OBJECTIVE: To investigate the diagnostic efficacy of seven glomerular filtration rate (GFR) evaluation formulas Schwartz2009, Schwartz1976, Counahan-Barratt, Filler, CKD-EPI_scysc, Cockrofi-Gault, CKD-EPI_ScysC-Scr in high concentration of methotrexate (HDMTX) chemotherapy dose adjusted cut-off point (GFR ≤85 ml/min) in children with acute lymphoblastic leukemia (ALL). METHODS: One hundred and twenty-four children with ALL were included in the study. GFR determined by renal dynamic imaging (sGFR) was used as the standard to evaluate the accuracy, consistency of eGFR calculated by seven formulas and sGFR, and the diagnostic efficacy of each formula when the sGFR ≤85 ml/min boundary. RESULTS: All of the accuracy of eGFR estimated by Schwartz2009 were greater than 70% in the 0-3, >4 and ≤6, >6 and ≤9, >9 and ≤16 years old group and male group, and the consistency exceeded the professional threshold. When the sensitivity of the ROC curve sGFR ≤85 ml/min was 100% of CKD-EPI_scysc in the 0-3, >3 and ≤4 years old group, Filler in the >3 and ≤4 years old group, and Cockrofi-Gault in the >6 and ≤9 years old group, the specificity was 73.02%, 78.95%, 78.95%, 69.32%, respectively, and the AUC under the ROC curve was the largest (P<0.05). CONCLUSION Schwartz2009 formula predicts the highest accuracy of eGFR in the 7 glomerular filtration rate. CKD-EPI_scysc, Filler, and Cockrofi-Gault formulas have more guiding signi-ficance for the adjustment of HDMTX chemotherapy in pre-adolescence in children with ALL when sGFR ≤85 ml/min.
Adolescent ; Humans ; Male ; Child ; Child, Preschool ; Glomerular Filtration Rate ; Methotrexate ; Creatinine ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Renal Insufficiency, Chronic/diagnosis*

OBJECTIVES: To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN. METHODS: The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups. RESULTS: A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05). CONCLUSIONS There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.
Child ; Humans ; Antineoplastic Agents, Phytogenic/adverse effects* ; Cohort Studies ; Peripheral Nervous System Diseases/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Vincristine/adverse effects* ; Infant ; Child, Preschool ; Adolescent

OBJECTIVE: To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1⁺ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis. METHODS: The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1⁺ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed. RESULTS: There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM^- group (79.3%±5.3%) was significantly better than that of MRD-FCM⁺ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR⁺ group and MRD-PCR^- group, and the 5-year EFS rate of MRD-FCM^-/PCR^- group (85.4%±5.5%) was significantly better than that of MRD-FCM⁺/PCR⁺ group (40.0 %±21.9%) (P =0.026). CONCLUSION In children with TCF3/PBX1⁺ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.
Male ; Female ; Child ; Humans ; Infant ; Child, Preschool ; Adolescent ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Neoplasm, Residual/diagnosis* ; Clinical Relevance ; Retrospective Studies ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Burkitt Lymphoma ; Basic Helix-Loop-Helix Transcription Factors/therapeutic use*

OBJECTIVE: To evaluate the prognosis value of average daily platelet amount increase in children with B-cell acute lymphoblastic leukemia(B-ALL) treated by CCCG-ALL-2015 regimen. METHODS: 106 children with primary B-ALL were retrospective analyzed, standardized MRD test protocol was used to detect the MRD level (19 d and 46 d) after chemotherapy. The platelet count was measured by Sysmex XE-2100. Kaplan-Meier survival curve statistics was used to analyze the event free survival(EFS) rate of the children. RESULTS: The trend of negative correlation existed between PPC and TPR (r_s=-0.519, P=0.021). The 3-year EFS rate of the patients in Ap>5.4×10⁹/L group was 95.7%, which was significantly higher than those in Ap≤5.4×10⁹/L group(79.5%) (χ²=5.236, P=0.035); multivariate analysis showed that Ap≤5.4×10⁹/L was the independent prognostic factor affecting survival of the patients (RR=3.978; 95%CI: 1.336-11.523, P=0.041). With both MRD and Ap≤5.4×10⁹/L as candidate variables, Ap≤5.4×10⁹/L lost its independent prognostic value (RR=1.225; 95%CI: 0.892-13.696, P=0.089), the correlation between d 19/d 46 MRD levels and Ap>5.4×10⁹/L (χ²=4.318, P=0.038) could explain the phenomenon. CONCLUSION Ap can reflect the effect of B-ALL chemotherapy and can be used to monitor the curative effect and prognosis of B-ALL children.
Blood Platelets ; Burkitt Lymphoma ; Child ; Disease-Free Survival ; Humans ; Neoplasm, Residual/diagnosis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

BACKGROUND: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a subset of ALL with poor prognosis. Here, we analyzed the outcomes and prognostic factors of children with Ph+ ALL who received imatinib and chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR). METHODS: Thirty-one Ph+ ALL patients (female 10) diagnosed from January 2005 to December 2016 were included in the study. All patients were treated with imatinib and chemotherapy before HCT. Bone marrow (BM) evaluations included real-time quantitative polymerase chain reaction (RQ-PCR) study of the BCR-ABL1 fusion transcript. All patients received HCT with total body irradiation (TBI)-based conditioning at a median of 6.4 (range, 4.2–47.1) months from diagnosis. RESULTS: Compared to values at diagnosis, the median decrement of RQ-PCR value post-consolidation, and prior to HCT was −3.7 Log and −4.8 Log, respectively. The 5-year event-free survival (EFS) and overall survival of the patients were 64.5±9.4% (20/31) and 75.0±8.3% (23/31) respectively. Events included relapse (N=5) and death in CR post-HCT (N=6). The 5-year incidence of molecular relapse was 30.9±9.1% (9/31). An RQ-PCR decrement of at least −4 Log post-consolidation significantly predicted lower incidence of molecular relapse: 7.7±7.7% for ≥−4 Log decrement, 50.0±13.8% for <−4 Log decrement (P=0.027). CONCLUSION: Decrement in RQ-PCR for the BCR-ABL1 transcript that was determined after consolidation was the only significant prognostic factor for incidence of molecular relapse. In the post-induction TKI initiation setting, steadfast imatinib treatment during consolidation may allow for optimum post-HCT outcomes.
Bone Marrow ; Cell Transplantation ; Child ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Imatinib Mesylate ; Incidence ; Philadelphia Chromosome ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence ; Transplants ; Whole-Body Irradiation

BACKGROUND: Pneumocystis is difficult to culture or detect in laboratory environments. Its ecology including the timing and method of transmission as well as environmental sources and communicability remain unclear. METHODS: We retrospectively evaluated the pattern and treatment outcome of Pneumocystis jirovecii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL) who received chemotherapy. RESULTS: A total of 56 patients with ALL were evaluated. While on chemotherapy, all patients received PCP prophylaxis. PCP were found in a total of 6 patients, including definite PCP in 2, probable PCP in 2, and possible PCP in 2 patients. There were no significant differences in sex, age group, National Cancer Institute risk group, or pneumocystis prophylaxis type between PCP and non-PCP groups. However, there was a significant statistical difference in the times of ALL diagnosis. Regarding recent chemotherapy at the time of PCP diagnosis, there were one induction, one consolidation, and four maintenance cases. All PCP patients were treated with high-dose sulfamethoxazole (100 mg/kg/day) and trimethoprim (20 mg/kg/day) intravenously. Five patients survived, while one patient with endotracheal mechanical ventilation therapy died due to respiratory failure in spite of aggressive treatment. CONCLUSION: Pediatric PCP became extremely rare due to routine prophylaxis in clinical practice of pediatric malignancy. Nevertheless, we analyzed patients with acute lymphoblastic leukemia who had received PCP prophylaxis for 14 years, and analyzed the clustered outbreaks of PCP. It is still important to emphasize the need for prophylaxis and to increase the level of attention and isolation under environmental and personal risk factors.
Child ; Compliance ; Diagnosis ; Disease Outbreaks ; Drug Therapy ; Ecology ; Humans ; Methods ; National Cancer Institute (U.S.) ; Pneumocystis jirovecii ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Respiration, Artificial ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Sulfamethoxazole ; Treatment Outcome ; Trimethoprim

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*

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a subtype of B-lineage ALL (B-ALL) that displays a gene expression profile (GEP) similar to Philadelphia chromosome-positive ALL (PhALL). It has a diverse range of genetic alterations that activate cytokine receptor genes and kinase signaling pathways, frequently accompanied by abnormal transcription factors related to lymphatic development. Children with Ph-like ALL account for 15% of children with high-risk B-ALL. It has adverse clinical features and a poor prognosis. Tyrosine kinase inhibitors combined with chemotherapy can significantly improve the prognosis of children with PhALL, suggesting that targeted therapy based on the molecular cytogenetic abnormalities of Ph-like ALL has good research prospects. This paper expounds the genetic alterations, pathogenesis, clinical features, diagnostic measures, and potential therapeutic approaches of Ph-like childhood ALL based on recent research progress in Ph-like ALL.
Humans ; Janus Kinase 2 ; genetics ; PAX5 Transcription Factor ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; genetics ; Proto-Oncogene Proteins c-abl ; genetics

We describe our experience regarding metronidazole-induced encephalopathy in a patient with acute lymphoblastic leukemia during chemotherapy. A 17-year-old girl was admitted to our institution with complaints of abdominal pain and mucoid stools. She was diagnosed with acute lymphoblastic leukemia and had been undergoing intensified chemotherapy protocol. During the fifth week of interim maintenance-1 therapy, she developed a fever and complained of chills. On stool examination, stool occult blood was positive and Clostridium difficile toxin A/B test was positive. She was started on metronidazole treatment for possible Clostridium difficile infection and other inflammatory gastrointestinal diseases. Ten days later, the patient complained of dizziness and nausea. A brain MRI was performed to make a differential diagnosis of any chemotherapy- induced CNS complication such as necrotizing leukoencephalopathy. The brain MRI showed features of metronidazole-induced encephalopathy. Metronidazole was discontinued and symptoms started to subside four days after. A follow-up brain MRI performed at four weeks showed that lesions of the dentate nucleus had disappeared.
Abdominal Pain ; Adolescent ; Brain ; Brain Diseases ; Cerebellar Nuclei ; Chills ; Clostridium difficile ; Diagnosis, Differential ; Dizziness ; Drug Therapy ; Female ; Fever ; Follow-Up Studies ; Gastrointestinal Diseases ; Humans ; Leukoencephalopathies ; Magnetic Resonance Imaging ; Metronidazole ; Nausea ; Occult Blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

OBJECTIVETo explore the clinical and prognostic features as well as treatment response of childhood B-cell non-Hodgkin's lymphoma/acute lymphoblastic leukemia (B-NHL/B-ALL), so as to better modify the treatment for further improving the prognosis.

METHODSThe clinical data of 43 patients with newly-diagnosed childhood B-NHL/B-ALL from July 2005 to December 2013 in West China Second Hospital of Sichuan University were retrospectively analyzed with particular focus on clinical presentations, laboratory findings and histology. Among them 26 patients received B-NHL-2010 protocol and 17 patients received LMB-89 protocol treatment. Kaplan-Meier method was used to compare the survival rates between groups, while multiple factor logistic regression was used to identify the prognostic factors.

RESULTS(1) The median age at diagnosis was 7.58 (2.42-13.67) years. The male-to-female ratio was 2.9 : 1. No significant difference was found in the median age at diagnosis between male and female children with B-NHL/B-ALL (P = 0.837). (2) Burkitt's lymphoma was the most common (34/43, 79.07%), followed by diffuse large B cell lymphoma (4/43, 9.3%), ALL-L3 (3/43, 6.98%) and others (2/43, 4.65%) in decreasing frequency. (3) According to St. Jude staging classification, 4 patients (9.30%) were divided into stage I, 9 patients (20.93%) into stage II, 23 patients (53.49%) into stage III and 7 patients (16.28%) into stage IV; (4) Clinically, the common predilection sites were as following: ileocecus (11/43, 25.58%), nasopharynx (10/43, 23.26%), faciomaxillary (9/43, 20.93%), superficial lymphadenopathy (8/43, 18.60%), other sites such as mediastinum and bone marrow (5/43, 11.63%). (5) With a median follow up of 24 months (0.7-105 months), the 2-year overall survival (OS) rate and event-free survival (EFS) rate were 79.8% ± 6.5%% and 71.0% ± 7.2%, respectively. The 2-year OS and EFS rates in patients treated with B-NHL-2010 protocol were 79.1% ± 8.4% and 74.1% ± 8.4%, while those in patients treated with LMB-89 protocol were 87.5% ± 8.3% and 66.7% ± 12.4%, respectively, but there was no significant difference between them (P > 0.05). The 2-year EFS rate in patients with LDH > 2N and bone marrow infiltration were significantly lower than that of other groups (P < 0.05). (6) 8 patients (18.6%) relapsed. The median relapsed time was 6 months (2-9 months). 1 patient suffered progressive disease. Male, systemic symptom, elevated LDH, bone marrow and CNS infiltration and advanced stage (stage III and stage IV) were associated with relapse /progressive disease. Logistic regression analysis showed that LDH > 2N was an independent unfavorable prognostic factors (OR = 31.129, P = 0.02).

CONCLUSIONOutcome of B-NHL/B-ALL is greatly improved by current intensive and short-time chemotherapy regimen. The 2-year event-free survival (EFS) rate is 71.0% ± 7.2%. There is no significant difference in EFS rate between patients treated with B-NHL-2010 protocol and LMB89 protocol. The long-term survival rate in patient with advanced disease need to be further improved.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Burkitt Lymphoma ; diagnosis ; drug therapy ; Child ; Cyclophosphamide ; therapeutic use ; Cytarabine ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Etoposide ; therapeutic use ; Female ; Humans ; Hydrocortisone ; therapeutic use ; Leucovorin ; therapeutic use ; Logistic Models ; Lymphoma, B-Cell ; diagnosis ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; drug therapy ; Male ; Methotrexate ; therapeutic use ; Multivariate Analysis ; Neoplasm Staging ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; Prednisone ; therapeutic use ; Prognosis ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use