Comparison of three different types of donor hematopoietic stem cell transplantation for intermediate and high-risk myelodysplastic syndrome / 中华血液学杂志

Objective@#To investigate three different types of donor hematopoietic stem cell transplantation (HSCT) for intermediate and high-risk myelodysplastic syndrome (MDS) .@*Methods@#Between August 2001 and May 2015, 167 consecutive patients with MDS in intermediate and high-risk who underwent allogeneic HSCT were analyzed retrospectively.@*Results@#With the median follow up of 60 (12-177) months, The total 5-year DFS was 67.8% (95%CI 60.0%-75.6%) . Among three different types of donor, 5-year DFS rates were 68.0% (95%CI 54.1%-81.9%) in MSD-HSCT vs 77.4% (95%CI 62.1%-92.7%) in MUD-HSCT vs 64.0% (95% CI 52.4%-75.6%) in Haplo-HSCT (P=0.632) , respectively. Univariate analysis showed that median disease course before HSCT was the influencing factor of DFS (P=0.018) . Five-year relapse and TRM had no correlation with the above-mentioned factor.@*Conclusions@#Haplo-HSCT for intermediate and high-risk MDS achieved similar effect produced by MUD or MSD, Haplo-HSCT could be used as an important alternative donor. allo-HSCT must be performed on intermediate and high-risk MDS patients as early as possible after diagnosis.

Effect of minimal residual disease monitoring by multiparameter flow cytometry pre-conditioning on prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To investigate the effect of minimal residual disease (MRD) monitoring by multiparameter flow cytometry (MFC) pre-conditioning on prognosis of acute myeloid leukemia in first complete remission (CR1-AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and to explore the value of MRD monitoring by MFC in the prognosis evaluation on allo-HSCT in CR1-AML.@*Methods@#Between April 2012 and March 2015, consecutive 186 patients with CR1-AML who underwent allo-HSCT were analyzed retrospectively. MRD in BM before conditioning was detected by eight-color MFC. Any level of residual disease was considered to be MRD positive.@*Results@#①Of 186 patients, MRD was negative in 151 patients, positive in 35 patients (<1% in 25 patients and 1% to 3% in 10 patients) . ② With the median follow up of 18 (5-41) months, two-year DFS was 80.0% (95%CI 68.5%-92.3%) . Univariate analysis showed that MRD positive patients had lower DFS[62.9% (95%CI 50.6%-75.2%) vs 88.9% (95%CI 76.6%-100.0%) , P<0.001], higher relapse[11.4% (95%CI 4.1%-29.0%) vs 3.3% (95% CI 0.6%-20.9%) , P=0.003] and higher NRM [25.7% (95% CI 8.1%-43.3%) vs 7.9% (95% CI 1.3%-26.5%) , P=0.001] after HSCT compared with that of MRD negative patients. Secondary AML showed lower DFS than primary AML [60.0% (95% CI 42.4%-76.6%) vs 86.0% (95% CI 68.4%-100.0%) , P=0.004]. ③Multivariate analysis indicated that MRD positive pre-HSCT was the independent risk factor on DFS [HR=4.565 (95%CI 2.918-9.482) , P<0.001], relapse [HR=5.854 (95%CI 1.538-22.288) , P=0.010] and NRM [HR=3.379 (95%CI 1.361-8.391) , P=0.009] after allo-HSCT in CR1-AML.@*Conclusion@#MRD positive pre-conditioning was the only negative impact factor for patients with CR1-AML after allo-HSCT. MRD by MFC can be used to assess the prognosis of CR1-AML after allo-HSCT.

Effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To analyze the effect of NCCN (2015) risk stratification on prognosis of patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .@*Methods@#Retrospective analysis of 258 patients with AML in CR (186 cases in CR1, 72 cases in CR2) who underwent allogeneic HSCT in our hospital between April 2012 and March 2015 according to NCCN (2015) risk stratification. Of them, 63 cases were classified as low risk, 112 cases intermediate risk and 83 cases high risk.@*Results@#①With the median follow up of 18 (5-41) months, two-year disease free surviva (DFS) in 258 patients was 78.0% (95% CI 60.4%-96.6%) . Two-year DFS in AML after transplantation was 78.6% (95% CI 61.0%-96.2%) in low risk, 76.0% (95% CI 84.0%-93.6%) in intermediate risk and 80.3% (95% CI 62.7%-97.9%) (P=0.886) in high risk groups respectively. ②Univariate analysis showed that DFS has no significant difference in patient age, the median disease course before HSCT, the WBC number at the beginning of the disease, blood routine and chromosomes examination before transplantation, extramedullary disease before transplantation, disease status before transplantation, conditioning regimen, donor type, donor and recipient sex, recipient blood type, transfused MNC number, transfused CD34+ cell number and transfused CD3+ cell number. DFS was significant lower in primary AML than that in secondary AML (P=0.006) and also lower in MRD positive than that in MRD negative (P=0.003) . The accumulative relapse was significant higher in CR2 compared to that in CR1 (P=0.046) . Accumulative non-relapse mortality (NRM) was significanlyt higher in secondary AML compared to that in primary AML (P=0.004) and also higher in MRD positive compared to that in MRD negative (P=0.010) . ③Multivariate analysis showed that MRD positive was the only significant factor in DFS and NRM.@*Conclusion@#Allo-HSCT treatment of AML CR patients could achieve a high efficacy, which is similar between CR1 and CR2 patients. There is no significant correlation between NCCN (2015) risk stratification and the prognosis of AML patients with allo-HSCT treatment. Pre-conditioning MRD status monitored by multiparameter flow cytometry was the only impact factor on DFS and NRM in allo-HSCT for CR-AML patients.

HLA- haploidentical donor hematopoietic transplantation for severe aplastic anemia achieved comparable outcomes with HLA- unrelated donor transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of HLA- haploidentical donor hematopoietic transplantation (Haplo- HSCT)for severe aplastic anemia (SAA)by compared with the same period of unrelated donor transplantation (UD- HSCT).</p><p><b>METHODS</b>Of a cohort of 50 SAA patients between September 2012 and July 2014, 26 patients underwent UD- HSCT and 24 patients Haplo- HSCT.</p><p><b>RESULTS</b>OS rate was 91.3% with a median follow-up of 9 (2-26)months. According to transplant type, there was no significant difference between UD- and Haplo-HSCT (96.1%vs 86.0%,P=0.30). 3 of 50 (6%)patients had primary engraft failure. Haplo- HSCT developed higher significantly incidence of Ⅱ- Ⅳ aGVHD (37.5%vs 3.83%,P=0.003)and cGVHD (37.5%vs 15.3%,P=0.030)than UD-HSCT. Haplo-HSCT also had significantly higher incidences of CMV viremia (78.2%vs 46.1%,P=0.005)and EBV viremia (43.1%vs 16.0%,P=0.040), respectively than UD-HSCT. But the incidences of hemorrhagic cystitis were similar between two transplant types (39.1%vs 23.0%,P=0.120).</p><p><b>CONCLUSION</b>This study showed favorable outcome of Haplo-HSCT for SAA, which was comparable with UD-HSCT.</p>

Stady on the clinical characteristics of 10 patients with idiopathic cytopenia of undetermined significance / 重庆医学

Objective To analyze the clinical and pathologic features in patients with ldiopathic cytopenia of undetermined signif-icance (ICUS) ,and provide the diagnostic basis .Methods 10 ICUS patients who did not fulfil minimal diagnostic criteria for MDS but suffered from constant (>6 months) progressive cytopenia ,with no marked dysplasia (<10% in three-major cell lineages) and abnormal karyotype were reported .Results 2 of 10 patients transited to MDS ,bone marrow review showed that ≥2 cells appeared diagnostic pathology development .Karyotype analysis showed that 1 case was still normal ,1 case lost a normal chromosome 20 (20q-) ,the rest 8 cases had been efollowed up for 6 to 25 months and still maintain ICUS .Conclusion Patients with MDS who fail to meet the diagnostic criteria of ICUS ,must carry out regular follow-up .There are some patients can transition to public MDS after a certain incubation period ,in fact it is Pre-MDS or MDS-early before ,which shows that ICUS should cause clinical attention ,so that avoid missed diagnosis .

Value of bone marrow biopsy histopathological finding in diagnosing myelodysplastic syndrome / 重庆医学

Objective To evaluate the value of plastic-embedded bone marrow (BM ) biopsy sections in diagnosing myelodysplas-tic syndrome(MDS) .Methods HGF and Gomori stained .Glycol methacrylate(GMA) embedded BM biopsy specimens were detec-ted from 125 MDS patients with 25 cases in good health as control .Dyshematopoiesis and abnormal stroma cell responses were se-lected as main observed projects .Results Bone marrow biopsy sections gave an exact assessment of cellularity ,19 cases (15 .2% ) showed a decrease of cellularity as hypocellular MDS .66 cases(52 .8% ) of these cases did show abnormal localization of erythro-blastic clusters ,biopsy of 64(62% ) of low risk group 103 cases did show abnormal localization of immature precursors such as blasts and promyelocytes(ALIP positive) .Numeration of megakaryocytes and mast cells within 1mm2 acre of BM tissue were all much in MDS group than in control group .Gomori′s stain revealed moderate increase in reticulin fibres in 65 cases ,10 cases(8 .0% ) showed degree of myelofibrosis were + + + as hyperfibrotic MDS .Among 125 cases ,33 cases(26 .4% ) of bone marrow biopsies showed different types of erythrocytic and granulocytic immature cells with unusual intrasinusoidal bone marrow infiltration .Con-clusion It is clear that GMA embedded BM biopsy section is helpful in making diagnosis of MDS ,and has important clinical appli-cation value .

Haploidentical blood and marrow transplantation for advanced chronic myeloid leukemia / 中华器官移植杂志

ObjectiveTo investigate the efficacy of haploidentical blood and marrow transplantation (haplo-BMT) in the treatment of advanced chronic myeloid leukemia (CML).MethodsFrom November 2002 to October 2007,35 patients with advanced CML received haplo-BMT.Eleven patients achieved the second chronic phase (CP2) after treatment with imatinib or chemotherapy or both before pre-conditioning,but there were 13 cases in accelerated phase (AP) and 11 patients in blast phase (BP) at the time of transplantation.By the last follow-up date October 31,2011,the median follow-up time among living patients was 67 months (range,49 to 100 months).ResultsThe cases of HLA-antigen mismatched between donors and recipients as 1,2,and 3 antigens were 1,12,and 22 respectively.The number of mean mononuclear cells and CD34+ cells was (7.19+ 1.37) × 108/kg and (2.54± 1.50) × 106/kg,respectively.All but one patient achieved durable hematopoietic reconstitution. Hyperacute graft-versus-host disease (GVHD) occurred in 28.6％ (10/35) patients.The cumulative incidence of grade Ⅱ to Ⅳ acute GVHD was 48％.Among 27 patients who survived longer than 100 days after transplant,16 (60 ％) had chronic GVHD.Fiveyear overall survival (OS) rate was 46.2％ and 45.5％ in CML-AP and BP (P =0.97),respectively.Five-year probability of OS rate was 81.8％,30.8％ and 27.3％ in patients with CML-CP2,CML-AP and BP at transplant,respectively.The OS of CML-CP2 was significantly higher than CML-AP and BP at transplant (P＜0.01 ).ConclusionHaplo-BMT is a feasible therapeutic mean for patients with advanced CML who have no matched donors available.It is better to perform haplo-BMT at CML-CP2 other than CML-AP or BP.

The study of gene mutations in unknown refractory viral infection and primary hemophagocytic lymphohistocytosis / 中华内科杂志

Objective To study the type and corresponding clinical characteristics of primary hemophagocytic lymphohistocytosis (HLH) associated immune gene mutations in the refractory virus infection or HLH of unknown causes. Methods From December 2009 to July 2010, the patients with refractory virus infection or HLH of unknown causes were screened for the primary HLH associated immune genes mutations by DNA sequence analysis, including PRF1, UNC13D, STX11, STXBP2, SH2D1A and XIAP. The clinical characteristics and outcomes were followed up. Results Totally 25 patients with refractory virus infection or HLH of unknown causes were investigated for the 6 genes and 13 cases were found carrying gene mutations, composing of 6 of PRF1 mutation, 3 of UNC13D, and each one of STX11,XIAP, SH2D1A and STXBP2, respectively. Among the 13 cases with gene mutations, 5 suffered from Epstein-Barr virus associated HLH( EBV-HLH), 1 human herpes virus 7 associated HLH (HHV7-HLH),1 HLH without causes, 4 chronic activated EB virus infection (CAEBV) with 1 progressing to Hodgkin's lymphoma carrying abnormal chromosome of t ( 15; 17 ) (q22; q25 ) and hyperdiploid, 2 EBV associated lymphoma. Among the other 12 patients without gene mutation, 4 suffered from EBV-HLH with 1 progressing to peripheral T lymphoma, 8 suffered from CAEBV. Conclusions Primary HLH associated immune gene mutations are critical causes of refractory virus infection of unknown causes, most patients manifest as HLH,some cases appear in CAEBV and EBV associated lymphoma. DNA sequence analysis is helpful to early diagnosis and correct decision-making for treatment.

Monitoring of early Epstein-Barr virus reactivation and preemptive therapy after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To investigate early Epstein-Barr virus (EBV) reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied (haploidentical 116,unrelated 75, matched sibling 86). Conditioning regimens were mainly busulfan (BU) + cyclophosphamide ( CY)/fludarabine(Flu) or total body irradiation (TBI) + CY/Flu. Antihuman thymocyte globulin (ATG)was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction (RQ-PCR). EBV viremia was diagnosed when EBV DNA was more than 5 × 102 copies/ml but without symptoms. Acyclovir (10 mg/kg, intravenous drip, 8 h) was used for preemptive therapy and immnuo-suppressants were decreased if possible. Results Totally 33 patients ( 11.9% ) developed EBV viremia with a median time at day 44 (day 19 to day 84). The incidences of EBV viremia in the transplants from matched sibling,haploidentical, unrelated donors were 0, 15.5%, 20. 0%, respectively. There was no significant difference between haploidentical and unrelated transplants ( P = 0. 09 ), but much less EBV viremia was seen in matched sibling transplant ( P = 0. 001 ). Twenty of 33 patients ( 60. 6% ) had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 (4-56) d. The median duration of preemptive therapy was 21 (14-60) d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease (GVHD) were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia (54. 2% vs 72. 1%, P = 0. 006 ). Conclusions Our large clinical study has demonstrated that preemptive therapy with acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.

An analysis of etiological and genetic factors of a patient with familial hemophagocytic lymphohistiocytosis / 中华内科杂志

Objective To analyze the etiological factor and genetic feature of a familial hemophagocytic lymphohistiocytosis patient with PRF1 mutation (FHL2) with human herpesvirus 7 (HHV7)infection and its family constellation. Methods Clinical characteristics, laboratory examinations of a FHL2 case with HHV7 infection were reported. HHV1-HHV8 virus DNA was screened by PCR; NK cell function was analyzed by flow cytometry; PRF1 gene mutations were analyzed by PCR and direct sequencing, structure of mutant PRF1 proteins were analyzed using ExPasy and I-TASSER server and genetics pedigree were analyzed. Results The patient's HHV7 viral was detected positive with DNA copy number of 350/106 peripheral nucleated cells. Flow cytometry analysis showed decrease both in proportion of perforin positive NK cells and perforin protein expression. Genetic testing showed PRF1 biallelic heterozygote mutations (c. 503G ＞ A/p. S168N and c. 1177T ＞ C/p. C393R) and pedigree analysis showed they were inherited. The patient was then treated with antivirus therapy, dexamethasone and VP16 therapy, but only achieved partial response. The patient was then followed by human leukocyte antigen 10/10 allele identical nonconsanguinity allogeneic hematopoietic stem cell transplantations (allo-HSCT) and soon the successful implantation of donor hematopoietic cells and persistent recovery was achieved. The patient was now surviving without recurrence for 9 months after allo-HSCT. Conclusions FHL is prone to be misdiagnosed as lymphoma. Genetic analysis of related gene mutation and herpes simplex virus detection will help in early and accurate diagnosis. Allo-HSCT is a fundamental treatment of FHL.

A study of the central nervous system complications after hematopoietic stem cell transplantation / 中华内科杂志

Objective To study the incidence, risk factors and prognosis of central nervous system (CNS) complications after hematopoietic stem cell transplantation ( HSCT) in order to prevent or reduce its occurrence, provide better diagnosis and treatment and improve the survival of the patients.Methods A total of 640 patients who consecutively underwent HSCT in our hospital between May 2001 and December 2007 were included.The clinical outcomes of the patients who developed CNS complications were analyzed.Results The patients received stem cells from haploidentical family members ( Haplo, n = 289 ) , identical siblings (IS, n = 237) , unrelated donors ( URD, n = 83) , unrelated cord blood (n = 14) , syngeneic siblings (n = 9 ) or autologous peripheral blood ( n = 8 ).Fifty-seven of 640 patients (8.9% ) developed CNS complications.The incidences were 12.0%, 13.5% and 3.4% in URD-HSCT, Haplo-HSCT and IS-HSCT respectively ( P <0.001).The incidences of CNS complications were 19.4% and 8.3% in cases who received or did not receive conditioning with TBI ( P = 0.047 ).There was no significant difference in the incidences of CNS complications between children (15.3% ) and adults(8.3% ) (P = 0.072).Similar incidences of CNS complications were seen in patients with hematological malignancies (8.9%) and non-malignant hematological disorders (7.7%)(P = 1.000).Five of the 57 patients developed two kinds of CNS complications.The patterns of CNS complications included relapse (17 cases) , infections (15 cases) , cyclosporine or FK506 encephalopathy (9 cases) , cerebral hemorrhage ( 8 cases) , cerebral infarction (2 cases), Wernicke's encephalopathy (1 case), skull fracture (1 case), drug-related meningitis (1 case), hepatic encephalopathy (3 cases), post-transplant lymphoproliferative disorder (1 case) and undetermined causes (4 cases).The overall mortality in the patients who developed CNS complications was 57.9% and 66.7% of them died of CNS complications.Conclusions CNS complications are not uncommon after HSCT and they have high mortality and poor prognosis.Our data suggest that haplo-HSCT,URD-HSCT and conditioning with TBI, but not the age and types of hematological diseases are the risk factors for development of CNS complications.Relapse and infections are the most common CNS complications in HSCT recipients.Early diagnosis and appropriate management are crucial to the improvement of clinical outcomes in these patients.

FIP1L1/PDGFRα fusion gene-negative chronic eosinophilic leukemia with t(5; 12)(q31;p13): a case report and review of literatures / 中华内科杂志

Objective To deepen the understanding of chronic eosinophilic leukemia (CEL).Methods The course of diagnosis and treatment in a case of FIP1L1/PDGFRα fusion gene negative CEL was reported. Flow cytometry was used to analyze the immunophenotype of the cells in peripheral blood and pleural fluid. Karyotype was analyzed with G-banding. The expression of FIP1L1/PDGFRα fusion gene was detected by RT-PCR technique. Routine pathological examination of the tissues from bone marrow, lung and spleen were performed. Result A sixteen-year-old girl had severe anemia, fever, splenomegaly,thrombocytopenia and dominant hypereosinophilia lasting for 22 months. Trephine biopsy showed a hypercellular marrow with eosinophilic proliferation and moderate reticular fibrosis. Eosinophilic infiltration was found in lung and spleen and embolism was also found in spleen. She had a clonal chromosomal abnormality t(5;12)(q31;p13). The expression of FIP1L1/PDGFRα was negative. An abnormal clone of T cells expressing CD3-,CD4-,CD8- was found in peripheral blood and pleural fluid, in which the cional T cell accounted for 5.43% and 1.66% of the total lymphocytes respectively. The patient was refractory to treatment with hydroxyurea, prednisone and interferon alpha. She had poor response to a combination of therapy with low dose cytosine arabinoside, mitoxantrone, vincristine, cyclophosphamide, methotrexate and prednisone. She did not respond to imatinib and died of multiple organ failure. Conclusion The present case fulfilled the WHO diagnostic criteria of FIP1L1/PDGFRα(-) CEL which did not respond to routine treatment and imatinib. Allogenic stem cell transplantation should be considered as early as possible in this case. It is noteworthy that clonal CD3-,CD4-,CD8- T-cell abnormality is related to the pathogenesis of CEL.

An in vitro study of cytotoxic and antineoplastic effect of Solanum nigrum L extract on U266 / 北京大学学报(医学版)

Objective: To study cytotoxicity and antineoplastic effect in vitro Solanum nigrum L extract on U266. Methods: U266 cells were cultured together with the extract of Solanum nigrum L. Cytotoxicity assay was tested by CCK-8. Cell cycle and apoptosis were determined using flow cytometry (FCM) analysis. Results: Extract of Solanum nigrum L showed strong cytotoxicity against U266 cells. The IC_ 50 was about 117 mg/L. After exposure of U266 cells to the drug for 48 hours, the cell cycle distribution was changed compared with the controls. There was decrease of cells in the G_0/G_1 phase with increase of cells in the S phase and G_2/M phase. Apoptosis of U266 cells could be shown with staining of Annexin V FITC/PI or TFAR19 testing through FCM. The proportion of apoptotic cells increased in parallel with the increase of the drug dosage. Conclusion: Solanum nigrum L extract showed strong cytotoxicity effect on U266 cells. The antineoplastic effect of the drug can partly be ascribed to its apoptotic inducing effect.

Detection of single nucleutide polymorphisms in CD_(31) 563 codon by denaturing high-performance liquid chromatography / 中华检验医学杂志

Objective Detection of single nucleutide polymorphisms in CD31-563 codon by denaturing high-performance liquid chromatography(DHPLC). Methods The eighth exon fragments of CD31 code gene in chromosome 17q23 were amplified by PCR. The fragments were analysed with DHPLC and were sequenced and compared with the sequences available in National Center for Biotechnology Information ( NCBI) database. Results The length of the amplified fragments is 203bp. There are three kinds of pictures when the fragments are analysed by DHPLC, after comparing with direct sequencing, the pictures of G/G homozygous、A/A homozygous、G/A heterozygous are obviously different, thus the individuals with the three kinds of genetype can be distinguished accurately. In 74 healthy people studied,the gene frequencies of CD31-563S(AGC) is 0.514, the gene frequencies of CD31-563N( AAC) is 0. 486. Conclusion DHPLC can effectively, economically and accurately detect the single nucleutide polymorphisms in CD31 -563 codon.

An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.</p><p><b>METHODS</b>Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).</p><p><b>RESULTS</b>Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.</p><p><b>CONCLUSION</b>Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.</p>

The relationship between donor TNFalpha - 308 (G/A) genotype and recipient acute GVHD in allo-BMT / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the relationship between donor TNFalpha - 308 (G/A) genotype and recipient acute graft versus host disease (aGVHD).</p><p><b>METHODS</b>TNFalpha - 308 (G/A) and TNFalpha - 308 (G/G) genotypes were analyzed by DHPLC and DNA sequence in twenty-one degree III/IV (III/IV) aGVHD patients, and twenty-eight degree 0/I (0/I) aGVHD patients. Serum TNFalpha levels were determined by ELISA.</p><p><b>RESULTS</b>The frequency of TNFalpha - 308 (G/A) genotype was significantly higher in III/IV aGVHD patients than in 0/I aGVHD patients (8/21 vs 1/28) (P < 0.05); and so did for higher serum TNFalpha levels (P < 0.05). TNFalpha levels were higher in III/IV aGVHD patients than in 0/I aGVHD patients in TNFalpha - 308 (G/G) patients (P < 0.01).</p><p><b>CONCLUSION</b>TNFalpha - 308 (G/A) is positively related to serum TNFalpha levels and most likely contributes to high risk for III/IV aGVHD.</p>

Allogeneic peripheral blood stem cell transplantation in the treatment of hematologic malignancies / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the application of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in the treatment of hematologic malignancies.</p><p><b>METHODS</b>Between October 1995 and August 2001, fifty-one patients with hematologic malignancies (median age 34 years, range 5.5 approximately 52 years) received allo-PBSCT from HLA-identical (50) or 1-antigen mismatched sibling donors with conditioning regimens of TBI + CY or modified BU/CY2. Thirty-one patients were acute leukemia (AL) (15 in CR(1), 7 in CR(2) or greater, 10 in relapse including 2 relapse after allo-BMT and the other one never achieved remission); 12 chronic myeloid leukemia (CML) (CP 5, AP 2, BC 4 and relapse after allo-BMT 1); 7 MDS (RAEB 1, RAEB-T 1, AL secondary to MDS 5); Burkitt's lymphoma 1. A combination of cyclosporine and methotrexate was administered for GVHD prophylaxis.</p><p><b>RESULT</b>All patients were engrafted. The median time (range) to neutrophil >/= 0.5 x 10(9)/L and platelet >/= 20 x 10(9)/L was 14 (10 approximately 20) and 11 (7 approximately 45) days post-transplant, respectively. Grade II approximately IV acute GVHD occurred in 20/51 (39%) and grade III approximately IV aGVHD in 2 patients. Clinical chronic GVHD was diagnosed in 23 of 44 (52%) evaluable patients. Fourteen patients died: 8 died of transplant related complications, 6 of relapse. Thirty-seven patients are alive with a median follow-up of 399 (75 approximately 2 176) days, and among them 34 are in continuous complete remission, the other 3 relapsed. The 2-year probability of overall survival, disease-free survival (DFS) and relapse is 64%, 61% and 24%, respectively.</p><p><b>CONCLUSION</b>Allogeneic PBSCT is safe for both donors and recipients, and results in a rapid and stable engraftment without increase in incidence or severity of acute GVHD.</p>

Allogeneic bone marrow transplantation for the treatment of Bruton disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of allogeneic bone marrow transplantation (allo-BMT) for the treatment of Bruton disease.</p><p><b>METHODS</b>HLA-matched sibling bone marrow transplantation was performed for the treatment of 2 cases of X-linked agammaglobulinemia. One of them received allo-BMT twice.</p><p><b>RESULTS</b>Recovery of hematopoiesis was gained at day 20 and day 13 after allo-BMT in the two cases respectively. Serum immunoglobin rose gradually to normal level in three months. Their humoral immuno-system was reconstituted and life quality improved. These two patients are still in disease-free survival for 13 and 2 years respectively. There was no serious graft-versus-host-disease.</p><p><b>CONCLUSION</b>Stem cell transplantation is a choice for the treatment of Bruton disease.</p>

Analysis the immunophenotyping of chronic lymphoid leukemia / 中华检验医学杂志

Objective To investigate the characteristic immunophenotype of B cell chronic lymphoid leukemia in china. Method Single and multiparameter flow cytometry were used to analysis 163 cases of B cell chronic lymphoid leukemia. Results 71.8%(117/163) of cases co-expressed CD5 and B cell markers. The patients were classified into category of B cell chronic lymphocytic leukemia(B-CLL), hairy cell leukemia(HCL) and other B-cell lymphoproliferative disorders(LPDs) by using the scoring system that was recommended by world health organization (WHO). The B-CLL typically display the composite phenotypes: CD5+,CD23+,CD20+,CD19+,HLA-DR+,but the CD22,CD11c,CD25 and FMC7 were variable present in some B-CLL cases.CD103 seems the most specific marker for HCL.To differentiate diagnosis of atypical B-CLL with B-prolymphocytic leukemia(B-PLL) or mantle cell lymphoma(MCL), one must not rely exclusively on immunophenotypic dates, cytogenetic or molecular biology detection would be helpful. The index of froward scatter( FSC) and antigens expression of tumor B cells could be calculated by dividing the relevant value of residual normal T cell within same sample as internal control, so the cell size and the intensity of antigen expression could be comparable each other and quantitative between different investigations. Conclusion immunophenotypic analysis is an extremely useful adjunct in the diagnosis of chronic lymphoid leukemia.

Simvastatin selectively inhibits proliferation and induces apoptosis of chronic myelogenous leukemia cells / 北京大学学报(医学版)

Objective: To explore the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme of cholesterol synthesis) on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells. Methods: Both normal and CML bone marrow progenitor cells were assayed in semisolid methylcellulose culture after incubation for 24 hours in suspension culture with 10 mg*L－1 simvastatin. Also, sub-G1 cells and DNA end-labeling positive cells as apoptotic cells were identified by flow cytometry after being exposed to simvastatin for 72 hours. Results: Simvastatin selectively inhibited proliferation and induced apoptosis of CML cells, but had no much influence on normal bone marrow cells. Conclusion: CML cells are more sensitive to a short-term exposure to simvastatin than normal bone marrow cells. It will be a promisingly effective chemotherapeutic agent or in vitro purging agent in autologous stem cell transplantation for the treatment of CML.