Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Clinical Characteristics and Survival Analysis of Patients with Chronic Myelomonocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics, prognostic factors and efficacy of hypomethylating agent (HMA) in patients with chronic myelomonocytic leukemia (CMML).@*METHODS@#The clinical data of 37 newly diagnosed patients with CMML was analyzed retrospectively, and their clinical characteristics and the efficacy of HMA were summarized. Kaplan-Meier and Log-rank test were used for univariate survival analysis, and Cox proportional hazards regression model was used for multivariate analysis.@*RESULTS@#The median age at diagnosis was 67 years old. Their common manifestations included fatigue, bleeding, abnormal blood routine and fever. Most patients had splenomegaly. According to FAB classification, there were 6 cases of myelodysplastic CMML and 31 cases of myeloproliferative CMML, while according to WHO classification, 8 patients belonged to CMML-0, 9 patients to CMML-1 and 20 patients to CMML-2. At the time of diagnosis, the median white blood cell count was 32.84×109/L, median hemoglobin (Hb) was 101 g/L, median platelet count was 65×109/L, median absolute monocyte count was 9.53×109//L, median absolute neutrophil count (ANC) was 11.29×109//L and median lactate dehydrogenase (LDH) was 374 U/L. Cytogenetic abnormalities were found in 4 cases among the 31 patients who underwent karyotype analysis or fluorescence in situ hybridization detection. There were 12 patients who had analyzable results and gene mutations were identified in 11 cases, including ASXL1, NRAS, TET2, SRSF2 and RUNX1. Among the 6 patients who were treated with HMA and could be evaluated for efficacy, 2 patients achieved complete remission, 1 patient achieved partial remission and 2 patients achieved clinical benefit. Compared with the non-HMA treatment group, overall survival (OS) time was not significantly prolonged in the HMA treatment group. Univariate analysis showed that Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and peripheral blood (PB) blasts ≥5% were significantly associated with poor OS, while WHO classification CMML-2, Hb<100 g/L, ANC≥12×109/L, LDH≥250 U/L and PB blasts≥5% were significantly associated with poor leukemia-free survival (LFS) (P<0.05). Multivariate analysis showed that ANC≥12×109/L and PB blasts≥5% were significantly associated with poor OS and LFS (P<0.05).@*CONCLUSION@#CMML has high heterogeneity in clinical characteristics, genetic changes, prognosis and treatment response. HMA can not significantly improve the survival of CMML patients. ANC≥12×109/L and PB blasts≥5% are independent prognostic factors of OS and LFS in patients with CMML.

Clinical features and prognosis of juvenile myelomonocytic leukemia: an analysis of 63 cases / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.

Clinical analysis of seven cases of juvenile myelomonocytic leukemia / 中国基层医药

Objectives:To analyze the clinical features of juvenile myelomonocytic leukemia (JMML) and investigate the characteristics of diagnosis and treatment of this disease.Methods:The clinical data of seven children patients with JMML who received treatment in The First Affiliated Hospital of Xinxiang Medical University between April 2015 and February 2020 were retrospectively analyzed. The clinical efficacy of different treatments was analyzed.Results:The median age at diagnosis of JMML was 8 months and 4 days for seven children patients. Fever was the principal cause of treatment, and it was mostly accompanied by hepatosplenomegaly. The median value of peripheral blood leukocyte count was 36.1 × 10 9/L, and it was 4.5 × 10 9/L for mononuclear cell count, 88 g/L for hemoglobin level, and 47 × 10 9/L for platelet count. Myeloid immature cells were found in peripheral blood smears of six patients. Chromosome examination results revealed 7-monomer in one patient, and normal karyotype in six patients. Hemoglobin level was increased in six patients. Gene detection results revealed PTPN11+NF1 mutation in one patient, N-RAS mutation in two patients, and K-RAS mutation in one patient. Three patients gave up treatment, three patients received low-intensity chemotherapy , and these six patients died of complicated infection. One patient received allogeneic hematopoietic stem cell transplantation and the patient survived without any event after 14 months of follow-up. Conclusion:The age of JMML onset is low. JMML has poor clinical specificity. Gene detection is helpful for early diagnosis of JMML. Low-intensity chemotherapy can prolong survival period, but it can not improve prognosis. Infection is the principal cause of death in patients with JMML. Hematopoietic stem cell transplantation is the only possible method to cure the disease.

A Case of Chronic Myelomonocytic Leukemia: the Onset of which was Manifestedby Hypokalemia and Hypocalcemia / 罕见病研究

Intractable hypokalemia and hypocalcemia are rare complications in leukemia patients. This article reports a patient with chronic myelomonocytic leukemia (CMML)with refractory hypokalemia, hypocalcemia, hypochloridemia, hypomagnesemia-a 48-year-old man complained of fatigue, nausea, and face numbness for over one month. The number of monocytosis in peripheral blood and bone marrow increased remarkably. At the same time, the patient developed hypokalemia, hypochloridemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, massive proteinuria, and increase in plasma aldosterone and renin. After two coursea of treatment using Azacitidine therapy, complete remission of bone marrow was achieved and the electrolyte disturbance was almost corrected, except hypomagnesemia. We summarize the clinical characteristics of the patient so as to raise the clinical awareness of such cases.

Chronic myeloid leukemia with a significant increase of monocytes and rare karyotype: A case report and literature review / 中南大学学报(医学版)

Chronic myeloid leukemia with a significant increase of monocytes is rare and difficult to identify from chronic myelo-monocytic leukemia in clinic. A 31-year-old male patient with systemic pain was initially diagnosed as chronic myelo-monocytic leukemia, who was finally diagnosed as chronic myeloid leukemia by fusion gene and chromosome examination. In addition to the typical Ph chromosome, a rare chromosome translocation t(2; 7)(p13; p22) was observed. The detection of monocyte subsets by multi-parameter flow cytometry is a diagnostic marker to distinguish the above 2 diseases. The relationship between fusion genes and mononucleosis is not clear. Tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation can be used in the treatment for this disease.

Decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes and chronic myelomonocytic leukemia / 中国实用内科杂志

OBJECTIVE: To evaluate the clinical efficacy of decitabine combined with arsenious acid in the treatment of patients with higher-risk myelodysplastic syndromes(MDS) and chronic myelomonocytic leukemia(CMML). METHODS: Totally 39 patients with MDS and 8 patients with CMML received the treatment of decitabine and arsenious acid from April 2016 to December 2018. Decitabine [20 mg/(m~2·d)] and arsenious acid [0.15 mg/(m~2·d)] were administered intravenously for 5 consecutive days every 4-6 weeks. Patients who achieved complete or partial remission entered into the consolidation cycle. Efficacy and influencing factor were analyzed. RESULTS: Clinical response were observed in 31 patients after a median of 2 courses(ranging 1-12) of treatment. The overall response rate(ORR) was 66.0%. The median duration of response was 16 weeks(ranging 2-52 weeks). There were 8 cases(17.0%) of complete remission(CR), 10 cases(21.3%) of partial remission(PR),12 cases(25.5%) of hematological improvement(HI), 1 case(2.1%) of marrow complete remission(mCR), 8 cases(17.0%) of stable disease(SD), and 1 case(2.1%) of progressive disease(PD). By next generation sequencing, 25 genes mutated with 70 times in 33 cases. The mutation frequency of epigenetic regulators(57.6%) was higher than splicing factors(33.5%), transcription factors and kinase signaling(54.5%),and TP53(21.2%)(P<0.01). There was no significant difference in response rates among these patients(47.4%, 54.5%, 50.0% and85.7%, P=0.977). Gene mutation frequency(VAF) of patients who responded to the regimen declined significantly(16.67% vs. 10.26%,P=0.014). CONCLUSION: Decitabine combined with arsenious acid has significant effect in the treatment of patients with higher-risk MDS and CMML and is well-tolerated. Gene mutation test results by next generation sequencing might be related to clinical response.

Expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia and their significances / 白血病·淋巴瘤

Objective To investigate the expressions of BAP1 and TET2 proteins in bone marrow of patients with chronic myelomonocytic leukemia (CMML) and their relationship with the prognosis of CMML. Methods The bone marrow paraffin specimens of 41 cases from 41 adult CMML patients diagnosed by Shanghai Sino-US Joint Leukemia Coordination Group from September 2003 to May 2007 were collected. The immunohistochemistry was used to detect the expressions of BAP1 and TET2 proteins in 41 CMML patients. The expressions of TET2 and BAP1 proteins were also detected by the same method in 40 adult patients with acute myelomonocytic leukemia (AMML) and 20 patients with iron deficiency anemia (IDA) diagnosed at the same time as the comparison. The clinical data of 41 CMML patients were analyzed by using retrospective cohort study. The count data were compared by using chi-square test. The correlation between expressions of BAP1 and TET2 proteins was analyzed by using Pearson correlation analysis. Kaplan-Meier method was used to calculate the survival time, and Log-rank test was used for single factor analysis. Results In 41 CMML patients, the positive expression rate of BAP1 was 31.7％ (13/41), including 28.6％ (8/28) in CMML-1 patients and 38.5％ (5/13) in CMML-2 patients; the positive expression rate of TET2 was 41.5％ (17/41), including 39.3％ (11/28) in CMML-1 patients and 46.2％ (6/13) in CMML-2 patients. In 40 AMML patients, the positive expression rate of BAP1 was 32.5％ (13/40), and the positive expression rate of TET2 was 35.0％ (14/40). In 20 IDA patients, the positive expression rate of BAP1 was 5.0％ (1/20), and TET2 had no positive expression. There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML-1 and CMML-2 patients (χ 2 = 0.40, P = 0.53; χ 2 = 0.17, P = 0.68). There was no significant difference in the expressions of BAP1 and TET2 proteins between CMML and AMML patients (χ 2 = 0.01, P = 0.94; χ 2 = 0.36, P = 0.64). There were significant differences in the positive expression rate of BAP1 and TET2 proteins between hematological neoplastic disease (CMML+AMML) and hematological non-neoplastic disease (IDA) (χ 2 = 6.01, P < 0.05; χ 2 = 11.04, P < 0.01). Pearson correlation analysis showed that there was no correlation between expressions of BAP1 and TET2 proteins (r = 0.35, P = 0.27). Univariate analysis showed that anemia (Hb < 60 g/L), mature monocyte count ≥ 2.0×109/L, neutrophil count (1.5×109/L), abnormal karyotype were associated with poor prognosis for CMML. Protein expressions of BAP1 and TET2 were not related with the prognosis of CMML (χ 2 = 0.28, P = 0.600; χ 2 = 0.53, P = 0.460). Conclusion Both BAP1 and TET2 proteins have high positive expression rates in CMML patients, but the expressions of them are not related to the prognosis.

MICM classification for a case of acute myelomonocytic leukemia M / 临床检验杂志

Objective@#To describe the MICM (morphology, immunology, cytogenetics and molecular biology) characteristics of a case of acute myelomonocytic leukemia M 4C . @*Methods@#The medical history data of the case of M 4C admitted to our hospital was reviewed. The results of bone marrow cell morphology, cytochemical stains, bone marrow biopsy, immunophenotype, cytogenetics, molecular test and NGS (next-generation sequencing) of the case were analyzed. @*Results@#The bone marrow smear showed markedly active proliferation of bone marrow cells in which the myelomonocytic cells accounted for 85.6%. Cytochemical stains showed peroxidase (POX) stain partially and weakly positive; specific esterase AS-DCE partially positive; non-specific esterase α-NBE partially positive and smothered by sodium fluoride; non-specific esterase AS-DAE partially positive and smothered by sodium fluoride. Bone marrow biopsy showed hyperproliferative cells and diffused hyperplasia of blasts. Immunophenotype analysis showed that the abnormal cell population was positive for CD11B, CD64, CD56, cMPO, CD33, CD41, CD61, CD38 and CD58, but negative for CD13, CD34, CD117, CD7, CD123, HLA-DR, CD10, CD19, CD20, CD2, CD14, CD235, CD15, CD303, CD304, CD25, cCD79a, cCD3, cCD22, CD1a and TDT. Cytogenetic analysis showed 47, XY, t(9;11) (p22;q23),+mar. The molecular test for leukemia showed MLLT3/KMT2A gene rearrangement. NGS showed NRAS and TET2 mutation. The case was finally diagnosed as AML (acute myelomonocytic leukemia) M 4C with t(9;11)(p22;q23), MLLT3-KMT2A. @*Conclusion@#Leukemia M 4C may show the characteristics of both granulocytes and monocytes with complex morphological features. The combined examination of MICM should be necessary for the diagnosis of M 4C with great significance.

Poor Prognostic Implication of ASXL1 Mutations in Korean Patients With Chronic Myelomonocytic Leukemia

BACKGROUND: Molecular genetic abnormalities are observed in over 90% of chronic myelomonocytic leukemia (CMML) cases. Recently, several studies have demonstrated the negative prognostic impact of ASXL1 mutations in CMML patients. We evaluated the prognostic impact of ASXL1 mutations and compared five CMML prognostic models in Korean patients with CMML. METHODS: We analyzed data from 36 of 57 patients diagnosed as having CMML from January 2000 to March 2016. ASXL1 mutation analysis was performed by direct sequencing, and the clinical and laboratory features of patients were compared according to ASXL1 mutation status. RESULTS: ASXL1 mutations were detected in 18 patients (50%). There were no significant differences between the clinical and laboratory characteristics of ASXL1-mutated (ASXL1+) CMML and ASXL1-nonmutated (ASXL1−) CMML patients (all P>0.05). During the median follow-up of 14 months (range, 0–111 months), the overall survival (OS) of ASXL1+ CMML patients was significantly inferior to that of ASXL1− CMML patients with a median survival of 11 months and 19 months, respectively (log-rank P=0.049). An evaluation of OS according to the prognostic models demonstrated inferior survival in patients with a higher risk category according to the Mayo molecular model (log-rank P=0.001); the other scoring systems did not demonstrate a significant association with survival. CONCLUSIONS: We demonstrated that ASXL1 mutations, occurring in half of the Korean CMML patients examined, were associated with inferior survival. ASXL1 mutation status needs to be determined for risk stratification in CMML.

The 2016 WHO versus 2008 WHO Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.

Analysis of prognostic factors in children with acute myeloid leukemia(M4/M5) / 中华实用儿科临床杂志

Objective To investigate the clinical efficacy and prognostic factors for M4/M5subtypes in chil-dren with acute myeloid leukemia(AML).Methods A retrospective analysis of the clinical data of M4/M5subtypes in Shanghai Children′s Hospital Affiliated to Shanghai Jiaotong University,from January 2009 to December 2014 was carried out.The long-term efficacy,prognosis and relapse factors were analyzed.Results The clinical data of 46 ca-ses were collected,among which 38 cases were treated with more than 2 courses,including 22 male,16 female,19 cases M4and 19 cases M5.The median age was 5 years.5-year overall survival(OS)rate and 5-year event-free survival (EFS)rate were(57.7 ± 9.3)% and(47.2 ± 8.9)%,and 5-year EFS of M4and M5were(52.4 ± 12.7)% and (45.4 ± 11. 9)%. Compared with the international risk stratification:5-year EFS rate of favorable-risk, intermediate-risk and poor-risk were(77.2 ± 12.4)%,(49.5 ± 14.9)% and(25.0 ± 19.8)%(χ2=6.305,P=0.043).Single factor analysis showed that extramedullary infiltration(χ2=4.828,P=0.028),Chromosome karyotype (χ2=10.178,P=0.017),the eighth day assessment(χ2=5.382,P=0.020)and course of treatment(χ2=4.771, P=0.029)were prognostic factors;multivariate analysis showed extramedullary infiltration(HR =5.323,95%CI:1.620-17.490,P=0.006)and less-than-6 courses of treatment(HR=6.186,95%CI:1.726-22.176,P=0.005)were the independent risk factors of affecting survival.Conclusions (1)Strengthening treatment and ade-quate courses of treatment are the critical to improve the overall curative effect in children with M4/M5subtypes.(2) Extramedullary infiltration was the risk factor for survival and recurrence in M4/M5subtypes.(3)It is suggested that the children who have the initial symptoms and molecular biology with poor prognostic factors choose hematopoietic stem cell transplantation as early as possible.

Understanding the Molecular Basis of Juvenile Myelomonocytic Leukemia and Its Application for Novel Drugs Development / 임상소아혈액종양

To date, hematopoietic stem cell transplantation (HSCT) is the only choice of therapy for most patients with juvenile myelomonocytic leukemia (JMML). Relapse remains a major problem. Approximately 90% of patients carry either somatic or germline mutations of genes participating in RAS signal transduction such as PTPN11, CBL, K-RAS, N-RAS, or NF1 in their leukemic cells, allowing an understanding of the molecular pathophysiology of JMLL and the development of novel drugs. As these genetic aberrations are mutually exclusive, the genetic change observed in JMML helps us to establish the diagnosis of JMML. Furthermore, the genetic abnormalities of JMML are an important prognostic factor, as the type of abnormality may determine disease progression. Recent studies have revealed a strong association between hypermethylation of some genes and already known poor prognostic factors such as older age, elevated fetal hemoglobin at diagnosis, and somatic mutation of PTPN11. These molecular characteristics may be the basis for a guideline to determine the treatment, especially when to proceed with HSCT. Recently, novel drugs have been used based on these molecular characteristics. 5-Azacitidine, an inhibitor of DNA methyltransferase and tipifarnib, a selective farnesyl transferase inhibitor, have been used to improve the outcome of JMML. In addition, drugs which inhibit the RAS signal transduction have been developed, which are less toxic and will improve outcome in the near future.

Usefulness of Middle Meningeal Embolization to Prevent Recurrent Spontaneous Chronic Subdural Hemorrhage

Spontaneous chronic subdural hematoma (SDH) is a rare condition that could develop in association with hematologic disease. A 66-year-old male developed a chronic SDH as an initial manifestation of chronic myelomonocytic leukemia (CMML). He experienced recurrent chronic subdural hemorrhage and newly developed intracerebral hemorrhage. Considering the scheduled long-term chemotherapy, bilateral middle meningeal artery (MMA) embolization was performed to prevent recurrence of subdural hemorrhage. Although pancytopenia occurred during the 7 months' follow-up period, residual chronic subdural hemorrhage was absorbed without recurrence. To our best knowledge, this is the first report of CMML with spontaneous chronic SDH. MMA embolization is potentially a useful and safe treatment option in the challenging clinical situations with underlying pathologies.

Relevancia del xantogranuloma juvenil en pacientes con neurofibromatosis tipo 1: Revisión de un caso clínico / The relevance ofjuvenile xanthogranuloma in neurofibromatosis type i patients. Aclinical case

El xantogranuloma juvenil es una forma de histiocitosis de células no Langerhans que suele afectar a los niños y niñas dentro de los primeros años de vida. Su principal relevancia radica en la posible asociación a neurofibromatosis tipo 1, ya que su presentación conjunta conlleva un mayor riesgo de desarrollo de leucemia mielomonocítica crónica juvenil. Se presenta el caso de un lactante diagnosticado con neurofibromatosis tipo 1 en que se detectan lesiones múltiples compatibles con xantogranuloma juvenil.

Juvenile xanthogranuloma is a form of non-Langerhans cell histiocytosis which usually affects boys and girls in their early years. Its importance stemsfrom its possible association with neurofibromatosistype 1 asthe combined presentation brings a heightened risk of developing chronic juvenile myelomonocytic leukemia. We present the case of an infant diagnosed with neurofibromatosistype I who was found to have multiple lesions compatible with the diagnosis of juvenile xanthogranuloma.

Juvenile myelomonocytic leukemia:a clinical and gene analysis of 21 cases / 中华实用儿科临床杂志

Objective To analyze the clinical characteristics of juvenile myelomonocytic leukemia(JMML) and the PCNA levels of the hyperoxia -exposure group (6 h)decreased,and the difference in PCNA protein expres-sion levels was significant of gene diagnose for JMML.Methods Clinical data were retrospectively analyzed in 21 pa-tients suffering from JMML based on new 2009 World Health Organization diagnostic criteria from January 201 3 to June 201 4 in Beijing Children′s Hospital,Capital Medical University.Results There were 85.7% (1 8 /21 cases)patients within 4 -year -old children,and the median age was 23 months (2 -86 months).Fever and abdominal symptoms were the prominent clinical symptoms,52.4% (1 1 /21 cases)with fever,38.1 % (8 /21 cases)with abdominal dis-tention,diarrhea and other abdominal symptoms,80.5% (1 9 /21 cases)had splenomegaly (mild 1 9.1 %,middle 33.3%,severe 38.1 %),and some patients had other tissue infiltration,such as rash,yellow tumor and lymphnode enlargement.Peripheral blood cell count showed that the white blood cells increased because of anemia or thrombocyto-penia,ranging from 1 0.40 ×1 09 /L to 82.1 4 ×1 09 /L(median,26.1 0 ×1 09 /L),and the monocyte counts ranged from 1 .46 ×1 09 /L to 21 .60 ×1 09 /L(median,3.79 ×1 09 /L),characteristics of JMML gene abnormality was detected in 1 7 cases:including 1 1 single gene mutation,and 6 cases with double gene mutations.PTPN11 was the highest frequency of occurrence,accounting for 52.9% (9 /1 7 cases),and NF1 mutation was 35.3% (6 /1 7 cases).All the patients were followed up by phone call,the median follow -up time was 371 days (57 -562 days),6 patients were lost to follow -up,7 patients died,2 patients were alive after hematopoietic stem cell transplantation,1 patient converted to acute non lymphocytic leukemia,and 5 patients were still alive after receiving symptomatic treatment.Among dead cases,PTNT11 gene mutation and NF1 gene mutation were detected in 6 patients;among living children after hematopoietic stem cell transplantation,RAS and PTNT11 mutations were detected in 2 patients;among living children after symptomatic treat-ment,RAS mutation was detected in 2 patients and PTPN11 +CBL mutation in 1 case.Conclusions The symptom and laboratory examination of JMML have no specificistics,with poor prognosis,gene diagnose has guiding significance for JMML diagnose and for selecting therapy.

Déficit adquirido de factor X en leucemia mielomonocítica crónica: reporte de un caso / Isolated factor X deficiency in chronic myelomonocytic leukemia: Report of one case

Bleeding disorders are commonly associated with hemato-oncologic diseases. We report a 68 years old male with a chronic myelomonocytic leukemia derived from a long lasting mielodysplastic syndrome that did not respond to treatment with Azacitidine. The patient was hospitalized due to tonic clonic seizures. A CAT scan showed a hematoma in the frontal lobe. A new assessment of hemostasis revealed an isolated deficiency of Factor X. We speculate that this deficit could be secondary to consumption due to the chronic Myelomonocytic Leukemia.

A Case of Long-term Survival with Autologous Recovery after Double Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia / 임상소아혈액종양

A 1.1 year old boy was admitted to the Seoul National University Children's Hospital because of incidental findings of hepatosplenomegaly, skin lesion and multiple intra- abdominal lymphadenopathies. Anemia and thrombocytopenia were found based on the initial complete blood count (CBC) measurements. Because of bicytopenia and hepatosplenomegaly, bone marrow examination was performed which revealed hypercellular marrow with increased monocytes and granulopoiesis. The hemoglobin F level was high for his age, and monocyte production was increased. The patient was diagnosed with juvenile myelomonocytic leukemia at the age of 1.2 years. Chemotherapy with cytarabine, etoposide, vincristine, and isotretinoin was initiated. After 6 cycles of chemotherapy, the CBC normalized. He underwent double cord blood transplantation (dCBT), but chimerism studies showed autologous recovery. However, he did not show relapse during the 5 years post-transplant during which he received isotretinoin. He is surviving disease-free 9 years after dCBT.

A Case of Long-term Survival with Autologous Recovery after Double Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia / 임상소아혈액종양

A 1.1 year old boy was admitted to the Seoul National University Children's Hospital because of incidental findings of hepatosplenomegaly, skin lesion and multiple intra- abdominal lymphadenopathies. Anemia and thrombocytopenia were found based on the initial complete blood count (CBC) measurements. Because of bicytopenia and hepatosplenomegaly, bone marrow examination was performed which revealed hypercellular marrow with increased monocytes and granulopoiesis. The hemoglobin F level was high for his age, and monocyte production was increased. The patient was diagnosed with juvenile myelomonocytic leukemia at the age of 1.2 years. Chemotherapy with cytarabine, etoposide, vincristine, and isotretinoin was initiated. After 6 cycles of chemotherapy, the CBC normalized. He underwent double cord blood transplantation (dCBT), but chimerism studies showed autologous recovery. However, he did not show relapse during the 5 years post-transplant during which he received isotretinoin. He is surviving disease-free 9 years after dCBT.

Leucemia mielomonocítica crónica / Chronic myelomonocytic leukemia

La leucemia mielomonocítica crónica es un desorden clonal de las células progenitoras hematopoyéticas clasificado como neoplasia mielodisplásica mieloproliferativa. Se caracteriza por la presencia de monocitosis absoluta y persistente en la sangre periférica (> 1.0 x 10 9/L) con la presencia de displasia celular y mieloproliferación en la médula ósea. Los pacientes presentan síntomas relacionados a las citopenias y al estado de hipercatabolismo y al examen físico se encuentra esplenomegalia. El diagnóstico se establece con la combinación del examen de la lámina de sangre periférica, el aspirado medular y la biopsia de médula ósea, el inmunofenotipaje y el estudio molecular de las anomalías que se presentan. El pronóstico de la enfermedad es malo. El tratamiento de elección es el trasplante alogénico de progenitores hematopoyéticos con régimen de acondicionamiento de toxicidad reducida. En alrededor del 30 por ciento de los pacientes la enfermedad se transforma en una leucemia mieloide aguda...

Chronic myelomonocytic leukemia is a clonal hematopoietic stem cell disorder classified as a myelodysplastic/myeloproliferative neoplasm. It is characterized by absolute monocytosis (>1.0 x 10(9)/ L) in the peripheral blood that persists for at least 3 months, with dysplastic and myeloproliferation in the bone marrow. Patients may show symptoms related to cytopenias and hypercatabolic state with splenomegaly. The diagnosis is established by combination of complete blood count, peripheral blood smear, bone marrow aspirate, bone marrow biopsy, immunophenotypic profile and study of molecular abnormalities. The prognosis is bad. The treatment of election is the hematopoietic allogeneic stem cell transplantation with regimen of reduced toxicity. In around 30 percent of these patients the disease transforms to acute myeloid leukemia...