Objective: To summarize the therapeutic effects of Chinese Children Leukemia Group-acute lymphoblastic leukemia (CCLG-ALL) 2018 regimen in children with T cell acute lymphoblastic leukemia (T-ALL) and to find out risk indicators for prognosis. Methods: This study was a prospective multicenter cohort study involving 299 newly diagnosed T-ALL children in 21 Grade A tertiary hospitals nationwide. All patients received CCLG-ALL 2018 regimen and clinical data for treatment efficacy evaluating was collected. Variables associated with event free survival (EFS) rate, overall survival (OS) rate and cumulative recurrence rate were evaluated by Lasso regression analysis (including variables selection, model construction and hazard ratio calculating). Results: A total of 299 newly diagnosed T-ALL children were included, accounting for 9.9% (299/3 026) of all ALL patients. Among these patients, there were 224 males and 75 females, and the age of onset was 7.0 (4.7, 10.6) years. All patients received CCLG-ALL 2018 regimen treatment. After 31.1 (17.3, 43.8) months follow-up, 3-year EFS, 3-year OS and cumulative recurrence rate of them were (83.2±2.7)%, (91.3±1.8)%, and (7.9±1.7)%, respectively. Minimal residual disease (MRD) greater than 10.00% on day 15 of induction therapy was a risk factor for EFS (HR=1.89, 95%CI 1.04-3.44), OS (HR=2.82, 95%CI 1.35-5.92), and cumulative recurrence rate (HR=3.05, 95%CI 1.46-6.34). Compared with the medium-risk group, the high-risk group had higher induction failure rate (5.2% (7/134) vs. 0 (0/145), P=0.016) and lower complete remission rate (88.8% (119/134) vs.97.9% (142/145),P=0.004). Most complications happened during induction therapy (95 cases), and the most common complication was serious infection (158 cases). Conclusions: CCLG-ALL 2018 regimen shows good prognosis. MRD greater than 10.00% on day 15 of induction therapy is a strong risk factor, which can indicate the prognosis in the early stage of the disease and guide the appropriate treatment.
Male ; Female ; Humans ; Child ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Disease-Free Survival ; Prospective Studies ; Cohort Studies ; East Asian People ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Treatment Outcome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Neoplasm, Residual

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*

The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
Antigens, CD19/therapeutic use* ; Antineoplastic Agents/pharmacology* ; Humans ; Immunotherapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; T-Lymphocytes

BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.
B-Lymphocytes ; Chungcheongnam-do ; Cranial Irradiation ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Female ; Humans ; Male ; Medical Records ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, T-Lymphoid ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; T-Lymphocytes*

Tumor lysis syndrome is a serious complication of malignancy, resulting from the massive and rapid release of cellular components into the blood. Generally, it occurs after initiation of chemotherapy. The onset of spontaneous tumor lysis syndrome (STLS) before anti-cancer treatment is rare and occurs mostly in Burkitt lymphoma and non-Hodgkin's lymphoma. There are only a few case reports in children. Here, we report a case of STLS secondary to T-cell acute lymphoblastic leukemia (ALL), which presented with urinary stone and subsequent acute kidney injury with severe hyperuricemia. Occult malignancy should be considered in case of unexplained acute kidney injury with extreme hyperuricemia.
Acute Kidney Injury* ; Burkitt Lymphoma ; Child ; Drug Therapy ; Humans ; Hyperuricemia* ; Lymphoma, Non-Hodgkin ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; T-Lymphocytes ; Tumor Lysis Syndrome* ; Urinary Calculi*

OBJECTIVETo explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients.

METHODSA total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups.

RESULTSIn group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control.

CONCLUSIONWith higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Asparaginase ; therapeutic use ; Humans ; Lymphoma, T-Cell ; drug therapy ; Polyethylene Glycols ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Survival Rate

BACKGROUND: Among pediatric non-Hodgkin lymphomas, there are 4 major subtypes: Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma. Understanding of other rare subtypes derives only from small pediatric case series. We report our institutional experience with rare pediatric NHLs.METHODS: Thirty-six cases of rare NHL subtypes diagnosed at the Asan Medical Center from 1995 to 2015 were evaluated. We retrospectively reviewed the clinical and pathologic features and outcomes of these patients, excluding peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), and extranodal NK/T-cell lymphoma (ENKL), on which we have previously reported.RESULTS: There were 23 cases of T-cell lineage (13 PTCL, 6 ENKL, 2 subcutaneous panniculitis-like T-cell lymphoma, 1 primary cutaneous CD4+2016-11-22 small/medium sized T-cell lymphoma, 1 enteropathy-associated T-cell lymphoma) and 13 cases of B-cell lineage lymphoma (5 marginal zone lymphoma, 6 primary mediastinal large B-cell lymphoma, 2 immunoblastic and plasmablastic lymphoma). All patients were treated with chemotherapy with or without surgery, except 4 out of 5 patients with marginal zone lymphoma who received surgery only. Two patients died and 6 patients relapsed. One patient with primary mediastinal large B-cell lymphoma received autologous peripheral blood stem cell transplantation. The 5-year overall survival and event-free survival rates of rare pediatric NHL excluding PTCL, NOS, and ENKL was 80.0% and 72.0%, respectively.CONCLUSION: Children diagnosed with rare pediatric NHL other than PTCL, NOS, and ENKL showed variable incidence and treatment outcomes. Multicenter studies in larger cohorts are needed for better understanding of these rare NHL subtypes in childhood.
B-Lymphocytes ; Burkitt Lymphoma ; Child ; Chungcheongnam-do ; Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Humans ; Incidence ; Lymphoma ; Lymphoma, B-Cell ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell ; Lymphoma, T-Cell, Peripheral ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; T-Lymphocytes

T-lymphoblastic lymphoma (T-LBL) is a rare form of aggressive non-Hodgkin's lymphoma. The standard approach for management of T-LBL involves intensive multiagent chemotherapy regimens for induction and consolidation phases with central nervous system prophylaxis and a maintenance phase lasting 12-18 months. We report on a case of long-term survival after one cycle of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) and high-dose methotrexate. A 30-year-old woman diagnosed with T-LBL with a large mediastinal mass underwent one cycle of hyper-CVAD. Four days after the start of treatment, the mediastinal mass was markedly reduced. Treatment continued with one cycle of consolidation chemotherapy, comprising high-dose methotrexate and high-dose cytarabine. The patient then refused all further chemotherapeutic treatment. Seven years have passed without relapse.
Adult ; Central Nervous System ; Consolidation Chemotherapy ; Cyclophosphamide ; Cytarabine ; Dexamethasone ; Doxorubicin ; Drug Therapy ; Female ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin ; Methotrexate ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; Remission Induction ; T-Lymphocytes* ; Vincristine

A seven months old male infant visited Severance Children's Hospital for evaluation of anterior mediastinal mass. With chest computed tomography (CT) image and biopsy, precursor T-cell lymphoblastic lymphoma was suspected but the ultrasonography guided biopsy specimen was insufficient to confirm the disease. Because there was a life-threatening risk to perform open biopsy to the small infant, we started chemotherapy empirically. The mass decreased, however, the lesion increased again and did not respond to the drugs. Finally we decided to resect the anterior mass with sternostomy and the pathology report finally resulted in thymoma.
Biopsy ; Drug Therapy ; Humans ; Infant ; Male ; Pathology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Thorax ; Thymoma ; Ultrasonography

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon subtype of Non-Hodgkin lymphoma (NHL), accounting for only 0.3% of NHL in adults and less than 10% of all LBL cases. Unlike T-cell LBL, it usually presents with extranodal involvement while sparing the bone marrow (BM). Among the 27 patients with LBL treated in the Asan Medical Center between January 2007 and March 2012, 3 had B-LBL. All had a good performance status and low International Prognostic Index. However, unlike most previously reported cases, the patients had lymphoma in their bone marrow and extranodal sites such as bone and lung. After intensive combination chemotherapy, one patient achieved a complete response and the other 2 patients, a partial response. Our experience suggests that multiple extranodal sites may be involved in B-LBL and BM involvement may not be as infrequent as previously thought. Furthermore, intensive chemotherapy seems to be effective.
Adult ; Bone Marrow ; Chungcheongnam-do ; Drug Therapy ; Drug Therapy, Combination ; Humans ; Lung ; Lymphoma ; Lymphoma, Non-Hodgkin ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma* ; T-Lymphocytes