Subcutaneous panniculitislike T-cell lymphoma with hemophagocytosis: complete remission with BFM-90 protocol

SUMMARY: Subcutaneous panniculitislike T-cell lymphoma (SPTCL) is an uncommon type of cutaneous lymphoma. In many cases, SPTCL is accompanied by hemophagocytic syndrome (HPS), resulting in prominent systemic symptoms. The natural history, optimal treatment strategy, and prognostic factors associated with this malignancy are not well defined. We report an 11-year-old boy of SPTCL with HPS who was initially treated with conventional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but progressed later on therapy. Subsequently, the child was treated with multiagent combination chemotherapy as per BFM-90 protocol and achieved complete remission, and has remained so for 3 years. This report suggests the value of this particular multiagent combination chemotherapy regimen in the treatment of patients with SPTCL and HPS.     

环磷酰胺治疗儿童肾病综合征随机对照试验的系统评价

目的 评价环磷酰胺治疗儿童原发性肾病综合征的有效性与安全性，探讨最佳治疗方案。 方法 检索MEDLINE、OVID数据库、中国期刊全文数据库等，同时手工检索并从参考文献中追诉。纳入环磷酰胺治疗儿童原发性肾病综合征的随机对照试验。使用国际Cochrane中心推荐的方法进行文献质量评价，并用RevMan4.2软件进行统计分析。 结果 共检索出1351篇文献，纳入13篇随机对照试验。分析显示1年内应用环磷酰胺联合激素治疗复发率有明显降低，RR=0.39，95%CI为（0.18，0.87），1年到2年无资料显示环磷酰胺比单用激素治疗复发率更低。1年后的总缓解率基本相等，差异无统计学意义，RR=0.94，95%CI为（0.30，2.98）。环磷酰胺静脉给药与口服给药比较，能有效提高治疗后6个月和治疗后1年的缓解率，差异有统计学意义,RR总=1.76，95%CI为（1.03，2.98）。 结论 环磷酰胺联合激素治疗1年内患儿复发率有明显降低，环磷酰胺静脉给药比口服缓解率更高，累积剂量更小，更安全、对性腺损害小。对于环磷酰胺的远期疗效评价仍需更多设计严密的、科学的、大样本随机对照试验进一步证实。     

去甲氧柔红霉素联合方案治疗难治性急性淋巴细胞白血病的远期疗效

目的探讨应用去甲氧柔红霉素（ＩＤ）为主的联合化疗方案治疗难治性儿童急性淋巴细胞白血病（ＡＬＬ）的远期疗效及其临床应用价值。方法初治诱导缓解方案用ＶＩＬＰ（长春新碱、去甲氧柔红霉素、左旋门冬酰胺酶、泼尼松）。完全缓解（ＣＲ）后作巩固治疗及庇护所治疗，然后再用ＶＩＬＰ作早期强化治疗。复发者诱导治疗用ＩＡ（去甲氧柔红霉素、阿糖胞苷）方案。ＣＲ后巩固和早期强化治疗用初治者同样方案。结果１０例初治患儿９例获ＣＲ，７例复治患儿５例获ＣＲ，总ＣＲ率为８２％（１４／１７）。ＣＲ的１４例中持续ＣＲ（ＣＣＲ）＞３年者４例，＞２年者４例，＞１年者１例。结论用去甲氧柔红霉素为主的联合方案是治疗难治性儿童ＡＬＬ有效的方法，对初治患儿作为一线药物其远期疗效会更好。     

Malignant histiocytosis: therapeutic results in 27 children treated with a single polychemotherapy regimen

Twenty-seven children with histologically proven malignant histiocytosis were treated in the same institution from January, 1975 to December, 1986 with a combination chemotherapy regimen containing vincristine, cyclophosphamide, doxorubicine, and prednisone. Twenty-two patients achieved complete remission, one partial remission, and four no remission. Eight patients relapsed and were treated with Lomustine (CCNU), vinblastine, and bleomycin. In seven cases, a second complete remission was obtained. The overall survival rate is 81% at 5 years and the relapse-free survival rate is 54.5% at 5 years. Prognostic factors were fever and age under 10 at diagnosis, which were correlated with a higher incidence of relapse or no remission.     

Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.     

Chemotherapy with cyclophosphamide,vincristine, cytosine arabinoside,and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL)

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness in markedly diminished in patients with prior bone marrow relapse.     

Angioimmunoblastic lymphadenopathy (AIBL): a case report from Saudi Arabia

Angio immunoblastic lymphadenopathy (AIBL) is a recently described disease. It occurs most commonly in elderly patients with an average age of about 60 years. In children, few cases have been reported so far in the English literature (three occurred after thymic transplant and one case after infectious mononucleosis). AIBL has characteristics manifested by clinical, pathological and laboratory findings. Steroids, alone or with chemotherapy, are used for treatment with variable results. Herein, we report one child with AIBL who was treated with prednisone initially and then relapsed. Chemotherapy (cyclophosphamide, vincristine and prednisone) was added and she has been in remission for more than 3 years. The purpose of this report is to add AIBL to the differential diagnosis of acute generalized lymphadenopathy in children.     

Modified cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy for posttransplantation lymphoproliferative disease in pediatric patients undergoing solid organ transplantation

PURPOSE: The authors report the use of a cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP)-based chemotherapy regimen in treating six children with posttransplantation lymphoproliferative disorder (PTLD) that developed after solid organ transplantation. MATERIALS AND METHODS: The chemotherapy regimen consisted of a 29-day induction with CHOP and then as many as 15 cycles of maintenance therapy using methotrexate and cytarabine alternating with vincristine, adriamycin, mercaptopurine, and prednisone. RESULTS: All patients attained remission. One patient died of sepsis while in remission. Four of the five remaining patients have been followed-up in remission for as long as 8 years without losing the graft. One of the patients experienced relapse after completing therapy and subsequently died with disease. CONCLUSIONS: The authors conclude that pediatric patients with PTLD after solid organ transplantation that fails conservative management can be treated successfully with CHOP-based chemotherapy.     

Primary follicular lymphoma of the testis in children and adolescents

This study reports 6 cases of primary follicular lymphoma of the testis (PFLT) in children and adolescents correlated with clinical presentation, pathologic features, treatment, and outcome. All 6 patients (age, 3 to 16 y; median, 4 y) had PFLT grade 3 with disease limited to the testis, completely resected and treated with 2 courses of chemotherapy (cyclophosphamide, vincristine, prednisone, doxorubicin). Event-free survival was 100% (follow-up: median, 73 mo; mean, 53 mo; range, 6 to 96 mo). In conclusion, clinical outcome in children and adolescents with PFLT is excellent with treatment including complete surgical resection and 2 courses of cyclophosphamide, vincristine, prednisone, doxorubicin.     

Pattern of response to prednisone in idiopathic, minimal lesion nephrotic syndrome as a criterion in selecting patients for cyclophosphamide therapy

Twenty-three children with idiopathic, relapsing minimal lesion nephrotic syndrome were divided according to their pattern of response to prednisone: (1) steroid dependent, if the relapse occurred while the dosage of prednisone was being decreased; and (2) frequent relapser, if the relapse occurred at variable periods of time (one week to two months) after discontinuing prednisone therapy. All patients received cyclophosphamide for eight weeks in a single daily dose of 2 mg/kg, in order to prolong the length of the remission. The percentage of patients who continued in remission at the end of the first year and thereafter was greater in the frequent relapser group (P = 0.05). This study suggests that the pattern of response to prednisone may be another criterion for the selection of patients who will benefit from cyclophosphamide therapy.     

Allogeneic bone marrow transplantation for chemotherapy-refractory hepatosplenic gammadelta T-cell lymphoma: case report and review of the literature

Hepatosplenic gammadelta T-cell lymphoma is an uncommon pediatric disease and is associated with an aggressive and often fatal course. The authors describe the case of an 8-year-old girl who presented with transaminitis and hepatosplenomegaly. Liver biopsy and peripheral blood flow cytometry were diagnostic of hepatosplenic gammadelta T-cell lymphoma. She was treated with multi-agent chemotherapy with cyclophosphamide, vincristine, prednisone, doxorubicin, and high-dose methotrexate but failed to achieve durable remission. She underwent an allogeneic bone marrow transplant from her HLA-identical brother with a preparative regimen including total body irradiation and cyclophosphamide. She is currently alive and has remained in remission for 30 months after transplantation. The authors also review the literature for similar pediatric cases.     

Systemic histiocytosis: an unusual cause of perianal disease in a child

A male child first presented with chronic perianal skin disease at 33 months of age and later developed gingival disease and loose teeth associated with alveolar bone erosion. Biopsy of gingival and perianal lesions showed histiocytic proliferation. Following therapy with vinblastine, prednisone, methotrexate, and cyclophosphamide, the lesions healed but disease recurred in the mastoid and was successfully treated with vinblastine alone. Although the perianal area is an unusual site of skin involvement in systemic histiocytosis, this disorder should be considered in any child with chronic unexplained perianal disease, and biopsy of these lesions should be obtained.     

4-Aminoimidazole-5-carboxamide excretion in acute leukemia.

The urinary excretion of 4-aminimidazole-5-carboxamide (AIC) as been reported to be increased in children with acute leukemia and has been correlated with disease status. Using a modification of the method of Skibba et al [5], determinations were made on urine from 26 children with acute leukemia. The urine from ten normal children served as controls. The effect of chemotherapy on urinary AIC was studied comparing patients on vincristine and prednisone (V+P) with those on 6-mercaptopurine, methotrexate, and cyclophosphamide (Triple Rx). Patients in remission on Triple Rx had lower levels of urinary AIC than did patients on Triple Rx in relapse or patients on V+P in either remission or relapse. Twenty patients had sequential measurements. Values for individual patients were not predictive of disease status. One such patient is described. This study demonstrates that chemotherapy, as well as disease status, affects the urinary excretion of AIC in children with acute leukemia.     

Avascular necrosis of bone following combination chemotherapy for acute lymphocytic leukemia

Avascular necrosis of bone (AVNB) is a known complication of systemic adrenocorticosteroid therapy, and one which is thought to be dose-related. However, despite the large amounts of prednisone which have been used in the standard treatment of acute lymphocytic leukemia (ALL), AVNB rarely has been reported in children with that disease. We described our experience with one adolescent with ALL who developed multifocal AVNB presenting as bone pain after aggressive chemotherapy that included a high cumulative dose of corticosteroids as well as other antitumor agents, some of which also have been associated with AVNB. Four similar cases from the literature are reviewed. Because the bone pain of AVNB can mimic that of leukemic relapse, this is an important entity to be aware of, and one which may become more common with increasingly aggressive combination chemotherapy.     

MALIGNANT HISTIOCYTOSIS Histiocytic Medullary Reticulosis

ABSTRACT. Three cases of malignant histiocytosis occurring in children aged 2 months, 10 months and 14 years, are described. In all children the diagnosis was based on anaemia, granulocytopenia or thrombocytopenia, splenomegaly and marked erythrophagocytosis by bone marrow and lymph node atypical histiocytes. Two children aged 10 months and 14 years, underwent splenectomy after which combined chemotherapy with cyclophosphamide, vincristine and prednisone (COP) was started. In the older child a complete remission was achieved. The younger child died soon after the onset of the treatment. The youngest child was treated with bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone (BACOP). He died of pneumonia and sepsis two months after the start of the treatment.     

Malignant histiocytosis. Histiocytic medullary reticulosis.

Three cases of malignant histiocytosis occurring in children aged 2 months, 10 months and 14 years, are described. In all children the diagnosis was based on anaemia, granulocytopenia or thrombocytopenia, splenomegaly and marked erythrophagocytosis by bone marrow and lymph node atypical histiocytes. Two children aged 10 months and 14 years, underwent splenectomy after which combined chemotherapy with cyclophosphamide, vincristine and prednisone (COP) was started. In the older child a complete remission was achieved. The younger child died soon after the onset of the treatment. The youngest child was treated with bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone (BACOP). He died of pneumonia and sepsis two months after the start of the treatment.     

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.     

OBSTRUCTIVE JAUNDICE: An Unusual Initial Manifestation of Intra-Abdominal Non-Hodgkin Lymphoma in a Child

Obstructive jaundice is an unusual manifestation of non-Hodgkin lymphomas in children. Although surgical drainage is one of the initial treatment choices in some cases, usually lymphomatous masses rapidly response to chemotherapy and jaundice decreases due to regression of the mass, without any surgical procedure. The authors report the case of a 16-year-old girl who presented with biliary obstruction due to a neoplasm involving the duodenum. Histological examination of the specimen, which was taken from the mass by endoscopic biopsy, revealed Burkitt lymphoma infiltrating the duodenum. Chemotherapy including cyclophosphamide was started immediately. In a few days, jaundice decreased rapidly by the shrinkage of the mass. Neither surgery nor percutaneous drainage were needed. In conclusion, biliary tract obstruction due to non-Hodgkin lymphoma can be effectively treated with chemotherapy alone without any surgical procedure.     

Obstructive jaundice: an unusual initial manifestation of intra-abdominal non-Hodgkin lymphoma in a child

Obstructive jaundice is an unusual manifestation of non-Hodgkin lymphomas in children. Although surgical drainage is one of the initial treatment choices in some cases, usually lymphomatous masses rapidly response to chemotherapy and jaundice decreases due to regression of the mass, without any surgical procedure. The authors report the case of a 16-year-old girl who presented with biliary obstruction due to a neoplasm involving the duodenum. Histological examination of the specimen, which was taken from the mass by endoscopic biopsy, revealed Burkitt lymphoma infiltrating the duodenum. Chemotherapy including cyclophosphamide was started immediately. In a few days, jaundice decreased rapidly by the shrinkage of the mass. Neither surgery nor percutaneous drainage were needed. In conclusion, biliary tract obstruction due to non-Hodgkin lymphoma can be effectively treated with chemotherapy alone without any surgical procedure.     

BK virus-associated hemorrhagic cystitis in pediatric cancer patients receiving high-dose cyclophosphamide

Hemorrhagic cystitis (HC) is a known complication of oxazophosphorine chemotherapy. BK virus (BKV) has been commonly found to be associated with hematuria in stem cell transplant patients; however, it has rarely been reported after cyclophosphamide chemotherapy alone. The authors present 3 cases of BK viruria with HC in nontransplant pediatric oncology patients. The 3 patients with BKV had more prolonged hematuria (14 to 16 wk) compared with 1 patient with BKV-negative HC (10 wk). The HC necessitated chemotherapy delays and also prolonged supportive care. One patient was treated with intravenous cidofovir with resolution of BK viruria and hematuria. BKV may have an association with the development of HC in nonstem cell transplant patients receiving high-dose oxazophosphorine chemotherapy. HC may present early and be more prolonged in patients with BK viruria. Patients with HC after cyclophosphamide or ifosfamide with negative bacterial cultures should be studied for BKV. Cidofovir may be beneficial in certain patients with BK viruria and HC; however, definitive data will require a clinical trial.