X-linked hyper-IgM syndrome with T-cell large granular lymphocytic leukemia: report of one case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical features, the key point of diagnosis and treatment methods of X-linked hyper-IgM syndrome (XHIGM).Methods:The clinical characteristics and laboratory data of a patient aged 23 years who was diagnosed as XHIGM complicated with T-cell large granular lymphocytic leukemia (TLGLL) in Institute of Hematology & Blood Diseases Hospital in March 2020 were analyzed retrospectively, and the literatures were reviewed.Results:This male patient presented with recurrent infection when he was 17 years old, and was found neutropenia, anemia accompanied by obvious splenomegaly, lower level of IgG and IgA after the visit. The level of IgM was lower than the normal level and the typical XHIGM was manifested with the normal or increased level of IgM, however CD40L homozygous mutation (chromosome: chrX; location: 135730438; variation of amino acid: NM_000074:exon1:c.31C>T:p.R11X; nonsense mutation) was confirmed by next generation sequencing. CD40L heterozygous mutation was detected in his mother, but it was not in his father. The patient was diagnosed as XHIGM. Anemia and neutropenia were alleviated after splenectomy in the patient, who was diagnosed as T-cell large granular lymphocyte elevation and clonal proliferation by flow cytometry, TCR gene rearrangement positive and bone marrow histopathological immunohistochemistry results because of the increasing leukocyte. The patient was eventually diagnosed as XHIGM complicated with T-LGLL.Conclusions:A small number of patients with XHIGM may develop symptoms in adulthood and may present with atypical clinical features of significant reduction in IgG, IgA, and IgM. The confirmed diagnosis of XHIGM is established by identification of CD40L gene mutation. XHIGM gene screening is required in male patients with recurrent infection, IgG level lower than normal and neutropenia. A few XHIGM patients are complicated with T-LGLL.

A study of clinical characteristics and prognosis of primary myelofibrosis patients with thrombocytopenia in varied degrees / 中华血液学杂志

Objective@#To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees.@*Methods@#Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated.@*Results@#320 subjects (47%) presented severe thrombocytopenia (PLT<50×109/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×109/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×109/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×109/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival.@*Conclusion@#PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL).</p><p><b>METHODS</b>A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases.</p><p><b>RESULTS</b>Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases.</p><p><b>CONCLUSIONS</b>The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.</p>

The clinic and pathologic significance of plasma cell myeloma with CCND1 / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical and pathologic features of multiple myeloma(MM) with CCND1.</p><p><b>METHODS</b>Retrospectively analyzed the clinical and pathologic profiles of 158 patients with MM from 2010 to 2013. The clinical and morphologic features of bone marrow aspiration, biopsy and immunophenotypic analysis which was carried out by flow cytometry and immunohistochemistry were analyzed in all patients with MM respectively. CCND1 translocation was studied by FISH method in all cases. Classical cytogenetic studies of bone marrow were performed in 24 cases whose CCND1 was positive.</p><p><b>RESULTS</b>In the 158 patients with MM, CCND1 was detected in 31 patients (19.6%）. In 31 patients, type IgA, IgD, IgG, IgM, light-chain only and nonsecretory MM were 4 cases,4 cases,11 cases,1 case, 6 cases and 5 cases respectively. A high incidence of CCND1 was observed in IgD and nonsecretory MM comparied with IgA and IgG respectively (P<0.05). but no statistical significance was reached between κ and λ type patients (P=0.627). The morphology of plasma cell in bone marrow biopsies were small Lymphocyte- Like 24 cases,mature plasma cell 6 cases and immature plasma cell 1 case. Immunophenotype of all 31 cases was CD38⁺CD138⁺CD19⁻CD45⁻, (CD56⁺ in 11 cases, CD20⁺ in 9 cases, CD117⁺ in 3 cases. MM with CCND1 showed a strong association with CD20 expression, the lack of CD56 expression. Immunohistochemistry showed positive for cyclinD1 in 22 cases.</p><p><b>CONCLUSION</b>A high incidence of CCND1 was detected in the IgD and nonsecretory MM, and correlated with Small Lymphocyte- Like, higher positive rate of CD20, cyclinD1 and the lack of CD56 expression. MM with CCND1 must be distinguished from LPL and other mature B cell lymphomas which have plasmacytoid differentiation.</p>

Clinical and biological characteristics of non-IgM lymphoplasmacytic lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the clinical and biological characteristics of Non-IgM-secreting lymphoplasmacytic lymphoma (LPL) and draw the differences between non-IgM LPL and Waldenström macroglobulinemia (WM).</p><p><b>METHODS</b>Records of 13 patients with non-IgM LPL were retrospectively analyzed between January 2000 and December 2013. The cytogenetic aberrations were detected by fluorescence in situ hybridisation (FISH).</p><p><b>RESULTS</b>In the cohort, 7 males and 6 females with a median age of 63 years (range 43 to 74), two patients were IgA secreting, 6 with IgG secreting and 5 patients without monoclonal globulin. The major complaint at diagnosis included anemia associated symptom (53.8%), mucocutaneous hemorrhage and superficial lymphadenopathy (15.4%). Eight patients had B symptom at diagnosis. All of the 13 patients had bone marrow involvement and anemia, and 10 patients had 2 or 3 lineage cytopenia. In 5 patients with available immunophenotypic data, all expressed CD19, CD20, CD22 and CD25, but missed the expression of CD10, CD103 and CD38. Two cases had CD5 or sIgM positive alone. Another 2 patients were CD23 or CD11c positive and 3 patients were FMC7 positive. Cytogenetic aberrations had been detected by FISH in 7 patients, but only two (28.6%) patients had aberrations with del(6q).</p><p><b>CONCLUSION</b>The clinical and biological characteristics had no significantly difference between non-IgM LPL and WM.</p>

Effects of virus coinfection on the severity of respiratory syncytial virus bronchiolitis / 中国基层医药

Objective To investigate the effects of virus coinfection on the severity of respiratory syncytial virus(RSV)bronchiolitis through the clinical analysis of 286 cases.Methods Various virus antibody were measured by using ELISA in 286 cases of RSV bronchiolitis.The frequency of respiratory virus coinfection on the severity of RSV bronchiolitis was observed.Results RSV bronchiolitis complicated with virus coinfection ratio reached 29.37%,especially with the double infection.Compared to patients with RSV infection,the severe cases increased sig-nificantly in patients with virus coinfection(χ2 =128.7,P<0.01).Conclusion Other respiratory viruses coinfection are not uncommon in infants with RSV bronchiolitis and may increase the severity of RSV bronchiolitis.

Distinct characteristics and new prognostic scoring system for Chinese patients with Waldenström macroglobulinemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Waldenström macroglobulinemia (WM) is an uncommon lymphoid malignancy. The characteristics and prognosis of WM have never been systematically studied in the East.</p><p><b>METHODS</b>We analyzed the clinical characteristics and the prognostic factors of 90 Chinese WM patients, and compared them with the Western reports.</p><p><b>RESULTS</b>The median age was 62 years old with a male-to-female ratio of 3.74. The most common symptoms at diagnosis were fatigue (77.8%) and bleeding (20%), while only 6 patients (6.7%) were asymptomatic. In the univariate analysis, age >62 years, thrombocytopenia, leucopenia, cytopenias ≥ 2, and high risk on the international prognostic scoring system for WM were the adverse risk factors, but only age >62 years and ≥ 2 cytopenias were the independent prognostic factors in the multivariate analysis. Using age <62 years and ≥ 2 cytopenias, three significantly different prognostic groups could been distinguished, with 5-year overall survival of 71.6%, 48.6%, and 17.0% (P < 0.001).</p><p><b>CONCLUSION</b>Distinct characteristics exist in WM in China compared to the West and we describe a new simple prognostic model for newly diagnosed WM patients.</p>

CSF3R, ASXL1,SETBP1, JAK2 V617F and CALR mutations in chronic neutrophilic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the CSF3R, ASXL1, SETBP1, JAK2 V617F and CALR mutations in patients with chronic neutrophilic leukemia (CNL).</p><p><b>METHODS</b>Twelve suspected "CNL" patients were retrospectively reviewed according the WHO criteria (2008). CSF3R,ASXL1,SETBP1 and CALR mutations were sequenced, and JAK2 V617F was tested by allele specific (AS)-PCR.</p><p><b>RESULTS</b>6 of 12 cases were diagnosed as CML, and all of the 6 carried. 4 of 6 patients also had ASXL1 and SETBP1 mutations and one had a CALR mutation (c.1154-1155insTTGTC). Two patients with monoclonal gammopathy with uncertain significance (MGUS) combined with CNL-like symptoms had no CSF3R, ASXL1, SETBP1, JAK2 V617F or CALR mutation. The same results were also seen in other 4 cases with secondary neutrophilic leukocytosis.</p><p><b>CONCLUSION</b>CSF3R, ASXL1 and SETBP1 mutations differential diagnosis of CNL, and should be included in the diagnostic protocol so as to improve diagnostic accuracy for CNL.</p>

A study of prognostic value of cytogenetics in patients with primary myelofibrosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic value of cytogenetics in Chinese with primary myelofibrosis (PMF).</p><p><b>METHODS</b>Four hundred and thirty-nine Chinese patients with PMF were retrospectively analyzed. The Kaplan-Meier method, the Log-rank test, the likelihood ratio test and the COX proportional hazards regression model were used to evaluate the prognostic scoring systems.</p><p><b>RESULTS</b>Four hundred and thirty-nine Chinese patients with PMF were analyzed with a median age of 56 years (range: 8-83), including 298 males and 141 females. The DIPSS-plus system could effectively evaluate prognosis in Chinese patients with PMF. There was significantly higher predictive power for survival for the DIPSS-plus group compared with the DIPSS group (P=0.006, -2 log-likelihood ratios of 989.5 and 1001.9 for the DIPSS-plus and DIPSS systems, respectively). Univariate analysis indicated that the patients with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only had better survival. Following two cytogenetic risk categories were constructed: favorable karyotype including subjects with a normal karyotype, a complex karyotype that was not a monosomal karyotype, +8 only or a balanced translocation only and unfavorable karyotype included all others. The modified DIPSS-Chinese prognostic model was proposed by adopting cytogenetic categories and DIPSS- Chinese risk group. The median survival of patients classified in low risk (163 subjects), intermediate-1 risk (187 subjects), intermediate-2 risk (82 subjects) and high risk (7 subjects) were not reached, 74 (95% CI 42-106), 39 (95% CI 26-52) and 12(95% CI 1-25)months, respectively, and there was a statistically significant difference in overall survival among the four risk groups (P<0.01).</p><p><b>CONCLUSION</b>The DIPSS-plus had significantly higher predictive power than the DIPSS group in Chinese patients with PMF and the modified DIPSS-Chinese system based on the cytogenetic features of Chinese patients was proposed and worked well for prognostic indication.</p>

Bone marrow pathologic features and differentiation of Waldenstr(o)m macroglobulinemia / 白血病·淋巴瘤

Objective To explore the bone marrow pathology ,diagnosis and differential diagnosis of Waldenstrom macroglobulinemia(WM). Methods 19 WM patients was examined by bone marrow aspiration (BMA) and bone marrow biopsy (BMB) for morphology. Flow cytometry (FCM) and immunohistochemistry (IHC) for immunophenotyping. Results Plasmacytoid lymphocytes were identified in 11 BMA. All of 19 BMB were involved by lymphoma cells. 17 cases showed a predominance of small lymphocytes and 2 of plasmacytoid lymphocytes. Typically plasmacytoid lymphocytes were not seen in 4 cases. Patterns of bone marrow involvement were as follow: diffuse (12 cases), nodular (4 cases), interstitial (3 cases). Immunophenotypically, FCM showed all cases were CD_(19)~+, CD_(20)~+, CD_(22)~+, CD_5~- and CD_(10)~-. IHC revealed small lymphocytes and plasmacytoid lymphocytes were Pax5~+ CD_(20)~+ and plasma cells were CD_(38) CD_(138)~+ CD_(20)~- Pax5~-. Conclusion Small lymphocytes proliferation with plasmacytic differentiation is the typical bone marrow pathologic features of WM. IHC is benefit for identifying lymphocytes and plasma cells components. The Combination of morphology, FCM and IHC is contributive to the diagnosis and differentiation of WM.

Plasma adrenomedullin and urotensin Ⅱ concentrations in children with capillary bronchitis / 中华临床感染病杂志

Objective To evaluate the plasma levels of adrenomedullin (ADM) and urotensin Ⅱ ( U-Ⅱ ) in children with capillary bronchiolitis, and their clinical significance. Methods One hundred and fifty three children with capillary bronchiolitis and 36 healthy children were recruited. Plasma levels of ADM and U- Ⅱ were measured at acute stage ( <7days) and convalescent stage (>14days) of airway inflammation. The relationship of plasma ADM and U-Ⅱ levels with symptom scores was evaluated. Results Plasma levels of ADM and U-Ⅱ in acute stage of capillary bronchiolitis were significantly higher than those in convalescent stage and healthy controls ( ADM: t = 20. 57 and 26. 26, P < 0. 01; U-Ⅱ: t = 14. 27 and 7. 61, P < 0. 01 ) , and there were significant differences among mild, moderate and severe capillary bronohiolitis (F = 245. 94 and 304. 79, P <0. 01). Plasma level of U-Ⅱ in convalescent stage of capillary bronchiolitis was lower than that of healthy controls (t = 6. 99, P <0. 01 ) , but ADM was still in a higher level ( t = 8. 98, P < 0. 01 ). In the convalescent stage, there was significant difference on U-Ⅱ levels among mild, moderate and severe capillary bronchiolitis ( F = 25.69, P < 0. 01 ) , but no significant difference was observed for ADM levels (F = 2. 25 , P > 0. 05 ) . Plasma levels of ADM and U- Ⅱ in acute stage showed positive correlation with symptom scores, and the regression coefficients were 0.884 (P =0. 000) for ADM and 0. 943 (P = 0. 000) for U-Ⅱ . Conclusion Plasma ADM and U-Ⅱ levels in children with capillary bronchiolitis are increased in acute stage and correlated with the symptom scores, which may serve as laboratory indicators for assessing the severity of the disease.