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.

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>

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>