[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

[Efficacy analysis of Venetoclax combined with TKI and dexamethasone-containing low-dose chemotherapy for relapsed/refractory Ph+acute B-lymphoblastic leukemia].

The clinical data of five cases of relapsed/refractory (R/R) Philadelphia chromosome-positive acute B-lymphocytic leukaemia (Ph+B-ALL) treated with Bcl-2 inhibitor venetoclax combined with tyrosine kinase inhibitor (TKI) and dexamethasone-containing low-dose chemotherapy regimen at Zhengzhou University Cancer Hospital were analyzed, and the efficacy and safety were evaluated. Ponatinib was used in two of the five patients with T315I mutation, and flumatinib was used in other three patients. The results showed that, of the four minimal residual disease (MRD) positive patients, three achieved complete molecular remission (CMR) in the short term and one was ineffective. Another patient with morphological recurrence reached CR in one month. The overall response rate was 80%. Treatment related adverse reactions included mild skin pigmentation, gastrointestinal reactions, fatigue, and grade Ⅰ-Ⅱ bone marrow suppression.

[Targeted immunotherapy efficacy analysis in patients with relapsed/refractory B cell acute lymphocytic leukemia].

Objective: Comparison of conventional chemotherapy and immunotargeted therapy efficacy in patients with relapsed/refractory (R/R) acute B cell leukemia (B-ALL) . Methods: The clinical data of 212 patients with R/R B-ALL in the Affiliaed Cancer Hospital of Zhengzhou University from January 2008 to July 2020 were analyzed retrospectively to compare the response rate and survival time difference between conventional chemotherapy and immunotargeted therapies (antiCD19 CAR-T and CD3CD19 bi-specific antibody blinatumomab) , and to explore the related factors affecting prognosis. Results: The CR rate of patients with R/R B-ALL treated with anti-CD19 CAR-T cells was 80.4% , patients treated with blinatumomab was 62.5% , and patients treated with chemotherapy was 38.6% . There was significant difference in the CR rate among the three therapies (P<0.001) . CAR-T cells 1-year OS rate was 41.5% , which was significantly higher than that of the chemotherapy group (10.3% ) (P<0.001) . The 1-year PFS rate of CAR-T cells (30.1% ) was also significantly higher than that of the chemotherapy group (9.7% ) (P<0.001) . The median OS of patients with bridging allo-HSCT after CR treatment by CAR-T cells was 18.5 months, which was higher than that of patients without allo-HSCT (8 months) (P=0.027) . The median PFS of patients with allo-HSCT was 17 months, which was higher than that of patients without allo-HSCT (4 months) (P=0.001) . The 1-year OS rate of patients treated with blinatumomab was 14.3% , which was higher than that of the chemotherapy group (10.3% ) (P=0.018) . The 1-year PFS rate (14.6% ) was also higher than that of the chemotherapy group (9.7% ) (P=0.046) . The median OS and median PFS of patients with bridging allo-HSCT were 13 and 11 months, respectively, which was higher than that of patients without allo-HSCT (9.5 and 6 months) . The cytokine release syndrome (CRS) incidence in patients with R/R B-ALL treated with anti-CAR-T cells was 89.8% . Grades 3-4, grade 2, and grade 1 CRS were experienced by 30.2% , 11.3% and 58.5% patients, respectively. Only three patients (37.5% ) with blinatumomab developed CRS, all of which were grade 1. Conclusion: The response rate and survival rate of patients with R/R B-ALL treated with CD19 CAR-T cells and blinatumomab were significantly better than those treated with conventional chemotherapy.

[Safety and efficacy of patients with refractory B-lymphoblastic leukemia treated with anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation].

Objective: To investigate the efficacy and side effects of anti-CD19 CAR-T cell bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) regimen for refractory B-lymphoblastic leukemia. Methods: 10 patients with refractory B-lymphoblastic leukemia with minimal residual disease (MRD) negative after anti-CD19 CAR-T cell treatment, then bridging to allo-HSCT from November 2017 to March 2019 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Results: ①Among 10 patients, 5 were males and 5 females, with a median age of 23.6 (10-31) years. 9 patients were diagnosed refractory acute lymphoblastic leukemia and the other one was chronic lymphoblastic leukemia. 10 patients reached MRD negative 30 days after anti-CD19 CAR-T cell. ②The donors were identical sibling (2 cases) and haploidentical family member (8 cases) . The median time from MRD negative after CAR-T treatment to transplantation were 32.5 (20-60) days. ③10 patients obtained complete haploidentical engraftment. The median time of neutrophil implantation was 15 (15-21) days, and 19 (17-30) days of platelet implantation. ④ After conditioning, no hepatic venoocclusive disease and hemorrhagic cystitis occurred. One patient had leakage syndrome and got improved after intervention such as limited water entry, albumin supplementation and diuresis. 8 (80%) patients had fever, 2 cases experienced acute graft-versus-host disease (GVHD) grade Ⅱ, 1 case with aGVHD grade Ⅲ. Among 9 survivals, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 262 (150-540) days and the estimated 1-years overall survivaln (OS) and disease free survival (DFS) were (90.0±1.0) % and (85.7±1.3) %, respectively. Conclusion: Anti-CD19 CAR-T cell bridging to allo-HSCT regimen is a feasible choice with favorable outcome for refractory B-lymphoblastic leukemia.

[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.

[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.

[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.

[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].

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.

[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.

[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 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.

[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.