The clinical significance of evolution of paroxysmal nocturnal haemoglobinuria clones in aplastic anemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of evolution of paroxysmal nocturnal hemoglobinuria (PNH) clones in aplastic anemia (AA) patients.</p><p><b>METHODS</b>The positive rate of PNH clones in 678 AA cases at first diagnosis from January 2002 to December 2009 were analyzed, and to compare the response rate and overall survival (OS) between AA patients with or without PNH clones. All patients were sequentially followed-up to assess the incidence rate and risk factors for AA evolving to overt PNH.</p><p><b>RESULTS</b>(1) Of 119/678 (17.6%) AA patients at initial diagnosis presented with PNH clones,the positive rates of PNH clones among non-severe AA (NSAA), severe AA (SAA) and very severe AA (VSAA) were 16.7% (37/ 222), 17.3% (45/260) and 18.9% (37/196), respectively. There was no statistical difference among the three groups. (Chi2 = 0.369; P = 0.832); (2) 678 newly diagnosed AA cases were divided into 5 subgroups according to PNH clones, severity of disease and treatment regimens. There was no statistical difference among the five subgroups regarding 6m-response rate (RR) and OS. (3) Serial follow-up revealed that persistent PNH negative clones were found in 516 (76.1%) cases, and evolved to PNH positive clones after therapy in 43 (6.3%) cases. Persistent PNH positive clones were found in 72 (10.6%) cases, and disappeared the clones after treatment in 47 (6.9%) cases. There was no statistical difference among the four subgroups in terms of the 6m RR (Chi2 = 2.489,P = 0.426) and OS (P = 0.477); (4) 17 out of 678 AA cases (2.5%) evolved to overt PNH and the estimated incidence of evolution to overt PNH was (3.7 +/- 0.9)% at 10 years. The incidences of AA patients with or without PNH clones at initial diagnosis evolved to overt PNH were 3.4% and 2.3%, respectively. There was no statistical difference between the two groups, (Chi2 = 0.111; P = 0.739); and so was found in OS by Kaplan-Meier analysis (P = 0.868). Cox regression model analysis showed that none of the severity of AA, with or without PNH clone at initial diagnosis, treatment regimen and 6m RR was the risk factor for evolution to overt PNH.</p><p><b>CONCLUSION</b>There is no difference between AA patients presented with or without PNH clones at initial diagnosis regarding the RR and prognosis. The appearance of PNH clones in AA is not identified as a risk factor for developing into overt PNH.</p>

Long-term follow-up of malignant clonal evolution in patients with acquired aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the incidence and risk factors for evolution of acquired aplastic anemia (AA) into myelodysplastic syndrome/acute myeloid leukemia (MDS/AML).</p><p><b>METHOD</b>A total of 1003 AA patients hospitalized in our institute hospital between January 1991 and December 2009 enrolled into this study. The incidence and risk factors for AA developing MDS/AML by the Kaplan-Meier method and Cox proportional hazards models, respectively.</p><p><b>RESULTS</b>The median follow-up was 62 (2 - 423) months and the projected 5-year survival rate was (78.0 +/- 1.0)%. Twenty-seven patients evolved to MDS/AML, of whom 11, 6 and 10 were from NSAA, SAA and VSAA subgroups, respectively. The estimated cumulative incidence of MDS/AML transformation for these 1003 patients after diagnosis was (4.5 +/- 1.0)% at 10 year. The incidence of MDS/AML transformation in VSAA subgroup [(12.8 +/- 3.5)%] was significantly higher than in NSAA subgroup [(4.1 +/- 1.9)%] (P < 0.001) and SAA subgroup [(3.5 +/- 1.4)% ] (P = 0.008), but no difference between the latter two subgroups (P = 0.616). Age [RR = 3.527 (95% CI: 1.598 - 7.784), P = 0.002], severity of disease [RR = 5.122 (95% CI: 2.214 - 11.853), P < 0.001], the duration (days) of rhuG-CSF therapy [RR = 10.782 (95% CI: 4.600 - 25.269), P < 0.001] and exposure to ray, chemicals or drugs [RR = 3.401 (95% CI: 1.535 - 7.534), P = 0.003] were risk factors for the transformation in both univariate and multivariate analyses.</p><p><b>CONCLUSION</b>Long-term follow-up is essential to assess the incidence and risk factors for evolutions of acquired AA into MDS/AML, and to administer salvage therapy for transformation in time during follow-up.</p>

Analysis of efficacy and related factors in 85 chronic myeloid leukemia patients treated with imatinib mesylate / 中国实验血液学杂志

The objective of this study was to evaluate the efficacy of Imatinib on patients with chronic myeloid leukemia (CML) in chronic phase and to analyze its influencing factors. 85 patients received Imatinib mesylate at a dose of 300-600 mg orally per day, and were evaluated for hematologic, cytogenetic, and molecular responses. The results showed that the median follow-up was 21 (range 9 - 78) months. Cumulative complete hematological remission (CHR) rate was 100%, major cytogenetic remission (MCyR) rate was 80%, complete cytogenetic remission (CCyR) rate was 67.1% and complete molecular remission (CMoR) rate was 36.4%. The median time to complete hematological remission (CHR) was 1 (range 1 - 3) month, to complete cytogenetic remission (CCyR) was 6 (range 1 - 24) months. The estimated overall survival rates for patients who received Imatinib for 1, 2, 3 years were (98.7 +/- 1.3)%, (96.5 +/- 2.5)% and (90.1 +/- 6.6)% respectively. The estimated progression-free survival rates at 1, 2, 3 years were (97.6 +/- 1.6)%, (96.1 +/- 2.2)% and (90.0 +/- 1.4)% respectively. The CHR, MCyR and CCyR between low risk, intermediate risk and high risk groups according to the Sokal scoring system and between primarily treated and retreated groups all had no difference. The overall survival of patients who achieved MCyR or CCyR was better than that in patients only achieved hematologic remission (p = 0.026), but there was no significant difference in progression-free survival between them. Univariate analysis for efficacy of Imatinib mesylate revealed that WBC count < 100 x 10(9)/L (p = 0.024), Hb level > or = 130 g/L (p = 0.036), and peripheral basophil count < or = 0.05 (p = 0.024) before therapy were independent favourable factors for achieving MCyR or CCyR. It is concluded that the patients with CML in chronic phase treated with Imatinib can achieve the best hematologic remission and higher cytogenetic remission, it should be considered that the imatinib is a drug of the first-line therapy for untreated and treated patients with CML.

Treatment of severe aplastic anemia with intensified immunosuppressive therapy and two different regimens with recombinant human granulocyte colony-stimulating factor: a retrospective study based on long-term follow-up / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of two different regimens with recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with intensified immunosuppressive therapy (IIST) in severe aplastic anemia (SAA).</p><p><b>METHODS</b>Retrospectively analyzed 176 SAA treated with IIST and rhG-CSF in our hospital from March 1994 to December 2007. Regimen A (Group A, n = 96), rhG-CSF 300 µg/d was initiated on day 31 after IIST and subcutaneously administered 1-3 days a week for 3 months. Regimen B (Group B, n = 80), rhG-CSF was initiated at 5 µg·kg(-1)·d(-1) before IIST until hematologic recovery.</p><p><b>RESULTS</b>(1) The early response rate of Group B (67.5%) was significantly higher than that of Group A (37.5%) (P < 0.01), the interval from IIST to response in Group B was shorter than that in Group A. Moreover, infection-related deaths during first 4 months after IIST were significantly reduced in Group B (6.3%) when compared with Group A (16.7%) (P = 0.034). The cumulative incidence of survival at 4 years in Groups B [(77.7 ± 4.9)%] was also significantly higher than that in Group A [(57.2 ± 5.1)%] (P = 0.006). (2) With regard to 93 refractory patients with no response 4 months after IIST, rhG-CSF therapy was continued in Group B meanwhile stopped in Group A. There were no differences between two groups in terms of survival and the response rates (P = 0.288, 0.066), but there was an increasing risk of evolving into MDS/AML in Group B (22.3%) when compared with Group A (3.71%) (P = 0.023). (3) By multivariate analysis, the severity of disease (P = 0.010, RR = 1.922) and the early response (P < 0.01, RR = 5.749) were associated with the overall survival. Moreover, the number of days of rhG-CSF therapy was the only significant risk factor for SAA evolving into MDS/AML (P = 0.017, RR = 1.004).</p><p><b>CONCLUSIONS</b>The early initiation of rhG-CSF therapy with proper dose might contribute to a desirable early response and reduced infection-related death rate, but extended administration of rhG-CSF did not improve the long-term outcome of refractory SAA and may further facilitate the progression of SAA into MDS/AML.</p>

Prognostic factor analysis in 203 patients with chronic lymphocytic leukaemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore prognostic factors in patients with chronic lymphocytic leukemia (CLL).</p><p><b>METHODS</b>Two hundred and three CLL patients in our hospital between 2000 to 2007 were retrospectively reviewed for prognostic factor analysis. Survival was analysed by Kaplan-Meier analysis, univariate analysis by Log-rank test and multivariate analysis by COX regression model.</p><p><b>RESULTS</b>With a median follow-up time of 48.0 (3.0-156.0) months, the 5-year overall survival (OS) rate was (87.3 +/- 2.4)% and 10-year OS rate was (77.4 +/- 3.3)%. Forty-eight (23.6%) patients died. Univariate analysis indicated that advanced clinical stage, B symptoms, extranodal involvement, number of lymph node regions involved > or = 3, enlarged liver, Hb < 100 g/L, BPC < 100 x 10(9)/L, absolute lymphocyte count (ALC) > 50 x 10(9)/L, atypical cell morphology, progression to stage, non-response to treatment, complicating infections and secondary cancer or disease transformation were associated with poor prognosis. And on multivariate analysis, lymph node region involved > or = 3 and atypical cell morphology were independent poor prognostic factors. Based on the two independent poor prognostic factors, three risk groups were defined: low--(0 factor), intermediate--(one factor) and high--(two factors) groups. The 5 year OS rates were (89.8 +/- 3.5)%, (66.4 +/- 7.2)% and (15.0 +/- 13.8)%, respectively, and the difference between them was statistically.</p><p><b>CONCLUSION</b>The number of lymph node region involved and cell morphology are useful for assessing CLL patients prognosis.</p>

Analysis of relationship between bcr-abl transcription level detected by real-time quantitative polymerase chain reaction and clinical status of CML patients / 中国实验血液学杂志

This study was aimed to investigate the bcr-abl transcription level and its relationship with the clinical status of patients so as to provide some bases for predicting patient status according to absolute value of bcr-abl transcript. The bcr-abl/abl values (%) of bone marrow samples from 30 newly diagnosed CML patients at the baseline bcr-abl/abl value obtained in CML patients with bcr-abl positive were defined, then 161 bone marrow samples from 82 patients were detected at virions time points, and the bcr-abl/abl value of each sample was compared with baseline value and its relationship with clinical status of patient at same time point was investigated. The results showed that bcr-abl/abl values (%) of 30 patients showed positive skew distribution and a large variation with mean 13.5631 (1.0206 - 98.3159) and mathematical mean of 21.1491 (95% CI: 12.3532 - 29.9450). For strict standard, the baseline value of bcr-abl/abl (%) was set as 1, the lower limit of these values. In the detected results of 161 samples, there were 33 samples' values above the baseline value, in which resistance/relapse/progression (R/R/P) 13 (39.4%, 13/33), no remission (NR) 17 (51.5%, 17/33) and complete hematologic remission (CHR) 3 (9.1%, 3/33) were observed. the values of 26 samples decreased by 0 - 1 order of magnitude (0.1 < or = bcr-abl/abl % < 1), in which R/R/P 6 (23.1%, 6/26), NR 7 (26.9%, 7/26), CHR 7 (26.9%, 7/26) and cytogenetic remission (CyR) 6 (23.1%, 6/26) were observed, the values of 19 samples decreased by 1 - 2 order of magnitude (0.01 < or = bcr-abl/abl % < 0.1), in which NR 2 (10.5%, 2/19), CHR 3 (15.8%, 3/19) and CyR 14 (73.7%, 14/19) were determined. 7 samples decreased by 2 - 3 order of magnitude (0.001 < or = bcr-abl/abl % < 0.01) in which major CyR (MCyR) 2 (28.6%, 2/7) and complete CyR (CCyR) 5 (71.4%, 5/7) were determined, the values of 76 samples decreased by 3 or more order of magnitude (bcr-abl/abl % < 0.001), and all these were CCyR. In conclusion, the using decrease degree of one time point-detected value compared to the baseline could well assess the patient clinical status. The bcr-abl/abl % < 0.01 can reliably reflect CyR obtained by patients at the time point, and bcr-abl/abl % < 0.001 can reflect CCyR obtained by patients. However, exact judgments of patient status relies on dynamic and serial monitoring.

Clinicopathologic studies of 13 cases of chronic eosinophilic leukemia / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the role of bone marrow biopsy (BMB) in diagnosis and differential diagnosis for chronic eosinophilic leukemia (CEL).</p><p><b>METHODS</b>Clinical and pathological features of thirteen CEL patients were analyzed retrospective. Routine histologic examination was performed on H-G-E, reticulin fiber and toluidine blue stained sections of plastic material emdedded samples of bone marrow biopsies.</p><p><b>RESULTS</b>(1)The male-to-female ratio was 12:1. The median age was 40 (23-67) years old. They presented as fever, anemia, hemorrhage and so on. Most of organs and tissues were also be involved. (2) Peripheral blood counts characterized by eosinophilia (18.1 +/-16.2) x 10(9)/L, (3) BMB showed eosinophils were predominant components, others such as neutrophils, erythrocytes, megakaryocytes were decrease. Degree of reticular fiber was from (1+) to (3+). (4) Follow-up information was available in only 4 patients, whose conditions were stable.</p><p><b>CONCLUSION</b>Combine with the clinical manifestations of CEL patients, it is important in diagnosis and differential diagnosis for CEL by observing the histomorphology features of bone marrow biopsy carefully.</p>

The clinical and laboratory features of 263 cases of chronic lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical and laboratory features of chronic lymphocytic leukemia (CLL).</p><p><b>METHODS</b>Retrospective investigation of 263 patients with CLL in our hospital between Feb. 2000 and Jan. 2007.</p><p><b>RESULTS</b>The median age was 60 years with male/female ratio of 2.17 : 1. Patients who were asymptomatic at diagnosis (35.4%) had low Rai grades. Fatigue and lymphadenopathy (54.8%) were the most common features at presentation. Infections, connective tissue diseases and secondary tumors frequently occurred in CLL. WBC counts were between (10 - 100) x 10(9)/L, with lymphocytes percentages more than 0.50 in 97.1% patients. Bone marrow was normal- to hyper-cellularity with lymphocytes percentages more than 0.300 in 99.4% patients. Diffuse infiltrations in bone marrow section were found in 72.2% patients. There were lower CD5 (85.1%) and higher CD25 (78.9%) positivities in the present series as compared with that in other reports. Hypogammaglobulinemia, especially hypo-IgM, usually occurred. Chromosome abnormality were rarely found by routine chromosome examination.</p><p><b>CONCLUSIONS</b>There were some clinical and laboratory characteristics different from that of abroad data. Further exploration of new markers is required for prognosis prediction and treatment choice.</p>

Clinical analysis of 438 patients with essential thrombocythemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the clinical feature and natural course of essential thrombocythemia (ET).</p><p><b>METHODS</b>A retrospective analysis was conducted in ET patients treated in our hospital during May 1980 to December 2006.</p><p><b>RESULTS</b>Four hundred and thirty eight patients (201 males and 237 females with a median age of 48 years) were diagnosed. Hemorrhage occurred in 101 cases (23.1%), thrombosis in 86 cases (19.6%), and both hemorrhage and thrombosis in 13 cases (3.0%). Splenomegaly occurred in 150 cases and hepatomegaly occurred in 60 cases. One hundred and forty-nine cases (34%) had no symptoms at diagnosis and 145 cases (33.1%) confirmed by routine blood tests due to other diseases. The median platelet count at diagnosis was 1000 x 10(9)/L [(533 -3740) x 10(9)/L]. Bone marrow biopsy was performed in 255 cases which showed mainly increase of enlarged mature megakaryocytes with hyper-lobulated nuclei and local proliferation of reticular fiber was revealed in 51 cases. JAK2V617F mutation was detected in 90(78.9%) of 114 patients studied. Karyotype analysis was performed in 180 cases and 6 (3.3%) had clonal chromosomal aberrations. Two hundred and sixty-one patients were followed up over 12 months with a median of 60 months (range from 12 to 300 months). Seventeen cases (6.5%) evolved into marrow fibrosis (MF) and one case into polycythemia vera (PV). One case evolved into PV 6 years and then MF 20 years after diagnosis of ET. Three cases developed acute monocyte leukemia (M5), myelodysplastic syndrome (MDS) and multiple myeloma (MM), respectively.</p><p><b>CONCLUSIONS</b>ET is a chronic myeloproliferative disorder characterized predominantly by thrombocytosis and hemorrhage. The percentage of asymptomatic cases is high. The prognoses for most cases were good with a few cases may evolve into MF.</p>

Analysis of long-term treatment outcome and related factors in 95 chronic myeloid leukemia patients treated with imatinib / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of imatinib in the treatment of chronic myeloid leukemia (CML) and analyse the treatment outcome and related factors.</p><p><b>METHODS</b>Ninety five CML patients were treated with imatinib in our hospital from May 2002 to May 2006. The outcomes and related factors were analysed.</p><p><b>RESULTS</b>(1) One year after therapy, there were 95.5% of chronic phase (CP) patients achieved complete hematologic response (CHR). Fifty-two patients with complete cytogenetic dates were divided into primary-therapy group (n = 19) and secondary-therapy group (n = 33). The major cytogenetic responses (MCyR) at 6-, 12-, 18-, 24- and 30-months after therapy for the former group were 84.2%, 84.2%, 89.5%, 89.5% and 94.7%, and for the latter group were 36.4%, 39.4%, 39.4%, 39.4% and 39.4%, respectively (P < 0.01). The expected survival at 12-, 24-, 36- and 50-month after imatinib treatment for CP group was (98.1 +/-1.9)%, (87.8 +/- 7.1)%, (81.9 +/- 8.7)% and (81.9 +/- 8.7)%, respectively. (2) Twelve month after therapy, there are 70% of accelerated phase (AP) patients achieve CHR and 10% get MCyR. The expected survival at 12-, 24- and 36-month after imatinib treatment for AP group was (63.0 +/- 17.7)%, (15.8 +/- 14.3)% and (15.8 +/- 14.3)%, respectively. (3) Six month after therapy, 57.9% of blast crisis (BC) patients achieve CHR, with the expected survival at 12- and 24-month of (40.6 +/- 12.3)% and 0, respectively. (4) COX analysis CP group indicated that imatinib therapy administered for previously untreated was an independent favorable prognostic factor. Conclusion (1) Imatinib as a primary treatment for CP CML can significantly improve the survival time as compared with that AP or BC patients or with that used in previously treated patients. (2) Imatinib could induce hematologic, even cytogenetic response to a certain extent, in CP or BC patients and prolong the survival time.</p>

Myelodysplastic syndromes associated with acquired hemoglobin H disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To report 7 cases of acquired hemoglobin H in myelodysplastic syndromes.</p><p><b>CASE DATA AND DISCUSSION</b>Clinical materials of the 7 cases were retrospectively presented. Clinical features of the similar cases in literatures were reviewed. The criteria for diagnosis of this entity by Steensma and its pathogenesis were discussed.</p><p><b>CONCLUSION</b>This entity is a new subtype of MDS with unique clinical features and pathogenesis, and might be a proper model in the study of MDS transformation.</p>

The analysis of prognostic variables in 123 patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To assess the prognostic value of biological features and therapy-related factors in multiple myeloma (MM).</p><p><b>METHODS</b>123 patients with newly diagnosed MM between January 1998 and May 2005 were enrolled in this retrospective study. Biological features at presentation and therapy-related factors were analysed. The overall survival (OS) and time to progression (TTP) were estimated by Kaplan-Meier analysis and the distribution of OS and TTP were compared using log-rank test. Cox regression was used to identify the independent prognostic factors.</p><p><b>RESULTS</b>(1) The univariate analysis indicated that more immature plasma cells in bone marrow biopsy, C-reactive protein >8. Omg/L, CD117 expression, serum beta2-microglobulin (beta2-MG) (3.5 approximately 5.5 mg/L), abnormal cytogenetics aberration of chromosome 13 (Delta13), hypodiploid, poor response to chemotherapy, interferon(IFN) therapy less than 6 months were associated with shorter OS(P <0.05). Lytic bone lesions at presentation, more immature plasma cells in bone marrow biopsy, serum beta2-MG (3.5 approximately 5.5 mg/L), poor response to chemotherapy, and IFN therapy less than 6 months as well as abnormal cytogenetics, hypodiploid and Delta13 were associated with shorter TTP (P <0.05). (2) Multivariable COX analysis indicated IFN therapy more than 6 months was a protective factor for OS and TTP, and more immature plasma cells in bone marrow biopsy was an independent poor prognostic factor for TTP.</p><p><b>CONCLUSION</b>The morphology of myeloma cells is useful for assessing the prognosis. And IFN therapy more than 6 months could lengthen OS and TTP.</p>

The risk factors for thrombosis, myelofibrosis and leukemia transformation in patients with polycythemia vera / 中华血液学杂志

<p><b>OBJECTIVE</b>To reassess the natural history of polycythemia vera (PV) in Chinese and evaluate the relationship between the incidence of thrombosis, post-polycythaemic myelofibrosis with myeloid metaplasia( PPMM) , leukemia transformation and the therapeutic outcome and prognostic factors.</p><p><b>METHODS</b>The clinical manifestations, laboratory parameters and treatment were retrospectively analyzed in 287 patients with PV. Univariate analysis of prognostic factors was performed using Log-rank model and multivariate analysis using COX model in term of the incidence of thrombosis, PPMM, hematologic or non hematologic cancers and mortality.</p><p><b>RESULTS</b>Of the 287 patients, the median follow-up time was 46 (8-360) months. 208 thromboses were recorded in 115 patients. Twice or more thrombotic events occurred on 59 patients (51.34%). Most of these episodes occurred either at presentation or in the 2 years before diagnosis. Elder patients, prior thrombosis, poor response to therapy were associated with poor prognosis. With these three adverse prognostic factors, the patients could be separated into different risk groups. The incidence of thrombosis was higher in high risk group. 36 patients progressed to PPMM, the median time to PPMM was 80 (7-190) months. Higher WBC count, splenomegaly and treatment with alkylating agent and hydroxy-carbamide (HU) were associated with poor prognosis. 2 cases progressed to AML. 1 to lymphoma and 1 to nonhematologic cancer. 13 patients died, the cause of death was fatal thrombosis in 9 and AML in 2.</p><p><b>CONCLUSION</b>The incidence of thromboembolism is higher and the time to myelofibrosis was shorter in Chinese PV patients than in western PV patients. The main factors that influence the survival of PV patients are thromboembolism and leukemia transformation.</p>

Study of 161 chronic idiopathic myelofibrosis patients for clinicopathological staging / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the significance of clinicopathological stage of chronic idiopathic myelofibrosis (CIMF) in WHO classification of 2001.</p><p><b>METHODS</b>Histopathological analysis of bone marrow biopsy plastic-embedded sections stained with H-G-E and Gomori's stains and clinical features of 113 cases previously diagnosed as primary myelofibrosis (PMF) and 48 cases MPD-U (total of 161 cases which including male 79 and female 82) were studied retrospectively.</p><p><b>RESULTS</b>There was no significant differences on the clinical features among the cellular phase, collagen fiber phase, sclerotic phase and osteomyelosclerosis of 113 previously diagnosed patients. According to WHO classification 2001 of CIMF, previously diagnosis in 48 cases with MPD-U was WHO pre-CIMF, and in 113 cases with PMF was WHO CIMF-Fs. There were significant differences between of WHO pre-CIMF and WHO CIMF-Fs about clinicopathological features except age. The percentage of immature granulocytes, normoblasts, lymphocytes in peripheral blood, the size of hepatosplenomegaly, and the percent age of tear drop-like red blood cells in pre-CIMF were significantly lower than those in CIMF-Fs (P < 0.05). However, the number of hemoglobin and platelets in patients with pre-CIMF were significantly higher than that with CIMF-Fs (P < 0.01).</p><p><b>CONCLUSION</b>pre-CIMF and CIMF-Fs in clinical and histopathological features were different development stage of CIMF, while osteomyelosclerosis is a variant of CIMF, but not an independent disease.</p>

The outcome analysis of different treatment regimens in 206 patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the outcome of different regimens for the treatment of patients with multiple myeloma (MM).</p><p><b>METHODS</b>Response rate, median survival time and overall survival rate of 206 MM patients treated with different protocols were retrospectively analysed.</p><p><b>RESULT</b>The median survival time, 3- and 5-year overall survival (OS) of 200 MM patients treated with conventional therapy were 30.5 months, 32.0% and 15.8%, respectively. The total response rate and complete response (CR) rate of 195 patients treated with MP regimen and combination chemotherapy (CCT) were 45.6% and 14.9%, respectively. The response rates were higher for the patients treated with CCT than for those treated with MP (50.3% versus 30.4%, P < 0.05). The median survival time, 3- and 5- year OS in MP versus CCT group were 30.0 versus 30.5 months, 22.0% versus 35.0%, 13.2% versus 16.7%, respectively, but all of them have no statistical difference. Compared with those without IFN alpha maintenance therapy, patients received IFN alpha therapy showed a higher response rate (34.4% versus 53.6%, P < 0.05) and a longer median survival time (27 versus 52 months, P < 0.01). The total response in patients received thalidomide was 65.5%. Of the 6 patients received hematopoietic stem cell transplantation (HSCT), 5 remained alive in CR or PR with a mean survival time of (73.0 +/- 12.5) months.</p><p><b>CONCLUSIONS</b>CCT yields higher response rates, but not longer survival time than MP does for the treatment of MM. The response rate as well as the overall survival rate increased when IFN alpha was used as maintenance therapy. Thalidomide can improve response rate as well. HSCT could prolong survival time in patients aged < 60 years with good status.</p>

Expression of apoptosis related proteins in CD34 positive bone marrow cells of patients with polycythemia vera / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of apoptosis receptor FAS (CD95) and apoptosis related protein Bcl-2 and Bax in CD34 positive bone marrow cells of the patients with polycythemia vera (PV).</p><p><b>METHODS</b>The expressions of apoptosis receptor FAS (CD95) and apoptosis related protein Bcl-2 and Bax in bone marrow CD34(+) cells from 21 PV patients, 8 essential thrombocythemia (ET) and 11 normal persons were assessed by bicolor flow cytometry (FCM), and the expressions of Bcl-2 and Bax mRNA were assessed by RT-PCR, and their correlation was analysed.</p><p><b>RESULTS</b>There was no difference between the expressions of CD95 in CD34(+) bone marrow cells of PV patients (42.65 +/- 15.56)%, and that of ET patients (45.31 +/- 17.62)% and of normal person (37.55 +/- 15.19)% (P > 0.05). There was no difference between the expression of Bax in CD34(+) bone marrow cells of PV patients (35.83 +/- 9.33)% and of normal persons (41.65 +/- 9.04)% (P > 0.05). The expression of Bcl-2 in CD34(+) bone marrow cells of PV patients (79.35 +/- 14.43)% was significantly higher than that of normal controls (55.84 +/- 13.43)% (P < 0.01). The ratio of Bax/Bcl-2 of PV patients (0.47 +/- 0.14) was significantly lower than that in normal controls (0.76 +/- 0.24) (P < 0.01). The expression of Bcl-2 mRNA in PV patients' bone marrow hematopoietic cells was higher than that of normal controls (P < 0.01). There was no difference between the expression of Bax mRNA in bone marrow hematopoietic cells of PV patients and that of normal controls. Bcl-2 expression was negatively correlated with Annexin V expression in CD34(+) bone marrow cells of PV patients.</p><p><b>CONCLUSION</b>Over-expression of Bcl-2, one of anti-apoptosis genes, in CD34(+) bone marrow cells might be involved in the lower apoptosis of PV patients.</p>

Morphologic and clinical study of 131 cases of plasma cell myeloma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the characteristics histologic and cytologic features and clinical usefulness of plasma cell myeloma (PCM) subtyping according to WHO PCM classification.</p><p><b>METHODS</b>Bone marrow biopsy plastic-embedded sections were stained with H-G-E and Gomori's stains, and bone marrow aspirate smears were stained with Wright's stain. The clinicopathologic findings were then analyzed.</p><p><b>RESULTS</b>Of the 131 cases with PCM, three types of growth patterns were noted: interstitial (21 cases, 16.0%), nodular (46 cases, 35.1%) and packed (64 cases, 48.9%). Besides, there were three cytologic subtypes: mature plasma cell type (43 cases, 32.8%), immature (81 cases, 61.8%) and pleomorphic (7 cases, 5.3%) types. The age of patients with mature plasma cell type was significantly higher than that of immature type (P = 0.005); and the number of tumour cells in bone marrow smears was significantly higher than that of immature type (P = 0.003). The numbers of WBC and platelets in peripheral blood were also significantly higher than that of pleomorphic type (P = 0.024, P = 0.002, respectively). On the other hand, the number of platelets in peripheral blood of immature type was significantly higher than that of pleomorphic type (P = 0.019). Marrow fibrosis was more frequently observed in immature type than in mature plasma cell type (P = 0.000). The incidence of marrow fibrosis and osteolytic lesions was higher in high risk group than in low risk group (P = 0.000, P = 0.023 respectively). Twenty-one cases (56.8%) of the 37 cases treated with MP or MP and M2 chemotherapeutic regimens showed good response. However, there was no significant difference in treatment response and survival between different subtypes.</p><p><b>CONCLUSIONS</b>Each subtype of PCM carries different clinicopathologic features in some aspects. The classification carries important value in pathologic diagnosis and probably in predicting prognosis.</p>

Apoptosis and proliferation of CD34 positive bone marrow cells in patients with polycythemia vera / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the apoptosis and proliferation of CD(34) positive (CD(34)(+)) bone marrow cells (BMC) in patients with polycythemia vera (PV).</p><p><b>METHODS</b>The expression of Annexin V and Ki67 of the CD(34)(+) BMC in 20 PV patients and control cases [10 essential thrombocythemia (ET), 12 normal persons] were assessed by bicolor flow cytometry (FCM), and the correlation between apoptosis and clinical situation was analysed in PV patients.</p><p><b>RESULTS</b>The Annexin V expressions of CD(34)(+) BMC were (15.96 +/- 1.45)% in PV patients and (15.53 +/- 1.76)% in ET patients which were lower than that in normal subjects [(23.61 +/- 3.89)%, (P < 0.05)]. The Ki67 expression of CD(34)(+) BMC was (48.79 +/- 11.68)% in PV patients and (49.60 +/- 9.98)% in ET patients, which were significantly higher than that in normal controls (33.87 +/- 6.82)%. The ratio of apoptosis/proliferation in PV patients was 0.33 +/- 0.10 and in ET patients 0.32 +/- 0.02 which were significantly lower than that in normal controls 0.72 +/- 0.11 (P < 0.01). The apoptosis of CD(34)(+) BMC was negatively correlated with the hemoglobin (Hb) levels (r = -0.481, P = 0.037), white blood cells (WBC) (r = -0.538, P = 0.026) and the numbers of endogenous erythroid colony (EEC) (r = -0.632, P = 0.50), and the ratio of apoptosis/proliferation was negatively correlated with the Hb (r = -0.537, P = 0.018) and WBC (r = -0.667, P = 0.003) in PV patients.</p><p><b>CONCLUSION</b>There were lower apoptosis and higher proliferation in CD(34)(+) BMC of PV patients. Lower apoptosis was correlated with the severity of the disease.</p>

Endogenous erythroid colony assay in patients with polycythemia vera and its clinical significance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Polycythemia vera (PV) is a malignant disorder of hemaopoietic stem cells which is characterized by clonal hyperproliferation and a low rate of apoptosis. This study was to assess endogenous erythroid colony (EEC) formation in the bone marrow of PV patients and determine its clinical significance.</p><p><b>METHODS</b>The bone marrow mononuclear cells of 26 patients with PV, 2 patients with secondary erythrocytosis (SE), and 19 normal controls were cultured by Marsh's method for EEC evaluation, and the clinical significance was evaluated.</p><p><b>RESULTS</b>EECs appeared in 25 patients with PV but not in 2 patients with SE and 19 normal controls. The number of EECs and the EEC ratio [EEC/erythropoietin (EPO)-dependent colony forming unit-erythroid (CFU-E)] in PV patients positively correlated with hemoglobin (Hb) levels. Their EEC number did not correlate with white blood cell (WBC) counts, platelet (PLT) counts, or leukocyte alkaline phosphatase (LAP) scores. Their EEC did not correlate with serum EPO levels. Fifteen patients with PV were treated with hydroxyurea (Hu) and/or interferon-alpha (IFN-alpha). Their EEC ratio before treatment positively correlated with the treatment time required for complete remission (CR) and negatively correlated with the time before relapse. The EEC numbers of 7 PV patients treated with Hu/IFN-alpha decreased after the blood cell counts dropped to normal levels. There was a positive correlation between the EEC ratio and the incidence of attacks of vascular thrombosis in PV patients. The numbers of apoptosised bone marrow mononuclear cells in PV patients were lower than those in normal controls. The EEC numbers of PV patients negatively correlated with the rate of apoptosis of bone marrow mononuclear cells.</p><p><b>CONCLUSIONS</b>EEC formation is characteristic in PV patients. EEC number in PV patients positively correlates with Hb levels, the time required for CR, and the incidence of attacks of vascular thrombosis. EEC number negatively correlates with the time before relapse. Bone marrow suppressive treatment might decrease EEC number. Thus, EEC number is a sensitive and specific parameter reflecting the abnormal hematopoietic clone burden induced by polycythemia vera. EEC number is an important diagnostic parameter for PV patients.</p>

Analysis and identification of variant Ph chromosome translocation in patients with chronic myelogenous leukemia by conventional cytogenetics and fluorescence in situ hybridization / 中国实验血液学杂志

The objective of this study was to explore the cytogenetic profiles of variant Ph chromosome translocations (VT) in patients with chronic myelogenous leukemia (CML) and to assess the applications of fluorescence in situ hybridization (FISH) technique for analysis of CML patients with variant translocation by using dual color-single fusion signal (DC-SF) and dual color-dual fusion signal (DC-DF) probe. 42 CML patients with VT were studied by conventional cytogenetic analysis (CCA). Among them, nine and eleven cases were analyzed by DC-SF-FISH and DC-DF-FISH, respectively. The results showed that 42 out of 643 (6.5%) CML cases received CCA were found to have VT, which were composed of 18 cases of simple VT, 23 of complex VT and one of masked VT. The VT involved all over the chromosomes but No. 4 and 6. Four patterns of them appeared recurrent because each occurred in at least two cases. VT with additional chromosomal aberrations were shown in 35.7% of patients with VT (15/42). 19 of 20 patients who received FISH detection were positive for bcr/abl fusion. DC-DF-FISH analysis revealed absence of abl/bcr fusion signal in all patients but one (8.8%) with abl/bcr positive cells. However, it was not an implication of gene loss but the translocation led to part of bcr retaining on der (9q34) and other part of bcr translocating to involve another chromosome. It was unable to observe variant signal features by DC-SF-FISH analysis. In conclusion, variant Ph translocations in CML involved almost all chromosomes in a varying frequencies and ways except chromosomes 9 and 22, and some of them showed recurrent aberrations. FISH provides accurate molecular diagnosis for CML with VT, while DC-DF-FISH facilitates the assessment of variant signals.