Myelodysplasia Syndrome Research Articles

Biallelic germline DDX41 variants in a patient with bone dysplasia, ichthyosis, and dysmorphic features.

DDX41 (DEAD‑box helicase 41) is a member of the largest family of RNA helicases. The DEAD-box RNA helicases share a highly conserved core structure and regulate all aspects of RNA metabolism. The functional role of DDX41 in innate immunity is also highly conserved. DDX41 acts as a sensor of viral DNA and activates the STING-TBK1-IRF3-type I IFN signaling pathway. Germline heterozygous variants in DDX41 have been reported in familial myelodysplasia syndrome (MDS)/acute myeloid leukemia (AML) patients; most patients also acquired a somatic variant in the second DDX41 allele. Here, we report a patient who inherited compound heterozygous DDX41 variants and presented with bone dysplasia, ichthyosis, and dysmorphic features. Functional analyses of the patient-derived dermal fibroblasts revealed a reduced abundance of DDX41 and abrogated activation of the IFN genes through the STING-type I interferon pathway. Genome-wide transcriptome analyses in the patient's fibroblasts revealed significant gene dysregulation and changes in the RNA splicing events. The patient's fibroblasts also displayed upregulation of periostin mRNA expression. Using an RNA binding protein assay, we identified DDX41 as a novel regulator of periostin expression. Our results suggest that functional impairment of DDX41, along with dysregulated periostin expression, likely contributes to this patient's multisystem disorder.

Diagnosing Non–Producers Non–Secretory Myeloma

Multiple myelomas (MM) is the proliferation of malignant plasma cells in the bone marrow, characterized by the production of monoclonal immunoglobulins that are secreted in the blood and urine. However, in 1 - 5% of cases, the protein is undetectable and defined as non-secretory type of myeloma.
 A 36-year-old woman presented with complaints of weakness in both legs so she could not walk. She also felt pain in the head, back, and thighs since one year before. Physical examination showed anemic conjunctiva, gibus as high as T4, hypoesthesia as high as T6 segment. She had anemia (Hb 10.2 g/dL), decreased kidney function (eGFR: 30 mL/min/1.73m2), and multiple lytic lesions in the calvaria, ribs, superior-inferior pubic ramus, and left humeral os in the 1/3 proximal to 1/3 distal. Protein electrophoresis and Bence Jonce protein were negative. There was no hypercalcemia, and bone marrow aspiration showed myelodysplasia syndrome. A thoracolumbar MRI showed an extradural solid mass and the histopathology examination result was plasmacytoma.
 Non-secretory MM was defined into two groups, non-producers and multiple non-secretory myeloma patients who produce tumor proteins but cannot be excreted. This patients was categorized as non-producers non-secretory MM because she did not show a protein that can be measured in blood nor urine, but has significant plasma cells in tissue biopsy.
 The absence of paraprotein in the blood does not rule out multiple myeloma. Suspicion of multiple myeloma needs to be increased in patients who have symptoms of CRAB (calcium, renal impairment, anemia, bone lytic).

GATA2 at 10: Emergence of Genotype-Phenotye correlations

GATA2 mutations cause adult-onset bone-marrow failure characterized by cytopenias, infections and increased risk of leukemia. We reviewed hospital records and referrals from 232 GATA2 mutation positive individuals from 122 families to gather hematopoietic and syndromic features.Mutations were categorized by effect on GATA2 protein: missense after the 2nd Zinc-finger (C-term, n = 10); missense in the 2nd Zinc-Finger (2nd Zf, n = 104); mutations producing stable truncated protein (truncation, n = 26); null alleles (mRNA instability, large deletions, n = 42); or enhancer (n = 50). Median age at first symptom presentation for the cohort was 20 years.Kaplan-Meier analysis for symptom onset showed differences in age at presentation across truncation and null mutations (median 15 and 18 years, respectively), 2nd Zf (22 years) and enhancer mutations (45 years). A similar analysis of four recurrently mutated 2nd ZF amino acids revealed later symptom onset for R361 and R398 mutations (median 22 and 34 years, respectively) compared to R396 or T354 (16 and 19 years, respectively). Mixed-effect Cox regression analysis corrected for relatedness across patients and confirmed these findings.There was decreased penetrance in enhancer (27/50, 54% symptomatic) and 2nd Zf (85/104, 81.7%) compared to truncation (24/26, 92.3%) and null (39/40, 97.5%) mutation patients. Grouping mutations by median onset before (null, truncation, R396, T354) or after (R361, R398, enhancer) age 20 revealed significantly increased incidence of cytopenias, HPV, myelodysplastic syndrome and hearing loss among the early onset mutation group. Additionally, age of cytopenia or myelodysplasia syndrome diagnosis was significantly younger in the early onset group (P = 0.0019, P = 0.0012 respectively).Males had more monosomy 7 (11/92 males, 4/142 females, P < 0.0001). Nontuberculous mycobacterial infection was the presenting symptom in 14/92 males vs 7/142 females (P = 0.0188). Warts/anogenital HPV were common (93/234, 39.7%). Non-hematologic manifestations included hearing loss (46/232; 19.8%), lymphedema (30/232; 12.8%), and non-hematologic malignancies (46/232, 19.8%), the majority being HPV-related ano-genital cancers. Hematologic malignancy occurred in 26/234 patients (11%).This comprehensive analysis demonstrates that GATA2 mutation type, and specific mutations, affect penetrance and expression. Gender is an independent risk for specific infectious complications and cytogenetic abnormalities.

Role of Bcl-2 inhibition in myelodysplastic syndromes.

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.

Severe anemia on the treatment of a Lepra patient with a history of long-term steroid consumption suspect of Cushing syndrome

ABSTRACT Anemia is a clinical symptom caused by the disruption of erythrocyte formation, bleeding, and premature blood hemolysis. Severe anemia can occur in patients taking dapsone for the treatment of leprosy. Long-term use of steroids is also a predisposing factor for the occurrence of hematological changes and raises the suspicion of Cushing's syndrome. Reportedly a 20-year-old woman with the main complaint of sudden shortness of breath, accompanied by a cough with phlegm. The patient has had a history of multibacillary type leprosy since a month ago. There was a history of steroid consumption for about two years and only stopped a couple of months ago. Physical examination showed the oxygen saturation was 93%, conjunctival anemia, hyperpigmented plaques, tenderness in the abdominal, meteorism, and pitting edema in the upper and lower extremities. Laboratory examination revealed hemoglobin (Hb) level 2.4 mg/dl, erythrocytes 0.8x106/ul, and albumin 3.2g/dl. Peripheral blood smear results suggest refractory anemia and myelodysplasia syndrome. After being treated for seven days, the patient was re-evaluated and controlled at the Internal Medicine outpatient clinic, Syekh Yusuf Hospital. Complex symptoms and limited investigations make it difficult to establish the exact cause. Immediate blood transfusion and management of the underlying disease causing anemia, such as discontinuation of dapsone, are the primary management of this case. Keywords : severe anemia, leprosy, steroid, Cushing syndrome.Correspondence : gedepadmawijaya@yahoo.com

Frequency of BCR-ABL P190 &amp; P210, and JAK2 Mutations in Myeloproliferative Patients in Iran

Background: Hematologic malignancies can be divided into two categories: myeloid and lymphoid, each of which is further divided into acute and chronic. Chronic myeloid diseases consist of Myelodysplasia Syndrome (MDS), Myeloproliferative Neoplasms (MPNs), and a rare group of MDS/MPN. According to genetic studies, the prevalence of some mutations related to cell division is higher in these patients. Given that gene analysis is an available way to diagnose the disease quickly, treat it on time, and help promote effective drugs, this study aims to investigate the frequency of JAK2, BCR-ABL P190, and BCR-ABL P210 mutations in patients with neoplasms who refer to Shahid Mostafa Khomeini Hospital, Tehran, Iran, between March 2017 and September 2020. Materials and Methods: The blood samples of the patients were analyzed by PCR for the expression of BCR-ABL P190, BCR-ABL P210, and JAK2 genes to investigate any potential relationship between malfunctioned genes and the existing medical condition. Results: The mean age of the study patients was 60.5±14.7 years. Of whom 28 (53.8%) were male, and the other 24 (46.2%) were female. Also, 29 patients (55.8%) had Essential Thrombocythemia (ET), 37 patients (71.2%) had at least one of the studied mutations, 21 patients (40.4%) had JAK2 mutation, and 16 patients (31.8%) had BCR-ABL mutation. There was no significant relationship between gender and any of the studied variables. Type of disease had a significant relationship with the studied mutations. Conclusion: All CML cases in this study had at least one of three types of mutations. The type of medical condition was significantly associated with the studied mutations, for example, CML patients had fewer JAK2 and more BCR-ABL gene mutations. gender was not significantly related to any factor in the study. There was no mortality during the study. All the patients were alive, and most of them (88.5%) were in remission.

Trisomy 8 Associated Clonal Cytopenia Featured With Acquired Auto-Inflammation and Its Response to JAK Inhibitors.

ObjectsIt has been recognized the nexus between trisomy 8 and auto-inflammatory features in myelodysplasia syndrome (MDS). Recent research about VEXAS syndrome proved clonal hematopoiesis could interfere with innate immune system far before occurrence of hematological malignancies. We reported a case series of clonal cytopenia with auto-inflammatory features in trisomy 8 patients.MethodsA total of six patients with isolated trisomy 8 excluded from MDS was retrospectively collected from the Department of Rheumatology, Renji Hospital, Shanghai. The clinical presentations and treatment outcomes were presented.ResultsWe report patients with trisomy 8 shared the auto-inflammatory features of recurrent fever, arthralgia, gastrointestinal involvement, and elevated inflammatory markers, especially hyperferritinemia, in addition to hematological findings such as macrocytic anemia and cytopenia of other lineages but without myelodysplasia. The symptoms of this disorder responded to the treatment of glucocorticoids but difficult to taper. JAK inhibitors were introduced to four patients with enhanced response along with glucocorticoids sparing effect and good tolerance.ConclusionClonal cytopenia harboring trisomy 8 presenting with auto-inflammatory features was identified. JAK inhibitor may be a promising anti-inflammatory option.

Better Therapeutic Approach after Comprehensive Geriatric Evaluation in Older Patients with ACUTE Myeloid Leukemia and Myelodysplasic Syndromes

Better Therapeutic Approach after Comprehensive Geriatric Evaluation in Older Patients with ACUTE Myeloid Leukemia and Myelodysplasic Syndromes

MyPal ADULT study protocol: a randomised clinical trial of the MyPal ePRO-based early palliative care system in adult patients with haematological malignancies

IntroductionThe systematic collection of electronic patient-reported outcome (ePRO) in the routine care of patients with chronic haematological malignancies such as chronic lymphocytic leukaemia (CLL) and myelodysplasia syndromes (MDS) can constitute...

Letter to the article “Spina bifida: a multidisciplinary problem (literature review)”

In the letter, the author relies on data from the foreign and domestic literature and his own experience and confirms the urgent problem of myelodysplasia syndrome in children. The letter summarizes the main advantages of the given abstract review and notes the provisions requiring addition. In general, the author of the letter highly appreciated the work done by the authors of the review.

Genetic and epigenetic orchestration of Gfi1aa-Lsd1-cebpa in zebrafish neutrophil development.

Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling neutrophil differentiation remains incompletely understood. GFI1 is associated with several myeloid disorders, but its role and the role of its co-regulators in granulopoiesis and pathogenesis are far from clear. Here, we demonstrate that zebrafish gfi1aa deficiency induces excessive neutrophil progenitor proliferation, accumulation of immature neutrophils from the embryonic stage, and some phenotypes similar to myelodysplasia syndrome in adulthood. Both genetic and epigenetic analyses demonstrate that immature neutrophil accumulation in gfi1aa-deficient mutants is due to upregulation of cebpa transcription. Increased transcription was associated with Lsd1-altered H3K4 methylation of the cebpa regulatory region. Taken together, our results demonstrate that Gfi1aa, Lsd1 and cebpa form a regulatory network that controls neutrophil development, providing a disease progression-traceable model for myelodysplasia syndrome. Use of this model could provide new insights into the molecular mechanisms underlying GFI1-related myeloid disorders as well as a means by which to develop targeted therapeutic approaches for treatment.

P18 - Topic: AS04-MDS Biology and Pathogenesis/AS04b-Clonal diversity & evolution: DIFFERENTIAL CLINICAL AND MUTATIONAL PROFILE OF HYPOPLASTIC MYELODYSPLASIC SYNDROMES

P18 - Topic: AS04-MDS Biology and Pathogenesis/AS04b-Clonal diversity & evolution: DIFFERENTIAL CLINICAL AND MUTATIONAL PROFILE OF HYPOPLASTIC MYELODYSPLASIC SYNDROMES

Myelodysplasia Syndrome, Clonal Hematopoiesis and Cardiovascular Disease

Simple SummaryThe development of blood cancers is a complex process that involves the acquisition of specific blood disorders that precede cancer. These blood disorders are often driven by the accumulation of genetic abnormalities, which are discussed in this review. Likewise, predicting the rate of progression of these diseases is difficult, but it appears to be linked to which specific gene mutations are present in blood cells. In this review, we discuss a variety of genetic abnormalities that drive blood cancer, conditions that precede clinical symptoms of blood cancer, and how alterations in these genes change blood cell function. Additionally, we discuss the novel links between blood cancer development and heart disease.The development of myelodysplasia syndromes (MDS) is multiphasic and can be driven by a plethora of genetic mutations and/or abnormalities. MDS is characterized by a hematopoietic differentiation block, evidenced by increased immature hematopoietic cells, termed blast cells and decreased mature circulating leukocytes in at least one lineage (i.e., cytopenia). Clonal hematopoiesis of indeterminate potential (CHIP) is a recently described phenomenon preceding MDS development that is driven by somatic mutations in hemopoietic stem cells (HSCs). These mutant HSCs have a competitive advantage over healthy cells, resulting in an expansion of these clonal mutated leukocytes. In this review, we discuss the multiphasic development of MDS, the common mutations found in both MDS and CHIP, how a loss-of-function in these CHIP-related genes can alter HSC function and leukocyte development and the potential disease outcomes that can occur with dysfunctional HSCs. In particular, we discuss the novel connections between MDS development and cardiovascular disease.

A clinical study on the factors associated with nasopharyngeal carcinoma among the Chinese population.

Nasopharyngeal carcinoma (NC) arises from the nasopharynx epithelium and the majority of NC cases globally are within China and Southeast Asia. Both short palate lung and nasal epithelium clone 1 (SPLUNC1) and myelodysplasia syndrome 1-ectopic viral integration site 1 (MDS1-EVI1) play an important role in carcinogenesis and have been found to be associated with nasopharyngeal carcinoma. In spite of their role in NC, the association between these genes and their polymorphisms in the development of NC has thus far not been studied. In the present study, the relationship between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms and their role in the development of NC among the Chinese population were investigated. From a Chinese population of 1,059 patients with NC and 891 controls, genotype frequencies and the distribution of SPLUNC1 and MDS1-EVI1 polymorphisms were analyzed for possible susceptibility to NC. It was observed that those with MDS1-EVI1 CC (OR, 2.76; 95% CI, 1.96-3.81) and MDS1-EVI1 CT (OR, 1.51; 95% CI, 1.22-2.14) polymorphisms had an increased risk of developing NC. Those with SPLUNC1 AA genotypes also observed a higher risk for NC compared with SPLUNC1 GG genotypes (OR, 2.15; 95% CI, 1.62-3.15). When observing the gene-gene interaction between SPLUNC1 and MDS1-EVI1 polymorphisms, it was found that the presence of both SPLUNC1 CC and MDS1-EVI1 AA alleles was associated with a higher risk for NC compared with those who did not carry both alleles (OR, 6.75; 95% CI, 3.41-12.11). The present study suggested that the association between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms may be a potent risk factor in the occurrence of NC.

Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy

AbstractGranulocyte colony-stimulating factor (G-CSF) has had a major impact on management of “severe chronic neutropenia,” a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital neutropenia, treated with G-CSF from 1987 to present. Treatment and patient demographic data were analyzed. The 352 congenital patients were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of malignant transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic neutropenia developed MDS/AML. Transformation was associated with acquired marrow cytogenetic clonal changes: 18 patients developed a partial or complete loss of chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML development was less than 2%. No significant relationships between age at onset of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P > .15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other patient demographics, we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML was not seen in cyclic or idiopathic neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF therapy may allow time for the expression of the leukemic predisposition that characterizes the natural history of these disorders. However, other factors related to G-CSF may also be operative in the setting of congenital neutropenia.

Peningkatan profil klinik-hematologi pada pasien sindrom mielodisplasia multilini paska splenektomi total

Myelodysplasia syndrome (MDS) is a hematologic disorder manifested by cytopenia and rarely with splenomegaly. Clinical complaints that often accompany symptoms of anemia and when experiencing splenomegaly, the patient feels a full stomach or sometimes pain in the upper left abdomen. We report a case of a 55 year old woman with a full stomach complaint with a history of thrombocytopenia. From the peripheral blood examination, observation of thrombocytopenia was obtained with suspicion of the inflammatory process and physical examination of splenomegaly. Bone marrow aspiration studies revealed a multi-line cytopenic refractory MDS. Patients receive immunosuppressant therapy without blood transfusions. After 1 year of treatment the patient complained of fatigue and upper left abdominal pain. The results showed pancytopenia and splenomegaly. The doctor and patient discussion agreed to the splenectomy. The patient had no complications after splenectomy and for 11 months the patient felt complaint free and normal hematological parameters with a good quality of life. This case report suggests that splenectomy can be an alternative therapy for MDS that is refractory to previous therapy and is complaining of splenomegaly. Splenectomy can improve the clinical complaints and hematologic profile of MDS patients with splenomegaly.

Clonal Hematopoiesis and Genetic Mutations in Individual Patients with Acquired Bone Marrow Failure Diseases

Clonal hematopoiesis (CH) is characterized by clonal expansion of hematopoietic stem/progenitor cells with the capability of multilineage differentiation and can be detected through the biomarker of genetic mutations. Bone marrow failure (BMF) diseases including idiopathic cytopenia of undetermined significance (ICUS), aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and myelodysplasia syndrome (MDS) are reported to partially coexist with CH. However, till now, the CH and genetic mutations in acquired BMF diseases are still not very clear. Therefore, we designed a panel that contains more than 500 candidate genes to perform a targeted sequencing of bone marrow cells isolated from 48 BMF patients, taking their mucosal cells as controls. In total, 75 somatic mutations and two germline mutations (PTCH1 c.1177G&amp;gt;A, CHEK2 c.1240C&amp;gt;T) were profiled in 30 patients, including 5 ICUS (also termed CCUS (clonal cytopenia of undetermined significance)), 14 AA, 3 PNH and 7 MDS patients. 67.53% missense mutations, 10.39% nonsense mutations, 10.39% frameshift mutations, 1.30% splicing mutations, 7.79% cds-del mutations, 2.60% CNV (copy number variations) can be found in our sequenced mutations. In comparison, the genetic mutation burden is relatively lower in AA and ICUS but higher in PNH and MDS, suggesting that the extent of CH possibly correlated with disease progression. Genetic mutations in our assay also implicated insightful views in the pathogenesis of BMF diseases. We can functionally divide genetic mutations into several types such as signaling transduction (21.6%), transcriptional regulation (19.6%), epigenetic regulation (15.5%), cell cycle regulation (7.2%), DNA repair (3.1%), cohesion complex (2.1%), immunity (3.1%), RNA splicing (4.1%) and others (3.1%). Specifically, we found a serial of novel genetic mutations. For example, the mutations in extracellular membrane receptors such as Notch (Notch1 c.4759A&amp;gt;C , Notch2 c.4819C&amp;gt;T, Notch3 c.3592A&amp;gt;C), CXCR4(c.598C&amp;gt;T), IGF1(c.341C&amp;gt;T), MPL(c.611C&amp;gt;T) suggest bone marrow environment is possibly associated with BMF diseases. In detail, Notch, IGF1, CXCR4 and MPL-mediated signaling are critical for HSC niche regulation, suggesting niche signals serve as a promoting factor for acquired BMF pathogenesis, which is consistent with previous reports. Also, we found the immunity-related mutations in HLA-A(c.750_751delGG) and CD58(c.475T&amp;gt;G), which are closely related with specific T cell recognition, implicated that clonal hematopoiesis and evolution to malignancies can be partially attributed to immune evasion possibly. The mutation ERBB4 (c.3424C&amp;gt;T), a membrane receptor which binds to and is activated by nerve cell released neuregulins, implicated that nerve fiber might involve in BMF. Additionally, we also found novel mutations in epigenetic factors such as KDM5C (c.265delA) and CHD3 (cds-del c.222GCC [7&amp;gt;6]) in PNH and MDS patients. Interestingly, LRP1B (c.13771G&amp;gt;A) that plays an important role in lipid metabolism was found in PNH patient firstly. These gene mutations provide clues for potential biomarkers for BMF diagnosis and prognosis and need more functional investigations. To systemically observe the clonal hematopoiesis at individual patient-level, we delineated the mutational composition in 30 individual BMF patients. We found that 56.7% patients have more than two mutations (eg. MDS 85.71%, PNH 100%, CCUS 60% and AA 35.7%), suggesting that multiple gene mutations-driven clonal expansion constitutes a complex mutational composition and their interaction possibly influences disease progression. At individual patient-level, mutational composition better promotes our understanding on BMF pathogenesis and clinical diagnosis. For example, an MDS patient bearing several mutations in ASXL (non-sense mutation, c.3187C&amp;gt;T, VAF: 18.2%), DNMT3A (missense mutation, c.2644C&amp;gt;T, VAF: 3.01%) and RUNX1 (missense, c.602G&amp;gt;A, VAF: 2.08%) suggested a complex pathological process and poor prognosis. Therefore, mutational composition structure can be revealed in individual acquired BMF patients, promoting precise diagnosis and prognosis. In conclusion, our study not only found a serial of novel genetic mutations that need further investigations, but also provided potential clues for the identification of biomarkers in acquired BMF diseases. Figure Disclosures No relevant conflicts of interest to declare.

A favorable inductive remission rate for decitabine combined with chemotherapy as a first course in

In acute myeloid leukemia (AML), myelodysplasia‐related changes contribute to a poor prognosis. This retrospective, propensity score‐matched study analyzed 108 newly diagnosed AML patients with features of myelodysplasia syndrome (MDS) (aged 14‐60 years) from 2014 to 2018, who received either idarubicin and cytarabine (IA) or decitabine, idarubicin and cytarabine (DAC+IA), and compared efficacy and toxicity between the two regimens. After propensity score matching, there were 54 patients in each group. The rate of complete remission (CR) was higher in the DAC+IA group than in the IA group (85.2% vs 68.5%, P = .040) after the first course, and toxicities were comparable in both groups. Multivariate analysis indicated that the combination with DAC was independent factor for CR rate after the first induction therapy (OR = 2.978, 95% CI:1.090‐8.137, P = .033). Subgroup analysis showed a CR advantage for DAC+IA (vs IA) for patients of intermediate‐high risk status according to National Comprehensive Cancer Network prognostic stratification. In conclusion, DAC+IA is therefore offered as a new induction choice for newly diagnosed AML patients with features of MDS, aged <60 years old, especially in intermediate‐high risk status.

Outcomes and prognostic factors of myelodysplastic syndrome patients with allogeneic hematopoietic stem cell transplantation

目的评价异基因造血干细胞移植（allo-HSCT）治疗骨髓增生异常综合征（MDS）的疗效，并分析预后相关因素。方法回顾性分析2010年1月至2018年3月接受allo-HSCT治疗的165例MDS患者，主要观察患者总体生存（OS）率、无病生存（DFS）率、复发率及非复发死亡率（NRM），并分析影响预后的危险因素。结果全部165例患者中，男105例，女60例，3年OS、DFS率分别为72.5%（95%CI 64.9%~80.1%）、67.4%（95%CI 59.2%~75.6%），3年累积复发率为12.1%（95%CI 7.0%~18.6%），NRM为20.4%（95%CI 14.2%~27.6%）。多因素分析显示，allo-HSCT合并症指数（HCT-CI）是影响OS的独立危险因素（P=0.042，HR=2.094，95%CI 1.026~4.274）。对于难治性贫血伴原始细胞增多（RAEB）及转化为急性髓系白血病（sAML）患者，移植前应用化疗或去甲基化治疗对总体OS无影响[（67.0±7.5）%对（57.7±10.9）%，χ2=0.025，P=0.874]。结论allo-HSCT是治疗MDS的有效手段，非复发死亡是影响生存的主要原因。移植前化疗或去甲基化治疗或许不能使RAEB和sAML患者获益。

Etiologyical Analysis of 133 Patients with Elderly Macrocytic Anemia and Diagnostic Significance of Laboratory Tests

To study the etiology of macrocytic anemia in elderly patients and to evaluate the diagnostic significance of laborotory tests. 133 elderly macrocytic anemia patients, whose age>60 years old, hemoglobin<100 g/L, mean red cell volume(MCV)>100 fL, and bone marrow cell test was performed, and these patients were grouped according to diseases, and the bilirubin, lactate dehydrogenase, folic acid, vit B12 and serum ferritin were tested, then the results of tests were compared and analyzed. The majority of the cases were diagnosed as megaloblastic anemia (MA), myelodysplasia syndrome (MDS), acute leukemia/multiple myeloma (AL/MM) and hemolytic anemia (HA). Usually HA was a simple anemia, while others were accompanied by decrease of other 1 or 2 series. HA patients were often with significant high level of well volume (MCV), red cell distribution width(RDW), reticulocytes (RC) and indirect bilirubin (IBIL) (P<0.01). However, MA patients were often with high level of LDH. Serum ferritin (SF) level was significantly higher in both MDS and AL/MM groups (P<0.01). Common causes of macrocytic anemia in elderly patients are MA, MDS, AL/MM and HA. The combination detection of MCV, RDW, RC, LDH, IBIL and SF contributes to enhancing the accuracy of diagnosis.