[Analysis of the clinical characteristics of acute myeloid leukemia related to the treatment of hematological and solid tumors].

Objective: To compare and analyze the clinical characteristics of acute myeloid leukemia (AML) related to the treatment of hematological tumors and solid tumors. Methods: The laboratory and clinical data of 41 patients with treatment-related AML (t-AML) in the Department of Hematology, Henan Cancer Hospital from January 2014 to December 2021 were retrospectively analyzed, and they were divided into hematological tumor group and solid tumor group. Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: The median interval from the first tumor diagnosis to t-AML in 41 patients was 21.0 (16.5-46.0) months; 24 (58.5%) had abnormal expression of lymphoid antigen, 28 (68.3%) had abnormal karyotype, 18 cases (43.9%) were positive for fusion gene, and 28 cases (68.3%) were positive for gene mutation; the median recurrence-free survival (RFS) was 11.0 months, and the median overall survival (OS) was 11.5 months. The proportion of acute promyelocytic leukemia ([APL], 0.0, 0/13), complete response ([CR],18.2%, 2/11), median OS (4.5 months) and median RFS (2.5 months) of t-AML patients in the hematological tumor group were significantly lower than those in the solid tumor group (35.7%, 10/28; 68.0%, 17/25; not reach; not reach), but the proportion of M4 /M5 (93.2%,12/13) was significantly higher than that in the solid tumor group (53.6%,15/18; all P values<0.05). Through subgroup analysis, the proportion of patients with positive PML-RARa and good prognosis karyotypes in the solid tumor group (35.7%, 10/28; 46.4%, 13/28) was significantly higher than that in the hematological tumor group (0.0, 0/13; 0.0, 0/13; P<0.05), while the proportion of patients with intermediate karyotypes (42.9%, 12/28) was significantly lower than that in the hematological tumor group (84.6%, 11/13; P<0.05), the difference was statistically significant. The CR rate (90.0%, 9/10), median OS (not reach) and median RFS (not reach) in the t-APL group were higher than those in the t-AML (without t-APL) group (38.5%, 10/26; 6 months; 8 months; P<0.05). After excluding the effect of t-APL patients, there was no significant difference in the CR rate, median OS and median RFS between the solid tumor group (8; 9 months; not reach) and the hematological tumor group (2; 4 months; 2 months; P>0.05). Univariate analysis showed that the primary tumor belongs to hematological tumor was a common risk factor for OS and RFS in t-AML patients (P<0.10). Conclusions: Compared with patients with t-AML secondary to solid tumors, patients with t-AML secondary to hematological tumors have poorer treatment effects and poorer prognosis. After excluding the effect of t-APL patients, there are no significant differences in the treatment efficacy and prognosis between the two types of t-AML patients.

[Clinical analysis of 12 cases of acute myeloid leukemia complicated with synchronous primary solid tumor].

Objective: To explore the clinical characteristics of acute myeloid leukemia (AML) complicated with simultaneous multiple primary cancer (SMPC). Methods: The data of 12 AML patients with SMPC hospitalized in the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital of Nanyang Medical College, the Xinhua District Hospital of Pingdingshan City and the First People's Hospital of Pingdingshan City from March 2014 to July 2019 were analyzed retrospectively, and their clinical features, treatment and prognosis were summarized. Results: Among the 12 patients, there were 6 males and 6 females, with a median age of 58 years (39-70 years). AML classification: according to French-American-British (FAB) classification, the 12 AML patients were classified as M0 1, M1 1, M2a 5, M2b 1, M3 2, M5 2; according to National Comprehensive Cancer Network (NCCN) prognosis stratified, low risk group 1 case, medium risk group 4 cases, high risk group 7 cases; classification of solid tumors: 3 cases of lung cancer, 1 case of breast cancer, 2 cases of gastric cancer, 3 cases of esophageal cancer, 1 case of rectal neuroendocrine tumor, 1 case of invasive hydatidiform mole and 1 case of sigmoid colon cancer. The median time interval for the diagnosis of two primary malignant tumors was 4 (from 2.6 to 5.6) months. Results of gene mutation detection: AML prognostic gene detection results: a total of 12 kinds of gene abnormalities including ASXL1, JAK2, TET2, U2AF1, ABCB1, FLT3-ITD, RUNX1, SETBPIT, TET2 (single nucleotide polymorphism, SNP), p53, IKZF1 and IDH2 were detected, and solid tumor related genes were detected: a total of 4 kinds of gene abnormalities including Her-2, EGFR, K-RAS and MSI were detected. Survival: among the 12 patients, 1 case was lost during follow-up, 2 cases were still in treatment, 3 cases ended treatment and the condition was stable, 6 cases died. The median overall survival of 12 patients was 12.5 (from 3.8 to 48.0) months. Conclusions: It is not clear whether there is a certain correlation between the simultaneous occurrence of AML and solid tumors. Patients with AML and synchronous solid tumors are not unusual. Both tumors should be treated aggressively at the same time.

[The safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with inermediate or higer-risk myelodysplastic syndrome].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine combined with arsenic trioxide in patients with intermediate or high-risk myelodysplastic syndrome (MDS). Three of the total 11 MDS patients achieved complete remission (CR) and 6 achieved hematological improvement (HI), 1 stable disease (SD), and 1 progressive disease (PD). One patient was treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median follow-up time was 413(90-1 275) d. Nine patients were still alive. Low dose subcutaneous decitabine combined with arsenic trioxide can be an alternative regimen for intermediate or high-risk MDS patients.

[Efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio in patients with diffuse large B-cell lymphoma].

Objective: To investigate the efficacy and prognosis of the dynamic monitoring lymphocyte to monocyte ratio (LMR) in patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of 261 patients with DLBCL in the Affiliated Cancer Hospital of Zhengzhou University between March 2012 to March 2018, were analyzed retrospectively. The optimal cut-off values of LMR was determined using the receiver operating characteristic curve (ROC) method. Patients were divided into low LMR group and high LMR group according to the optimal cut-off value. The changes of LMR before and after treatment in two groups were dynamically monitored, and the relationship between LMR and efficacy and survival were analyzed. Results: Complete remission (CR) rate in patients with high LMR (64.7%) before treatment was significantly higher than that in patients with low LMR (33.3%) (P<0.05). Compared with the 5-year overall survival(OS) and progress free survival(PFS) (56.96% and 43.55%, respectively) in the low LMR group, the 5-year OS and PFS (82.92% and 66.25%, respectively) in the high LMR group were higher, and the difference was statistically significant (all P<0.05). Patients with elevated LMR after treatment in the high or low LMR group had a significant higher 5-year OS and PFS compared with patients with LMR reduction(P<0.05). LMR in both high and low LMR group were significantly lower at the last follow-up than those at the disease recurrence (all P<0.05). Both single and multivariate analyses showed that low LMR was an independent prognostic factor in patients with DLBCL (all P<0.05). Conclusions: LMR can be used as an indicator of risk stratification, efficacy, disease replase and prognosis in patients with DLBCL. Low LMR before and after treatment were poor prognostic factors in patients with DLBCL.

[Long-term clinical outcome of children and adolescents with Burkitt's lymphoma treated with rituximab combined with modified NHL-BFM-90 regimen].

Objective: To evaluate the efficacy and safety of rituximab combined with the modified NHL-BFM-90 protocol in childhood and adolescence with Burkitt's lymphoma (BL). Methods: A retrospective analysis of 67 untreated childhood and adolescence patients with BL was made. All patients were treated with the modified NHL-BFM-90 protocol with or without rituximab. Results: The 64 patients (95.52%) achieved complete remission (CR), 3 patients (4.48%) partial remission (PR), and the overall response rate (CR+PR) was 100%. 67 patients were followed up for a median of 44 (3-89) months. The 3 and 5-year overall survival (OS) were 92.54% and 88.98%, respectively. The 3 and 5-year progression-free survival (PFS) were all 90.34%. The 5-year OS were 100%,91.7% and 80.0% in low risk, moderate risk and high risk group, respectively, and the difference was statistically significant (P=0.048). Of the 67 patients, 55 patients (82.09%) were treated with rituximab plus chemotherapy. Compared with the 5-year OS and PFS of 74.3% and 78.6% in the chemotherapy group, the 5-year OS and PFS in the rituximab plus chemotherapy group were 95.2% and 95.5%, respectively, and the difference was statistically significant (P value was 0.021, and 0.036, respectively). Major toxicity was myelosuppression and mucositis. No treatment related death was found. Conclusions: Rituximab combined with the modified NHL-BFM-90 protocol was highly effective for children and adolescents with BL, and significantly improved long-term survival.

[The clinical safety and efficacy of low dose subcutaneous decitabine in treating acute myeloid leukemia and intermediate- or higer-risk myelodysplastic syndromes in the elderly patients].

To retrospectively analyze the safety and efficacy of low dose subcutaneous decitabine regimen in patients with acute myeloid leukemia (AML) and intermediate- or higer-risk myelodysplastic syndrome (MDS). Of 6 AML cases, 2 achieved complete remission (CR), 2 with partial remission(PR), 1 with stable disease(SD), 1 with progressive disease(PD). As to the 8 MDS patients, one achieved CR and 6 with hematologic improvement (HI), 1 case SD. Low dose subcutaneous decitabine regimen could be an alternative choice of older AML or MDS patients.

[Clinical characteristics and analysis of patients with hematological diseases and HCV-Ab positive].

Objective: To observe the biological characteristics of patients with hematological diseases and hepatitis C antibodies positive and to investigate features of HCV infection and reactivation. Methods: A total of 85 patients with seropositive HCV at the hematology ward in Henan Cancer Hospital between October 2010 and October 2015 were analyzed. The clinical characteristics and laboratory data were retrospectively reviewed. Original disease treatment information was obtained from the medical records. Results: The positive rate of HCV-Ab was 1.2%, which was significantly higher than that of the general population(1.2% vs 0.4%, P<0.001). Of the 25 patients who showed anti-HCV seroconversion during the period of treatment or follow-up, serum ALT level was elevated in 15 patients(60.0%)and AST level got synchronous increase in 14 patients (56.0%). Of the 85 patients with positive HCV-Ab, 13 (15.3%) patients suffered from HCV reactivation with hepatic injury in varying degrees after chemotherapy or HSCT. Conclusions: Patients with hematological diseases have high incidence of HCV infection and reactivation, and most of them have hepatic injury. Chemotherapy and HSCT are important risk factors for HCV reactivation.

[Thalidomide combined with interferon and interleukin-2 in treatment of relapsed or refractory acute myelogenous leukemia].

In 12 patients with relapsed or refractory acute myelogenous leukemia (AML), the efficacy and safety of a novel regimen, namely thalidomide combined with interferon and interleukin 2 (IL-2), were initially explored.All the patients have received the triple-drug regimen for at least one cycle.Three patients achieved incomplete remission (CRi), 3 patients with partial remission.The overall response rate (ORR) was 50%.

[Therapeutic effect of combined use of interferon alpha-1b, interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia].

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.

[Comparison of clinical efficacy between first-generation and second-generation tyrosine kinase inhibitors based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia].

Objective: To explore the clinical efficacy and prognostic factors of first-generation and second-generation tyrosine kinase inhibitors (TKI) based regimen in the treatment of patients with BCR-ABL positive acute lymphoblastic leukemia (ALL) . Methods: Retrospectively analyze the clinical characteristics and prognostic factors of 89 patients with BCR-ABL positive ALL from April 2012 to June 2018 in our hospital, the clinical efficacy of first-generation and second-generation TKI was compared. Results: 60 patients were classified into the first-generation TKI (imatinib) group, and 29 patients were in the second-generation TKI (dasatinib) group. There were no significant differences in gender, age, WBC, hemoglobin concentration, PLT, chromosomal karyotype, the types of fusion genes, allogeneic hematopoietic stem cell transplantation (allo-HSCT) and TKI initiation time between the two groups. The first-generation and second-generation TKI groups, for which the complete remission (CR) rate at the fourth week of induction therapy was 83.3% and 89.7% (P=0.637) , respectively, and the complete molecular remission (CMR) was 48.3%and 58.6% (P=0.363) , respectively, the difference was not statistically significant. The 2-year overall survival (OS) rate of first-generation and second-generation TKI group was 34.9% and 64.0% (χ(2)=4.743, P=0.029) , the 2-year relapse free survival (RFS) rate was 17.2% and 55.0% (χ(2)=8.801, P=0.003) , respectively. Multivariate analysis showed that complete molecular remission (HR=0.281, 95%CI 0.151-0.523, P<0.001) was independent favorable prognostic factor for overall survival (OS) , complete molecular remission (HR=0.209, 95%CI 0.112-0.390, P<0.001) and second-generation TKI (HR=0.318, 95%CI 0.158-0.641, P=0.001) were independent favorable prognostic factors for RFS. Conclusion: For TKI-based regimen of BCR-ABL positive ALL, second-generation TKI is superior to first-generation TKI in OS and RFS time.

[Clinical analysis of autologous hematopoietic stem cell transplantation in the treatment of advanced/recurrent nasal type extranodal NK/T-cell lymphoma].

Objective: To analyze the efficacy and safety of asparaginase based chemotherapy bridging autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of 16 patients with nasal type extranodal NK/T-cell lymphoma (ENKTL). Methods: From January 2012 to June 2017, 16 patients with nasal type extranodal NK/T-cell lymphoma reached complete remission by L-asparaginase based regimens, and then received auto-HSCT. Results: ①Of the 16 patients, 12 were males and 4 females, with a median age of 35.5 (14-61) years. There were 11 patients in the first complete remission (CR1) and 5 in the second CR (CR2) before transplantation, respectively. EB virus (EBV) DNA (EBV-DNA) was negative and positive in 13 and 3 cases respectively before transplantation. ②Hematopoietic reconstitution was achieved in all 16 cases. The median time for neutrophils implantation was 12 (8-17) days, and that of platelet implantation was 15.5 (12-24) days. ③To the last follow-up, there were no transplant related deaths, 3 patients died of disease progression. The median overall survival (OS) time and progression-free survival time (PFS) were not reached. Seven patients lived with no disease progression more than 2 years. ④The OS and PFS of patients at CR(1) before auto-HSCT are better than that of patients at CR(2), but there was no statistically significant difference (P=0.162, P=0.123). There was no significant difference in OS and PFS between EBV-DNA negative and positive patients before transplantation (P=0.280, P=0.244). Conclusions: L-asparaginase based regimens bridging auto-HSCT is a safe and highly effective for advanced-stage and relapsed ENKTL treatment.

[The expression of CRLF2 in adult Ph negative acute B lymphocytic leukemia and its prognostic significance].

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.

[Synchronous lymphoma and carcinoma-clinical analyses of 17 patients].

Objective: To explore the clinical features of patients with synchronous lymphoma and carcinoma. Methods: The clinical data of 17 patients with Synchronous lymphoma and carcinoma from February 2012 to October 2017 were analyzed retrospectively. Results: Among 17 patients of lymphoma, 1 case HL, 2 cases B-NHL, 6 cases MZBL, 3 cases DLBCL, 1 case mantle cell lymphoma (MCL) , 3 cases NK/T- cell lymphoma, 1 case anaplastic large cell lymphoma(ALCL). In terms of 17 patients with carcinoma, 3 cases esophageal carcinoma, 3 cases gastric carcinoma, 2 cases colorectal carcinoma, 7 cases thyroid carcinoma, 1 case hepatocellular carcinoma and lung cancer. Up to 15 patients received operation, and some of them combined with chemotherapy, radiotherapy and autologous transplant. Follow-up analysis showed that 3 cases was undergoing treatment, 2 cases lost follow-up, 4 cases died, 3 cases achieved CR, 3 cases remained to be at SD, and 2 cases assessed for progression or recurrence. Conclusion: The relationship between lymphoma and carcinoma was under discussion, patients with synchronous lymphoma and carcinoma were not unusual. We herein should raise awareness to avoid misdiagnosis.

[Sorafenib in combination with chemotherapy as first-line therapy for FLT3-ITD positive acute myeloid leukemia].

Objective: To analyze the clinical features of acute myeloid leukemia patients with Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation and the therapeutic effect of sorafenib in combination with chemotherapy as first-line therapy for these patients. Methods: Clinical features and therapeutic effect were retrospectively analyzed in 53 AML patients with FLT3-ITD mutation diagnosed in Henan Cancer Hospital from January 2013 to August 2016. The biological characteristics and clinical efficacy of chemotherapy in combination with or without Sorafeinb were analyzed. Results: FLT3-ITD mutation was identified in 53 AML patients, 22 cases (41.5%) were M(5) subtype. The median of the peripheral WBC was 61.00 (0.98-920.00) ×10(9)/L, and there were 50 (94.3%) patients with WBC>10×10(9)/L. The median of blast cell in bone marrow was 0.730 (0.234-0.966) . The total remission rate of all these 53 patients was 56.6% (30/53) . The complete remission (CR) rates in patients treated with chemotherapy in combination with sorafenib and patients with chemotherapy alone were 86.4% (19/22) and 35.5% (11/31) , respectively. The 1-year overall survival rates of the two groups were 78.3%% and 50.0% (P=0.041) , and 1-year progression free survival rates were 75.9% and 42.4% (P=0.044) , respectively. Conclusion: AML patients with FLT3-ITD mutation have the characteristics of high peripheral WBC, high blast cells in bone marrow and accompanying with M(5) subtype. Sorafeinb combined with chemotherapy can significantly improve CR rate and short term survival.

[A clinical study of fungal esophagitis in 13 patients with hematologic malignancies].

OBJECTIVE: To improve the clinical understanding of fungal esophagitis in patients with hematologic malignancies. METHOD: The clinical data of a cohort of 279 patients with hematologic malignancies who underwent gastroscopy between 2012 and 2015 in the Endoscopy Center of Henan Tumor Hospital were retrospectively analyzed. To investigate the clinical characteristics and prognosis of fungal esophagitis in patients with heratologic malignancies. RESULTS: 13 of the 279 patients were diagnosed as fungal esophagitis (4.66% ). C. albicans was prevalent (12/13), and only 1 case was cryptococcus. All of the 13 patients had lymphatic systemic diseases (8 cases with diffuse large B cell lymphoma, 1 with peripheral T-cell lymphoma, 2 with acute lymphoblastic leukemia, and 1 with multiple myeloma). 6 patients had gastrointestinal symptoms (3 cases with nausea and anorexia as well as the sentation of having a foreign body in pharyngeal, 2 cases with pain or a burning sensation behind the sternum, and 1 case having difficulty or pain when swallowing), while 7 patients had no obvious manifestations. 6 patients accepted fluconazole 400 mg/d for 2 weeks and achieved satisfactory results; Meanwhile 7 cases were given nystatin 1 million uint 3 times a day for 2 weeks, of which 6 cases responded well, and 1 case was not relieved until he was given fluconazole 400 mg/d for 1 week. Treatmentassociated adverse events included mildly elevated aminotransferase (1 case) and mild gastrointestinal adverse reaction (1 case). CONCLUSION: The fungal esophagitis in patients with hematologic malignancies was not rare. Most of those patients had lymphatic systemic diseases and the main pathogen was candida albicans. The clinical manifestations of fungal esophagitis were quite atypical and about more than half of those patients had no gastrointestinal symptoms. Either fluconazole or nystatin was safe and effective treatment with slight adverse reactions.