Long-term follow-up of renal function after high-dose methotrexate treatment in children.

BACKGROUND: High-dose methotrexate (HD-MTX) is commonly used in treatment of pediatric leukemias and lymphomas. Transient deterioration in renal function is frequently noted during HD-MTX treatment, but possible long-term changes are less well known. In this study we aimed to study long-term renal prognosis after HD-MTX treatment, and to find possible underlying risk factors for reduced renal function. PROCEDURE: Medical records of pediatric cancer patients treated with HD-MTX were reviewed retrospectively after follow-up of 1-10 years. Renal function before and after chemotherapy was investigated in a total of 28 patients. Assessment of glomerular and tubular function was prospectively evaluated in each case. Glomerular function was evaluated by either (51)Cr-EDTA or (99m)Tc-DTPA clearance methods, and by urinary albumin excretion. Tubular function was assessed by measuring blood electrolyte levels and urinary alpha(1)- or beta(2)-microglobulin. RESULTS: A decrease in glomerular filtration rate (GFR) was statistically significant as follow-up time increased (P = 0.02). Age at the time of diagnosis and exposure to potentially nephrotoxic antibiotics during cancer treatment had no influence on GFR. However, albuminuria was observed more often in patients treated with amphotericin B or gentamycin (P = 0.04). No changes in tubular function were observed. CONCLUSIONS: Our results show that HD-MTX treatment significantly decreases GFR and may cause albuminuria in pediatric cancer patients several years after treatment. Long-term renal follow-up of these patients is therefore important.

Long-term prospective follow-up study of cardiac function after cardiotoxic therapy for malignancy in children.

PURPOSE: To evaluate cardiac function by means of conventional and three-dimensional echocardiography (3DE) and measurement of natriuretic peptides in children and adolescents previously treated for childhood malignancy using individual follow-up data and matched control children as reference criteria. PATIENTS AND METHODS: Thirty-nine survivors of childhood malignancy were examined in 1994 and 1998. The mean time from the diagnosis was 8.6 (3.9 to 16.8) years and between cardiac evaluations was 4.1 (3.3 to 5.1) years. Patients were divided into two groups according to therapies given (group I (n = 30): no cardiac irradiation, median cumulative anthracycline dose 210 mg/m2; group II (n = 9): irradiation in the cardiac region, median cumulative anthracycline dose 180 mg/m2). RESULTS: Fractional shortening (FS) in 1994 was higher than in 1998 (32.5 +/- 4.3 vs. 30.3% +/- 3.3%, P =.009). 33% of patients in group I and 56% in group II in 1994 and 30% of patients in group I and 67% in group II in 1998 had N-terminal of the propeptide-atrial natriuretic peptide (NT-proANP) levels exceeding the 90th percentile of controls. In 1998, both groups (I and II) had lower ejection fraction (EF) measured by 3DE than their matched controls (52.9 +/- 5.2 vs. 58.8% +/- 3.1%, P <.001 and 50.0 +/- 6.6 vs. 60.8% +/- 3.2%, P =.024, respectively). Left atrial maximum volumes/body surface area were smaller in the patients than in controls. B-Type natriuretic peptide values did not differ significantly in either group. CONCLUSION: Left ventricular contractility decreases slowly even years after cardiotoxic cancer therapy in children. 3DE and NT-proANP measurements are effective methods to evaluate the cardiac function in these patients.

Intensive Chemotherapy Without Radiotherapy Gives More than 85% Event-Free Survival for Non-Hodgkin Lymphoma Without Central Nervous Involvement: A 6-Year Population-Based Study From the Nordic Society of Pediatric Hematology and Oncology.

BACKGROUND: The prognosis in childhood non-Hodgkin lymphoma (NHL) has improved dramatically during recent decades. The authors report the results from a 6-year population-based study of clinical characteristics and treatment results of NHL from the five Nordic countries. METHODS: All children younger than 15 years of age at diagnosis with NHL diagnosed from 1995 to 2000 were stratified and treated according to immunophenotypic classification and stage of disease. RESULTS: A total of 230 patients were diagnosed with primary NHL, which gives an annual incidence of 0.9/100.000 children, with a median age of 8 years. Seven percent of the children were below 3 years of age at diagnosis. The male/female ratio was 2.3 and was unrelated to age. Patients with pre-B and T-cell NHL constituted 33%, B-cell NHL 53%, and anaplastic large cell lymphoma (ALCL) 14%. According to Murphy's classification, 14% had stage 1, 17% stage 2, 50% stage 3, and 19% stage 4 disease, 12 of whom (28%) had central nervous involvement (CNS) at diagnosis. By January 1, 2003, four children had died during induction, three children died in remission (2, 6, and 26 months from diagnosis), and 24 children experienced a relapse. At 5 years, the probability of event-free survival (p-EFS) was 86 ± 2% for all children. The 5-year p-EFS values for stages 1 through 4 were 94%, 97%, 83%, and 79%, respectively. The 5-year p-EFS values were 91% for B-cell, 87% for pre-B, 81% for ALCL, and 79% for T-cell NHL. The 12 patients with CNS involvement at diagnosis had a significantly poorer outcome than stage 4 patients with CNS involvement (p-EFS = 50% vs. 90%, P < 0.01). The 218 patients without CNS disease at diagnosis had a 5-year p-EFS of 88%. CONCLUSIONS: With modern intensive chemotherapy, more than 85% of NHL patients will achieve long-lasting first remission. In the future, preventing death during induction and remission and improving therapy for patients with CNS disease would have a major impact on the overall p-EFS.

Intensive chemotherapy without radiotherapy gives more than 85% event-free survival for non-Hodgkin lymphoma without central nervous involvement: a 6-year population-based study from the nordic society of pediatric hematology and oncology.

BACKGROUND: The prognosis in childhood non-Hodgkin lymphoma (NHL) has improved dramatically during recent decades. The authors report the results from a 6-year population-based study of clinical characteristics and treatment results of NHL from the five Nordic countries. METHODS: All children younger than 15 years of age at diagnosis with NHL diagnosed from 1995 to 2000 were stratified and treated according to immunophenotypic classification and stage of disease. RESULTS: A total of 230 patients were diagnosed with primary NHL, which gives an annual incidence of 0.9/100.000 children, with a median age of 8 years. Seven percent of the children were below 3 years of age at diagnosis. The male/female ratio was 2.3 and was unrelated to age. Patients with pre-B and T-cell NHL constituted 33%, B-cell NHL 53%, and anaplastic large cell lymphoma (ALCL) 14%. According to Murphy's classification, 14% had stage 1, 17% stage 2, 50% stage 3, and 19% stage 4 disease, 12 of whom (28%) had central nervous involvement (CNS) at diagnosis. By January 1, 2003, four children had died during induction, three children died in remission (2, 6, and 26 months from diagnosis), and 24 children experienced a relapse. At 5 years, the probability of event-free survival (p-EFS) was 86+/-2% for all children. The 5-year p-EFS values for stages 1 through 4 were 94%, 97%, 83%, and 79%, respectively. The 5-year p-EFS values were 91% for B-cell, 87% for pre-B, 81% for ALCL, and 79% for T-cell NHL. The 12 patients with CNS involvement at diagnosis had a significantly poorer outcome than stage 4 patients with CNS involvement (p-EFS = 50% vs. 90%, P < 0.01). The 218 patients without CNS disease at diagnosis had a 5-year p-EFS of 88%. CONCLUSIONS: With modern intensive chemotherapy, more than 85% of NHL patients will achieve long-lasting first remission. In the future, preventing death during induction and remission and improving therapy for patients with CNS disease would have a major impact on the overall p-EFS.