Transformation of primary myelofibrosis to B-cell acute lymphoblastic leukemia: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the pathogenesis and prognosis of transformation of primary myelofibrosis (PMF) to B-cell acute lymphoblastic leukemia (B-ALL).Methods:The diagnosis and treatment process of a patient transferred from PMF to B-ALL in Affiliated Tumor Hospital of Zhengzhou University in November 2018 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 64-year-old female, she was initially diagnosed with PMF, and then she developed B-ALL 17 months later after receiving treatment of prednisone, danazole, levamisole, aspirin, thalidomide and jaktinib. After induction therapy, the patient received 8 months of continuous remission, and then the reexamination showed relapse. There was no remission after reinduction therapy. The patient gave up treatment and was discharged 2 months later. JAK2 V617F gene mutation was positive before and after leukemia transformation.Conclusions:The patients with transformation of PMF to B-ALL have poor clinical prognosis and short survival time. The possible mechanism of its transformation may be related to additional genetic events or certain high-risk genes. However, the specific mechanism is still unclear, and further investigation of the etiology is needed to seek targeted treatment.

Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia / 中华血液学杂志

Objective@#To explore the effect of combination regimen of interferon alpha-1b, interleukin-2 and thalidomide (ITI regimen) on minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) who were in hematologic remission but MRD-positive.@*Methods@#Eighteen patients (17 from Tumor Hospital of Zhengzhou University and 1 from the First People's Hospital of Pingdingshan City) with AML admitted from July 2016 to June 2018, who were in hematologic remission but MRD-positive were treated with different doses of ITI regimen, and the MRD levels were monitored.@*Results@#Among 18 patients who received a conventional dose of ITI regimen for 1 to 2 months, 7 patients had undetectable MRD, 3 had significant decrease in MRD levels, 3 had elevated MRD level and had hematologic recurrence. Three patients with elevated MRD level received a higher dose of ITI regimen, 2 of them turned to MRD negative and the other 1 patient had decreased MRD level. The total response rate was 72.2%, and the response rate in patients with MRD > 1.0% was 57.1% (4/7) , and that of patients with MRD < 1.0% was 81.8% (9/11) , respectively.@*Conclusion@#The ITI regimen can reduce the MRD level of patient with AML who are in hematologic remission but MRD-positive. The therapeutic effect could be improved by a higher dose administration of ITI regimen, and therapeutic effect may be negatively correlated with MRD level before treatment.

Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review / 中华血液学杂志

Objective@#To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration.@*Methods@#One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed.@*Results@#The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy.@*Conclusion@#CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.

The value of biparametric MRI in the detection of prostate cancer / 中华放射学杂志

Objective To explore the difference in efficacy between multiparametric MRI (Mp-MRI) based on prostate imaging reporting and data system version 2 (PI-RADS v2) and abbreviated biparametric MRI (Bp-MRI) in detecting prostate cancer (PCa) and clinically significant prostate cancer (csPCa), and to evaluate the consistency of image interpretation between different readers. Methods The imaging, pathological and clinical data of patients with prostatic Mp-MRI in our hospital from February 2015 to June 2018 were retrospectively analyzed. At the beginning, 250 patients were randomly selected. Two radiologists visually evaluated the images of those patients using two 5-point scoring schemes based on Mp-MRI and Bp-MRI. The remaining cases were independently proceeded by one of the radiologists using two schemes respectively. Weighted Kappa test was used to assess the consistency of the results interpreted by the two radiologists. The receiver operating characteristic (ROC) curve was used to evaluate the efficiency of the two scoring schemes in detecting PCa and csPCa, and with Z test to investigate whether there was any difference in detection efficiency between the two schemes. Results Nine hundred and seventy eight patients were eventually enrolled in the study. The results of the consistency assessment showed that there was good agreement between the two radiologists, whether using Mp-MRI or Bp-MRI, with the weighted Kappa coefficient of 0.800 and 0.812, respectively. The ROC curve analysis showed that the area under the curve (AUC) of PCa detected by Mp-MRI and Bp-MRI was 0.873 and 0.879, respectively, and the AUC of csPCa detected was 0.922 and 0.932, respectively. In addition, there was no statistically significant difference between the AUC of PCa and csPCa detected by the two schemes (P>0.05). Conclusion The Bp-MRI scoring scheme has good stability in the evaluation of benign and malignant prostate, and its detection efficiency of PCa or csPCa is not lower than that of standard Mp-MRI based on PI-RADS v2.

Clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in treatment of medium﹣and high﹣risk myelodysplastic syndromes / 白血病·淋巴瘤

Objective To explore the clinical efficacy and safety of low﹣dose decitabine subcutaneous injection combined with arsenicals in the treatment of medium﹣ and high﹣risk myelodysplastic syndromes (MDS). Methods Eight cases of medium﹣ and high﹣risk MDS without allogeneic hematopoietic stem cell transplantation in the Affiliated Cancer Hospital of Zhengzhou University and Xinhua Area Hospital of Pingdingshan City from January 2015 to August 2018 were retrospectively analyzed. The patients were given subcutaneous injection of low﹣dose decitabine combined with arsenicals. The specific regimen was as follow:0.1-0.2 mg/kg of decitabine, subcutaneous injection 2 times/week, 4 weeks in total; arsenic injection 10 mg/time or 0.16 mg/kg, intravenous administration, 1 time/d, 4 weeks; compound Huangdai tablets 60 mg/kg per day, 3 times orally. The efficacy and adverse reactions were observed. Results In 8 patients, there were 5 male and 3 female, with an average age of 61.4 years old (44-80 years old) Eleven cases were refractory anemia with excess blasts (RAEB), 6 cases were RAEB﹣2, 1 case was refractory cytopenia with multilineage dysplasia (RCMD) with bone marrow fibrosis (MF). Three of the patients had previously received treatment with decitabine. All patients completed the treatment successfully and no treatment﹣related deaths occurred. By the end of follow﹣up, 2 patients had complete remission, 4 patients had complete bone marrow remission with hematologic improvement, 1 patient had stable disease, and 1 patient had disease progression. For 2 patients who had been treated with decitabine regimen, the regimen of re﹣administered decitabine plus arsenic was still effective. Eight patients had more than level 2 of myelosuppression, except for one patient with intestinal infection due to unclean diet and one patient with mild pulmonary infection. The remaining 6 patients had no associated infection and heart, liver, kidney and other adverse reactions. Conclusion Low﹣dose decitabine subcutaneous injection combined with arsenicals is safe and could be a new treatment for the medium﹣ and high﹣risk MDS.

The expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia and its prognostic significance / 中华血液学杂志

Objective@#To detect the expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia (B-ALL) in newly diagnosed cases, and to investigate the relationship between CRLF2 and the general clinical characteristics, efficacy and prognosis.@*Methods@#103 cases of newly diagnosed adult B-ALL patients were investigated from Apr 2016 to Dec 2017 in the Department of Hematology, Henan Cancer Hospital. Bone marrow samples was used to detect the expression of CRLF2 in leukemic cells. The expression of CRLF2 ≥20% was defined as CRLF2-high group and <20% was defined as CRLF2-low group. The clinical characteristics and prognosis of the two groups were compared.@*Results@#The Median overall survival (OS) and disease free survial (DFS) in CRLF2-high group were 9.0 months and 4.25 months, respectively. CRLF2-low group were 15.5 months and 10.25 months, respectively. There was a statistically significant difference in median OS and DFS between the two groups (P=0.007, P=0.000) . The 18-month OS and DFS in CRLF2-high group were 38.6% and 25.1%, respectively. CRLF2-low group were 57.8% and 42.3%, respectively. Multivariate analysis showed high expression of CRLF2 was an independent risk factor for OS (HR=2.991, 95% CI 1.429-6.261, P=0.004) and DFS (HR=2.374, 95%CI 1.146-4.960, P=0.041) in patients.@*Conclusion@#Patients with high expression of CRLF2 had poor prognosis.

Correlation between histogram analysis of dynamic contrast enhanced MRI and diffusion weighted imaging intravoxel incoherent motion quantitative parameters and Gleason score of prostate cancer / 中华放射学杂志

Objective To investigate the value and diagnostic efficiency of the quantitative dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) parameters using three dimention (3D)-histogram analysis for discriminating the Gleason score (GS) of prostate cancer. Methods A total of 53 patients pathologically confirmed as prostate cancer by systemic prostate biopsy who had routine , DCE and DWI-MRI scans were retrospectively analyzed. There were 15 cases for low-risk and 38 cases for intermediate/high-risk prostate cancer. The 3D ROI of all lesions based on T2WI was achieved by image registration to get the quantitative parameters of DCE-MRI and DWI-IVIM. The parameters of DCE-MRI contains: transfer constant (Ktrans), rate constant (Kep) and extracellular-extravascular volume fraction (Ve).The DWI-IVIM related quantitative parameters were ADC, diffusion coefficient (D), diffusion coefficient related to perfusion (D*) and perfusion fraction (f). Then the histogram analysis of these quantitative parameters was performed to get the mean, median, 25th percentile, 75th percentile, Skewness and Kurtosis. Using the Spearman rank correlation analysis to evaluate the correlation of these parameters and GS of prostate cancer. The diagnostic performance of these quantitative histogram parameters related to the GS in identifying low-risk and intermediate/high-risk of prostate cancer was carried by ROC. Results The Kep and Ktrans (mean, median, 25th, 75th) of DCE-MRI were positively correlated with GS (r value was 0.346 to 0.696, P<0.05). The ADC (mean, median, 25th, 75th), D (mean, median, 25th, 75th, Skewness, Kurtosis) and D*(25th) of DWI-IVIM were correlated with GS (r value was-0.544 to 0.428, P<0.05). The DCE-MRI quantitative parameters Kep (25th) had the highest area under curve (AUC, 0.961); The ADC (median) and D (25th) had higher AUC( 0.832, 0.888) in the quantitative parameters of DWI-IVIM, the difference between Kep(25th) and ADC (median) was statistically significant (Z value was 2.212, P value was 0.027). The difference of AUC between Kep (25th) and D (25th), D (25th) and ADC (median) was not statistically significant (Z values were 1.027 and 1.398, P values were 0.162 and 0.304, respectively).Conclusion DCE and IVIM quantitative parameters (Kep, Ktrans, ADC, D) histogram analysis results are correlated with GS, and can be used for distinguishing low-risk from intermediate/high-risk prostate cancer.

Characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.</p><p><b>RESULTS</b>In 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.</p><p><b>CONCLUSION</b>T315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.</p>

Incidences of hematological adverse reactions in 435 patients with chronic myeloid leukemia treated by imatinib mesylate / 白血病·淋巴瘤

Objective To explore the hematology adverse reactions of imatinib mesylate (IM) in the treatment of chronic phase (CP) of chronic myeloid leukemia (CML).Methods The clinical data of 435 CML-CP patients treated with IM were analyzed respectively in the Affiliated Cancer Hospital of Zhengzhou University from Jan 2013 to Jan 2015.The hematology adverse reactions were followed up regularly and the incidences in different groups with various factors were compared.Results Until the end of follow-up,74 (17.0 ％) patients had hematology adverse reactions.61 (14.02 ％) patients had neutropenia,including 9 (14.75 ％) patients who had level Ⅲ-Ⅳ neutropenia.60 (13.79 ％) cases had thrombocytopenia including 11 (18.33 ％) patients with level Ⅲ-Ⅳ thrombocytopenia.Anemia occurred in 50 (11.49 ％) patients,of whom 5 (10.00 ％) cases were grade Ⅲ-Ⅳ anemia.33 (7.59 ％) cases experienced pancytopenia.The incidence of hematology adverse reactions was influenced by nine factors,including the course before treatment,the size of spleen,Sokal scores,the use of interferon,fusion genes,chromosomes,complete cytogenetic response,main molecular reaction and Karnofsky scores (all P ＜ 0.05),while it was not influenced by age,gender,BMI,smoking and drinking (all P ＞ 0.05).Conclusions During the initial treatment of CML-CP,if patients experienced level Ⅰ-Ⅱ hematology adverse reactions,they can continue to taking IM.However,when level Ⅲ-Ⅳ hematology adverse reactions happened,they need to reduce the dose or stop taking,and one month later,hemocyte will get well.In the long-term treatment of CML,once level Ⅲ-Ⅳ hematology adverse reactions occur,the patients need to receive some related inspections,such as bone marrow morphology and molecular biology detection,to clear the disease stage.When it is necessary,the patients can take the second generation of tyrosine kinase inhibitors.

Detection of food allergen-specific IgE and IgG in patients with chronic urticaria / 中华皮肤科杂志

Objective To evaluate the roles of food allergen detection in patients with chronic urticaria.Methods Food allergen-specific IgE and IgG were detected in 502 patients with chronic urticaria and 100 normal human controls.Double-blind,placebo-controlled food challenge (DBPCFC) test was performed in patients who were proved to be positive or negative for food-specific IgG or IgE.Results Food-specific IgE was detected in 37.45％ (188/502) of the patients,with cashew,peanuts and soybeans as the most common allergens.The detection rate of food-specific IgG was 72.11％ (361/502),with the major allergens being milk,egg,shrimp and crab.DBPCFC revealed false positivity and negativity in the detection of food-specific IgG and IgE.Conclusions Clinicians should pay attention to food allergen detection in the treatment of chronic urticaria,especially in the treatment of allergy mediated by IgG antibodies.