A case report: hepatic posttransplant lymphoproliferative disorder in a non-liver transplant patient.

Posttransplant lymphoproliferative disorder (PTLD) is the most common malignancy in children after solid organ transplantation. We present a patient, who developed Epstein-Barr virus (EBV)-related PTLD in the liver after renal transplantation. A 10-year-old EBV-seronegative boy with cystinosis underwent a living related preemptive renal transplantation. He received antiviral prophylaxis with valacyclovir. At 5.5 months posttransplantation he displayed a primary EBV infection with an high fever, hepatosplenomegaly, monocytosis, and positive EBV DNA levels. Two months there after, a hypoechoic nodular 20-mm lesion in the left lobe of liver was detected on abdominal ultrasonography, performed because of anorexia and weight loss. EBV-DNA copy number was 7820 copies per milliliter. Liver biopsy showed a diffuse large B-cell lymphoma that was compatible with PTLD. We stopped all immunosupressive agents other than prednisolone. Chemotherapy consisting of two courses of cyclophosphamide, vincristine, prednisolone, and adriamycin was followed by rituximab. Within 2 months, the lesion resolved and within 18 months, he was free of disease.

Posttransplant lymphoproliferative disorders in transplant recipients.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% and 32%. The incidence of PTLD mainly depends on the transplanted organ, the immunosuppressive drugs, the viral serology, and the age of the recipient. The aim of our study was to analyze our patients diagnosed with PTLD. Among 1040 transplantations, including 931 renal, 14 heart, 55 liver and 40 allogeneic peripheral blood stem cell (PBSC), 8 patients (7 male, 1 female) were diagnosed with PTLD. Five patients had undergone renal, one cardiac, one liver, and one PBSC transplantations. Four patients were diagnosed within the first year of transplantation. Six patients presented with abdominal disease, one with convulsions, and one with peripheral lymph node involvement. According to the World Health Organization classification system, six patients were diagnosed as diffuse large B-cell lymphoma, one patient Burkitt's lymphoma, and one polymorphic PTLD. At the time of diagnosis, 7 patients showed positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Ig G and negative Ig M; one patient, positive EBV Ig M and negative CMV Ig G and M. EBV viral load was extremely high in the plasma of two patients by polymerase chain reaction. One of these patient's pathologic tissue revealed positive EBV DNA, which was not detected in six of the other eight patients. This patient was an 8-year-old boy diagnosed with Burkitt's lymphoma at 31 months after liver transplantation. Seven patients died of disease or complications of chemotherapy. Only one patient survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate was high among our patients with PTLD. To decrease the incidence of PTLD and related mortality, risk factors must be evaluated in multicenter studies.

High-dose acyclovir and pre-emptive ganciclovir in prevention of cytomegalovirus disease in pediatric patients following peripheral blood stem cell transplantation.

Cytomegalovirus (CMV) disease remains an important cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). We evaluated high-dose acyclovir (HDACV) and pre-emptive ganciclovir to prevent CMV disease in 76 children who underwent peripheral blood stem cell transplantation (PBSCT) and were at risk for CMV reactivation and disease (both recipient and donor seropositive) from May 1998 to April 2003. All received HDACV from day -9 to 6 months post transplant in conjunction with weekly CMV pp65 antigenemia monitoring. The incidence of antigenemia in this cohort was 19.7%, at a median of 22 days post-PBSCT. The frequencies were 26.4 and 4.4% in allogeneic and autologous groups, respectively (P=0.03). Patients with nonmalignant disease had higher CMV antigenemia than those with malignant disease (30.8 vs 8.1%, P=0.02). Age at PBSCT, sex, graft-versus-host disease (GVHD) prophylaxis regimen and presence of acute GVHD did not affect the risk of CMV antigenemia. None of the patients who had positive pp65 antigenemia developed CMV disease during the study period. We conclude that pp65 antigenemia-guided HDACV and pre-emptive ganciclovir may prevent CMV disease in children undergoing PBSCT.

Peripheral blood stem cell transplantation in children with beta-thalassemia.

Fifteen patients with beta-thalassemia received an allogeneic peripheral blood stem cell transplant. Median age was 3.5 years (1-15 years). Six were class I, four class II and five class III according to the Pesaro criteria. All of the donors were HLA-phenotypically identical (13 siblings and two parents). Nine patients were given BU + CY and six BU + CY plus ATG as conditioning. All patients received MTX (+1, +3, +6) and CsA (9-12 months) post transplant for GVHD prophylaxis. The median neutrophil and platelet engraftment times were day 12 and day 16, respectively. cGVHD was observed in three patients. Two patients died. Thirteen patients are well, and transfusion-independent 2-30 months after PSCT. No recurrences of thalassemia have been seen. Overall and event-free survival were 86.6%. In conclusion, we suggest that PSCT can be considered a safe and effective treatment for children with beta- thalassemia.

Peripheral stem cell transplantation in a child with amegakaryocytic thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is an unusual cause of thrombocytopenia without radial or other congenital anomalies in the newborn. Generalized bone marrow dysfunction developing later in life has been reported. We present a 13-month-old girl who was diagnosed as having congenital amegakaryocytic thrombocytopenia and was successfully treated with allogeneic peripheral stem cell transplantation (PSCT) from her fully matched sibling donor. The neutrophil engraftment was on post transplant day 12 and platelet engraftment was on day 14. Her last hemogram revealed platelets of 168 x 10(9)/l 20 months post transplant.

Hodgkin's disease and renal paraneoplastic syndromes in childhood.

The purpose of this study was to investigate children followed as having both Hodgkin's disease (HD) and nephropathy and discuss the factors which might play roles in the pathogenesis of this association by reviewing the pertinent literature. Our experience among 661 children with HD revealed ten cases (1.5%) with nephropathy; eight of these were biopsy proven. Tissue diagnoses were amyloidosis (AA type) in four cases, and membranoproliferative glomerulonephritis and minimal change glomerulopathy in two cases each. Sex distribution was equal. There was a predominance of the mixed cellular (MC) histologic type in our patients with HD. Nephropathy was shown to antedate the diagnosis of HD in two cases and to herald a relapse in one. In brief, the development of a nephropathy in a patient with HD can be considered as a paraneoplastic phenomenon. Renal amyloidosis may already be present at the time of diagnosis of HD and must be kept in mind as a cause of proteinuria due to preexisting nephropathy. Developing renal paraneoplastic syndrome, even in early-staged HD, in children, may be a poor prognostic factor.

Hodgkin's disease in Turkish children: clinical characteristics and treatment results of 210 patients.

Although Hodgkin's disease (HD) is one of the common malignancies in childhood, there is limited information from developing countries in English literature. The aim of this study is to give epidemiologic features and treatment results of 210 previously untreated children with HD from a developing country. Between 1 June 1984 and 31 December 1992, all children seen who were younger than 18 years old with newly diagnosed, untreated, biopsy-proven Hodgkin's disease were included in this study. A clinical staging system was used to determine the dissemination of the disease. While patients with stage I-II disease received canapé treatment protocol (three cycles COPP [cyclophosphamide, vincristine, procarbazine, prednisolone] or ABVD [doxorubicin, bleomycine, vinblastine, dacarbazine] plus low-dose involved-field radiotherapy), patients with stage III-IV disease were treated by sandwich protocol (six cycles COPP plus low-dose involved-field radiotherapy). A total of 210 patients with a median age of 8 years were eligible for this study. Male to female ratio was 3:1 and 37 (17.6%) were less than 5 years of age. The major histologic subtype was mixed cellularity (69.6%). Overall survival rates were 91.5 and 87.7%, and event-free survival rates were 71.5 and 70.5% at 5 and 10 years, respectively. No secondary malignancy has been observed so far. The prevalence of Hodgkin's disease in young children is higher and the distribution of histologic subtypes is also different from many Western countries. Canapé and sandwich treatment protocols could be used safely in clinically staged childhood HD with tolerable toxicity.

Failure of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in a patient with Kostmann syndrome.

We present a seven-month-old boy referred to our hospital with a history of recurrent suppurative infections starting in his neonatal period. Anemia, absolute neutropenia absolute neutrophil count (ANC: 500 cells/microl), pneumonia, purulent otitis media and maturational arrest of granulocytes at promyelocyte-myelocyte level in bone marrow were detected on his admission. He was diagnosed as Kostmann syndrome and recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy was started at a dose of 10 microg/kg/d, gradually increasing up to 120 microg/kg/d in sequential seven-day courses. As there was no response, rhG-CSF was stopped and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was started subcutaneously with 2.5 microg/kg/d and was escalated by doubling the dose every seven days to 20 mg/kg/d. By this therapy absolute neutrophil count (ANC) transiently reached above 500 cells/microl, but eosinophilia developed with a total white cell count of 88.200 cells/microl, and a differential count showing 86 percent eosinophils. Since eosinophilia of this magnitude has deleterious effects, and neutrophil production did not significantly increase, we tried combined therapy with rhG-CSF and rhGM-CSF at doses of 10-20 microg/kg/d and 5-10 microg/kg/d, respectively, without any effect on absolute neutrophil count. The patient succumbed from sepsis eight months after the diagnosis.

Veno-occlusive disease-like hepatotoxicity in two children receiving chemotherapy for Wilms' tumor and clear cell sarcoma of kidney.

We report two pediatric cases who developed veno-occlusive disease-like hepatotoxicity while receiving chemotherapy for Wilms' tumor and clear cell sarcoma of kidney. The chemotherapeutics, including vincristine, actinomycin D, and epirubicin in case 1 and vincristine and actinomycin D in case 2, were given before the hepatotoxicity developed. Other possible causes of hepatotoxicity were excluded. Recovery was observed with supportive therapy after 2 and 1 weeks, respectively. After recovery, the children tolerated continued chemotherapy without any decrease in the doses of drugs. We conclude that vincristine and actinomycin D were the cause of this rare from of hepatotoxicity and that chemotherapy for the underlying malignant disease could be given safely after clinical recovery.

Childhood cancer and hypercalcemia: report of a case treated with pamidronate.

Hypercalcemia in a 4-year-old boy with non-Hodgkin lymphoma treated with pamidronate is presented. The child had relapsed disease with bone metastasis. Hypercalcemia is rare in children, and bisphosphonates are relatively new agents for the treatment of hypercalcemia. Information concerning their use in the treatment of hypercalcemia in childhood is limited. We found that pamidronate is effective and has no significant side effects in a child.

A linkage analysis in two families with bilateral retinoblastoma.

Using polymerase chain reaction (PCR) amplification from blood samples, Xbal and BamHI polymorphisms were analyzed in two families with bilateral retinoblastoma. In one of the families it was predicted using the BamHI polymorphism that the 200 bp allele co-segregates with the disease. This family was uninformative for Xbal polymorphism. The second family was uninformative for both Xbal and BamHI polymorphism.

Vasculitis as a cause of diarrhea and gastrointestinal hemorrhage: a case report.

A 13-year-old girl was hospitalized for fever, malaise, intractable diarrhea, and intermittent gastrointestinal hemorrhage. Despite aggressive antimicrobial and supportive treatment, she died with massive bleeding from the upper gastrointestinal tract. Autopsy study revealed systemic polyarteritis nodosa of classic form in the right lung and gastrointestinal tract and of microscopic form in kidneys.