Clinical features and laboratory data analysis of decreased glycosylated hemoglobin related to hemolytic disease / 中华血液学杂志

Objective@#To compare the effects of different hemolytic diseases on the level of glycosylated hemoglobin (HbA1c) to further explore the relationship between HbA1c and laboratory indexes to disclose implications of HbA1c in hemolytic diseases.@*Methods@#The distribution of 192 decreased HbA1c cases in 4 categories of hemolytic diseases was analyzed. Laboratory indexes related to hemolysis were tested and analyzed in each kind of disease, and relationship between laboratory indexes and HbA1c was statistically explored.@*Results@#Diagnoses of decreased HbA1c cases mainly included erythrocyte membranopathies (88 cases), immunohemolytic anemia (72 cases), hemoglobinopathy (4 cases) and erythrocyte enzymopathy (5 cases). The distribution of HbA2 and normal HbF subjects in immunohemolytic anemia and hemoglobinopathy was significantly different from those of HbA2 and / or abnormal HbF subjects (41.7% vs 22.0%, χ2=5.574, P=0.018; 0.7% vs 7.3%, P=0.031). Compared with non-hemolytic disease patients, those who suffered from 4 categories of hemolytic diseases showed lower HbA1c level and higher reticulocyte percentage (Ret), indirect bilirubin (IBIL) and free hemoglobin (F-Hb). Different levels of Ret, reticulocyte hemoglobin content (Ret-He), mean corpuscular volume (MCV), IBIL and F-Hb among the 4 kinds of diseases were observed, but the causes of the differences were not the same. HbA1c was negatively correlated with other laboratory indexes in erythrocyte membranopathies and immunohemolytic anemia.@*Conclusions@#Hemolytic disease resulted in false lower HbA1c, but impact of difference on HbA1c between different diseases was not significant. HbA1c was closely connected to laboratory indexes related to hemolysis, which might have potential implications for hemolytic diseases such as erythrocyte membranopathies and immunohemolytic anemia.

Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia / 中华血液学杂志

Objective@#To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA).@*Methods@#Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up.@*Results@#Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years.@*Conclusion@#The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.

Clonal evolution and clinical significance of trisomy 8 in acquired bone marrow failure / 中华血液学杂志

Objective@#To analyze clonal evolution and clinical significance of trisomy 8 in patients with acquired bone marrow failure.@*Methods@#The clinical data of 63 patients with acquired bone marrow failure accompanied with isolated trisomy 8 (+8) from June 2011 to September 2018 were analyzed retrospectively, the clonal evolution patterns and relationship with immmunosuppressive therapy were summarized.@*Results@#Totally 24 male and 39 female patients were enrolled, including 39 patients with aplastic anemia (AA) and 24 patients with relatively low-risk myelodysplastic syndrome (MDS) . Mean size of+8 clone in MDS patients[65% (15%-100%) ]was higher than that of AA patients[25% (4.8%-100%) , z=3.48, P=0.001]. The patients were was divided into three groups (<30%, 30%-<50%,and ≥50%) according to the proportion of+8 clone. There was significant difference among the three groups between AA[<30%:55.6% (20/36) ; 30-50%: 22.2% (8/36) ; ≥50%22.2% (8/36) ]and MDS patients[<30%:19.0% (4/21) ; 30%-<50%:19.0% (4/21) ; ≥50%61.9% (13/21) ] (P=0.007) . The proportion of AA patients with+8 clone <30% was significantly higher than that of MDS patients (P=0.002) ; and the proportion of AA patients with+8 clone ≥50%was significantly lower than that of MDS patients (P=0.002) . The median age of AA and MDS patients was respectively 28 (7-61) years old and 48.5 (16-72) years old. Moreover, there was no correlation between age and+8 clone size in AA or MDS (rs=0.109, P=0.125; rs=-0.022, P=0.924, respectively) . There was statistical difference in total iron binding capacity, transferrin and erythropoietin between high and low clone group of AA patients (P=0.016, P=0.046, P=0.012, respectively) , but no significant difference in MDS patients. The immunosuppressive therapy (IST) efficacy of AA and MDS patients was respectively 66.7% and 43.8% (P=0.125) . Comparing with initial clone size (27.3%) , the +8 clone size (45%) of AA patients was increased 1-2 year after IST, but no statistical difference (z=0.83, P=0.272) . Consistently, there was no significant change between initial clone size (72.5%) and 1-2 year clone size (70.5%) after IST in MDS patients. There was no significant difference in IST efficient rate between +8 clone size expansion and decline group of in AA patients at 0.5-<1, 1-2 and>2 years after IST. We found four dynamic evolution patterns of +8 clone, which were clone persistence (45%) , clone disappearance (30%) , clone emergence (10%) and clone recurrence (15%) .@*Conclusions@#AA patients had a low clone burden, while MDS patients had a high burden of +8 clone. The +8 clone of AA patients didn’t significantly expanded after IST, and the changes of +8 clone also had no effect on IST response.

Comparison of hemolytic characteristics among paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia and hereditary spherocytosis / 中华血液学杂志

Objective@#To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), autoimmune hemolytic anemia (AIHA) and hereditary spherocytosis (HS).@*Method@#The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared.@*Results@#①Reticulocyte percentage (Ret%) of PNH patients [6.70% (0.14%-22.82%)] was significantly lower than that of AIHA [14.00%(0.10%-55.95%), P<0.001] and HS patients [11.83%(0.60%-57.39%), P<0.001]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia [7.63%(1.87%-29.20%)% vs 11.20%(3.31%-22.44%), z=-2.165, P=0.030]. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 (11.2-244.0) μmol/L vs 57.6 (7.6-265.0) μmol/L, z=5.469, P<0.001; 79.3(11.2-244.0) μmol/L vs 26.2(4.6-217.7) μmol/L, z=-2.165, P<0.001], and the proportion of HS patients with TBIL more than 4 times the upper limit of normal (ULN) (64.1%) was significantly higher than that of AIHA (37.7%, χ2=19.896, P<0.001) and PNH patients (4.6%, P<0.001). ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [1 500 (216-5 144) U/L vs 487 (29-3 516) U/L, z=-9.556, P<0.001; 1 500 (216-5 144) U/L vs 252 (132-663) U/L, z=-11.518, P<0.001], and the proportion of PNH patients with LDH more than 1 000 U/L (79.1%) was significantly higher than that of AIHA patients (13.0%, χ2=93.748, P<0.001) and HS patients (0, P<0.001). ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients (P<0.001), and 63.0% of AIHA patients (P<0.001) and 90.4% of HS patients (P<0.001) were with severe splenomegaly. ⑤The prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients (10.5%, P<0.001) and PNH patients (2.9%, P<0.001).@*Conclusion@#The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.

Comparison of age-based clinical and abnormal immune parameters in patients with Henoch-Schönlein purpura / 中华血液学杂志

Objective@#To explore age-based clinical and immune parameters in Henoch-Schönlein purpura (HSP) to determine clinically useful markers reflecting disease characteristic.@*Methods@#A cohort of 502 patients with HSP were enrolled into this retrospective study to evaluate their clinical and immune data.@*Results@#Majority HSP cases occurred at age ≤14 years and showed significant immune imbalances of ESR, CD3+ cells, CD4+ cells, CD3-CD16+CD56+ cells, CD4+/CD8+ cells, IgG, IgA, IgM, IgE, complements C3/C4 and ASO in the acute phase. Compared to patients aged >14 years, symptoms of joint were more frequent at disease onset in patients aged ≤14 years (20.8% vs 7.6%, χ2=13.547, P<0.001) , and involvement of digestive tract and joint were also more frequent (57.4% vs 33.8%, χ2=24.106, P<0.001; 55.9% vs 32.5%, χ2=23.768, P<0.001, respectively) , but not for involvement of kidney (21.4% vs 51.3%, χ2=42.440, P<0.001) . The patients aged ≤14 years had distinct immune state, reductions of CD3+ cells, CD4+ cells and IgG were more frequent than patients aged >14 years, also increase of ASO (33.1% vs 20.0%, χ2=6.656, P=0.010) , but not increase of IgA (2.6% vs 39.4%, χ2=15.582, P<0.001) . In addition, reduction of IgG and increase of IgE were positively associated with digestive tract involvement (P<0.001, P=0.001, respectively) , reduction of CD3+CD4+ cells and normal IgM were positively associated with joint involvement (P=0.004, P=0.003, respectively) , increase of CD3+CD8+ cells and normal CD3+ cells were positively associated with kidney involvement (P=0.032, P=0.014, respectively) .@*Conclusion@#HSP showed significant immune imbalance in the acute phase, patients between aged ≤14 and >14 years had distinct clinical and immune characteristic, and abnormal immune parameters were significantly associated with organ involvements.

Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.</p><p><b>METHODS</b>A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.</p><p><b>RESULTS</b>All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.</p><p><b>CONCLUSIONS</b>AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.</p>

Clinical characteristics and evolution of paroxysmal nocturnal hemoglobinuria clones in patients with acquired aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical characteristics, and the effect of paroxysmal nocturnal hemoglobinuria (PNH) clone size and its evolution on response and survival in aplastic anemia (AA) patients.</p><p><b>METHODS</b>The clinical data of 90 AA cases with PNH clones from 316 AA patients between January 2011 and September 2014 were retrospectively reviewed, their clinical characteristics were analyzed, and the influence of PNH clone evolution and size on response and survival were explored.</p><p><b>RESULTS</b>① Of 316 patients, 90 cases (28.5%) with PNH clones. Of 83 cases with long-term follow-up data available, the complete (CR) and partial response (PR) rates were 43.4% and 33.7% respectively, with the overall responsive rate of 77.1%. The 3-year and 5-year overall survival (OS)rates were 79.4% and 76.1% respectively. ② After immunosuppressive therapy (IST), the PNH clone changed from negative to positive in 24 cases, persistently positive PNH clones were observed in 22 cases, disappeared in 10 cases. There were no significant differences in terms of overall responsive rates, survival rates, absolute reticulocyte value, TBIL, IBIL and LDH among the three groups (P >0.05). Ten cases became AA-PNH after a median time of 15.6 months, no significant differences were found in overall responsive and survival rates between the 10 cases and the other 46 cases who were monitored for PNH clones (P values were 0.896, 0.688, respectively). ③ According to univariate analysis, age≥55, infection, VSAA, ANC <0.5 × 10(9)/L and absolute reticulocyte value <0.012 × 10(12)/L had significant influence on survival (P values were 0.026, 0.000, 0.001, 0.000 and 0.010, respectively). Cox regression model analysis identified that age, infection and ANC were independent prognostic factors affecting survival (P values were 0.050, 0.012 and 0.050, respectively). The PNH clone size had no significant influence on response and survival based on univariate and Cox analyses.</p><p><b>CONCLUSION</b>The PNH clone size and its evolution had no significant influence on response and survival.</p>

Acquired aplastic anemia developing myelodysplastic syndrome/acute myeloid leukemia: clinical analysis of nineteen patients and literatures review / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features of clonal evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (AML) and review of literatures.</p><p><b>METHODS</b>AA developing MDS/AML patients between December 1994 and December 2011 enrolled into this study to analyze their clinical characteristics.</p><p><b>RESULTS</b>During the median follow-up of 49(15-97) months, 19 patients evolved to MDS/AML, of whom 10, 8 and 1 were from VSAA, SAA and NSAA subgroups, respectively. The median G-CSF therapy was 270(29-510) days. There were monosomy 7 in 11(57.9%) of 19 patients with AA evolved to MDS/AML. The median AA evolved to MDS/AML was 33(11-88) months. The median MDS/AML transformation in responders (54.2 months) was significantly longer than of non-responders (25.7 months, P<0.01).</p><p><b>CONCLUSION</b>AA patients could evolved into MDS/AML concomitant with abnormal karotype and worse prognosis.</p>

Flow cytometric test using eosin-5'-maleimide (EMA) labelling of red blood for diagnosis of hereditary spherocytosis / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the sensitivity and specificity of eosin-5'-maleimide (EMA)assay for the diagnosis of hereditary spherocytosis (HS), and to verify the stability of reagent and samples.</p><p><b>METHODS</b>EMA flow cytometry test, NaCl-osmotic fragility test and acidified glycerol lysis test were performed using peripheral blood samples from 80 patients with HS and 44 patients with other blood diseases, the sensitivity and specificity of the three methods were compared, and the feasibility of EMA binding test was estimated. The stability of EMA reagent and HS samples stored at different temperatures were tested.</p><p><b>RESULTS</b>Among the 124 tested samples, the sensitivity and specificity of EMA binding test was 0.925 and 0.954, that of NaCl-osmotic fragility test was 0.950 and 0.455, and that of acidified glycerol lysis test was 1.000 and 0.318, respectively. Although the sensitivity of NaCl-osmotic fragility test and acidified glycerol lysis test was a little higher than that of EMA binding test, the specificity of the former two methods was poor, they couldn't clearly distinguish whether spherocytosis is hereditary spherocytosis. The experiment results showed that EMA was sensitive to the temperature and should not be stored in a small aliquots at -80 ℃ over a period of 6 months. The stability of the HS sample was better, 6 days storage at 4 ℃ and 3 days storage at room temperature had no influence on the results.</p><p><b>CONCLUSION</b>EMA binding test by flow cytometry showed good sensitivity and specificity for HS diagnosis. EMA reagent should be stored at-80 ℃ and the HS samples should be tested within 6 days storage at 4 ℃ and 3 days at room temperature.</p>

The gene mutation analysis of a Wiskott-Aldrich syndrome family with normal mean platelet volume / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the history of a Wiskott- Aldrich syndrome (WAS) family with normal mean platelet volume (MPV), analyse the WASP gene mutation of to better understand its clinical characteristics.</p><p><b>METHODS</b>A four- generation WAS family histories of 22 members were investigated. Peripheral blood samples were collected from propositus and his mother to analyse all exon mutations of WASP gene using sanger sequencing.</p><p><b>RESULTS</b>The MPV of both propositus and his elder brother were normal. The patient's clinical score was 5, antibodies to PM-Scl, PCNA and PO were positive with very high level of ASO, the patient co- suffered from autoimmune disease, anemia, abnormal renal function, fungal infection and scleritis. A homozygous mutation (C>T) was found at 173 bp of exon 2, corresponding to amino acids Pro (P) 58 abnormally changed to Leu (L). His mother was the carrier of the mutation. Of 112 blood diseases- related genes, mutation frequencies of CBL, CREBBP, DNM2 and ADAMTS13 were higher than normals.</p><p><b>CONCLUSION</b>This was the first report the phenotype 173C>T mutation of WASP without eczema, but with normal MPV and autoimmune disease in Chinese, WAS should be recognized earlier and diagnosed correctly by genomic methods.</p>

Salvage therapy for severe aplastic anemia after allogenenic hematopoietic cell transplant / 中华血液学杂志

<p><b>OBJECTIVE</b>To probe a practical salvage strategy for relapse or failure patients with severe aplastic anemia (SAA) after allogenenic hematopoietic cell transplant (allo-HSCT).</p><p><b>METHODS</b>The clinical characteristics and initial treatments of allo-HSCT, and the responses of a novel salvage therapy of cyclosporine alternately combined with levamisole (CsA & LMS regimen) plus danazol (DNZ) in 2 patients were reviewed and evaluated.</p><p><b>RESULTS</b>(1) Patient 1 achieved partial response (PR) at 3 months and complete response (CR) at 6 months after CsA & LMS regimen, respectively; Patient 2 also achieved PR 3 months and nearly CR at 6 months after the salvage therapy, respectively. (2) Increased numbers of T regulatory cells and colony forming unit-erythroid, burst-forming unit-erythroid, colony forming unit-granulocytes/macrophages after CsA & LMS regimen in both patients were observed.</p><p><b>CONCLUSION</b>This was the first report of successful salvage by a novel strategy of CsA & LMS regimen for relapse or failure patients with SAA after allo-HSCT.</p>

Survey on the intake of dietary nutrients for 132 aduit patients with acute and chronic leukemia / 白血病·淋巴瘤

Objective To study the dietary nourishment of adult patients with leukemia and compare acute leukemic patients with chronic leukemic patients. Methods Adopting dietary review of 24 hours and seven consecutive days of dietary records method to obtain the food category and quantity of 122 patients with acute leukemia and 10 patients with chronic leukemia. Using statistic software SPSS11.0 to calculate the patients'intake of various kinds of nutfiments. and the difiences between acute and chronic leukemic patients were analyzed. Results The rate of most ontrients of patients'intake reaches RNI/AI is lower,especially vitamin A,vitamin C and caleium.There's a tendency that intake diet,energy and nourishments of acute leukemic patients is lower than that of those chronic leukemic patients. Conclusion There is a tendency of unbalanced dietary intakes in leukemic patients.including the low intakes.There is the tendency that nutritional status of acute leukemic patients iS poorer than that of chronic leukemic patients.