Long-term follow-up of short intensive multiagent chemotherapy without high-dose methotrexate ('Orange') in children with advanced non-lymphoblastic non-Hodgkin's lymphoma: a children's cancer group report.

Despite prolonged therapy (18 months), children with advanced non-lymphoblastic, non-Hodgkin's lymphoma (NHL) treated on previous Children's Cancer Group (CCG) trials achieved less than a 60% 5-year event-free survival (EFS). In this study we piloted a shorter but more intensive protocol ('Orange') to determine the feasibility, safety, and efficacy of this alternative treatment approach. Thirty-nine children received a CHOP-based induction, etoposide/ifosfamide consolidation, DECAL (dexamethasone, etoposide, cisplatin, cytosine arabinoside (Ara-C) and L-asparaginase) intensification, and either one or two similar but less intense maintenance courses. Patients were stratified to standard-risk (5 months) vs high-risk (7 months) treatment. High risk was defined as either bone marrow disease, CNS disease, mediastinal mass > or = one-third thoracic diameter at T5 and/or LDH > or =2 times institutional upper limits of normal. All other patients were considered to be standard risk. Results were compared with the previous CCG NHL study (CCG-503). Sixteen and 23 patients were considered standard- vs. high-risk, respectively. The 5-year EFS and overall survival (OS) were 77 +/- 7% and 80 +/- 7%, respectively. The 5-year EFS and OS were significantly better in the standard- vs. high-risk subgroups (100% vs. 61 +/- 11%) (P < 0.003) and (100% vs. 65 +/- 11%) (P < 0.01), respectively. Lactate dehydrogenase (LDH) > or =2 x normal (NL) was associated with significantly poorer outcomes (LDH > or =2 x NL vs. <2 x NL) (5-year EFS: 55 +/- 12% vs. 100%) (P < 0.0004). This CCG hybrid regimen, 'Orange', of short and more intensive therapy resulted in a significant improvement in outcomes compared with the previous CCG trial of more prolonged but less intense therapy. This regimen that deletes high-dose methotrexate, if confirmed in a larger trial, could be considered as an alternative treatment approach in children without high tumor burdens (LDH <2 x NL) and Murphy stage III disease.

Characterization of t(11;19)(q23;p13.3) by fluorescence in situ hybridization analysis in a pediatric patient with therapy-related acute myelogenous leukemia.

This case presents a Caucasian girl diagnosed with early pre-B cell acute lymphoblastic leukemia at age 2 years. The only chromosomal anomaly detected in her bone marrow cells at this time was an add(12p). By age 4 years, she had a bone marrow and central nervous system (CNS) relapse of ALL and was treated with chemotherapy that included etoposide. She was in complete remission for 2 years following chemotherapy with etoposide, but later developed therapy-related acute myeloid leukemia (t-AML). At this time, a t(11;19)(q23;p13.3) rearrangement was detected in her bone marrow cells. The AML relapsed again 1 year after allogeneic bone marrow transplant (BMT). The presence of a chromosome 11 abnormality involving band 11q23 in this patient suggests that the transformation from ALL to t-AML was a consequence of etoposide included in her chemotherapy. Studies have shown that the 11q23 breakpoint in the t(11;19) rearrangement is consistent, and involves the MLL gene in t-AML patients. However, the breakpoint in 19p is variable in that it could be located either at 19p13.1 or 19p13.3 and thus could involve either of two genes: ELL (11-19 lysine-rich leukemia gene) on 19p13.1 or ENL (11-19 leukemia gene) on 19p13.3. In this study, the t(11;19)(q23;p13.3) was further characterized and the breakpoint regions were defined by fluorescence in situ hybridization (FISH) analysis.

Stage 4 squamous cell carcinoma of the tongue in a child: complete response to chemoradiotherapy.

This report describes a complete response to a chemoradiotherapy regimen in a child with an advanced and unresectable squamous cell carcinoma of the tongue. An 8-year-old girl had stage 4 squamous cell carcinoma of the tongue (T4N2M0), causing severe trismus and dysphagia. She received hyperfractionated external beam radiotherapy (total 74.4 Gy) and concomitant intravenous infusion of hydroxyurea (0.313 mg/m2 per min) for 43 days. Grade 3 mucositis and myelosuppression were the main toxicities. There was marked symptomatic improvement, and the patient achieved a complete response. She is disease-free 24 months after treatment, and all the acute symptoms have resolved. The regimen was well tolerated with acceptable toxicity and led to a complete objective response. This regimen needs further evaluation to confirm its efficacy and to ascertain its long-term effects in children.

Lymph node manifestations of limited Churg-Strauss syndrome.

Churg-Strauss syndrome is a systemic vasculitis characterized by asthma, tissue and blood eosinophilia, and granulomatous vasculitis. Lymph node involvement as part of systemic disease or as the primary site of involvement is rare. We report a single case of primary (isolated) nodal Churg-Strauss syndrome occurring in an 11-year-old boy with asthma, fever, night sweats, and cervical adenopathy. The clinical diagnosis was lymphoma. The unusual presentation of Churg-Strauss syndrome limited to lymph nodes is important to recognize and diagnose correctly because the administration of steroid therapy is associated with a favorable outcome.

Advances in the Treatment of Adolescents with Sickle Hemoglobinopathies.

This detailed review of sickle hemoglobinopathies covers their incidence and epidemiology, pathophysiology, diagnosis, clinical manifestations, complications, and organ changes. Issues such as pregnancy and birth control in patients with sickle cell disease, surgery and anesthesia, and medical management are also discussed.

Needle biopsy in the diagnosis of testicular leukemia in children.

Aggressive chemotherapy in patients with acute lymphoblastic leukemia has resulted in a marked upsurge in patient survival. In the course of their management, testicular biopsy and rebiopsy have an important role. We evaluated the histological findings in 50 sets of open wedge and simultaneous needle core biopsy specimens from 44 testes of children with acute lymphoblastic leukemia to determine the accuracy of the needle biopsy technique in the evaluation of testis involvement in acute lymphoblastic leukemia. We conclude that needle biopsy of the testis in acute lymphoblastic leukemia is highly accurate and correlates well with the conventional open wedge biopsy, and it may have a role in the management of children with acute lymphoblastic leukemia.

Sickle cell crisis as evaluated from measurements of hydroxybutyrate dehydrogenase and myoglobin in plasma.

Data on plasma hydroxybutyrate dehydrogenase activity (I) and myoglobin concentration were used to evaluate painful sickle cell crises. I was increased during non-crisis steady state in patients with sickle cell disease as compared to normal values (232, SD 79.7 vs 85, SD 33 Sigma units/mL). During crisis, the mean value for I increased further to 379 (SD 139) Sigma units/mL. For 12 patients evaluated both during steady state and crisis, there was a mean increase in plasma I of 131% (SD 76%). Repeated determinations of I in sickle cell disease patients during several months while they were in steady state showed that baseline I varied by no more than 20% from the mean. Plasma myoglobin in patients with sickle cell disease was not above normal, but during crisis 21 of 39 patients tested had increased plasma myoglobin concentrations. Our data suggest that I may be a useful indicator of sickle cell crisis when the patient's own baseline value is available for comparison. Plasma myoglobin measurements give evidence of muscle damage during crisis with high specificity but low sensitivity.

Hyponatremia in sickle cell disease. A renal salt-losing state.

Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of "crisis".