Expression of cMPO in 502 cases of acute myeloid leukemia (AML) and its diagnosis significance in AML subtypes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the myeloperoxidase (cMPO) expression pattern by flow cytometry (FCM) in patients with acute myeloid leukemia (AML) and its role in classifying AML.</p><p><b>METHODS</b>Eight- color multiparametric FCM with CD45/SSC gating was used to determine the cMPO expression in 502 AML patients.</p><p><b>RESULTS</b>The positive rate of cMPO in all patients was 58.0%, in which the proportion of normal positivity, dim positivity and partial positivity was 21.5%, 34.1% and 2.4%, respectively. The remaining case (42.0%) were all negative. In AML with t (15;17）(q22;q12)/PMLRARα, the positive rate was the highest (100%) and the intensity was similar to that of the normal granular leukocytes, followed by AML with t (8;21（q22;q22/RUNX1-RUNX1T1, the positive rate was 91.4% and the intensity was mostly dim. AML with minimal differentiation and acute megakaryoblastic leukemia were all cMPO negative. The positive rates of cMPO in the remaining subtypes were between 22.7% and 76.2%.</p><p><b>CONCLUSION</b>The positive rate and intensity of cMPO were significantly different among different subtypes of AML.</p>

Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or without human granulocyte colony-stimulating factor in children with acquired severe aplastic anemia / 中华儿科杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).</p><p><b>METHOD</b>The authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.</p><p><b>RESULT</b>(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.</p><p><b>CONCLUSION</b>The use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.</p>

IL-18 single nucleotide polymorphisms in hematologic malignancies with HLA matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Single- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed.</p><p><b>RESULTS</b>In comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes.</p><p><b>CONCLUSION</b>IL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.</p>

Treatment outcome of childhood standard-risk and median-risk acute lymphoblastic leukemia with CCLG-2008 protocol / 中华儿科杂志

<p><b>OBJECTIVE</b>To estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).</p><p><b>METHOD</b>Totally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.</p><p><b>RESULT</b>Among these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P < 0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P < 0.05). After the adjustment the risk group was more significant in the assessment of prognosis.</p><p><b>CONCLUSION</b>The reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.</p>

Role of IL-10 gene polymorphisms in promotor region in HLA matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华器官移植杂志

Objective To explore the impact of IL-10 gene polymorphisms on the outcome in HLA matched sibling hematopoietic stem cell transplantation (HSCT).Methods PCR-sequencespecific primer (PCR-SSP) assay was used to analyze the SNP of IL-10 in 77 recipient and donor pairs:-1082 A/G,-819 T/C,-592 C/A.Results IL-10 ATA/ATA (1082,-819,-592) genotype in recipients significantly decreased the incidence of grade Ⅱ-Ⅳ acute graft vursus-host disease (aGVHD) (6.1％ vs.25.0 ％,P＜0.05),reduced 5-year transplant-related mortality (TRM) (10.7 ％± 5.9％ vs.29.7％ ± 5.2％,P＜0.05) and increased disease free survival (DFS) (81.8％ ± 6.7％ vs.56.8％ ± 7.5％,P＜0.05).With regard to the donor genotype,the incidence of grade Ⅱ-Ⅳ aGVHD,extensive chronic GVHD,5-year TRM and DFS had no signicant difference between IL-10 ATA/ATA and non ATA/ATA subgroup.Multivariable analysis also revealed that IL-10 non-ATA/ATA genotype in recipients and high-risk status of disease were two independent risk factors for DFS (HR =2.911,P =0.029; HR =2.686,P =0.027).Conclusion In HLA-matched sibling HSCT,the presence of recipient IL-10 ATA/ATA significantly decreased the incidence of grade Ⅱ-Ⅳ aGVHD and TRM,and increased DFS.

A new prognostic stratification for patients with acute myeloid leukemia / 中华内科杂志

Objective To evaluate the impact of the percentage of residual blasts in bone marrow at the end of induction chemotherapy ( T1 ) or during myelosuppression phase (T2) on prognosis of de novo acute myeloid leukemia(AML) (non M3) in 105 cases.To refine AML risk-stratification by combining the percentage of residual blast cells (T1 or/and T2) with cytogenetic data based the South West Oncology Group (SWOG) criteria.Methods The data of 105 de novo AML ( non M3 ) patients hospitalized between January 1st 1999 and February 1st 2008 were retrospectively reviewed.Results were analyzed with SPSS15.0 software.Results ( 1 ) Patients were divided into two subgroups by a cutoff of 5% residual bone marrow blasts at T1 or 12 time point.Patients with percentage of residual bone marrow blast cells <5% had better complete remission (CR) rate,relapse-free survival (RFS) and overall survival (OS) than the patients with percentage ≥5% at T1 or T2.The percentage of residual bone marrow blast cells at T1 was correlated with that at T2.(2) The prognosis of patients with intermediate karyotypes with percentage < 5 % at T1 or T2 was similar to that of the patients with favorable karyotypes.The patients with intermediate karyotypes and percentage of residual bone marrow blasts ≥5% at TI or T2 are defined as a subgroup with prognosis similar to that of patients with unfavorable karyotypes.(3) COX regression analysis showed that the percentage of residual bone marrow blasts at T1 or T2 is an independent prognostic factor of AML.The percentage of residual bone marrow blasts at T1 may be more helpful in prognostification than that at T2.Conclusion AML patients with percentage of residual bone marrow blasts < 5% after induction chemotherapy ( T1 or T2) have better CR rate,RFS,OS than the patients with percentage ≥5% at the same time point.Combination of cytogenetics and percentage of residual bone marrow blasts at T1 or T2 is helpful to divide patients with intermediate karyotypes into two subgroups with different prognosis.Thus,a better decision of treatment strategy can be designed.