High-dose intense chemotherapy in South African children with B-cell lymphoma: morbidity, supportive measures, and outcome

BACKGROUND: Twenty-five percent of South African children aged 6-71 months are undernourished and have stunted growth. The tolerance and efficacy of short, high-dose intense chemotherapy for B-cell lymphomas in such a population were unknown. PROCEDURE: Nineteen consecutive children diagnosed with B-cell lymphoma after 1993 at Tygerberg Hospital (TBH) in the Republic of South Africa (RSA) were treated according to the LMB-89 protocol. RESULTS: Among the 19 children treated according to the LMB-89 protocol, there were 3 children in group A (completely resected St. Jude stage I and abdominal stage II), 14 in group B (nonresected stage I, nonabdominal stage II, all stage III, stage IV with bone marrow involvement but <70% Burkitt cells and without CNS involvement) and 2 in group C (patients with >70% Burkitt cells in bone marrow and/or CNS involvement). Overall survival for these children was 79% (median follow-up 53.5 months,range 20-70 months) compared to 25% (median follow-up 131 months, range 71-173months) for 24 children who had been treated with COM+/-P prior to 1993 (P = 0.002). Toxicity was noteworthy in the children treated with LMB-89. They had a mean of 2.6 episodes of febrile neutropenia and 1.9 episodes of stomatitis per patient and required intensive support, but there were no toxic deaths. CONCLUSIONS: A major step forward was achieved for South African children with B-cell lymphoma. Despite a high prevalence of malnutrition and endemic infections in the RSA, the implementation of the LMB-89 protocol significantly improved survival with manageable morbidity. Our findings suggest that treatment centres that cannot measure methotrexate (MTX) serum levels should not exceed 3.0 g/m(2) of MTX. If supportive care facilities are limited, consideration should be given to reducing the doses of cyclophosphamide and of doxorubicin in the treatment schedules.     

Outcome of Early Stage Pediatric Non-Lymphoblastic Non-Hodgkin Lymphoma

There is lack of data on outcome of limited stage pediatric non-Hodgkin lymphoma (NHL) from south Asia. In view of this lacuna, authors evaluated patients of early stage (stage 1 and 2) non-lymphoblastic pediatric NHL patients treated with uniform short course, reduced-intensity protocol from Jan 2003 through Dec 2016. Of the total 280 subjects with pediatric NHL, 50 were of early stage of which 42 received uniform protocol. B-cell subtype was observed in 83% patients. Event-free-survival (EFS) and overall-survival (OS) were 85% and 90% respectively at 5 y (median-not reached). Age?>?13 y emerged as the only poor risk factor for EFS (p?=?0.05) on univariate analysis and same had a trend toward inferior prognosis in OS (p?=?0.09). Vincristine-induced neuropathy occurred in five patients. Febrile neutropenia was observed in 16% subjects with one patient requiring hospitalization. There was no treatment-related death. This largest data of limited stage pediatric non-lymphoblastic NHL from south Asia highlights that good outcomes may be achieved with less intense short course therapy without hospitalization, and that adolescent age is the only poor prognostic factor for outcome.     

Pediatric non-Hodgkin lymphoma: a retrospective 14-year experience with Berlin-Frankfurt-Münster (BFM) protocols from a tertiary care hospital in Serbia

Use of current intensive chemotherapy protocols in pediatric non-Hodgkin lymphoma (NHL) in high-income countries resulted in event-free survival (EFS) rates ranging from 80 to 90%. The results are inferior in less privileged countries with limited resources for medical care. There are no reports about comprehensive data analysis in pediatric NHL in Serbia. A retrospective study was carried out at University Children's Hospital, Belgrade, in children aged less than 18 years diagnosed with non-Hodgkin lymphoma from 1997 to 2011. Fifty-seven children were eligible for analysis. Fourteen were diagnosed with lymphoblastic lymphoma, 38 with mature B-cell NHL (B-NHL), and 5 with anaplastic large-cell lymphoma. Mean age at diagnosis was 9.2 years, with male to female ratio 2.35:1. Children were treated according to Berlin-Frankfurt-Münster (BFM) protocols. With median follow-up of 59.3 months, 5-year probability of EFS was 84.1% for all patients, whereas overall survival was 93%. These results with BFM protocol administration, although inferior to leading international groups, reflect good treatment outcome in our patients. To the best of the authors' knowledge, this article presents the first results regarding treatment and survival of childhood NHL in Serbia.     

TREATMENT OF PEDIATRIC B-CELL NON-HODGKIN'S LYMPHOMAS AT THE MOTOL HOSPITAL IN PRAGUE, CZECH REPUBLIC: Results Based on the NHL BFM 90 Protocols

Malignant non-Hodgkin's lymphomas (NHL) of childhood and adolescence are a heterogeneous group of diseases originating from the lymphoid cells. Unlike adults with non-Hodgkin's lymphoma, children typically have extranodal disseminated disease of high grade (Burkitt's lymphoma, large cell lymphoma, or lymphoblastic lymphoma). This study was conducted to determine the feasibility of treating children in the Czech Republic with B-cell non-Hodgkin's lymphomas according to very intensive protocols based on the German Berlin Frankfurt Munster (BFM) NHL 90 study. Treatments are divided in the BFM studies according to "B" and "non-B" immunophenotypes. The authors report only those treated according to the BFM B-cell protocol. From 1991 through 1997 eighty-two patients less than 18 years with NHL were admitted to the department. Seventy-three of them were classified as B-cell lymphoma and 54 were thus eligible for the BFM B-cell treatment. The entire group consisted of 38 males and 16 females (ratio 2.38). Median age was 11.6 years. Twelve had stage I disease, 3 stage II, 30 stage III, and 9 stage IV lymphoma. There were 21 patients with Burkitt's lymphoma, 29 with large cell lymphoma, of which 5 were patients with MALT lymphoma. In 3 cases B-cell NHL was not further classified and one child had a mediastinal B lymphoma. Patients were further stratified according to clinical stage and lactate dehydrogenase (LDH) level. Therapy consisted of a prephase and short (2, 4, or 6 courses), intensive 5-day therapy with 6 drugs. The probability of event-free survival (pEFS) for the entire group was 74% and overall survival at 5 years was 80%. There was a significantly better outcome for children classified as stage I. No difference was observed between the EFS of stage III and IV patients. Four patients died from treatment-related complications in complete remission. Treatment results were not identical between NHL subtypes, with large cell lymphoma patients doing significantly better (pEFS 90%, p=.008). The use of protocols based on BFM 90 study was feasible at this center. The treatment results are approximately 10% lower than those reported by BFM investigators, but comparable to results from other centers.     

Disseminated nonlymphoblastic lymphoma of childhood: A childrens cancer group study,CCG-552

(1) Purpose: To assess the efficacy of a chemotherapy-only regimen in pediatric patients with disseminated nonlymphoblastic lymphoma and acute B-cell leukemia (B-ALL). (2) Patients and Methods: Sixty-eight eligible patients with previously untreated disseminated non-lymphoblastic lymphoma were enrolled on a Childrens Cancer Group study. Therapy included cycles of chemotherapy, systemic and intrathecal (IT), ever 3 weeks for a total maximal duration of 57 weeks. Fifty-five patients had small non-cleaved cell lymphoma (SNCCL) and 13 had diffuse large cell lymphoma (DLCL). Forty-seven were stage III, six were stage IV, and 15 had B-ALL; 13 had central nervous system (CNS) involvement. (3) Results: Four year event-free survival (EFS) was 53% (SE ± 12%). Stage III SNCCL patients with LDH < 500 IU/L achieved an improved EFS compared to other SNCCL patients (86% vs. 42% 4 year EFS, P = .072). The primary site of failure for advanced stage SNCCL patients was the CNS. All Ki-1-positive DLCL patients relapsed. Patterns of failure, time to relapse, and outcome following relapse differed between SNCCL and DLCL patients. (4) Conclusions: Advanced stage SNCCL requires better CNS-directed chemotherapy to reduce the CNS failure rate; however, the achievement of durable disease-free survival in four of 11 patients with CNS disease without use of cranial irradiation suggests merit for further evaluation of chemotherapy-only strategies. DLCL patients do not need intensive CNS-directed chemotherapy. © 1994 Wiley-Liss, Inc.     

Malawi pilot study of Burkitt lymphoma treatment

BACKGROUND: Burkitt lymphoma (BL) accounts for 50% of childhood cancer in Malawi. Lack of resources precludes the use of new successful treatment approaches such as the LMB 89 group B protocol, which cures >80% of children with stage III BL with high dose chemotherapy and matching supportive care. Our objective was to achieve a good cure rate in Murphy stage I-III BL with manageable toxicity in Malawi at a drug cost of <1000 US dollars per patient. PROCEDURE: The intensity and toxicity of the LMB 89 group B protocol was reduced and adapted to Malawi realities. All stages received the same treatment. Children with suspected BL in the period July 1997-November 1999 were subjected to abdominal ultrasound, a tumor biopsy and/or fine needle aspirate (FNA) and bone marrow (BM), cerebrospinal fluid (CSF), and peripheral blood examination. HIV seropositive children were excluded. Endpoints are projected event free survival (EFS) at minimum 1 year, blood and gastro-intestinal tract toxicity, and risk for and severity of infections. RESULTS: Forty-four children were eligible for treatment and analysis. Their median age was 7.2 years, M:F ratio 1.4:1 with 10 stage I, 5 stage II, and 29 stage III patients. Projected Kaplan-Meier EFS for all was 57% (CI 41-73) at 1 year with 90% EFS in stage I and 52% EFS in stage III. The survival curve remained stable at 500 days. Toxicity and delays in appropriate supportive care contributed to ten deaths during treatment. Local recurrent tumor caused five and CNS recurrence one death. Two children died from progressive disease. The incidence of severe (grade 3 and/or 4) hematologic toxicity varied from 13% to 36%, gastro-intestinal toxicity (GIT) from 2% to 17%, and infections from 7% to 41% per chemotherapy module. CONCLUSIONS: It is possible to administer less intense and less costly multiagent chemotherapy to children with BL in a developing society with acceptable EFS rates. Adequate supportive care of the at-times associated severe toxicity must be made available to better the results.     

Henoch-schönlein purpura and elevated hepatitis C virus antibody in a girl with nasopharyngeal diffuse large B-cell lymphoma

Henoch-Sch?nlein purpura (HSP) or hepatitis C virus (HCV) infection was reported in association with malignancies. However, HSP and HCV infection rarely present in pediatric patients with non-Hodgkin's lymphoma. We describe an 8-year-old girl with Stage-IV diffuse large B-cell lymphoma who presented with HSP and elevated HCV antibody titer at diagnosis and at relapse. After treatment, purpura disappeared and HCV antibody titer returned to normal range. There was no recurrence of HSP or elevated HCV antibody during a follow-up of 2 years.     

Treatment of children with B-cell non-Hodgkin's lymphoma in developing countries: the experience of a single center in Brazil

PURPOSE: To treat non-Hodgkin's B-cell lymphoma (B-NHL) in children with manageable toxicity-related morbidity and without any decrease in survival. PATIENTS AND METHODS: Between January 1998 and April 2003, 53 consecutive patients (age 16 years or less) from a single institution were enrolled. The patients were stratified by risk factors (stage and LDH level) and treated with a BFM 86/90 (Berlin-Frankfurt-Münster)-based protocol with reduction of the methotrexate dose from 5 mg/m to 2 mg/m. RESULTS: The mean age of the patients was 6 years (range 1-16 years). Seventy-two percent of the patients had lymphomas classified as Burkitt type, 11% as diffuse large cell lymphoma, and 6% as Burkitt-like lymphoma, and 11% were not classified. At a median follow-up of 35 months, 44 patients (83%) survived in complete remission. The event-free survival rate for all patients was 78% (SE = 0.07): 100% (SE = 0.0) for stage I/II patients and 74% (SE = 0.08) for stage III/IV patients. Six patients suffered initial treatment failure and one patient relapsed, all of whom died. There was only one death from sepsis related to treatment. CONCLUSIONS: This strategy was very effective for treating B-NHL in a developing country. The results were comparable to those of the BFM 90 study and other contemporary groups and represented an increase in the cure rates in childhood B-NHL in Brazil.     

Clinical Features and Treatment Results of Children with Diffuse Large B-Cell Lymphoma

The demographic, clinical characteristics, and treatment groups of 33 children with diffuse large B-cell lymphoma (DLBCL) were recorded and analyzed among 1486 non-Hodgkin lymphoma (NHL) cases since 1972. The median age was 9.7 years (range 1.4–16.9) and male/female ratio was 24/9 = 2.6. Kaplan–Meier methods and logrank tests were used in treatment analysis. The frequency of DLBCL among 1486 NHL cases was 2.2%, however, the percentage was 9.3% in cases diagnosed after 2000. The event-free survival (EFS) and overall survival (OS) rates for 33 children were 61% and 65.1% at 5 years, respectively. The EFS and OS rates of low stage (stages I and II) disease decreased to lower level in advanced stage (stages III and IV) disease. Associated conditions and ages older than 14 years were found as poor prognostic factors in multivariate analysis. The survival rates in children with DLBCL need further improvement. This is mainly related with late referral of those children with advanced disease. The proper diagnosis and early referral is essential in these children for a better survival rate. The children with associated conditions and older children must be handled with care since these are found as poor prognostic factors.     

Clinical characteristics and treatment results of pediatric B-cell non-Hodgkin lymphoma patients in a single center

The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors' center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m2 of methotrexate instead of 5 g/m2/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5-16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level > or = 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.     

CLINICAL CHARACTERISTICS AND TREATMENT RESULTS OF PEDIATRIC B-CELL NON-HODGKIN LYMPHOMA PATIENTS IN A SINGLE CENTER

The aim of this study was to evaluate and compare the clinical characteristics of the B-cell non-Hodgkin lymphoma (NHL) patients and therapeutic efficacy of modified NHL BFM-90 and NHL BFM-95 protocols in the authors’ center. From January 1993 to December 2003, 61 newly diagnosed children with B-NHL were enrolled to the study. The patients were stratified by risk factors and treated either with a modified B-NHL BFM-90 or BFM-95 protocols. The use of 1 or 3 g/m² of methotrexate instead of 5 g/m²/24 h was the only important modification in BFM-90 protocol. Sixty-one children (12 girls, 49 boys) with a median age of 6.5 years (range: 2.5–16) were treated in the center. There were 14 patients in stage II, 28 in stage III, and 19 in stage IV. The most common initial primary tumor sites were abdomen, head, and neck. Forty-five patients were treated with modified B-cell BFM-90 and 16 patients were treated with B-cell BFM-95 regimens. The 5-year overall survival (OS) for all patients was 85.8%, and event-free survival (EFS) was 82.8%. The 5-year OS rates in modified BFM-90 and in BFM-95 protocols were 85.2 and 87.5%; the 5-year EFS rates in these 2 protocols were 84.6 and 70%, respectively (p >.05). Factors associated with lower EFS by univariate analysis were bulky disease, risk groups, and LDH level ≥ 500 IU/L. By multivariate analysis only LDH level was significant. In conclusion, the treatment results in this study were similar to those of BFM group.     

儿童伯基特和伯基特样淋巴瘤40例的临床研究

目的 认识儿童伯基特淋巴瘤(BL)和伯基特样淋巴瘤(BLL)的病理及临床特点,总结大剂量、短疗程化疗方案的疗效,探讨治疗相关的合并症及预后影响因素.方法 2003年2月-2006年4月住院治疗的淋巴瘤患儿40例,全部行活检病理形态及免疫组化检查,并按WHO新的病理分型标准进行分型,参照儿童非霍奇金淋巴瘤(NHL)的St.Jude分期标准进行分期.采用大剂量、短疗程的改良LMB89方案进行治疗.根据不同分期、不同危险因素及对治疗反应的评估结果,将患儿分成A、B、c三个治疗组.结果 临床特点:发病年龄2～14岁,中位发病年龄6.9岁;男33例,女7例,男:女=4.7:1;腹腔肿物及急腹症为最常见表现.病理示BL 30例、BLL 10例;7例(17.5%)在瘤组织中检测到EBER-1阳性细胞,19例血清中EB病毒抗体阳性.确诊时I～Ⅱ期患儿9例,Ⅲ～Ⅵ期患儿31例;伴中枢侵犯者3例,骨髓侵犯者2例.疗程2～8个月.随访率100%,中位追踪时间22.6个月.至2006年12月底,实际存活35例,1年生存率88.7%,预计3年无进展生存率81.8%.化疗中Ⅲ～Ⅳ度骨髓抑制的发生率在B组和C组分别为97.5%和100%,3例出现重症黏膜炎.5例死亡,其中2例为副作用相关死亡.单因素分析显示,临床分期为Ⅳ期、治疗3个月时评估有残留病灶、病程小于15 d与预后不良相关(P＜0.05).结论 采用大剂量、短疗程方案治疗BL和BLL疗效好,预计3年无进展生存率81.8%.病史小于15 d、诊断时为Ⅳ期、治疗3个月未达完全缓解者与预后不良相关.     

Primary mediastinal B‐cell lymphoma in the pediatric patient: Can a rational approach to therapy be based on adult studies?

The literature on adult and pediatric primary mediastinal B‐cell lymphoma (PMBCL) was reviewed and compared. Biologically, adult PMBCL has more similarities to Hodgkin Lymphoma (HL) than diffuse large B‐cell lymphoma (DLBCL). Pediatric studies suggest that the biology is similar to that in adults. Median age of children is 14.3 years and the overall survival (OS) is reported as 78.6% and event‐free survival (EFS) as 67.4%. Adverse prognostic factors included LDH >500 and mass size over 10 cm, with a trend towards better survival in younger patients. Studies in adults show better survival with intensified chemotherapy and the addition of rituximab. Data on the use of radiation therapy show improved CR rates and survival with addition of involved field radiation therapy (IFRT). Positron emission tomography (PET) with computerized tomography (CT) imaging response‐assessment after two courses and at therapy‐end may allow for the rational use of IFRT in pediatric/adolescent patients who are more susceptible to development of adverse late effects. Pediatr Blood Cancer 2009;52:566–570. © 2008 Wiley‐Liss, Inc.     

Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol

Background

Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more.

Procedure

Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine–bleomycin–cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide–cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.

Results

One hundred fifteen patients were included: median age of 12.8 years (0.4–18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80–92) and 95% (89–98), respectively (median follow-up: 3.5 years, range: 0.2–5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84–93), 5-year OS 93% (89–95), p = .561). The 5-year EFS were 93% (95% CI: 80–98), 88% (71–95) and 79% (62–90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66–97), 64% (30–85), 95% (72–99) and 87% (74–94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003–1.007).

Conclusion

Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.     

Treatment of advanced stage diffuse,small non-cleaved cell lymphoma in childhood: Further experience with total therapy B

Prior to the development of intensive treatments for patients with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL), the prognosis for such patients was dismal. A minority of patients attained long-term, disease-free survival. Since 1981, we have treated 28 children with advanced stage B-NHL with an intensive chemotherapeutic protocol, Total Therapy B. This regimen employs cycles of fractionated high-dose cyclophosphamide, doxorubicin, and vincristine alternating with sequential infusions of high-dose methotrexate and escalating doses of cytarabine, in addition to intensive intrathecal therapy. The planned duration of therapy is approximately 6 months. Two patients had B-cell acute lymphoblastic leukemia and 26 had stage III B-NHL; none had CNS involvement. The median age was 7 years. All 28 patients achieved complete remission (CR). Both patients with B-ALL and 21 of 26 with stage III B-NHL remain in CR, with a median follow-up of 51 months. Treatment failures included 3 patients with recurrent or progressive disease, 1 toxic death in CR, and 1 patient who developed a secondary mediastinal T-cell lymphoblastic lymphoma 4 1/2 years after the diagnosis of B-NHL. The 2- and 5-year event-free survival rates were 85.7 ± 6.6% (SE) and 79.6 ± 8.5%, respectively. Total Therapy B is a highly effective therapy for children with advanced stage B-NHL without CNS involvement. © 1994 Wiley-Liss, Inc.     

Non-Hodgkin lymphoma in children: a 20-year population-based epidemiologic study in western Sweden

PURPOSE: The aim of this study was to investigate incidence, clinicopathologic features, prognostic risk factors, and long-term survival in non-Hodgkin lymphoma (NHL) in a 20-year population-based study of children using Swedish health care organizations and their central registry for childhood malignancies. PATIENTS AND METHODS: The hospital registry, the Cause of Death Registry, and the two established Swedish registries for malignancy (the Swedish Cancer Registry and the National Registry for Solid Tumours in Childhood) were searched for children in western Sweden with NHL diagnosed from 1975 to 1994. The clinical files of all children with NHL were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. All sections from paraffin-embedded blocks of tumors with a diagnosis of malignant lymphoma were collected and reexamined histopathologically and immunohistochemically. To guarantee that no patients with NHL were misdiagnosed, a reexamination of other childhood malignancies collected from these registries was also performed. Median follow-up duration of surviving patients is 10 years. RESULTS: The annual incidence of NHL in children younger than 15 years of age was 9/million children, representing 6% of all childhood malignancies during the investigation time. The male-female ratio was 4.1:1.0. Immunologic marker studies were available for 64 of the 77 NHLs: 41 patients had B-cell, 17 had T-cell, and 6 had Ki-1-positive anaplastic large cell lymphoma (ALCL). Two patients with Ki-1-positive ALCL were originally thought to have malignant histiocytosis and Langerhans cell histiocytosis (LCH), respectively. Treatment was the most significant prognostic factor; event-free survival (EFS) was 19% in the preprotocol era (1975 to 1979) and 74% from 1980 to 1994. Other than treatment, stage was the most significant prognostic factor; EFS was 86% for patients (1980 to 1994) with stage I or II disease and 64% for patients with stage III or IV disease, with a dismal prognosis for children with initial involvement of the bone marrow or central nervous system (EFS was 38% and 20%, respectively). Bulky disease and performance state at diagnosis were independent prognostic factors. The patterns of relapse, including early recurrence of the B-cell lymphomas, are in accordance with previous experience. CONCLUSION: The incidence of NHL was found to be somewhat higher than reported in our previous Nordic study. The higher incidence found in this study might be the result of the thorough data collection (based on hospital registry and cross-checked with all registries for malignant diseases in Sweden) or because reexamination of the tissue material was performed. A more pronounced male predominance than found in previous investigations was observed. The immunophenotypic distribution and the stage distribution is in accordance with earlier investigations. Treatment was the most important factor affecting outcome. A dramatic improvement of survival was seen with the introduction of intensive therapy; treatment success can be expected in 86% of children with localized disease and 64% of children with extensive disease. The absence of improvement in survival despite further treatment stratification with the introduction of the BFM protocol for B-cell-NHL is surprising. LSA2L2-like protocols seem to be as effective. Future studies on treatment of NHL must also concentrate on reducing the intensity of therapy in patients with lower risk disease to minimize late toxic effects.     

儿童淋巴瘤75例临床病理分析

目的 探讨儿童淋巴瘤的临床和病理特点.方法 收集1996年- 2009年75例淋巴瘤患儿临床病理资料,进行光镜观察、免疫组织化学染色分析,对初步诊断为伯基特淋巴瘤和弥散大B细胞淋巴瘤的病例进行c-myc基因荧光原位杂交检测.根据WHO 2008年淋巴组织肿瘤分类标准进行分类.结果 75例儿童淋巴瘤中男57例,女18例,男女之比为3.17∶1.发病平均年龄8.74岁.发病部位:淋巴结内32例(42.7％);淋巴结外43例(57.3％),以胃肠道(29.3％)为主.组织类型包括:霍奇金淋巴瘤13例(17.3％),淋巴母细胞淋巴瘤16例(21.3％),间变性大细胞淋巴瘤12例(16.0％),伯基特淋巴瘤和弥散大B细胞淋巴瘤33例(44.0％),小淋巴细胞性淋巴瘤1例(1.3％).对初步诊断为伯基特淋巴瘤和弥散大B细胞淋巴瘤病例进行荧光原位杂交检测进行进一步诊断,结果显示,该组28例中存在c-myc基因改变者18例.结论 儿童淋巴瘤以男性多见,发病部位以淋巴结和胃肠道多见.最常见的组织学类型依次为伯基特淋巴瘤、淋巴母细胞淋巴瘤、霍奇金淋巴瘤、间变性大细胞淋巴瘤和弥散大B细胞淋巴瘤.     

Treatment of pediatric lymphoma in Japan: Current status and plans for the future

Results of pediatric lymphoma treatment have improved markedly over the past 30 years. In Hodgkin's lymphoma, the 5 year event‐free survival (EFS) was 81.5% in a retrospective study. In the ALB‐NHL03 study, the 5 year EFS according to clinical stage in patients with lymphoblastic T‐cell lymphoma (T‐LBL) was 70.6% for stage III and 88.9% for stage IV. In mature B‐cell lymphoma, the B‐NHL03 study indicated that the 4 year EFS according to treatment group was 94% for group 1, 98% for group 2, 84% for group 3, and 78% for group 4. Moreover, the 2 year EFS rate was 81% in Japanese advanced stage patients based on the international ALCL99 study. Thus, EFS >80% was achieved in any subtype of pediatric lymphoma. With regard to refractory or recurrent lymphoma, however, treatment methods for improvement of the survival rate in these patients still need to be developed. Also the difference between child, and adolescent and young adult patients still needs to be clarified, and treatment protocols developed. Although lymphoma treatment does not greatly change according to country, it does differ between other countries and Japan for some subtypes of lymphoma. In particular, the results of treatment of stage III T‐LBL in Japan are worse than those in the USA and Europe. The priority in future studies will be to collect data on these differences, and the reasons for these differences.     

MRD监测对儿童B系急性淋巴细胞性白血病疗效评估的意义

目的：研究监测微小残留白血病(MRD)在B系急性淋巴细胞白血病（ALL）患儿治疗中的作用。方法：回顾性研究了2001年9月1日至2005年4月31日,采用ALL-XH-99方案治疗的B系ALL患儿中进行MRD监测的患儿共124例。用四色多参数流式细胞仪监测ALL患儿治疗过程中不同时间点的MRD。结果：在124例进行过MRD监测的B系ALL患儿中,其中MRD<0.01%、0.01%~0.1%和>0.1%的分别有103例、13例和8例,其5年无复发生存率（RFS）分别为（88.9±3.9）%、（70.0±14.5）%和0%,而5年无事生存率（EFS）分别为（82.4±4.4）%、（21.2±18.0）%和0%,两者均P<0.01;将首次CR后半年内MRD检查分成阴性（<0.01％）和阳性两组,其5年RFS分别为（87.7±4.1）%和（58.3±14.2）%,（P<0.01）;5年EFS分别为（80.7±4.6）%和（25.6±13.8）%（P<0.01）;首次CR后半年以后MRD检查阴性和阳性两组的5年RFS分别为（92.0±3.6）%和（48.5±15.5）%（P<0.01）。多因素分析显示结果显示诱导缓解后MRD、泼尼松诱导窗口反应、第19天骨髓象是否达M-1级骨髓象和是否检出BCR-ABL或MLL-AF4融合基因对患儿治疗过程中是否发生复发有预后价值（P<0．05)。结论： 在B系ALL患儿治疗过程中,无论在诱导缓解达到CR时,还是在随后的治疗过程中,监测MRD水平对于评估ALL患儿疗效有重要意义。     

Variant histology,IgD and CD30 expression in low‐risk pediatric nodular lymphocyte predominant Hodgkin lymphoma: A report from the Children's Oncology Group

1 Background

Histologic prognostic factors have been described for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). This study examines histologic and immunophenotypic variants in a clinical trial for pediatric NLPHL.

2 Procedure

One hundred sixty‐eight cases of localized NLPHL were examined for histologic variants, CD30 and immunoglobulin D (IgD) expression, and outcome. Histologic types were scored categorically as 0 = 0, 1 ≤ 25%, and 2 > 25% of the sample.

3 Results

Fifty‐eight (35.1%) cases showed only typical nodular with or without serpiginous histology (types A and B). The remainder showed mixtures of histologies. The numbers of patients with score 2 are 85 (50.6%) type A, 21 (12.5%) type B, 46 (27.4%) with extranodular large B cells (type C), 3 with T‐cell‐rich nodular pattern (type D), 55 (32.7%) with diffuse T‐cell‐rich (type E) pattern, and 2 (1.2%) with diffuse B‐cell pattern (type F). Higher level of types C (P = 0.048) and D (P = 0.033) resulted in lower event‐free survival (EFS). Cytoplasmic IgD was found in 65 of 130 tested (50%), did not significantly associate with EFS but positively correlated with types C and E histology (P < 0.0001) and negatively correlated with types A (P = 0.0003) and B (P = 0.006). Seventeen (10%) expressed CD30, with no adverse effect.

4 Conclusions

Variant histology is common in pediatric NLPHL, especially types C and E, which are associated with IgD expression. Type C variant histology and possibly type D are associated with decreased EFS, but neither IgD nor CD30 are adverse features. Variant histology may warrant increased surveillance, but did not affect overall survival.