OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.
Adult ; Adolescent ; Humans ; Prognosis ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Hematopoietic Stem Cell Transplantation ; Lymphoma, T-Cell ; Unrelated Donors

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

OBJECTIVE: To investigate the efficacy of chemotherapy combined with antivirals in adult T-cell leukemia/lymphoma (ATLL) patients and the prognostic factors. METHODS: Forty nine patients with previously treated or treatment-nave ATLL from January 2018 to January 2021 were included in our study. The patients were divied into two groups according to whether they received antiviral treatment, twenty-seven patients were treated with chemotherapy combined with antivirals, including thirteen patients treated with recombinant interferon alpha-2b and CHOP therapy, eight patients treated with zidovudine combined with CHOP therapy, and 6 patients treated with CHOP regimen combined with interferon and zidovudine. Twenty-two patients were treated with CHOP therapy. The changes of symptom, hematological parameters, lactic dehydrogenase, β2-microglobulin, and the Ki-67 positive rate were compared between the two groups before and after treatments. The clinical efficacy of chemotherapy combined with antiviral therapy for ATLL was evaluated. The antiviral effect was assessed by detecting HTLV-1 virus copy number, and prognostic factors were analyzed. RESULTS: The median follow-up time was 14 months. Compared with the patients treated with chemotherapy alone, the patients treated with chemotherapy combined with antivirals had lower tumor and virus loads, lower white blood cell count, lower lactate dehydrogenase level, lower β2-microglobulin lever, and lower Ki-67 positive rate (all P<0.05). The total effective rate of patients treated with chemotherapy combined with antivirals was significantly higher than those of patients treated with chemotherapy alone (63.0% vs 31.8%, P=0.035). The one-year overall survival (OS) rates of chemotherapy combined with antivirals groups and chemotherapy alone group were (74.1±2.9)％ and (40.9±2.1)％ (P=0.021), respectively. The one-year progress free survival (PFS) rates were (51.9±3.3)％ and (13.6±2.8)％ (P=0.017), respectively. Multivariable Cox regression analysis showed that HTLV-1 virus load (HR=7.518, 95%CI: 2.517-36.192, P=0.013) and antiviral therapy ［HR=5.617 (95%CI 1.803-11.293), P=0.027］ were independent prognostic factors for the long-term efficacy. CONCLUSION Addition of antivirals to chemotherapy can prolong PFS and OS in ATLL patients. HTLV-1 virus load and antiviral therapy are independent prognostic factors for ATLL patients.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cyclophosphamide ; Doxorubicin ; Humans ; Interferon alpha-2/therapeutic use* ; Ki-67 Antigen ; Lactate Dehydrogenases ; Leukemia-Lymphoma, Adult T-Cell/drug therapy* ; Lymphoma/drug therapy* ; Oxidoreductases/therapeutic use* ; Vincristine/therapeutic use* ; Zidovudine/therapeutic use*

Adult ; Antigens, CD19 ; Cell- and Tissue-Based Therapy ; China ; Consensus ; Humans ; Immunotherapy, Adoptive ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen

B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar to those with childhood B-ALL, the rate of long-term disease-free survival (DFS) rate is significantly lower, once recurrence, the remission rate of routine chemotherapy is low and the prognosis is so poor. Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.
Adult ; Antigens, CD19 ; Antigens, Surface ; B-Lymphocytes ; Burkitt Lymphoma ; Child ; Humans ; Immunotherapy, Adoptive ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Antigen, T-Cell

Objective: To investigate the efficacy and predictors of autologous hematopoietic stem cell transplantation (auto-HSCT) in the treatment of T lymphoblastic lymphoma (T-LBL) . Methods: 41 patients with T-LBL who underwent auto-HSCT from April 2006 to July 2017 in the Department of Hematology, the First Affiliated Hospital of Soochow University and the Department of Lymphoma, Peking University Cancer Hospital were analyzed retrospectively. Results: ①Among 41 patients, there were 30 males and 11 females with median age of 24 (11-53) years old. According to the Ann Arbor staging, 33 (80.5%) patients were in stage Ⅲ/Ⅳ. 12 (29.3%) patients have mediastinal involvement, and 20 (48.8%) patients have bone marrow (BM) involvement. Before transplantation, there were 26 (63.4%) patients who achieved first complete remission (CR(1)) , the other 15 (36.6%) patients were in the non-CR(1) group, and there were 29 (70.7%) patients in the low-intermediate risk group (IPI<3 scores) , the other 12 (34.1%) patients were in the middle-high risk group (IPI≥3 scores) . ②The median follow-up was 29 (3-98) months. The 3-year overall survival (OS) and progression-free survival (PFS) for 41 patients were (64.3±8.2) % and (66.0±7.8) %, respectively. 3-year cumulative recurrence rate (CIR) was (30.7±7.4) %, and 3-year non-recurring mortality (NRM) was (4.8±4.6) %. ③The 3-year OS of the CR(1) group and the non-CR(1) group were (83.4±7.6) % and (38.9±12.9) % (P=0.010) , and the 3-year PFS of two groups were (83.8±7.4) % and (40.0±12.6) % (P=0.006) , respectively. The 3-year CIR of these two groups were (16.2±7.4) % and (53.3±12.9) % (P=0.015) , and the 3-year NRM were 0 and (14.3±13.2) % (P=0.157) , respectively. ④The 3-year OS of the IPI low-intermediate risk group and the high-intermediate risk group were (76.9±8.4) % and (35.7±15.2) % (P=0.014) and the 3-year PFS were (77.4±8.2) % and (40.0±14.6) (P=0.011) , respectively. The 3-year CIR of these two groups were (18.1±7.3) % and (60.0±14.6) % (P=0.006) , and the 3-year NRM were (5.6±5.4) % and 0 (P=0.683) , respectively. The OS and PFS of patients with low-intermediate risk group were significantly higher than the other group. Conclusion: Auto-HSCT could improve the survival of T-LBL. Pre-transplant status and IPI score are important predictors for survival T-LBL patients with auto-HSCT.
Adolescent ; Adult ; Child ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis ; Retrospective Studies ; T-Lymphocytes ; Transplantation, Autologous ; Treatment Outcome ; Young Adult

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.
Adolescent ; Adult ; Antigens, CD19 ; Child ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Retrospective Studies ; T-Lymphocytes ; Transplantation Conditioning ; Young Adult

To analyze the treatment and prognosis of T cell acute lymphoblastic leukemia(T-ALL)in adults. Method The clinicobiogical and survival data of 68 adult patients with newly diagnosis T-ALL were retrospectively analzyed. Results The median age of these 68 patients was 23 years(14-60 years).T-ALL was more common in men(81%).After the first cycle of treatment,complete remission was achieved in 50 patients(73%).The highest complete remission(CR) rate was in patients with cortex T-ALL(100%),followed by other T-ALL(73%)and early T-cell precursor lymphoblastic leukemia(54%),(=5.712,=0.058).The CR rate for adults aged >35 years was significantly lower than that of patients aged ≤ 35 years(40% 79%,=6.364,=0.012).The overall CR rate after the second treatment course was 93%.For patients treated with chemotherapy,autograft hematopoietic stem cell transplantation(auto-SCT),and allogeneic SCT,the median relapse free survival was 10 months,24 months,and not reached,respectively(=0.002).The 5-year overall survival rate was 25% for all patients;for patients treated with chemotherapy,auto-SCT and allogeneic SCT,the median overall survival was 24 months,34 months,and 30 months,respectively(=0.007),and the 5-year overall survival rate was 9%,33%,and 38%(=0.037).Multivariate analysis showed leukocyte count ≥100×10 /L was a risk factor for decreased relapse free survival(risk ratio 2.540,95%=1.058-6.099,=0.037). Conclusion Adult T-ALL patients have poor prognosis,which may be improved by SCT.
Adolescent ; Adult ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; therapy ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; therapy ; Prognosis ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Young Adult

Chimeric antigen receptor (CAR) T cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8 T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.
Adult ; Antigens, CD19 ; metabolism ; Bone Marrow ; metabolism ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Gene Expression Regulation, Leukemic ; Gene Regulatory Networks ; Humans ; Immunotherapy, Adoptive ; Male ; MicroRNAs ; genetics ; metabolism ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; immunology ; therapy ; RNA, Long Noncoding ; genetics ; metabolism ; Receptors, Antigen, T-Cell ; Transcription Factors ; metabolism ; Transcriptome ; genetics