[Clinical Features and Prognosis of Acute T-cell Lymphoblastic Leukemia in Children--Multi-Center Data Analysis in Fujian].

OBJECTIVE: To evaluate the efficacy of acute T-cell lymphoblastic leukemia (T-ALL) in children and explore the prognostic risk factors. METHODS: The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed, and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia (B-ALL) in the same period. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS), and COX proportional hazard regression model was used to evaluate the prognostic factors. Among 116 children with T-ALL who received standard treatment, 78 cases received the Chinese Childhood Leukemia Collaborative Group (CCLG)-ALL 2008 protocol (CCLG-ALL 2008 group), and 38 cases received the China Childhood Cancer Collaborative Group (CCCG)-ALL 2015 protocol (CCCG-ALL 2015 group). The efficacy and serious adverse event (SAE) incidence of the two groups were compared. RESULTS: Proportion of male, age≥10 years old, white blood cell count (WBC)≥50×109/L, central nervous system leukemia, minimal residual disease (MRD)≥1% during induction therapy, and MRD≥0.01% at the end of induction in T-ALL children were significantly higher than those in B-ALL children (P <0.05). The expected 10-year EFS and OS of T-ALL were 59.7% and 66.0%, respectively, which were significantly lower than those of B-ALL (P <0.001). COX analysis showed that WBC≥100×109/L at initial diagnosis and failure to achieve complete remission (CR) after induction were independent risk factors for poor prognosis. Compared with CCLG-ALL 2008 group, CCCG-ALL 2015 group had lower incidence of infection-related SAE (15.8% vs 34.6%, P =0.042), but higher EFS and OS (73.9% vs 57.2%, P EFS=0.090; 86.5% vs 62.3%, P OS=0.023). CONCLUSIONS: The prognosis of children with T-ALL is worse than children with B-ALL. WBC≥100×109 /L at initial diagnosis and non-CR after induction (especially mediastinal mass has not disappeared) are the risk factors for poor prognosis. CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

[Clinical Characteristics and Prognosis of MLL Rearranged Childhood Acute Lymphocyte Leukemia].

AbstractObjective: To investigate the clinical characteristics and prognostic factors in childhood acute lymphoblastic leukemia with MLL gene-rearrangement-positive (MLL-r+ ALL). METHODS: The clinical data of 1 414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed. The clinical characteristics and efficacy of MLL-r+ and MLL-r- subgroup were compared. The prognostic factors of MLL-r ALL were analyzed by COX regression model. RESULTS: Among all children with ALL, the proportion of patients aged less than 1 year old was 1.8%, and the detection rate of MLL-r+ was 3.4% (48/1 414). The positive detection rate of MLL-r in the age groups <1 year old, and ≥1 year old and ≤14 years old was 38.5% (10/26) and 2.7 (38/1 388), respectively, the difference was statistically significant (P<0.000). Compared with MLL-r- group, the MLL-r+ group had a higher proportion of patients with age <1 year, white blood cell (WBC) count ≥50×109/L, combined central nervous system leukemia (CNSL) and testicular leukemia(TL), while MRD <0.01% on d 33 or d 46 of induction chemotherapy was lower (all P<0.05). The expected 10-year event free survival(EFS) rate and overall survival(OS) rate of the MLL-r+ group were significantly lower than those of the MLL-r- group （EFS： 49.9% vs 77.0%； OS: 55.3% vs 82.9%， P<0.05). COX regression model analysis showed that age <1 year, minimal residual disease (MRD) ≥0.01% on d 33 or d 46 of induction chemotherapy were independent risk factors for worse OS and EFS in MLL-r+ ALL patients (all P<0.05). CONCLUSION: Age <1 year old, high WBC, concomitant CNSL and TL are more common in children with MLL-r+ ALL at initial diagnosis, with poor early treatment response and long-term prognosis. Age <1 year old at initial diagnosis and MRD positive after induction chemotherapy may be risk factors for poor prognosis.

[Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis. METHODS: The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed. RESULTS: The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L. CONCLUSION: High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

[Clinical features and prognosis of high hyperdiploid childhood acute lymphoblastic leukemia: a multicenter retrospective analysis in Fujian Province, China]. / é«˜è¶ äºŒå€ä½“æ ¸åž‹å„¿ç«¥æ€¥æ€§æ·‹å·´ç»†èƒžç™½è¡€ç— çš„ä¸´åºŠç‰¹å¾åŠé¢„åŽ.

OBJECTIVES: To study the clinical features and prognosis of high hyperdiploid (HHD) childhood acute lymphoblastic leukemia (ALL). METHODS: A retrospective analysis was performed on the medical data of 1 414 children who were newly diagnosed with ALL and were admitted to five hospitals in Fujian Province of China from April 2011 to December 2020. According to karyotype, they were divided into two groups: HHD (n=172) and non-HHD (n=1 242). The clinical features and treatment outcome were compared between the two groups, and the factors influencing the prognosis were further explored. RESULTS: Among the 1 414 children with ALL, 172 (12.16%) had HHD. Compared with the non-HHD group, the HHD group had significantly lower proportions of children with risk factors for poor prognosis at diagnosis (age of onset ≥10 years or <1 year, white blood cell count ≥50×109/L, and T-cell phenotype) or positive fusion genes (TEL-AML1, BCR-ABL1, E2A-PBX1, and MLL gene rearrangement) (P<0.05). The HHD group had a significantly higher proportion of children with minimal residual disease (MRD) <0.01% at the end of induction chemotherapy (P<0.05). The 10-year event-free survival (EFS) rate and overall survival (OS) rate in the HHD group were significantly higher than those in the non-HHD group (P<0.05). The univariate analysis showed that the number of chromosomes of 58-66, trisomy of chromosome 10, trisomy of chromosome 17, bone marrow MRD <1% on day 15 or 19 of induction chemotherapy, and bone marrow MRD <0.01% on day 33 or 46 of induction chemotherapy were associated with a higher EFS rate (P<0.05), and trisomy of chromosome 10 was associated with a higher OS rate (P<0.05). The multivariate Cox analysis showed that trisomy of chromosome 17 was closely associated with a high EFS rate (P<0.05). CONCLUSIONS: The ALL children with HHD have few risk factors for poor prognosis at diagnosis and often have good prognosis. The number of chromosomes and trisomy of specific chromosomes are associated with prognosis in these children.

[Comparison of the Early Efficacy and Serious Adverse Events between CCCG-ALL 2015 and CCLG-ALL 2008 in the Treatment of Pediatric Patients with Acute Lymphoblastic Leukemia].

OBJECTIVE: To evaluate the early efficacy and serious adverse events (SAE) related to chemotherapy of different protocols in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL), so as to improve the overall survival rate. METHODS: A comparison of the early efficacy and SAE was performed between pediatric patients treated with Chinese Children Cancer Group-ALL 2015 (CCCG-ALL 2015) protocol from January 2019 to June 2020 and those treated with Chinese Children Leukemia Group-ALL 2008 (CCLG-ALL 2008) protocol from January 2017 to December 2018. RESULTS: The remission rate before consolidation chemotherapy between the two groups was not significantly different (P=0.198), but the negative conversion rate of minimal residual disease (MRD) in CCLG-ALL 2008 group was significantly higher than that in CCCG-ALL 2015 group (P=0.000). The incidence of SAE in CCCG-ALL 2015 group was significantly lower than that in CCLG-ALL 2008 group (P=0.021), and the incidence of infection-related SAE was significantly higher in the latter (P=0.001), while the difference of non-infection-related SAE was not statistically significant (P=0.623). In addition, the treatment-related mortality in CCCG-ALL 2015 group was significantly lower than that in CCLG-ALL 2008 group (P=0.003). CONCLUSION: CCCG-ALL 2015 regimen reduces the intensity of chemotherapy, which can significantly decrease the chemotherapy-related SAE (especially infection-related SAE), as well as treatment-related mortality. However, the MRD negative conversion rate is low before consolidation treatment, and the overall long-term efficacy remains to be further observed.

[Clinical Features and Prognosis of Acute Lymphoblastic Leukemia Children with P2RY8-CRLF2 Gene Rearrangement].

OBJECTIVE: To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement. METHODS: A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification. RESULTS: Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×109/L. These patients presented different immunophenotype, including 3 cases of common B-ALL and 2 cases of pre B-ALL. Four patients carried a normal karyotype and 1 patient carried 46, XY, der (20) [22]/46, XY[2]. For the children with P2RY8-CRLF2 gene rearrangement, 1 patient (20%) could not achieve complete remission (CR), and minimal residual disease (MRD) of 2 patients (40%) was higher than 1% on day 33 of induction chemotherapy; while in group without P2RY8-CRLF2 gene rearrangement, all the patient achieved CR, and MRD in 6 patients (5.8%) was higher than 1% on day 33 of induction chemotherapy. The 3 year event-free survival (EFS) of ALL children in group with P2RY8-CRLF2 gene rearrangement was significantly lower than that in group without P2RY8-CRLF2 gene rearrangement (60.0%±21.9% vs 85.9%±3.9%) (P<0.05). CONCLUSION: The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.

[Clinical Effect and Safety of CCLG-ALL 2008 (high risk group) Protocol in the Treatment of Childhood Mixed Phenotype Acute Leukemia].

OBJECTIVE: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL). METHODS: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy. RESULTS: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033). CONCLUSION: The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.

[Analysis of Gene Mutation and Clinical Characteristics in 19 Children with Juvenile Myelomonocytic Leukemia].

OBJECTIVE: To analyze the gene mutations of children with juvenile myelomonocytic leukemia (JMML) and their correlation with clinical characteristics. METHODS: The genetic mutation results and clinical data of 19 children with JMML in Fujian from January 2015 to December 2018 were collected and analyzed retrospectively. According to the results of gene mutation, they were divided into PTPN11 gene mutation group and non-PTPN11 gene mutation group, and the clinical characteristics and prognosis of children with JMML between two groups were compared. RESULTS: Among the 19 children with JMML, 14 cases were male and 5 cases were female, and male/female ratio was 2.8∶1. The median age at diagnosis was 13(3-48) months, and 14 cases (73.68%) were less than 2 years old. Abdominal distension and pyrexia were the common initial symptoms, and all the children with JMML had splenomegaly. The median white blood cell count was 39.82(4.53-103.4)×109/L，and monocyte count was 4.37(1.04-23.12)×109/L. HbF was higher than the normal high value of the same age in 8 cases (42.11%). All JMML children's Philadelphia chromosome and BCR-ABL1 fusion gene were negative. Among the 19 patients, there were 1 case without any JMML related gene mutation, 7 cases (36.84%) with PTPN11 mutation, 6 cases (31.58%) with K-Ras mutation, 2 cases with NF1 mutation (10.53%), 2 cases with N-Ras mutation (10.53%), and 1 case (5.26%) with NF1 and N-Ras mutations simultaneously. Fifteen patients who only received supporting therapy all died, with a median survival time 9.2 (0.4-58.1) months. Whereas, among the four JMML children who received hematopoietic stem cell transplantation(HSCT), three cases survived and only one case died. Compared with the non-PTPN11 gene mutation group, the proportion of patients with hemoglobin F higher than the normal value of the same age was higher, and the median survival time was shorter in PTPN11 gene mutation group, and the differences were statistically significant (P=0.048 and 0.046, respectively). CONCLUSION: JMML is more common in male infancy and toddlerhood, and the main gene mutation types are PTPN11 and Ras mutations. Because the JMML children with PTPN11 mutations show particularly rapid disease progression, if there is no timely intervention, most children die in a short period of time. Therefore, early HSCT may improve the prognosis of the children with JMML.

[Clinical Characteristics and Prognostic Factors of Children with Non-Hodgkin's Lymphoma of Different Pathological Subtypes].

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of children with non-Hodgkin's lymphoma of different pathological subtypes. METHODS: Ninety-three patients with newly-diagnosed childhood NHL in Fujian Medical University Union Hospital from March 2011 to September 2017 were salected. The diagnosis of patients was performed according to the World Health Organization classification of tumors 2008 ys. The chemotherapy regimens were based on immune phenotype, pathological type and clinical stages. The 5-years event-free survival rate (EFS) were calculated and analyzed by Kaplan-Meier method, and difference of survival rate between groups were compared. The possible factors influencing 5-years EFS was analyzed using Cox proportional hazards model. RESULTS: Among the 93 patients, male to female ratio was 2.88:1, the median age at diagnosis was 6 (0.9 to 13) years old. According to pathological types, Burkitt's lymphoma was the most common, follow by ALK+ anaplastic large-cell lymphoma (ALCL) and lymphoblastic lymphoma (LBL). Clinically, the most common initial symptoms observed at diagnosis were swelling of superficial lymph node, and abdominal pain and abdominal mass in mature B-cell neoplasms, and the swelling of mediastinal lymph nodes in LBL, and hemophagocytic syndrome (HPS) in mature T-cell and natural killer cell NHL. Seventy-nine cases completed 2 courses of induction chemotherapy, and 64 cases (81.01%) reached complete remission (CR). In a median follow up for 32.5(1.0-88.5) months, ten patients (11.90%) relapsed, the median relapsed time was 5.7(3.4-15.7) months. 5-year EFS rate in 84 patients received standardized treatments were (77.1±4.9)%. As compared with lymphoblastic lymphoma and extranodal NK/T cell lymphoma, there was a trend towards better outcomes in B-LBL, and mature B-cell neoplasms and ALK+ ALCL showing 5-year EFS was (86.2±5.2)% and (93.8±6.1)% vs (53.3%±16.1)% and (28.6±17.1)%. Univariate analysis showed that B symptoms, LDH level, secondary HLH, immunophenotype, pathological subtypes, clinical stage and whether reached CR after induction chemotherapy significantly correlated with prognosis. Cox regression analysis showed that no CR after 2 courses was an independent unfavorable prognostic factor (HR0.001, 95%CI: 0.000-0.122). CONCLUSION: The clinical characteristics and prognosis of patients with NHL of different pathological types are different. Whether reached CR after induction chemotherapy is the imdependent risk factor affecting the prognosis.

[Clinical Features and Prognosis of 35 Children with Burkitt Lymphoma/Leukemia].

OBJECTIVE: To investigate the clinical features and prognostic factors of childhood Burkitt Lymphoma/leukemia. METHODS: The clinical data of 35 patients with newly-diagnosed childhood Burkitt lymphoma/leukemia from March 2011 to September 2017 in Fujian Medical University Union Hospital were retrospectively analyzed and summarized. Among 35 patients, 5 gave up treatment and one patient died of multiple organ failure before treatment, and 29 patients received CCCG-BNHL-2010 protocol chemotherapy. RESULTS: The 35 cases of BL/L includsd 31 males and 4 females (M∶F=7.75∶1) with the median age of 5(2.0-11) years. Clinically, the common infiltration sites were as follows: abdominal organs (especially ileocecus, 21/35, 60%), bone marrow (21/35, 60%), faciomaxillary (10/35, 28.57%), and central nervous system (8/35, 22.85%). According to St. Jude staging system, 6 patients were grouped into stage Ⅱ, and 8 into stage Ⅲ and 21 into stage Ⅳ, among which the bone marrow blasts of 17 patients were more than 25%. The analysis of therapeutic efficacy and prognosis showed that in median follow up of 23.4 (5.3-86.4) months, 5 patients relapsed (5/29, 17.24%), the median relapsed time was 5.7 (3.9-7.2) months; tow-year overall survival (OS) rate and progression-free survival (PFS) rate was 79.2%±7.6% and 78.3%±7.9%, respectively. Univariate analysis showed that the 2-year OS and PFS in patients with LDH＞2N, stage Ⅳ (bone marrow infiltration), central nervous system infiltration and no-CR after 2 courses of treatnent all were significantly lower than those in patients with LDH≤2N, stageⅡ-Ⅲ, without central nervous system infiltration as well as CR after 2 course of treatment (P values were 0.015, 0.015, 0.019 and 0.000, respectively). Cox regression analysis showed that no-CR after 2 course was an independent unfavorable prognostic factor (HR 0.34, 95%CI: 0.03-0.407). CONCLUSION: The childhood Buruitts lymphoma/leukemia is more freguently seen in males and school-age children, Advanced stage, bone marrow and contral nervous system infitration are common at the first visit to doctor, moreover the Burkitt's lymphoma/leykemia present repid progression and dangerous feature. The current intensive chemotherapy (high dose of drugs and short course) possess the significant therapeutic efficacy for this disease, but the patients should have very poor prognosis if they can not achieve CR after 2 course of chemotherapy.

[Effect of increasing the intensity of chemotherapy on the prognosis of acute lymphoblastic leukemia in children with IKZF1 deletion].

OBJECTIVE: To study the clinical features of acute lymphoblastic leukemia (ALL) in children with IKAROS family zinc finger 1 (IKZF1) deletion, and to observe the effect of increasing the intensity of chemotherapy on the prognosis of this disease. METHODS: A total of 278 children diagnosed with ALL between December 2015 and February 2018 were systematically treated according to the Chinese Children's Leukemia Group-ALL 2008 protocol (CCLG-ALL 2008). The patients were divided into an IKZF1-deleted group and a control group according to the presence or absence of IKZF1. The IKZF1-deleted group was treated with the regimen for high-risk group (HR) in the CCLG-ALL 2008 protocol, while the control group received different intensities of chemotherapy according to clinical risk classification. The clinical features and event-free survival rate (EFS) were compared between the two groups. RESULTS: A total of 24 (8.6%) cases of 278 children were found to have large deletions of exons of the IKZF1 gene. The IKZF1-deleted group had significantly higher proportions of cases with white blood cell count ≥50×109/L at initial diagnosis, BCR-ABL1 fusion gene positive, minimal residual disease ≥10% on the 15th day of induction remission treatment, minimal residual disease-high risk and clinical risk classification-high risk compared with the control group (P<0.05). The 3-year EFS rate (76%±10%) in the IKZF1-deleted group was lower than that in the control group (84%±4%), but with no significant difference between the two groups (P=0.282). The estimated 3-year EFS rate in the IKZF1-deleted-non-HR group (actually treated with the chemotherapy regimen for HR in the CCLG-ALL 2008 protocol) was 82%±12%, which was lower than that in the control-non-HR group (86%±5%), but there was no significant difference (P=0.436). CONCLUSIONS: ALL children with IKZF1 deletion have worse early treatment response, and increasing the intensity of chemotherapy might improve the prognosis.

[Clinical Features and Prognostic Factors of 18 Children with Anaplastic Large Cell Lymphoma].

OBJECTIVE: To analyze the clinical features and to explore the therapeutic efficacy and prognostic factors of children with anaplastic large cell lymphoma (ALCL). METHODS: The clinical data of 18 children with ALCL admitted in Department of Pediatric Hematology, Union Hospital of Fujian Medical University from April 2011 to November 2017 was collected and analyzed. RESULTS: The male to female ratio was 2∶1, the median age of onset was 6 (0.9-11.3) years old, and the B symptom was positive in 13 cases. The most common initial symptom was lymphadenopathy (in 17 cases). All patients were manifested with multiple organ involvements. 4 cases were classified as clinical stage Ⅱ, 11 cases as stage Ⅲ, and 3 cases as stage Ⅳ. Laboratory tests revealed 9 cases with leukocytosis and 8 cases with CRP＞20 mg/L. The pathological results showed all ALK-positive anaplastic large cell lymphoma with Ki-67 rate between 40%-90%. The median follow-up time was 41 months. 2 patients died before treatment, 1 patient was lost to follow-up. 15 patients accepted chemotherapy protocol of CCCG-BNHL-2011. 2 patients relapsed early, the 3 year event-free survival rate was (76.7±10.2)%. Kaplan-Meier survival analysis showed leukocytosis, increased CRP level, bone involvement and clinical stage were factors affecting prognosis. CONCLUSION: ALCL is a relatively rare subtype of childhood non-Hodgkin's lymphoma with high invasiveness. Leukocytosis, increased CRP level, bone involvement and clinical stage are poor factors affecting the prognosis of patients.

[Children's NK/T Cell Lymphoma-Associated Hemophagocytic Syndrome: Clinical Analysis of 6 Cases].

OBJECTIVE: To study the clinical features, treatment and prognosis of patients with NK/T cell lymphoma-associated hemophagocytic syndrome(NK/T-LAHPS). METHODS: Retrospective analysis was used to explore the clinical data of 6 children with NK/T-LAHPS who were admitted in Department of Pediatric Hematology of Fujian Medical University Union Hospital from July 2012 to June 2016. The 6 patients included 4 boys and 2 girls, with a median age of 4 years(range 1.75 to 11). In 4 patients the hemophagocytic syndrome(HPS) occurred as the main primary manifestations of underlying lymphoma, in the other 2 patients HPS occurred during lymphoma progression. The clinical manifestations included persistent fever(6/6), hepatomegaly(6/6), splenomegaly(6/6) and pancytopenia(6/6). Laboratory data indicated that the level of ferritin(2179-15000 ng/ml) , LDH(608-3899 IU/L) and EBV-DNA(>105 copies/ml ) was elevated obviously. The other common clinical features of NK/T-LAHPS were hypoproteinemia(6/6), hepatic dysfunction(5/6), hypofibrinogenimia(5/6), hypertriglyceridemia(3) and hemophagocytosis in bone marrow(5/6). RESULTS: After being treated according to the HLH-2004 protocol combined with supported therapy for 1 or 2 weeks, all the patients achieved a clinical response, and the laboratory indicators of HPS were improved. The combined chemotherapy of SMILE was given to 4 patients timely, among them 2 patients achieved complete remission(CR) and long term survival, 1 patient achieved partial remission(PR) and died of relapse after drug withdrawal and 1 patient died of aggravated lymphoma. The other 2 patients did not receive chemotherapy in time, HPS relapsed quickly, because of the progression of lymphoma, and all died of severe hepatic dysfunction and coagulopathy. CONCLUSION: The NK/T-LAHPS is an invariably fatal disease with poor prognosis, and typically occurrs at the advanced stage or the terminal phase of the disease. HLH-2004- based protocol in combination with comprehensive therapy is hopeful for the patients with NK/T-LAHPS, which may delay the disease progression and provide opportunities for the treatment of primary disease. Once the laboratory indicators of HPS are improved, it is important to treat lymphoma timely with the combined chemotherapy of SMILE, which is significant for improving the prognosis.