Molecular features of 109 patients with chronic myelomonocytic leukemia in a single center / 中华血液学杂志

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.

Clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm accelerated/blast phase / 中华血液学杂志

Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Mean corpuscular volume ≤100 fl was an independent prognostic factor in patients with myelodysplastic syndrome and bone marrow blast<5 percent / 中华血液学杂志

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Analysis of clinical characteristics, treatment response rate and survival of 77 myelodysplastic syndrome patients with del (5q) syndrome / 中华血液学杂志

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.

Clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes / 中华血液学杂志

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.

Ruxolitinib combined with prednisone, thalidomide and danazol for treatment of myelofibrosis: a pilot study / 中华血液学杂志

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.

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<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/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.

Analysis of Early-Death and Factors Affecting Prognosis of Patients with Acute Promyelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the factors affecting the early-death, overall survival (OS) and relapse-free survival (RFS) of acute promyelocytic leukemia (APL) patients.</p><p><b>METHODS</b>The clinical and laboratorial charachteristics of 176 APL patients in our center were analyzed retrospectively during January 2002 to Mar 2016. The risk factors of early death and factors affecting OS and RFS of patients were analyzed.</p><p><b>RESULTS</b>Among total of 176 patients, early death occured in 10 patients. Multivariate analysis showed both age ≥60 years and fibrinogen<1.5 g/L (HR=6.4, 95%CI 1.4-28.2) (P=0.015), (HR=12.2, 95%CI 1.5-102.8) (P=0.021), respectively were the independent risk factors for the early death during the induction therapy. Among 154 patients with full follow-up data (median follow-up time was 101(2-262) months), the estimated 5-year OS and RFS rate were (98± 1)% and (77± 4)%, respectively. Cox regression analysis showed relapse during treatment as well as initial WBC count≥30× 10/L were independent prognostic indicators for OS. Accompanied psoriasis indicated higher relapse rate of APL(HR=4.8, 95%CI 1.8-12.5)(P=0.002), while the low-risk APL indicated lower relapse rate (HR=0.4, 95%CI 0.2-0.99)(P=0.048).</p><p><b>CONCLUSION</b>Importance should be attached to the early-death events in elder and low-fibrinogen APL patients. As for patients with psoriasis or non low-risk group, emphasizing the intensified dynamic supervision during the treatment helps to detect the early-relapse events. For relapsed patients and patients with ≥30× 10/L WBC count, seeking more optimized therapy strategy seems allow this cohorts to get better prognosis.</p>

Targeted sequencing analysis of hyper-eosinophilic syndrome and chronic eosinophilic leukemia / 中华血液学杂志

Objective: Analysis of the molecular characteristics of eosinophilia. Methods: Targeting sequence to 24 patients with chronic eosinophilic leukemia (CEL) with rearrangement of PDGFRA, PDGFRB, or FGFR1 and 62 patients with hyper-eosinophilic syndrome (HES). Mutation annotation and analysis of amino acid mutation using authoritative databases to speculate on possible pathogenic mutation. Results: Thirty-seven kinds of clonal variant were detected from 17 patients with CEL, no recurrent mutation site and hot spot region were found. No pathogenic mutation was detected in 19 patients with PDGFRA rearrangement, but pathogenic mutations of ASXL1, RUNX1 and NRAS were detected from 2 patients with FGFR1 rearrangement who progressed to acute myeloid leukemia and 1 patient with PDGFRB rearrangement who progressed to T lymphoblastic lymphoma, respectively. One hundred and two kinds of clonal abnormalities were detected in 49 patients with HES. The main hot spot mutation regions included: CEBPA Exon1, TET2 Exon3, ASXL1 Exon12, IDH1 Y208C, and FGFR3 L164V. CRRLF2 P224L and PDGFRB R370C point mutations were detected separately in 2 patients with HES who treated with imatinib monotherapy and achieved hematologic remission. Conclusion: The pathogenesis of CEL with PDGFRA, PDGFRB or FGFR1 rearrangement is usually single, and the progression of the disease may involve other driver mutation. A variety of genes with hot mutation regions may be involved in the pathogenesis of HES, and some mutation sites are sensitive to tyrosine kinase inhibitors.

Relationship between polymorphisms of tumor necrosis factor alpha gene and primary myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleus polymorphisms(SNP)of tumor necrosis factor alpha (TNF-α) gene (-308 G>A and -238 G>A genotypes) with susceptibility to primary myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Two SNPs (TNF-α-308 G>A,TNF-α-238 G>A) of TNF-α gene were detected by Taqman probes in 341 MDS patients and 365 unrelated-healthy controls.</p><p><b>RESULTS</b>Compared to healthy controls, the frequency of TNF-α-308 AA+AG genotype and A allele increased (18% vs 10%, P=0.015, 9% vs 5%, P=0.021, respectively) in refractory cytopenia with multilineage dysplasia (RCMD) patients. There was no correlation of TNF-α-308 G>A genotype and allele frequency between MDS and controls. No difference in the genotype and allele frequency of TNF-α-238 G>A were found between controls and MDS or the subtypes of MDS (P>0.05). We did not find any linkage between plasma level of TNF-α and TNF-α-308 G>A or TNF-α-238 G>A genotype. Statistic differences were observed between platelet count[58(1-611)×10⁹/L vs 90(7-352)×10⁹/L]and bone marrow blasts in MDS patients carrying TNF-α-308 G>A GG and AA+AG genotype (P=0.024, 0.019, respectively).</p><p><b>CONCLUSION</b>TNF-α-308 G>A polymorphism was correlated with susceptibility to MDS-RCMD.</p>

Analysis of clinical features and prognosis of primary myelodysplastic syndromes with myelofibrosis patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognosis of the primary myelodysplastic syndrome with myelofibrosis (MDS-MF) patients and to improve the cognition of MDS-MF.</p><p><b>METHODS</b>Four hundred and sixty-six primary MDS patients with bone marrow (BM) biopsy were divided into two groups according to whether BM associated with fibrosis, the clinical features and prognosis of the two groups were analyzed retrospectively.</p><p><b>RESULTS</b>167 (35.8%) MDS cases revealed myelofibrosis, of which MF-1 123 cases (26.4%), MF-2 40 cases (8.6%), MF-3 4 cases (0.9%). The proportion of hepatosplenomegaly in MDS-MF group was significantly higher than in MDS without MF group, the difference had statistical significance (P = 0.031). The proliferation of BM biopsy in MDS-MF group was significantly more active than in MDS without MF group. The number of blasts, megakaryocytes and abnormal megakaryocytes in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P < 0.05). Among the 345 patients who had available results of cytogenetic analysis, 121 cases were MDS-MF patients, the proportion of middle and high-risk prognostic group according to IPSS karyotype prognosis groups in MDS-MF group were significantly higher than in MDS without MF group, the differences had statistical significance (P = 0.047). The median survival was 17 (1 - 60) months in MDS-MF group, and was 32 (1 - 62) months in MDS without MF group. The difference had statistical significance (P = 0.001). Myelofibrosis had independent prognostic significance by multi-variable analysis (P = 0.019).</p><p><b>CONCLUSION</b>The myelofibrosis in MDS is main the proliferation of reticular fiber. The proliferation of reticular fiber is closely related with the number of blast cells, the proliferation and developmental abnormalities of megakaryocytes and the karyotype. The prognosis of MDS-MF patients is poor.</p>

Clinical study on combination of homoharringtonine, Ara-C and idarubicin induction for treatment of newly diagnosed acute myeloid leukemia patients / 中国实验血液学杂志

The purpose of this study was to assess the efficacy and toxicity of HAI regimen [(homoharringtonine 2.5 mg/(m(2)×d), days 1 - 7; cytarabine 150 mg/(m(2)×d), days 1 - 7; idarubicin 9 mg/(m(2)×d), days 1 - 7)] for induction treatment of newly diagnosed acute myeloid leukemia (AML) (except acute promyelocytic leukemia). 31 patients with newly diagnosed AML, aged 39 (14 - 58) years, were enrolled in this clinical study. The complete remission (CR) rate, especially after one course, the overall survival (OS) rate and relapse free survival (RFS) rate were estimated. The outcomes were compared between different prognostic groups according to World Health Organization (WHO) classification, genetics and initial WBC count. Safety was evaluated using standard WHO criteria. The results showed that 26 patients (84%) achieved CR after 1 course of induction. The CR rate for the patients with favorable, intermediate and unfavorable cytogenetics was 90%, 88% and 60% respectively. All 7 patients with a high initial WBC count (≥ 100×10(9)/L) obtained CR, while 19 out of 24 without a high initial WBC count obtained CR. With a median follow-up of 15(range 2-56) months, the estimated 3-year OS rate for all patients and the patients with CR was 44% and 52% respectively. The 3-year RFS rate was 51%. The patients receiving induction chemotherapy died of the chemotherapy. Profound myelosuppression was seen in all patients after the HAI induction with the median duration of neutropenia (ANC < 0.2×10(9)/L) of 16 (6 - 24) days. As the most common toxicity, severe infections (grade III-IV) involved in all the patients and the duration of febris was 6 (1 - 36) days. The incidence of septemia and invasive fungus infection were 19.4% and 45.2% respectively. The incidence of non-infection fever, increased glutamic-pyruvic transaminase (GPT), diarrhea, increased bilirubin and oral cavity mucositis were 6.5%, 6.5%, 3.2%, 3.2%, 3.2% respectively, as the more frequent severe non-hematological toxicities. It is concluded that HAI regimen is a high efficient induction schedule for the newly diagnosed AML, and archive the higher CR rate after one course than DNR/Ara-C standard induction regimen. Side effects are acceptable, except severe infection.

Substance P and its receptors are involved in the effect of histamine H3 receptor agonist, IMETIT on nasal allergic symptoms in guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To explore the influence of histamine H3 receptor agonist, IMETIT and simultaneous use of IMETIT and H1-receptor antagonist, Loratadine, on the symptoms of allergic rhinitis (AR) and substance P(SP) secretion and expression of SP receptor (SP-R) mRNA in AR model in guinea pigs.</p><p><b>METHODS</b>Guinea pigs were divided randomly into 4 groups: AR group (group A), IMETIT group (group B), Loratadine group (group C) and IMETIT+Loratadine group (group D). The severity of AR was assessed by determining the extent of three markers of allergic symptoms (sneezing, nasal rubbing and nose blocking). The changes in the nasal mucosa were studied by pathological methods. The expression of positive cell of SP was detected by immunohistochemistry. SP-R mRNA expression in nasal mucosa was used to do reverse transcriptive-polymerase chain reaction (RT-PCR). Statistical analysis was performed using a SPSS 13.0 software.</p><p><b>RESULTS</b>In Group B, the mean (x ± s) number of sneeze [(15.0 ± 1.3) times], scratching nose [(16.5 ± 2.3) times] and respiratory frequency [(76.3 ± 4.1) times/min] were significantly improved than those in group A [(23.5 ± 2.6) times, (26.1 ± 4.1) times and (66.5 ± 5.8) times/min, respectively), P value were 0.000, 0.000 and 0.001, respectively]. The numbers of SP-positive cells [(11.6 ± 3.6)/HP] and SP-R mRNA expression (0.64 ± 0.04) in group B were reduced significantly compared to group A [(27.1 ± 9.7)/HP, (0.83 ± 0.03), P value were 0.000, 0.000, respectively]. Sneeze [(10.0 ± 2.3) times], scratching nose [(11.8 ± 1.7) times] and respiration [(90.0 ± 5.0) times/min] in Group D were improved significantly than those in group B (P value were 0.000, 0.002 and 0.000, respectively). SP-positive cells [(2.0 ± 1.7)/HP] and SP-R mRNA expression (0.52 ± 0.06) in Group D compared with group B were also significantly reduced (P value were 0.012 and 0.000, respectively). Pathological changes in guinea pig nasal mucosa in group B, group D were alleviated than those in group A. The combination of IMETIT and Loratadine had a synergistic effect on these effects (F value were 11.59, 8.28, 5.61, 5.48, 6.50, respectively, P value were 0.002, 0.008, 0.025, 0.027, 0.017).</p><p><b>CONCLUSIONS</b>IMETIT and the combination of IMETIT with Loratadine can effectively relieve the symptoms of AR in guinea pigs, its mechanism may be relevant to reduce SP secretion and the expression of SP-R mRNA, and the two has a synergistic effect. It may be useful as a novel therapeutic approach in nasal allergy.</p>