[Toxic megacolon complicated by ulcerative colitis in six patients: a case report and literature review].

OBJECTIVE: To summarize the clinical features of ulcerative colitis (UC) complicated by toxic megacolon for early diagnosis and proper treatment. METHODS: Six cases of toxic megacolon in the patients suffered from UC in Peking Union Medical College Hospital from 1983 to 2010 were analyzed, and related literature was searched and reviewed. RESULTS: The incidence of the toxic megacolon in the patients with UC in our center was 0.7%(6/824), which was lower than those reported in the literature. There were always risk factors triggering the disease. The prognosis of the patients was poor, even after medical care and surgery intervention. Evaluation of the patients and making right timing to perform the surgery would improve the prognosis of the patients in foreign literature. CONCLUSION: It's crucial to make early diagnosis of the toxic megacolon in the patients suffered from UC. The right choice and timing to perform urgent surgery or selective surgery may improve their prognosis.

Autoimmune enteropathy and primary biliary cholangitis after proctocolectomy for ulcerative colitis: A case report and review of the literature.

BACKGROUND: Autoimmune enteropathy (AIE) and primary biliary cholangitis (PBC) are both immune-mediated diseases. AIE or PBC complicated with ulcerative colitis (UC) are rare. There are no cases of AIE and PBC diagnosed after proctocolectomy for UC reported before, and the pathogenesis of these comorbidities has not been revealed. CASE SUMMARY: A middle-aged woman diagnosed with UC underwent subtotal colectomy and ileostomy due to the steroid-resistant refractory disease, and a restorative proctectomy with ileal pouch-anal anastomosis and proximal neoileostomy was postponed due to active residual rectal inflammation in January 2016. A few months after the neoileostomy, she began to suffer from recurrent episodes of watery diarrhea. She was diagnosed with postcolectomy enteritis and stoma closure acquired a good therapeutic effect. However, her symptoms of diarrhea relapsed in 2019, with different histological features of endoscopic biopsies compared with 2016, which showed apoptotic bodies, a lack of goblet and Paneth cells, and villous blunting. A diagnosis of AIE was established, and the patient's stool volume decreased dramatically with the treatment of methylprednisolone 60 mg/d for 1 wk and tacrolimus 3 mg/d for 4 d. Meanwhile, her constantly evaluated cholestatic enzymes and high titers of antimitochondrial antibodies indicated the diagnosis of PBC, and treatment with ursodeoxycholic acid (16 mg/kg per day) achieved satisfactory results. CONCLUSION: Some immune-mediated diseases may be promoted by operation due to microbial alterations in UC patients. Continuous follow-up is essential for UC patients with postoperative complications.

[The trends in clinical characteristics of colon cancer in last two decades].

OBJECTIVE: To explore the changing of clinical features of colon cancer within 20 years, in order to help early diagnosis and screening of colon cancer in China. METHODS: A total of 1233 cases of colon cancer in Peking Union Medical College Hospital during 1989 - 2008 were retrospectively studied. All patients were divided into two groups according to the date of onset (1989 - 1998 and 1999 - 2008), the demographic features, clinical manifestations, laboratory examination, colonoscopy characteristics and pathological stage were analyzed. RESULTS: Comparing with 1989 - 1998, in recently 10 years, the morbidity of colon cancer increased, more female and old patients appeared; hematochezia significant less (51.8% vs 31.7%, P < 0.05); abdominal mass and following ileus also decreased (30.2% vs 13.6%, P < 0.05); patients with low of Hb decreased, the positive of stool occult blood increased from 43.6% to 61.2% (P < 0.05), According with the more patients who detected serum CEA, the positive rate significant increased (32.4% vs 57.9%, P < 0.05). Colonoscopy became the mainly method for diagnosis, more and more early stage lesion and polyps were detected. The location of tumor from ascending colon in 1989 - 1998 (44.6%) shift to sigmoid colon (38.7%) and descending colon (22.7%) up to now. Operation was the first choice of treatment, the early stage (Duke A) patients significant increased (9.3% vs 23.8%, P < 0.05). CONCLUSIONS: In the recently 10 years, the morbidity of colon cancer obviously increased, the age was become elder and female patients were increased. The clinical manifestation became more nonspecific. According with the improvement of stool occult blood, serum CEA and colonoscopy detective method and wild spread using, more and more early stage patients were diagnosed. The location of tumor shift from right side to left side, and coincidence with west countries gradually.

Clinical evaluation of traditional Chinese medicine on mild active ulcerative colitis: A multi-center, randomized, double-blind, controlled trial.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. METHODS: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3-5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. DISCUSSION: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.

Similarities and differences in clinical and pathologic features of inflammatory bowel disease-associated colorectal cancer in China and Canada.

BACKGROUND: Colorectal cancer (CRC) has become one of the major life-threatening complications in patients with inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). This study aimed to explore the clinical-pathologic similarities and differences in the IBD-associated CRC (IBD-CRC) between patients in China and Canada. METHODS: Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing (China) and Calgary (Canada) over the same past 13 years, including 25 (22 UC-associated and three CD-associated) from Beijing group and 53 (32 UC-associated and 21 CD-associated) from Calgary group, were compared with regards to their clinical and pathologic characteristics. RESULTS: Several known features of IBD-CRC were seen in both groups, including long duration and large extent of colitis, active inflammation background, multifocal lesions, and advanced tumor-node-metastasis stage. Beijing group showed a significantly higher percentage of UC (88.0% vs. 60.4%, P = 0.018), younger age at diagnosis of CRC (48.6 ±â€Š12.8 years vs. 61.6 ±â€Š14.7 years, P < 0.001), lower ratio of mucinous adenocarcinoma (7.1% vs. 42.4%, P = 0.001) compared with Calgary group. None of the Beijing group had concurrent primary sclerosing cholangitis, while 5.7% of Calgary group did. Surveillance colonoscopy favored the detection rate of precancerous lesions (41.4% vs.17.0%, P = 0.002). CONCLUSIONS: As compared with patients from the Calgary group, the IBD-CRC patients in Beijing group were younger, less CD-associated and had less mucinous features, otherwise they were similar in many common features.

Pancreaticobiliary involvement in treated type 1 autoimmune pancreatitis: Imaging pattern and risk factors for disease relapse.

PURPOSE: To evaluate the imaging pattern of pancreaticobiliary lesions in patients with treated type 1AIP, to determine the incidence of disease relapse and malignancy, and to identify the risk factors. METHOD: The institutional review board approval was acquired. All patients gave written informed consent. From a prospective clinico-radiological database since 2012, consecutive patients with type 1 AIP who were treated and followed up (≥18 months) were identified. The presence/absence of pancreaticobiliary lesion(s) development during follow-up were assessed. The etiology was determined and the imaging pattern was compared to the initial attack. Risk factors were identified by univariate and multivariate analysis. RESULTS: Among 103 patients with treated type 1 AIP, 44 (42.7%) developed pancreaticobiliary lesions during follow up (median time interval to initial diagnosis: 17 months, range 3-62 months), mostly after steroid discontinuation (63.6%) or during maintenance therapy (29.5%). All lesions were disease relapse, which responded to steroid treatment. At relapse, pancreatic involvement was less frequent (81.8% vs 100%, p = 0.003), and the pancreas size was smaller (p < 0.01), whereas extra-pancreatic bile duct (ExPanBD) involvement was more severe and extensive (both p < 0.01). Multivariate analysis revealed ExPanBD involvement at initial diagnosis (hazard ratio 2.437, 95% CI 1.343-7.402, p = 0.002) and serum IgG4 response ratio at the induction phase (hazard ratio 0.357, 95% CI 0.055-0.804, p = 0.011) as significant independent predictors of relapse. CONCLUSIONS: In treated type 1 AIP, although imaging pattern may differ, pancreaticobiliary lesions are usually manifestations of disease relapse. ExPanBD involvement and poor serum response suggests high risk of relapse.

Clinical characteristics of ulcerative colitis-related colorectal cancer in Chinese patients.

OBJECTIVE: The prevalence of ulcerative colitis (UC) in China has been increasing, together with the incidence of ulcerative colitis-related colorectal cancer (UCRCC). In this study we aimed to investigate the clinical features of UCRCC in Chinese UC patients. METHODS: Clinical data of patients with UCRCC during January 2003 to December 2016 were retrieved from the Peking Union Medical College Hospital registration database and compared with that of sporadic colorectal cancer (CRC). RESULTS: During the study period, among the 10 110 patients with CRC 25 were found to have UCRCC, with an average age of 51 years and a median disease duration of 15 years. The cumulative prevalence of UCRCC was 0.25% in all CRC patients, with a significant increase from 2003-2007 to 2013-2016 (P < 0.01). Altogether 14 (56.0%) patients with UCRCC were men, and 5 (20.0%) had a family history of UC or cancer. Four (16.0%) patients had concurrent high-grade intraepithelial neoplasia with variable differentiated adenocarcinoma at other sites and 19 (59.4%) tumors were moderately or poorly differentiated. Twenty-three (92.0%) patients underwent surgery, of whom 10 (40%) were at stage III and IV according to the TNM staging system. Compared with the 10 085 patients with sporadic CRC, UCRCC patients were younger (P < 0.01) and were more likely to have descending colon involvement and multifocal lesions (P < 0.01). CONCLUSIONS: UCRCC patients have been increasing in recent years. Compared with patients with sporadic CRC, those with UCRCC are younger and are more likely to have descending colon involvement and multifocality.

[Recombinant adeno-associated virus 2-mediated green fluorescent protein expression in bone marrow mesenchymal stem cells derived from acute myelogenous leukemia patients].

OBJECTIVE: To explore the possibility of using autologous bone marrow mesenchymal stem cells (BMSC) as a vehicle to deliver recombinant adeno-associated virus 2-mediated enhanced green fluorescent protein (rAAV-2-eGFP) in vitro, therefore to find an alternative solution for gene therapy of hematological malignancy. METHODS: BMSCs isolated from the bone marrow of patients with acute myelogenous leukemia (AML) at the onset of disease were infected by rAAV-2-eGFP at different multiplicity of infection (MOI=10(2), 10(3), 10(4), 10(5), 10(6), and 10(7), respectively). Phase-contrast fluorescent microscope and flow cytometry were employed to evaluate the expression of enhanced green fluorescent protein (eGFP). RESULTS: Ten to fourteen days after the transfection, eGFP expression began to be detected and the transfection efficiency ranged between 0.3% to 2%, which failed to be increased with the increase of MOI. The transduced eGFP could maintain a long-term stable expression in vitro in the 61 days of observation, and from 12 to 33 days after transfection, eGFP percentage underwent a decrease from the initial 1.16% to 0.5%-0.6% and maintained this expression level till 61 days after transfection. CONCLUSION: rAAV can be used with BMSCs for in vitro gene therapy, but the poor transfection efficiency of these cells remains a significant obstacle for its further application.

[All-trans retinoic acid for thromboembolic events in patients with M3 leukemia: a case report].

A case of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) is reported. After the diagnosis was established, the patient was given oral ATRA (30 mg/d) in combination with small dose of hydroxyurea, platelet concentrates, and fresh frozen plasma etc. From day 19 after ATRA administration, successive thromboembolic events occurred. In spite of the partial remission on day 32, the patient died of cardiopulmonary insufficiency. Our experience from this case suggests that more attention should be given to thromboembolic events during ATRA therapy, and the use of active anti-coagulant may prove beneficial when signs of hypercoagulation are present in APL patients.

[STI 571 for treating 19 patients with chronic-phase chronic myeloid leukemia].

OBJECTIVE: To compare the therapeutic effects of STI 571 in treating Philadelphia chromosome (Ph)-positive patients with chronic-phase and acceleration phase chronic myeloid leukemia (CML-CP and CML-AP, respectively). METHODS: A total of 19 CML patients with Ph chromosome and/or fluorescence in situ hybridization (FISH)-bcr/abl fusion gene positivity rates over 90% and a median age of 38 years were recruited in this study, 12 of whom had previously failed to respond to interferon-alpha. Five of the 19 patients were in accelerated phase and 14 in chronic phase, 9 of the latter patient group in early stage of CML-CP (within 1 year since diagnosis) and 5 in advanced stage (3-6 years since diagnosis). All the patients were given oral STI 571 at the dose of 300-500 mg/d for a median treatment course of 5 months, and the 5 patients with CML-AP also received homoharringtonine at dose of 1-2 mg/d for an average of 1.5 treatment cycles (7-14 d for a complete treatment cycle). The Ph chromosome and the FISH-bcr/abl were analysed again 3 months after the treatment. RESULTS: STI 571 induced 100% complete hematological remission (CHR) and 79% major cytogenetic responses (MCR) in these patients. The complete cytogenetic remission (CCR) rates of CML-AP patients and CML-CP patients in advanced stage were lower than that of CML- CP patients in early stage (0% and 40% vs 88.9%). CONCLUSION: STI 571 can achieve high rate of CHR and MCR in CML-CP patients, especially in those in early stage of the disease.

[Analysis of prognostic factors in patients with refractory acute myeloid leukemia].

OBJECTIVE: To analyze the prognostic factors in patients with refractory acute myeloid leukemia, so as to provide theoretical basis for choosing an appropriate chemotherapy. METHODS: This study included 48 patients with refractory acute myeloid leukemia who received two standard DA regimens followed by chemotherapy with median dose of Ara-C and mitoxantrone. The factors such as age, gender, responses to the standard chemotherapy, cytogenetic abnormalities, blast cell counts in the bone marrow, peripheral blood cell counts, extramedullary infiltration exhibition and LDH were examined in light of their respective impact on the patients' survival. Cox regression model was used to analyze the prognostic factors. RESULTS: The results revealed that the factors such as achievement of the first complete remission after standard induction chemotherapy, the remission duration longer than 6 months, favorable cytogenetic abnormalities, blast cell counts less than 50% in bone marrow, absence of severe anemia, absence of liver or pancreatic enlargement or central nerves system (CNS) leukemia, and LDH less than 360 U/L, all indicated favorable prognosis of the patients. Age, gender, white cell counts in periphery blood or lymphadenopathy were not related to the survival of the patients. CONCLUSION: The patients with favorable prognostic factors should receive intensive chemotherapy for prolonged survival; allogeneic bone marrow transplantation should be performed as soon as possible in patients with unfavorable prognostic factors.

[Modified FLAG regimen in the management of refractory acute myeloid leukemia].

OBJECTIVE: To evaluate the therapeutic effect of modified FLAG regimen in the management of refractory acute myeloid leukemia (AML). METHODS: Sixteen patients with refractory AML were divided into two groups. In modified FLAG regimen group (n=10), the patients received fludarabine (Flu, 50 mg/d, VDx5 d) and Ara-c (200 mg/d, VDx5 or 7 d). The regimen for classic FLAG group (n=6) consisted of Flu (50 mg/d, VDx5d), Ara-C (500 or 1,000 mg/d, VDx5d) and G-CSF (300 microg/d, x5 d, subcutaneously injected 4-6 hours before chemotherapy). Each patient received subcutaneous G-CSF (300 microg/d) when the white blood cell count was lower than 1.0x10(9)/L till the condition was corrected. RESULTS: The total complete remission(CR) rate of the 16 patients was 50% (8/16). Seven patients in modified group achieved CR (70%) and only one of the classic group did (17%, P<0.05). Episodes of infections were lower in modified group than in the classic group (50% vs 83%). CONCLUSION: Modified FLAG regimen is more likely than classic FLAG regimen to achieve CR and reduce infections in patients with refractory AML.

[Immunophenotyping of 106 adult patients with acute leukemia by flow cytometry].

OBJECTIVE: To study the immunophenotyping of adult patients with acute leukemia and its association with the prognosis. METHODS: Immunophenotyping was performed in 106 adult patients with acute leukemia by three-color flow cytometry analysis using CD34/SSC gating. RESULTS: The antigens expressed in 71 patients with acute myeloid leukemia (AML) were mainly CD13, CD33, HLA-DR, CD34 and CD117. Lymphoid antigen expression was identified in 23.9% adult AML patients and CD56 antigen expression in 15.5% of the AML patients. In 29 patients with acute lymphoblastic leukemia (ALL), the expressed antigens were mainly HLA-DR, CD10, CD19, CD34 and CD7, and 34.5% of these patients were found to be positive for myeloid antigen expression. Complete remission (CR) rate in AML patients with lymphoid antigen expression after chemotherapy was lower than that in AML patients without lymphoid antigen expression (52.9% vs 77.8%, P<0.05), and no significant impact was noted of myeloid antigen expression in ALL on the CR of the patients (70.0% vs 94.7%, P>0.05). The CR rate in AML with CD56 antigen expression was lower than that in AML without CD56 expression (36.4% vs 78.3%, P<0.025), and the CR rate in CD34+ AML was lower than that in CD34- AML (56.0% vs 80.4%, P<0.05). CONCLUSIONS: Gating of CD45/SSC can eliminate the interference of normal cells to render more reliable immunophenotyping results. The expressions of CD56+, CD34+, lymphoid antigen in adult AML patients, who have lower CR rate, often signify poor prognosis.

[Pleuropulmonary blastoma in an adult women with pleurorrhea as the major clinical manifestation: report of a case].

OBJECTIVE: Pleuropulmonary blastoma (PPB) is a rare dysontogenetic neoplasm in children and has been recognized as a distinct clinicopathological entity different from the ordinary pulmonary blastoma of adulthood. We report a very rare adult case of PPB. A 43-year-old female patient presented with massive pleural infusion, and a misdiagnosis of pleural tuberculosis (TB) was made on the basis of ultrasound scan and CT images, for which therapy with TB drugs was administered for 3 weeks. Subsequent operation and pathologic examination of the mass revealed a multicystic neoplasm consisting of malignant mesenchymal cells immunohistochemically positive for vimentin and actin. Local recurrence occurred in the left pleural 20 months after the surgical tumor resection and 4 cycles of adjuvant chemotherapy.

[Are leukemic patient bone marrow mesenchymal stem cells malignant?].

The study was aimed to explore whether there are leukemic characteristics in the bone marrow mesenchymal stem cells (BMMSC) from leukemic patients as compared with normal controls. The mesenchymal stem cells from bone marrow of normal volunteers and patients with APL and CML were isolated, then cultured and proliferated in vitro. The morphology, growth curve and cell surface markers of two different sources mesenchymal stem cells were investigated for detecting whether the bone marrow mesenchymal stem cells derived from leukemia patients have the specific abnormal fusion gene of leukemia cells through fluorescent in situ hybridization. The results indicated that there was no significant difference between the mesenchymal stem cells derived from different subjects, the bone marrow mesenchymal stem cells derived from leukemia patients did not have the clonal malignant fusion gene as seen in the leukemia cells. Taken altogether, mesenchymal stem cells derived from leukemia patients had no biological differences as compared with those from normal volunteers, and no malignant clonal abnormality was found. It is concluded that mesenchymal stem cells derived from leukemia patients as an alternative vehicle may be used for assistant of autologous hematopoietic stem cell transplantation or cell therapy and gene therapy.

[Analysis of sequence-tagged site in bcr and abl genes by DNA pooling and dHPLC].

To investigate the relationship between the single nucleotide polymorphism (SNPs) of the bcr and abl gene and chronic myelogeous leukemia (CML), the 9 sequence-tagged sites (STS) in bcr and abl gene were screened by DNA pooling and denaturing high performance liquid chromatography (dHPLC), and the results were varified by sequencing. The results showed that the polymorphism sites were detected in 4 out of the 9 STS fragments and there were 3 bases different from the reference sequence found in 3 fragments. In conclusion, the novel SNP in U07000 fragment shows significantly different frequencies between CML and controled people.

[Glivec in combination with HA regimen for treatment of 20 patients with Ph chromosome positive acute leukemia].

BACKGROUND & OBJECTIVE: Glivec was approved by Food & Drug Administration (FDA) in May 2001 as a gene target drug for treatment of chronic myeloid leukemia (CML) and showed a good curative effect for patients with chronic myeloid leukemia in chronic phase. But its effectiveness was poor in patients with CML blast phase treated with Glivec alone. Glivec was reported having synergetic effect with other chemical agents in vitro, but there is few report in clinical combined application. In this paper, we analyzed effectiveness of Glivec in combination with homoharringtonine (HHT) and cytarabine (Ara-C) for patients with Ph chromosome positive acute leukemia (Ph(+)-AL), and investigated patients' tolerance to side effects of this trial. METHODS: A total of 20 patients (16 males and 4 females, median age was 43 years) were eligible. Blasts in peripheral blood (PB) or bone marrow (BM) were both more than 30%, bcr/abl fusion genes were detected positive in 90% cells by analysis of karyotype or fluorescence in situ hybridization (FISH). Five patients showed t(9;22) and other 15 patients showed more complicated chromosome abnormality. Of these 20 patients, 17 patients developed Ph(+)-ANLL from CML, 1 case developed Ph(+)-ALL, and other 2 cases were primary Ph(+)-ALL. The median interval from diagnosis to Glivec treatment was 4 months. Eighteen of 20 patients received different chemotherapy regimens for 2-4 treatment cycles, but no one reached hematological complete remission (HCR). All patients were given oral Glivec daily at the doses of 0.3-0.6 g in a median treatment time of 2.5 months (range, 1-6.5 months). Ph(+)-ANLL patients were infused with HHT over 6-24 hours daily at the doses of 1-2 mg intravenously and Ara-C 30-50 mg daily subcutaneously for 10-14 days; 3 patients with Ph(+)-ALL received HOAP or DOP combination treatment regimens (One cycle consists of HA with the same dosage described above for Ph(+)-ANLL patients for 7 days, daunorubicin at the dose of 40 mg/d intravenously for 3 days, vincristine at the dose of 2 mg/wk for two weeks, and prednisone at the doses of 60-80 mg/d for 14 days). Median treatment cycle was 2 (range, 1-3). The dosage of Glivec could be reduced or treatment was suspended when bone marrow inhibition happened. G-CSF was used when necessary. The curative effect was evaluated by international hematology and cytogenetics standards, in which bone marrow was examined every chemotherapy cycle and chromosome was analyzed 3 months later. RESULTS: Among the 20 patients receiving Glivec, 40% achieved HCR, and 25% achieved hematological partial remission (HPR), but only 15% patients approached a partial cytogenetic remission and no cytogenetic responses were found in other 85% patients. White blood cells (WBC) in peripheral blood reduced from 41+/-31 x 10(9)/L to normal level within 1 week. The blasts decreased from (50+/-30)% to(1.9+/-2.9)% (P< 0.001) in median time of 21.0+/-16.8 days. Three patients with high fever recovered normal temperature after 3 days treatment. When follow-up median time at 8 months, the total survival rate reduced to 40%, the rate of death and lost follow-up number of patients added to 60%. CONCLUSION: Regimen of Glivec in combination with HA could increase chemotherapy effect for the patients with Ph(+)-AL, prolong their life time and the side-effects were tolerable.

[Polymorphism analysis of 5' promotor region of BCR gene].

BACKGROUND & OBJECTIVE: BCR-ABL fusion gene is regarded as the molecular hallmark of chronic myelogenous leukemia (CML), and its expression is controlled by the BCR gene promoter. This study was designed to investigate the polymorphism of the promoter region of BCR gene, and its possible correlation with the disease. METHODS: A 1.13 kb fragment of BCR gene 5' promotor region was amplified and sequenced from 30 CML patients and 19 controls. Transcription factor binding sites and repeat sequences in this region were analyzed using softwares and online tools. RESULTS: Four novel single nucleotide polymorphisms (SNPs) and 3 bases different from the reference sequence were detected in the region studied. Among these 2 novel SNPs and 1 different base were located in or near several bases of binding sites. The gene frequencies of the novel SNPs had no significant difference between CML and control people. CONCLUSION: Sequence polymorphisms were found in the 5' promotor region of BCR gene, most of them being SNPs. No relativity can be validated between the SNPs and the disease. But it appears that some SNPs might have the probability of bringing influence to the transcription and expression of the gene.

[Effect of modified FLAG regimen therapy on 33 patients with relapsed/refractory leukemia].

BACKGROUND & OBJECTIVE: The hematological complete remission (CR) rate of the FLAG regimen [fludarabine and cytarabine (Ara-C) and granulocyte-colony stimulating factor] for relapsed and refractory acute non- lymphocytic leukemia (ANLL) was 50-64%. The aim of this study was to investigate the modified FLAG regimen (Ara-C reduced to 200 mg per day intravenous injection for 5 to 7 days, and the patients were not administrated G-CSF before fludarabine and Ara-C) to examine whether it can achieve the same effectiveness and minor side effects. METHODS: Of 33 patients with acute leukemia, there were 16 cases with ANLL, 12 cases with refractory acute lymphocytic leukemia (ALL) and 5 cases with relapsed ALL, respectively. All patients received fludarabine (Flu) 30 mg/m(2)/d intravenous injection for 5 days. And every patient received simultaneously Flu in combination with Ara-C intravenously for 5-7 days, 18 cases with Ara-C at a dose of 200 mg per day, 5 cases with Ara-c 500 mg/d and 10 cases with Ara-c 1000 mg/d, respectively. One course consisted of 7 days. ALL patients and the patients received Ara-C at a dose of 200 mg per day were not treated with G-CSF before chemotherapy. ALL patients received vincristine at a dose of 2 mg/w for 2 times and prednisone 60-80 mg/d for 14 days. Of these 33 patients, the cases with white blood cell(WBC) counts less than 1.0 x 10(9)/L were treated with G-CSF at a dose of 300 microg/d subcutaneously until WBC counts were more than 3.0 x 10(9)/L. All patient were examined for bone marrow after every course. RESULTS: The CR rate of 16 patients with refractory ANLL was 56.3%, whereas the CR rate of 12 cases with refractory ALL was 17% (P< 0.01). The CR rate of the patients with refractory ANLL who received Ara-C 200 mg/d was higher than those with refractory ANLL receiving Ara-C at the medial doses (70% versus 33%, P >0.05). The average durations of WBC< 0.6 x 10(9)/L and platelet< 15.6 x 10(9)/L were 5 days and 4.3 days, respectively. Infection rate of the patients receiving Ara-C 200 mg/d was significantly lower than those receiving Ara-C at the medial doses (58% versus 87.5%,P< 0.05). CONCLUSION: The CR rate of modified FLAG regimen is higher than classic FLAG, whereas the infection rate of the former is lower than the latter.

[Clinical efficacy and side effects of STI571 in treatment of patients with chronic myeloid leukemia].

BACKGROUND & OBJECTIVE: The aberrant regulation of the protein tyrosine kinase (PTK) activity of P210(BCR-ABL), which is the protein product of Bcr-Abl fusion gene leads to the pathogenesis of chronic myeloid leukemia (CML). Though STI571 can inhibit specifically the PTK activity of P210(Bcr-Abl) and greatly improve the clinic curative effect on CML in chronic phase, its effect on CML in accelerated phase and blast crisis is not clear. In this article, we attempted to analyze the clinic efficacy and side effect of STI571 treatment on CML patients in different phase. In addition, we analyzed the potential mechanism of STI571 resistance in accelerated/blast crisis CML with genetic methods. METHODS: A total of 22 cases of CML, 14 cases male and 8 female, 6 cases in chronic phase and 16 cases in accelerated/blast crisis phase, were treated with STI571. According to the efficacy standard, the hematological and cytogenetic response of 22 cases CML were analyzed, by determining the positive rate of Ph chromosome in bone marrow from the patients treated with STI571 for 3 months. Furthermore, the karyotype evolution of those patients showing STI571 resistance was analyzed. At the same time, the side effects and adverse events of STI571 treatment were evaluated. RESULTS: 6/6(100%) cases of CML patients in chronic phase acquired hematological CR and cytogenetic response. 4/16(25%) cases in accelerated phase or blast crisis acquired hematological CR and 8/16(50%) cases acquired cytogenetic response. 3 CML patients in blast crisis showed secondary STI571 resistance. The karyotype analysis shows 2 with 2 Ph chromosome and other additional abnormality. I/II grade non-hematological toxicity was observed in all the patients, including edema (77.3%), side effects of digestive system (36.4%) and myalgia (22.7%) et al. Severe hematological toxicities includes:(1)III/IV grade neutropenia (9 cases):1/6 cases of CML patients in chronic phase, 8/16 cases in accelerated phase or blast crisis; (2)III/IV grade thrombocytopenia (6 cases): 6/16 cases in accelerated phase or blast crisis. The percentage of III/IV grade neutropenia/thrombocytopenia in chronic phase and accelerated/blast crisis phase was compared and no significant statistical difference was observed. CONCLUSIONS: Hematological and cytogenetic responses of different degrees can be acquired in CML-CP and CML-AP/BC patients treated with STI571 and showing statistic difference. STI571 improves the clinic curative effect greatly on CML in chronic phase. CML patients in blast crisis have secondary STI571 resistance with novel 2 Ph chromosome and other additional abnormality, it furnishes the evidence of the gene changes. The slightness of non-hematological toxicity of STI571 in the treatment of chronic myeloid leukemia suggests this drug is relatively safe. Severe hematological toxicities, such as III/IV neutropenia and thrombocytopenia, are more common in accelerated/blast crisis than in chronic phase.