[Total parathyroidectomy, autoimplant and cryopreservation for the treatment of hyperparathyroidism of renal origin in children and young adults]. / Paratiroidectomía total, autoimplante y criopreservación para el tratamiento del hiperparatiroidismo de origen renal en pediatría y adultos jóvenes.

OBJECTIVES: To describe our initial experience in the treatment of hyperparathyroidism (HPP) of renal cause using total or subtotal parathyroidectomy, autoimplant and cryopreservation in pediatric patients. Secondary HPP is the increased function of the parathyroid hormone (PTH) due to an abnormal phosphocalcic metabolism in patients with chronic renal failure (CRF). This situation produces increased bone resorption resulting in osteodystrophy and endovascular calcifications. Surgical treatment is aimed to diminish the level of PTH in CRF patients, to avoid HPP complications. METHODS AND MATERIALS: Descriptive, monocentric and retrospective study of a case series of patients with secondary and tertiary hyperparathyroidism, who went through total or subtotal parathyroidectomy, autoimplant and cryopreservation between 2009 and 2016. We analyzed the following variables: age, calcemia, PTH, phosphatemia, alkaline phosphatase (ALP), follow-up and complications. The continuous variables are expressed in median and interquartile range or in mean and SD, according to their distribution. The categorical variables were expressed in percentages and frequencies (repeated sentence). RESULTS: Number of patients included: 13. Mean age of the patients was 16.7 years old. Preoperative median calcium dosage was 9.1 mg/dl (IQR: 8.9-9.5). Median PTH was 2,600 pg/ml (IQR: 1,400 pg/ml to 2,785 pg/ml). Intraoperatory dosage of PTH reported a median drop of 86.6% in the first 15 minutes (IQR: 80.5-95.9). After the first 48 hours, median calcemia was 9 mg/dl (IQR: 7.7-9.4) and median PTH was 40 pg/ml (IQR: 20-113). We did not identify intraoperatory complications. In the immediate post operatory stage, mean IV calcium therapy was 4 days (SD: 2.39). Median time of follow-up was 18 months (IQR 9-36). Two patients had hungry bone syndrome and one patient had a recurrence of the pathology as remote post operatory complications. After a year, median calcemia, was 9 mg/dl (IQR: 7.6-9.3) and median PTH was 50 pg/ml (IQR: 28.5-108). The decrease in PTH and ALP were statistically significant with p value < 0.05. CONCLUSION: In our study, total parathyroidectomy with auto implant is a safe and effective option for the treatment of secondary and tertiary hyperparathyroidism in pediatric patients. This could also prevent bone complications.

OBJETIVOS: Describir la experiencia en el tratamiento del hiperparatiroidismo (HPP) de origen renal con la técnica de la paratiroidectomía total o subtotal, autoimplante y criopreservación en pacientes pediátricos y adultos jóvenes. El HPP secundario es el aumento de la función de las hormonas paratiroideas debido a una alteración en el metabolismo fosfocálcico a partir de la insuficiencia renal crónica (IRC). Esto produce una mayor resorción ósea, provocando alteraciones en los huesos y calcificaciones en el endotelio vascular. El tratamiento quirúrgico se indica para disminuir el nivel de parathormona (PTH), y así prevenir las complicaciones del hiperparatiroidismo en pacientes con IRC terminal. MATERIAL Y METODOS: Estudio descriptivo, retrospectivo, monocéntrico de una serie de pacientes con diagnóstico de HPP secundario y terciario sometidos a paratiroidectomía total, autoimplante y criopreservación entre 2009 y 2016. Se analizaron las siguientes variables: Edad, Calcemia, PTH, Fosfatemia, Fosfatasa alcalina (FAL), tiempo de seguimiento y complicaciones. Las variables continuas se expresan en mediana y rango intercuartil o en media y DS, según su distribución. Las variables categóricas se expresaron en porcentajes y frecuencias. RESULTADOS: Se incluyeron 13 pacientes. La edad media fue 16,7 años (R= 11:24). La mediana de calcemia preoperatoria fue 9,1 mg/dl (RIQ: 8,9-9,5). La mediana preoperatoria de PTH fue 2.600 pg/ml (RIQ: 1.400-2.785). La medición del descenso porcentual de PTHi ultrarrápida informó una mediana de 86,6% en los primeros 15 minutos (RIQ: 80,5-95,9). No se identificaron complicaciones intraoperatorias. A las 48 horas posquirúrgicas, la mediana de calcemia fue de 9 mg/dl (RIQ: 7,7-9,4) y la mediana de PTH de 40 pg/ml (RIQ: 20-113). La media de aporte de calcio endovenoso posquirúrgico fue de 4 días (DS 2,39). La mediana de seguimiento fue de 18 meses (RIQ 9-36). Como complicaciones posoperatorias tardías se identificaron dos pacientes con síndrome de hueso hambriento y un paciente con recidiva de la enfermedad. Al año postoperatorio la mediana de calcemia, fue de 9 mg/dl (RIQ: 7,6-9,3). La mediana de PTH fue de 50 pg/ml (RIQ: 28,5-108)y la de FAL fue de 116 UI/L (RIQ 102:273). El descenso de PTH y de FAL fueron estadísticamente significativos con p valor < 0,05. CONCLUSIONES: En nuestro estudio, la paratiroidectomía total con autoimplante es una alternativa segura y efectiva para el tratamiento del hiperparatiroidismo secundario y terciario en pediatría, permitiendo prevenir así complicaciones óseas y cardiovasculares.

Paratiroidectomía total, autoimplante y criopreservación para el tratamiento del hiperparatiroidismo de origen renal en pediatría y adultos jóvenes / Total parathyroidectomy, autoimplant and cryopreservation for the treatment of hyperparathyroidism of renal origin in children and young adults

Objetivos. Describir la experiencia en el tratamiento del hiperparatiroidismo (HPP) de origen renal con la técnica de la paratiroidectomía total o subtotal, autoimplante y criopreservación en pacientes pediátricos y adultos jóvenes. El HPP secundario es el aumento de la función de las hormonas paratiroideas debido a una alteración en el metabolismo fosfocálcico a partir de la insuficiencia renal crónica (IRC). Esto produce una mayor resorción ósea, provocando alteraciones en los huesos y calcificaciones en el endotelio vascular. El tratamiento quirúrgico se indica para disminuir el nivel de parathormona (PTH), y así prevenir las complicaciones del hiperparatiroidismo en pacientes con IRC terminal. Material y métodos. Estudio descriptivo, retrospectivo, monocéntrico de una serie de pacientes con diagnóstico de HPP secundario y terciario sometidos a paratiroidectomía total, autoimplante y criopreservación entre 2009 y 2016. Se analizaron las siguientes variables: Edad, Calcemia, PTH, Fosfatemia, Fosfatasa alcalina (FAL), tiempo de seguimiento y complicaciones. Las variables continuas se expresan en mediana y rango intercuartil o en media y DS, según su distribución. Las variables categóricas se expresaron en porcentajes y frecuencias. Resultados. Se incluyeron 13 pacientes. La edad media fue 16,7 años (R= 11:24). La mediana de calcemia preoperatoria fue 9,1 mg/dl (RIQ: 8,9-9,5). La mediana preoperatoria de PTH fue 2.600 pg/ml (RIQ: 1.400-2.785). La medición del descenso porcentual de PTHi ultrarrápida informó una mediana de 86,6% en los primeros 15 minutos (RIQ: 80,5-95,9). No se identificaron complicaciones intraoperatorias. A las 48 horas posquirúrgicas, la mediana de calcemia fue de 9 mg/dl (RIQ: 7,7-9,4) y la mediana de PTH de 40 pg/ml (RIQ: 20-113). La media de aporte de calcio endovenoso posquirúrgico fue de 4 días (DS 2,39). La mediana de seguimiento fue de 18 meses (RIQ 9-36). Como complicaciones posoperatorias tardías se identificaron dos pacientes con síndrome de hueso hambriento y un paciente con recidiva de la enfermedad. Al año postoperatorio la mediana de calcemia, fue de 9 mg/ dl (RIQ: 7,6-9,3). La mediana de PTH fue de 50 pg/ml (RIQ: 28,5-108) y la de FAL fue de 116 UI/L (RIQ 102:273). El descenso de PTH y de FAL fueron estadísticamente significativos con p valor < 0,05. Conclusiones. En nuestro estudio, la paratiroidectomía total con autoimplante es una alternativa segura y efectiva para el tratamiento del hiperparatiroidismo secundario y terciario en pediatría, permitiendo prevenir así complicaciones óseas y cardiovasculares (AU)

Objectives. To describe our initial experience in the treatment of hyperparathyroidism (HPP) of renal cause using total or subtotal parathyroidectomy, autoimplant and cryopreservation in pediatric patients. Secondary HPP is the increased function of the parathyroid hormone (PTH) due to an abnormal phosphocalcic metabolism in patients with chronic renal failure (CRF). This situation produces increased bone resorption resulting in osteodystrophy and endovascular calcifications. Surgical treatment is aimed to diminish the level of PTH in CRF patients, to avoid HPP complications. Method and materials. Descriptive, monocentric and retrospective study of a case series of patients with secondary and tertiary hyperparathyroidism, who went through total or subtotal parathyroidectomy, autoimplant and cryopreservation between 2009 and 2016. We analyzed the following variables: age, calcemia, PTH, phosphatemia, alkaline phosphatase (ALP), follow-up and complications. The continuous variables are expressed in median and interquartile range or in mean and SD, according to their distribution. The categorical variables were expressed in percentages and frequencies (repeated sentence). Results. Number of patients included: 13. Mean age of the patients was 16.7 years old. Preoperative median calcium dosage was 9.1 mg/ dl (IQR: 8.9-9.5). Median PTH was 2,600 pg/ml (IQR: 1,400 pg/ml to 2,785 pg/ml). Intraoperatory dosage of PTH reported a median drop of 86.6% in the first 15 minutes (IQR: 80.5-95.9). After the first 48 hours, median calcemia was 9 mg/dl (IQR: 7.7-9.4) and median PTH was 40 pg/ml (IQR: 20-113). We did not identify intraoperatory complications. In the immediate post operatory stage, mean IV calcium therapy was 4 days (SD: 2.39). Median time of follow-up was 18 months (IQR 9-36). Two patients had hungry bone syndrome and one patient had a recurrence of the pathology as remote post operatory complications. After a year, median calcemia, was 9 mg/dl (IQR: 7.6-9.3) and median PTH was 50 pg/ml (IQR: 28.5-108). The decrease in PTH and ALP were statistically significant with p value (AU)

Platinum compounds and sodium metabolism in children with diencephalic glioma.

In this brief report we have described eight children affected by optic pathway/hypothalamus gliomas and treated with carboplatin and/or cisplatin, which developed a derangement of sodium and water metabolism, due to diabetes insipidus (DI) or to syndrome of inappropriate antidiuretic hormone secretion (SIADH) after surgical resection. In four out of these eight patients the treatment with platinum compounds produced prolonged haematological toxicity and in five out of them it caused neurosensorial bilateral hypoacusia. In addition cisplatin worsened electrolytes disturbances. Hence children with DI or SIADH should be carefully monitored before, during and after the treatment with platinum compounds.

Errors involving patients receiving intrathecal chemotherapy.

Errors involving patients receiving intrathecal chemotherapy are a significant problem in oncology. Despite the improvement in the management of antineoplastic agents, unintentional intrathecal administration of chemotherapic drugs that are indicated only for systemic administration or intrathecal overdose of drugs regularly used for intrathecal chemotherapy, continue to occur. These events can result in severe neurotoxicity, usually fatal in outcome. We review reported cases of medication errors in intrathecal administration of chemotherapy described in the literature. Diverse rescue therapies have been proposed but the most effective means of managing these errors remains prevention.

Treatment of childhood sarcoma with irinotecan: bilirubin level as a predictor of gastrointestinal toxicity.

Irinotecan is a promising anticancer agent for the treatment of childhood cancer unresponsive to conventional chemotherapy. Its active metabolite, 7-ethyl-10 hydroxycamptothecin (SN-38) is glucuronidated by a uridine-diphosphoglucuronosyltransferase (UGT1A1) to form an inactive metabolite. It was supposed that patients with the UGT1A1*28 polymorphism would have a greater prevalence of elevated pretreatment serum bilirubin levels and higher toxicity. The aim of our study was to investigate the predictive value of pre-treatment bilirubin levels in the development of severe diarrhea in solid tumor patients treated with irinotecan. The survey included 14 pediatric patients with refractory sarcomas treated with irinotecan (CPT-11). Patients were grouped based on the development of mild (G0-2) or severe (G3) gastrointestinal toxicity. The simple linear regression model and the non-parametric paired wilcoxon test were adopted for the analysis. p <0.05 was judged to indicate a significant difference. The results showed a significant increase in severity of diarrhea with increasing total pre-treatment bilirubin. therefore, we propose that pre-treatment bilirubin levels can predict gastrointestinal toxicity in pediatric cancer.

Anthracycline cardiotoxicity in childhood.

Over the last 40 years, a significant advance has been made in the treatment of childhood and adult cancers. However, the increase of the survival rate points out medium- and long-term adverse effects that constitute a serious limitation for the quality of life in adults survived from a childhood cancer. Cardiovascular disease is an important cause of morbidity and mortality in adults treated with chemo- and radiotherapy for childhood cancers. Although some antitumor treatments are potentially cardiotoxic, anthracycline therapy and radiotherapy are mostly responsible for long-term cardiac damage. Anthracycline toxicity is generally limited to the myocardium, while radiation can cause injury to all components of the heart. The purpose of this review is to discuss the mechanisms of action of anthracyclines, their cardiotoxicity, the feasibility of screening, and the prevention of cardiac damage after treatment in childhood.

The lumbar puncture in pediatric oncology.

In pediatric oncology, LPs are frequently performed for diagnostic and therapeutic purposes. A LP procedure may be helpful in diagnosing many diseases and disorders. In addition, a LP may be performed therapeutically, to inject medications directly into the spinal canal. Intrathecal administration of antineoplastic drugs allows to bypass the selective filter of BBB and to achieve significant concentrations of the antineoplastic agents in CSF reducing the likelihood of systemic toxicity. Lumbar puncture is generally well tolerated but might be characterized by several disadvantages and risks.

Nefritis tubulo intersticial asociada a parvovirus b19 / Tubulointerstitial nephritis associated with parvovirus beta19 infection

Paciente de 9 años, previamente sana, que ingresa en anasarca con síndrome nefrótico clínico y humoral, asociado a hipertensión arterial y microhematuria, con función renal normal y se comporta como corticorresistente. Se realiza 1° biopsia renal que informa glomerulonefritis proliferativa mesangial difusa con esclerosis focal y segmentaria. En tratamiento con ciclofosfamida y corticoides, presenta síndrome febril prolongado con anemia secundaria a crisis aplásica de la serie roja, asociada con una infección aguda por parvovirus B19, e insuficiencia renal aguda secundaria a nefritis tubulointersticial severa. La PCR para parvovirus B19 DNA fue positiva en tejido renal y médula ósea. La paciente evoluciona a insuficiencia renal crónica terminal. No se puede descartar que desde su inicio, el síndrome nefrótico estuviera asociado al daño glomerular por la infección viral, que comenzó como síndrome nefrótico con componentes nefríticos y que evoluciona inesperadamente a una nefritis tubulointersticial. Este sería el primer caso en el que se documenta como causa de insuficiencia renal crónica terminal, un daño tubulointersticial secundario a parvovirus B19.

Nefritis tubulo intersticial asociada a parvovirus b19 / Tubulointerstitial nephritis associated with parvovirus beta19 infection

Paciente de 9 años, previamente sana, que ingresa en anasarca con síndrome nefrótico clínico y humoral, asociado a hipertensión arterial y microhematuria, con función renal normal y se comporta como corticorresistente. Se realiza 1º biopsia renal que informa glomerulonefritis proliferativa mesangial difusa con esclerosis focal y segmentaria. En tratamiento con ciclofosfamida y corticoides, presenta síndrome febril prolongado con anemia secundaria a crisis aplásica de la serie roja

Treatment with nephrectomy only for small, stage I/favorable histology Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: Children younger than 24 months with small (< 550 g), favorable histology (FH) Wilms tumors (WTs) were shown in a pilot study to have an excellent prognosis when treated with nephrectomy only. PATIENTS AND METHODS: A study of nephrectomy only for the treatment of selected children with FH WT was undertaken. Stringent stopping rules were designed to insure closure of the study if the true 2-year relapse-free survival rate was 90% or lower. RESULTS: Seventy-five previously untreated children younger than 24 months with stage I/FH WTs for which the surgical specimen weighed less than 550 g were treated with nephrectomy only. Three patients developed metachronous, contralateral WT 1.1, 1.4, and 2.3 years after nephrectomy, and eight patients relapsed 0.3 to 1.05 years after diagnosis (median, 0.4 years; mean, 0.51 years). The sites of relapse were lung (n = 5) and operative bed (n = 3). The 2-year disease-free (relapse and metachronous contralateral WT) survival rate was 86.5%. The 2-year survival rate is 100% with a median follow-up of 2.84 years. The 2-year disease-free survival rate (excluding metachronous contralateral WT) was 89.2%, and the 2-year cumulative risk of metachronous contralateral WT was 3.1%. CONCLUSION: Children younger than 24 months treated with nephrectomy only for a stage I/FH WT that weighed less than 550 g had a risk of relapse, including the development of metachronous contralateral WT, of 13.5% 2 years after diagnosis. All patients who experienced relapse on this trial are alive at this time. This approach will be re-evaluated in a clinical trial using a less conservative stopping rule.

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency.

Bone marrow transplantation (BMT) for severe combined immunodeficiency (SCID) with human leukocyte antigen (HLA)-identical sibling donors but no pretransplantation cytoreduction results in T-lymphocyte engraftment and correction of immune dysfunction but not in full hematopoietic engraftment. A case of a 17-month-old girl with adenosine deaminase (ADA) deficiency SCID in whom full hematopoietic engraftment developed after BMT from her HLA-identical sister is reported. No myeloablative or immunosuppressive therapy or graft-versus-host disease (GVHD) prophylaxis was given. Mild acute and chronic GVHD developed, her B- and T-cell functions became reconstituted, and she is well almost 11 years after BMT. After BMT, repeated studies demonstrated: (1) Loss of a recipient-specific chromosomal marker in peripheral blood leukocytes (PBLs) and bone marrow, (2) conversion of recipient red blood cell antigens to donor type, (3) conversion of recipient T-cell, B-cell, and granulocyte lineages to donor origin by DNA analysis, and (4) increased ADA activity and metabolic correction in red blood cells and PBLs.

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors.

Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or non-biopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m2 BCNU, 900 mg/m2 thiotepa and 1500 or 750 mg/m2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both newly diagnosed and recurrent CNS tumors.

Autologous hematopoietic stem-cell transplantation for relapsed or refractory Hodgkin's disease in children and adolescents.

PURPOSE: To determine the treatment outcome and clinical factors that are of prognostic significance for children and adolescents with relapsed or refractory Hodgkin's disease (HD) who received treatment with high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: Fifty-three consecutive children and adolescents 21 years of age or younger with relapsed or refractory HD underwent HSCT. RESULTS: At day 100 after transplantation, 29 patients (55%) were in a complete remission or maintained a continuous complete response, six (11%) had a partial response, and 11 (21%) failed to respond or had progressive disease. The failure-free survival (FFS) at 5 years was 31%, and overall survival was 43%. Twenty-one patients died of progressive HD, and nine died secondary to transplantation-related complications, including two secondary leukemias. Prognostic factors important for FFS were normal pretransplantation lactate dehydrogenase levels (5-year FFS = 42%), compared with patients with elevated LDH levels (5-year FFS = 0%) (P < .001), and disease sensitivity at the time of HSCT with FFS in untreated relapse, sensitive disease, and resistant disease 44%, 35%, and 9%, respectively (P = .06). There was no statistically significant difference in FFS or overall survival between age subgroups that were analyzed (< 13, 13 to 18, 19 to 21) or in comparison with an adult cohort. CONCLUSION: HSCT is an effective treatment modality that can result in long-term cures and should be considered for children and adolescents with relapsed HD.

Allogeneic bone marrow transplantation for children with acute leukemia: long-term follow-up of patients prepared with high-dose cytosine arabinoside and fractionated total body irradiation.

High-dose therapy and allogeneic matched sibling bone marrow transplantation (BMT) is considered to be the treatment of choice for children with relapsed acute lymphoblastic leukemia (ALL), or for children with acute myeloid leukemia (AML) in first remission. However, the rate of bone marrow relapse after transplant for either of these diseases remains high. In this study, we assessed the efficacy and toxicity of high-dose cytosine arabinoside and total body irradiation (TBI) followed by allogeneic BMT, for children with acute leukemia or myelodysplastic syndrome (MDS). Sixty-five pediatric patients underwent allogeneic related (n = 57) or unrelated (n = 8) BMT. Twenty-seven were transplanted for ALL in second remission (CR2), and 16 for AML in first remission (CR1). The other 22 were high risk patients: six were transplanted for ALL in third remission (CR3), two for AML in CR2, two for myelodysplastic syndrome (MDS) and 12 for acute leukemia in relapse. Patients were prepared with cytosine arabinoside 3000 mg/m2 per dose twice daily for 6 days followed by 12000 cGy TBI as 200 cGy fractions twice daily for 3 days. Minimum follow-up is 21 months. Five-year event-free survival (EFS) and the actuarial relapse rate is 59 and 14% for patients with ALL in second remission, and 38 and 14+% for patients with AML in first remission. Twelve patients have relapsed (three are alive in remission after testicular or marrow relapse) and 28 have died of other causes. Acute GVHD with or without infection was the cause of death in 11 patients. Ten of the 11 patients who died of acute GVHD were considered at 'high risk' for GVHD (inadequate GVHD prophylaxis, or mismatched family donor or a matched unrelated donor). Toxicities in the immediate post-BMT period included diarrhea, oropharyngeal mucositis and conjunctivitis. Significant late toxicities included short stature, avascular necrosis of bone, and poor school performance (most often in patients who had received prior cranial irradiation). Our conclusions are that high-dose Ara-C and TBI followed by allogeneic bone marrow transplantation is effective therapy for children in second complete remission of their acute leukemia. However, significant late toxicities occur, and it is clear that more effective, less toxic therapies are necessary for these patients.

Treatment of veno-occlusive disease of the liver with bolus tissue plasminogen activator and continuous infusion antithrombin III concentrate.

Veno-occlusive disease (VOD) of the liver is a common complication of BMT and is accompanied by reduced levels of natural anticoagulants and by multi-organ dysfunction. We describe two cases of clinical VOD developing after autologous BMT and accompanied by ultrasonographic features of reversed portal venous flow. In both cases the patients had decreased levels of antithrombin (AT). Once the diagnosis of VOD was made, these patients were treated with tissue plasminogen activator (tPA) and continuous infusion AT. Each patient had radiographic and clinical resolution of VOD with the therapy. This novel treatment appears to have reversed the course of VOD without the increased risk of bleeding seen in the use of heparin therapy.

Computer-aided semen analysis: sperm concentration assessment by the Strömberg-Mika system.

The scope of this study was to evaluate the accuracy, precision and specificity of the sperm concentration measurements by the Strömberg-Mika Cell Motion Analyser (SM-CMA). Our data show that the instrument generally underscores the sperm concentration and therefore the uncorrected measurements must be corrected by the operator using the 'mouse'-driven option. In terms of precision, the system appears to have an excellent internal precision whereas its repeatability is influenced by the sperm concentration, the sample's homogeneity and the correction of the raw data. In order to increase the system's repeatability, we suggest that sperm counts should be carried out in various fields of the counting chamber, and the mean of the corrected values be taken as representative of the sperm concentration in the ejaculate if the various measurements show a homogeneous (poissonian) distribution. The correction of the raw data with the 'mouse'-driven correction option was also shown to improve the system's reproducibility. Concerning specificity, our data evidenced that, without technical correction, the instrument failed to correctly classify certain spermatozoa as such, thereby grossly underscoring sperm counts. This finding was more evident at low sperm counts. Overall, the SM-CMA requires additional laboratory time but the corrected sperm counts are comparable to manual counts and semi-automated counts with the added option that it provides the andrologists with various motility characteristics not possible with the latter methodologies.

Low numbers of CSF blasts at diagnosis do not predict for the development of CNS leukemia in children with intermediate-risk acute lymphoblastic leukemia: a Childrens Cancer Group report.

PURPOSE: This study was designed to evaluate the effect on CNS relapse (CNSR) and overall relapse rates of blast cells in the CSF containing < or = 5 cells/microL at the time of diagnosis of intermediate-risk acute lymphoblastic leukemia (ALL) in children entered onto a large randomized multicenter prospective therapeutic trial (Childrens Cancer Group [CCG]-105). PATIENTS AND METHODS: We studied outcome in terms of CNSR and event-free survival (EFS) in 1,544 patients who successfully completed remission-induction therapy and had been randomized to one of four systemic chemotherapy regimens and to one of two CNS prophylaxis regimens. We compared outcome between 1,450 patients who had varying degrees of pleocytosis but no blasts in the CSF at diagnosis (blast-negative group) with 94 who had blasts detected in the CSF after cytocentrifugation but had a total CSF WBC count of < or = 5/microL (blast-positive group). RESULTS: No statistically significant differences in overall CNSR or EFS rates were observed between the two groups and no differences were found when analyzed according to age or WBC count at diagnosis, sex, or type of CNS prophylaxis (intrathecal [IT] methotrexate [MTX] alone v IT MTX plus 18 Gy cranial irradiation [CXRT]). CONCLUSION: In intermediate-risk ALL, there was no significant difference in CNSR and systemic relapse rates after standard presymptomatic CNS therapy between patients with a CSF WBC count < or = 5/microL and those without identifiable blasts in the CSF. These findings suggest that certain approaches to therapy, such as that used in this study, may eliminate the need for any additional special treatment directed at this subset of patients with CSF blasts.

Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis after hematopoietic stem-cell transplantation.

PURPOSE: Oral mucositis following high-dose chemotherapy may result in systemic infection and airway compromise, and the severity of oral mucositis may be dose-limiting. Here we investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), which significantly shortens duration of neutropenia after hematopoietic stem-cell transplantation (HSCT) on oral mucositis. PATIENTS AND METHODS: Thirteen children undergoing HSCT were prepared with etoposide (VP-16), thiotepa (TT), and total-body irradiation (TBI), and 13 with VP-16, TT, and cyclophosphamide (CPM). Following transplantation, 14 patients received GM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion (six prepared with VP-16, TT, and TBI, and eight prepared with VP-16, TT, and CPM), and 12 patients received no growth factor. RESULTS: Mucositis was more severe and persisted longer in patients prepared with the TBI-containing regimen. For this regimen, the duration of severe oral mucositis was shortened by the administration of GM-CSF, although the severity of mucositis was unaffected. No statistically significant effect of GM-CSF could be shown in patients who received VP-16, TT, and CPM. The incidence of positive fungal oral or blood cultures did not appear different whether patients received GM-CSF or not. CONCLUSION: For patients undergoing stomatotoxic HSCT regimens, GM-CSF may reduce the duration of oral mucositis, but is unlikely to effect the severity of oral mucositis or risk of airway compromise, and the severity of mucositis is likely to remain dose-limiting.

Peripheral T-cell lymphoma in children and adolescents: role of bone marrow transplantation.

Although PTCL in children, as in adults, has a spectrum of clinical, morphologic, cytogenetic and immunologic features, there are several significant differences in these features between children and adults. Our data show that CD30 expression is much more common in pediatric PTCL than is reported in adult PTCL. Furthermore, the majority of children with CD30-positive PTCL do not have tumors with anaplastic large cell histology. Our data also suggest that the t(2;5) is not a specific marker of anaplastic large cell lymphoma in childhood. The likelihood of cure for children with PTCL is unclear, predominantly because of the lack of large numbers of pediatric patients with this less common entity. As with other NHL, we expect that treatment with conventional dose chemotherapy following relapse will be unsuccessful in most cases. Although the data are preliminary, it appears that high dose chemoradiotherapy followed by hematopoietic stem cell transplantation is an effective therapy in these patients. We have been particularly successful with a regimen based on thioTEPA, VP-16 and total body irradiation, but other regimens may also be efficacious. Further studies of this interesting group of tumors are clearly needed.