Adolescent ; Adult ; Child ; Elliptocytosis, Hereditary ; diagnosis ; genetics ; Female ; Humans ; Male

OBJECTIVETo assess the short term curative efficacy and long-term survival outcomes of severe aplastic anemia patients following antithymocyte globulin/lymphoglobulin (ATG/ALG) with or without cyclosporine (CsA).

METHODSA total of 345 cases hospitalized in our hospital between December 1982 and June 2011 were enrolled into this study. We assessed the response rates 3 and 6 months after ATG/ALG, and estimated the overall survival (OS) by Kaplan-Meier method for this cohort of patients.

RESULTSThe cohort of 345 patients was routinely followed-up with a median follow-up of 44.0 (range, 0.5 - 244.0) months. The response rates at 3 and 6 months were 29.9% and 45.4%, respectively. The differences in response rates at both 3 (39.2% vs 19.6%, P < 0.01) and 6 months (55.6% vs 34.0%, P < 0.01) between 184 non-severe aplastic anemia (mSAA) and 161 very severe aplastic anemia (VSAA) were statistically significant. The response rates among the different ATG preparations were comparative; but 3-(10.6%) and 6-month (25.5%) responses produced by rATG-Fresenius were significantly inferior to those by rATG-Sangstat (36.6% and 56.6%, respectively) (all P < 0.01). The 5-year OS was 61.7% (95%CI 55.4% - 68.0%) for the entire cohort of patients, and 5-year OS for mSAA patients \[71.0% (95%CI 62.9% - 79.1%)\] was superior to that of VSAA patients \[50.4% (95%CI 40.1% - 60.7%), P < 0.01\]; but for the patients treated from 2007, the difference of OS in the last 5 years between VSAA and mSAA was not significant \[ 73.7% (95%CI 52.2% - 95.2%) vs 89.7% (95%CI 79.5% - 99.9%); P = 0.24\]. Our study also confirmed the superiority of ATG/ALG + CsA regimen \[64.8% (95%CI 57.9% - 71.7%)\] over ATG/ALG alone \[32.6% (95%CI 15.7% - 49.5%)\] with regard to 5-year OS (P < 0.01); but the addition of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to ATG/ALG had no benefit in terms of OS. rATG-S produced significantly better 5-year OS \[66.1% (95%CI 55.8% - 76.4%)\] than rATG-F \[46.6% (95%CI 35.9% - 57.3%); P < 0.01\].

CONCLUSIONS(1) The outcome of mSAA was superior to that of VSAA, but the latter was markedly improved in the last 5 years; (2) rATG-F was inferior to rATG-S with regard to 5-year OS; (3) Immunosuppressive treatment with ATG/ALG plus CsA was more effective than ATG/ALG alone; (4) The addition of rhG-CSF to ATG/ALG had no benefit in terms of OS.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; therapeutic use ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Immunoglobulins ; therapeutic use ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the clinical significance of genetic detection and changes of red cell enzyme activities of pyrimidine 5' nucleotidase (P5'N), pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G-6-PD) in patients with α-thalassaemia (α-thal).

METHODSThree α-thal patients were further processed to gene detection by PCR-trans-dot blot and gap-PCR, and red cell enzymes activities by absorbance at 260 and 280 nm (A) for P5'N and fluorescence spot test for PK and G-6-PD.

RESULTSRed cells in 3 α-thal cases were microcytic hypochromic with obvious augmented target cells and basophilic stippling erythrocytes. Two patients had anemia, splenomegaly, hyperbilirubinemia and augmented LDH. HbH was positively identified by hemoglobin electrophoresis and hemoglobin cellulose acetate membrane electrophoresis; the other patient had no such abnormalities. Genotypes of 3 patients were of (-α(3.7)/--(SEA)), (αα(QS)/--(SEA))and (--(SEA)), respectively. The activity of P5'N (but not for PK and G-6-PD) in red cell reduced.

CONCLUSIONSThis is the first documented α-thal with P5'N deficiency. Genetic detection might be clinical significant for the diagnosis and pedigree screening of α-thal.

5'-Nucleotidase ; deficiency ; Adolescent ; Adult ; Erythrocytes ; enzymology ; metabolism ; Female ; Humans ; Male ; Middle Aged ; alpha-Thalassemia ; enzymology ; genetics

OBJECTIVETo 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.

METHODSThe 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.

RESULTS① 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.

CONCLUSIONThe PNH clone size and its evolution had no significant influence on response and survival.

Anemia, Aplastic ; complications ; pathology ; Clone Cells ; Hemoglobinuria, Paroxysmal ; complications ; pathology ; Humans ; Immunosuppression ; Reticulocytes ; Retrospective Studies

OBJECTIVETo analyze the clinical characteristics and risk factors on responses and survival of myelodysplastic syndromes (MDS) patients with paroxysmal nocturnal hemoglobinuria (PNH) clones.

METHODSThe clinical data of 31 MDS cases with PNH clones from October 2004 to June 2012 were retrospectively analyzed to reveal the influence of PNH clone size on responses and survival.

RESULTS①The chromosome karyotypes were analyzed in all patients, 23 patients with normal karyotype, 7 patients with abnormal karyotype [including 3 patients with +8, 2 -Y, 1 del(7q) and 1 Xp+] and 1 patient with no mitosis. 1 patient belonged to low-risk, 27 intermediate-1 risk, 2 intermediate-2 risk and 1 high-risk groups, respectively, according to IPSS. There were significantly statistical differences between responders and nonresponders in terms of infection, ANC, Reticulocyte count and IPSS (P values were 0.049, 0.006, 0.031 and 0.043, respectively). ②The overall responsive rate was 67.7%, no patients progressed to acute leukemia (AL) during median follow-up of 19 months after immunosuppressive therapy (IST). The 3-year and 5-year overall survival rates were 82.7% and 55.1%,respectively. ③According to univariate analysis,age, infection and ANC had significant influence on survival (P values were 0.050, 0.031 and 0.026, respectively). ④The PNH clone size had no significant influence on survival through univariate and COX analyses (P=0.393).

CONCLUSIONMDS patients with PNH clone had less cytogenetic abnormalities, higher probability of response to IST and lower probability of progression to AL; Furthermore, the PNH clone size had no significant influence on response and survival.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clone Cells ; Female ; Hemoglobinuria, Paroxysmal ; pathology ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; genetics ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the abnormalities of iron metabolism, the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA).

METHODSA cross-sectional study was conducted on 520 newly diagnosed AA patients.

RESULTSIron overload was observed in 66(13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections(19/86, 22%)than those without infections (47/434, 11%, P<0.01), but also in patients with hepatitis associated AA(HAAA) (6/22, 19%) than the idiopathic cases (60/488, 12%, P>0.05). Excluded the patients with infections and/or HAAA, 43 of 405(11%)cases had iron overload, including 14 of 248(6%) cases without history of blood transfusion and 29 of 157 patients (18%, P<0.01) with transfusion. In univariate analysis, higher levels of serum ferritin (SF), serum iron (SI) and transferrin saturation (TS) were mainly observed in adult male patients with severe AA (SAA) and significantly upward with increasing blood transfusion (P<0.01). No differences of soluble transferrin receptor (sTfR) were observed between adults and children, males and females, hepatitis and idiopathic AA. However, patients with infections had significantly lower level of sTfR (0.50 mg/L) than cases without infections (0.79 mg/L, P<0.01). The level of sTfR in SAA patients (0.70 mg/L) was only half of that in non-SAA (NSAA) (1.36 mg/L, P<0.01). Patients with increasing blood transfusion had significantly downward levels of sTfR (P<0.01). In multivariate analysis, more than 8 U blood transfusion (OR=10.52, P<0.01), adults (OR=3.48, P<0.01), males (OR=3.32, P<0.01) and infections (OR=2.09, P<0.01) were independent risk factors.

CONCLUSIONAA patients had higher iron burden and were high-risk populations occurring iron overload. The iron overload occurred in 18% of patients with blood transfusion and in 6% of patients without transfusion.

Anemia, Aplastic ; complications ; physiopathology ; Blood Transfusion ; Ferritins ; blood ; Hepatitis ; complications ; Humans ; Iron ; blood ; metabolism ; Iron Overload ; physiopathology ; Risk Factors

OBJECTIVETo study the clinical characteristics and pathogenesis of hematidrosis.

METHODSDetailed clinical manifestations and natural history of a patient with hematidrosis were presented. A series of laboratory examinations were performed, and skin pathohistologic features and ultra microscopic structures were observed.

RESULTSThe episodes of skin bleeding occurred on any site of the body spontaneously and promptly. The skin surface bloody extravasation has identical cell components as that of peripheral blood. All the results of laboratory tests were normal except a positive Trousseau's test. Skin pathohistological study revealed some intradermal bleeding and emphraxised capillaries. No abnormality was found in sweat glands, hair follicles and sebaceous glands.

CONCLUSIONThe pathological basis for hematidrosis might be a distinctive vasculitis.

Child ; Female ; Hemorrhage ; pathology ; Humans ; Skin ; blood supply ; pathology ; Skin Diseases ; pathology

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 (r_s=0.109, P=0.125; r_s=-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.

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.