 73.2% for the BSC, HMA, and HMA+IC groups, respectively (P = 0.269). A propensity score‐matching analysis confirmed that the 3‐year RFS rates were 81.9%, 87.5%, and 66.9% for BSC, cytoreduction complete remission (CR), and cytoreduction non‐CR groups, respectively (P = 0.051). Multivariate analyses demonstrated that pre‐HSCT cytoreduction, older patient age, monosomal karyotype, and interval between diagnosis and HSCT were poor prognostic factors for RFS. In the subgroup analyses, BSC was associated with longer RFS compared to cytoreduction among the younger patients, those with international prognostic scoring system intermediate‐2/high risk at diagnosis, and those with intermediate/poor cytogenetics. Conclusions Different pre‐HSCT therapies did not yield discrepant post‐HSCT outcomes. No benefit in terms of post‐HSCT outcomes were correlated with pre‐HSCT cytoreduction in advanced MDS even for cytoreduction CR patients. Early referral to HSCT is essential for advanced MDS patients.

Pregnancy may aggravate myelodysplastic syndrome. Cross‐matched platelets can be used in cases of refractory thrombocytopenia. Vaginal delivery can be attempted if the platelet count is at least 20 × 109/L.

Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Our data show that Ras/MAPK pathway mutations, alterations in RUNX1 or TP53, and KMT2A rearrangements are frequent somatic drivers, and we identify cases with aberrant MECOM expression secondary to enhancer hijacking. Unlike adults with tMN, we find no evidence of pre-existing minor tMN clones (including those with TP53 mutations), but rather the majority of cases are unrelated clones arising as a consequence of cytotoxic therapy. These studies also uncover rare cases of lineage switch disease rather than true secondary neoplasms., Paediatric therapy-related myeloid neoplasms (tMN) have a dismal prognosis and have not been comprehensively profiled. Here the authors characterise the molecular landscape of 84 paediatric tMN patients, and find that, unlike adult tMNs, these do not emerge from pre-existing clones and that MECOM dysregulation is frequent.

TO THE EDITOR : There is a critical unmet need for novel treatments for higher-risk myelodysplastic syndromes (MDS), higher-risk chronic myelomonocytic leukemia (CMML), and low-blast (LB) acute myeloid leukemia (AML). For patients ineligible for stem cell transplant (SCT), standard therapy with hypomethylating agents, such as azacitidine and decitabine, is not curative, with most patients relapsing within 2 years. [...]

For the majority of patients with lower-risk myelodysplastic syndrome (LR-MDS), one of the primary clinical goals is to alleviate the symptoms associated with the resultant cytopenias and to minimize the transfusion burden. While supportive red blood cell (RBC) transfusions and erythropoiesis-stimulating agents (ESAs) may lead to clinical improvement, frequent transfusions are often complicated by iron overload and decreased quality of life; furthermore, most patients either do not respond to ESAs or will eventually develop resistance. As such, there is a great need for further therapeutic options in the management of anemia related to MDS. Several additional therapeutics are now available in select patients with LR-MDS and symptomatic anemia including luspatercept, lenalidomide, and immunosuppressive therapy. Furthermore, several novel agents are currently in development to address this area of clinical need such as imetelstat and roxadustat. In this article, we review the currently available therapeutic options for symptomatic anemia in LR-MDS as well as review the therapeutic agents in development.

Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile. We investigated post-transplant outcomes in 1722 MDS patients following allo-HCT with FT (n=367), RIC (n=687) or MAC (n=668). FT and RIC recipients were older than MAC recipients, median age 59, 59 and 51years, respectively (P&nbsp

Background: Recently, various associations of NGAL with several hematological cancers have been reported. However, given that the regulation of NGAL gene expression by cytokines is tissue-specific, NGAL expression in relation to those of cytokine genes has not been analyzed in bone marrow (BM) tissue. The purpose of this study was to analyze the association between NGAL and 48 cytokine gene expression levels in mononuclear cells (MNCs) of BM at the time of diagnosis of hematological malignancy and to explore the expression pattern of NGAL and related cytokine genes in patients with hematological malignancies and controls. Methods: BM MNCs were isolated from 48 patients, who were classified as patients presenting myeloproliferative neoplasm, acute myeloid leukemia, myelodysplastic syndrome, and as controls. NGAL and cytokine genes were analyzed using NanoString. Data on hematological parameters were collected from medical records. Single and multiple regression analyses were performed to analyze relationships. Results: Normalized counts of 26 cytokine genes were related to NGAL normalized counts, while STAT3 and TLR4 normalized counts had the highest explanatory power. The following multiple regression model was developed: NGAL normalized counts=4316.825 + 9.056 × STAT3 normalized counts + 844.226 × IL5 normalized counts + 17.540 × TLR1 normalized counts - 28.206 × TLR2 normalized counts - 42.524 × IRAK4 normalized counts. In the multiple regression analysis, STAT3 and TLR4 normalized counts showed multicollinearity. NGAL, STAT3, IL5, and TLR4 normalized counts showed similar intergroup patterns. Conclusions: NGAL normalized counts was predicted by a multiple regression model, while they showed similar intergroup patterns to STAT3, IL5, and TLR4 normalized counts.

BACKGROUND In myelodysplastic syndrome (MDS), oxidative stress is closely related to iron overload and DNA damage. A recent study suggested the possibility that increased oxidative stress causes not only iron overload but also disease progression of MDS with DNA damage. We present a case of MDS with decreased reactive oxygen species (ROS) production in peripheral white blood cells (WBCs) and decreased diacron-reactive oxygen metabolites (d-ROMs) in serum after azacitidine therapy. CASE SUMMARY A 74-year-old man presented to the hematological department with the chief complaint of anemia. His vital signs were within normal limits at admission with a heart rate of 80 bpm and blood pressure of 135/60 mmHg. Laboratory tests indicated pancytopenia, a WBC count of 2190 cells/µL, a hemoglobin level of 6.2 g/dL and a platelet count of 7.4 × 104/µL. The patient was diagnosed with MDS with fibrosis after a bone marrow examination. This case showed decreased ROS production in WBCs, d-ROMs in serum and Wilms’ tumor 1 after azacitidine therapy, after which his hematopoiesis recovered. CONCLUSION Azacitidine therapy can improve hematopoiesis and decrease ROS and d-ROM production.

The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

The European Leukemia Net (ELN) guidelines for treatment of myelodysplastic syndromes (MDS) connect heterogeneous MDS subgroups with a number of therapeutic options ranging from best supportive care to allogeneic stem cell transplantation (alloSCT). However, it is currently unknown whether adherence to guideline recommendations translates into improved survival. The sizeable database of the Duesseldorf MDS Registry allowed us to address this question. We first performed a retrospective analysis including 1698 patients (cohort 1) to whom we retrospectively applied the ELN guidelines. We compared patients treated according to the guidelines with patients who deviated from it, either because they received a certain treatment though it was not recommended or because they did not receive that treatment despite being eligible. We also performed a prospective study with 381 patients (cohort 2) who were seen in our department and received guideline-based expert advice. Again, we compared the impact of subsequent guideline-adherent versus non-adherent treatment. For the majority of treatment options (best supportive care, lenalidomide, hypomethylating agents, low-dose chemotherapy, and intensive chemotherapy), we found that adherence to the ELN guidelines did not improve survival in cohort 1. The same was true when patient management was prospectively enhanced through guideline-based treatment advice given by MDS experts (cohort 2). The only exceptions were alloSCT and iron chelation (ICT). Patients receiving ICT and alloSCT as recommended fared significantly better than those who were eligible but received other treatment. Our analysis underscores the limited survival impact of most MDS therapies and suggests to pursue alloSCT in all suitable candidates. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00277-020-04325-7.

Anemia in patients with malignant neoplasms affects the quality of life of the patient and sometimes limits the timely implementation of antitumor treatment. In the pathogenesis of anemia of the malignant neoplasms the largest role play infiltration of the bone marrow by tumor cells, suppression of hematopoiesis by inflammation cytokines, development of functional iron deficiency, reduction of sensitivity of receptors to erythropoietin or its synthesis. The doctor can prescribe effective pathogenetic therapy after evaluating the mechanisms of anemia development in this category of patients. In the article are described in detail the methods of pathogenetic correction of anemic syndrome using parenteral iron preparations, recombinant erythropoietin, indications for their appointment, effectiveness in patients with cancer, as well as possible side effects and complications of therapy. The mechanisms of action, pharmacokinetics, and features of the use of different erythropoietin adents are described. It is shown the effectiveness of erythropoietin preparations in patients with lymphoproliferative disorders based on the results of our own study. A positive response was observed in 77.3 % of patients with non-Hodgkin’s lymphomas, in 61.8 % – with multiple myeloma and 60.9 % with chronic lymphocytic leukemia. It is presented the prognostic factors for the response to erythropoietin therapy and showed own datum in patients with myelodysplastic syndrome (in case of the serum erythropoietin

Behçet’s disease (BD) is a multisystem inflammatory disease of unknown origin. Rarely, BD occurs together with myelodysplastic syndrome (MDS). Interestingly, it is speculated that these are not simple coexistence but that the etiology of intestinal BD is at least partly derived from MDS itself. Furthermore, there is a relationship between MDS in patients with intestinal BD and trisomy 8. Immunosuppressive agents alone are insufficient to control MDS-associated BD, and many of these patients die of infection or hemorrhage. Surgery is considered for intestinal BD patients who are unresponsive to medical treatment or those with bowel complications such as perforation or persistent bleeding. We report a case of intestinal BD associated with MDS and trisomy 8. The patient was unresponsive to oral steroids and immunosuppressive treatment; the patient improved by surgical repair of a bowel perforation. Five years after the surgery, the patient is free of recurrence and not on medication. Our experience suggests that surgery may provide an effective therapeutic option for the treatment of MDS-related BD.

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative therapeutic option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Increasing data suggest that haploidentical donor (HID) transplantation achieve comparable outcomes with HLA‐matched sibling donor (MSD) in adult AML/MDS. This retrospective study compared the outcomes of AML or MDS patients age ≥50 years underwent HID and MSD transplantation. One hundred and fifty‐six patients were enrolled in this study, including 75 HID and 81 MSD transplantation. The 100‐day cumulative incidence of II‐IV° acute graft‐versus‐host disease (GVHD) was 33.3 ± 5.4% vs 22.2 ± 4.6%, respectively, in HID and MSD groups (P = .066), and III‐IV° acute GVHD was not significantly different between two groups (5.3%±2.6% vs 6.2%±2.7%, respectively, P = .823). The 2‐year cumulative incidence of limited and extensive chronic GVHD was not statistically different in HID and MSD groups (20.9 ± 5.5% vs 18.9 ± 4.8% and 13.0 ± 4.7% vs 19.7 ± 5.0%, P = .889 and P = .269, respectively). The 2‐year cumulative incidences of relapse (27.0 ± 5.6% vs 22.7 ± 5.1%, P = .509), 2‐year overall survival (63.0 ± 5.8% vs 66.7 ± 5.4%, P = .454), 2‐year transplant‐related mortality (17.2 ± 4.6% vs 17.4 ± 4.4%, P = .847), 2‐year progression‐free survival (59.3 ± 5.8% vs 64.5 ± 5.4%, P = .437), 2‐year GVHD‐free relapse‐free survival (42.6 ± 5.9% vs 40.9 ± 5.6%, P = .964) were not significantly different in the two groups. The present data showed equivalent outcomes in AML or MDS patients age ≥50 years underwent HID and MSD transplantation., We compared the transplant outcomes between HID and MSD transplants for AML and MSD aged ≥50 years. The results showed that HID transplant is feasible and safe for elderly AML/MDS patients.

We report a case with a broad spectrum of symptoms, related to GATA2 deficiency syndrome, which emerged as early as at 6 months of age. They ranged from lymphedema, deafness to myelodysplastic syndrome (MDS)., Non‐hematologic symptoms may long precede myelodysplastic syndrome diagnosis in patients with GATA2 mutations.

Lenalidomide is efficient in reducing red blood cell transfusion dependency and markedly lowering platelet counts in MDS/MPN‐RS‐T in the context of major platelet counts.

Background The lower-risk (low and intermediate-1 risk based on IPSS) myelodysplastic syndrome (MDS) has a negative impact on patients’ health-related quality of life (HRQoL). Patient Reported Outcomes (PROs) instruments, which are used to collect patients’ HRQoL data, should have established content validity in the target population to ensure that the instrument is comprehensive and comprehensible. The present study was conducted to evaluate the content validity of the Quality of Life in Myelodysplasia Scale (QUALMS) and the Functional Assessment of Cancer Therapy-Anemia (FACT-An) PRO instruments in patients with lower-risk MDS. Methods In this cross-sectional, qualitative study, 16 patients aged ≥18 years with lower-risk MDS, who were RBC transfusion dependent, literate and fluent in US-English were interviewed. Interviews were semi-structured comprising of two parts: concept elicitation (CE) explored symptoms and impacts important to patients, and cognitive debriefing (CD) assessed understanding and relevance of the QUALMS and FACT-An. A conceptual model was developed, which was used to map the concepts that emerged during CE onto the QUALMS and FACT-An to assess concept coverage and suitability of the instruments. Results The median age of participants was 67.5 years (range: 51–91), with half being female (n = 8). Nine (56.2%) participants had intermediate-1-risk MDS and 10 (62.5%) were relapsed or refractory to erythropoiesis-stimulating agent treatment. Fatigue/tiredness (100.0%), shortness of breath (87.5%), weakness (81.2%), and low energy (75.0%) were reported most commonly and were the most bothersome symptoms as well. Of seven high-level HRQoL domains identified, activities of daily living (n = 16, 100.0%), physical functioning (n = 15, 93.8%), emotional wellbeing (n = 13, 81.3%), social functioning (n = 12, 75.0%), sleep disturbance (n = 9, 56.3%), and impact on work (n = 9, 56.3%) were the most commonly reported. For CD, the QUALMS and FACT-An were found to be mostly relevant and very well understood; response options were easy to use, and recall period was appropriate. Conclusion Both QUALMS and FACT-An demonstrated a strong face and content validity in patients with lower-risk MDS, suggesting that these instruments are appropriate for assessing HRQoL in this population.

Objectives:Myelodysplastic syndrome (MDS) is a clonal disease that progresses with cytopenias and has leukemia transformation. Allogeneic Stem Cell Transplantation (ASCT) is a curative treatment in MDS patients. However, to which patient group the ASCT transplant will be applied, the treatments to be given before, and the conditioning regimens applied during the transplant are among the controversial topics. In this study, it was aimed to evaluate MDS patients who were diagnosed and underwent ASCT in our unit.Materials and Methods:Forty-four MDS patients that were diagnosed at our center and underwent ASCT at Stem Cell Transplantation Unit between 1992 and 2016 were evaluated retrospectively.Results:Of the 44 patients included in the study, 31 were male (71%) and 13 were female (29%). The median age was 41 years, six patients (14%) were over 60 years old. Twenty-two of 31 patients with cytogenetic analysis were at high risk according to R-IPSS and nine patients were at intermediate risk. While complete response was observed in 32 patients (73%) after ASCT, engraftment was not achieved in 10 patients (22%). Two patients (5%) were not responsive to treatment. Mucositis developed in all patients and diarrhea developed in 39 patients (89%). The relationship of mucositis, diarrhea and engraftment kinetics with age (60 years), R-IPSS, HCT-Cl score and the type of conditioning regimen was not shown. While 1-year overall survival was 73%, 1-year non-relapse mortality was 71%. In univariate regression analysis, high risk disease category, use of myeloablative conditioning regimen, acute graft versus host disease caused statistically significant decrease in overall survival. In the multivariate analysis, none of the factors affected the overall survival.Conclusion:Long term and sustainable response rates were achieved even if transplantation related toxicities were common in our cohort of MDS patients who underwent ASCT.