A study of the mutational landscape of pediatric-type follicular lymphoma and pediatric nodal marginal zone lymphoma. Modern pathology 2016; 29 (10): 1212-1220
Pediatric-type follicular lymphoma and pediatric marginal zone lymphoma are two of the rarest B-cell lymphomas. These lymphomas occur predominantly in the pediatric population and show features distinct from their more common counterparts in adults: adult-type follicular lymphoma and adult-type nodal marginal zone lymphoma. Here we report a detailed whole-exome deep sequencing analysis of a cohort of pediatric-type follicular lymphomas and pediatric marginal zone lymphomas. This analysis revealed a recurrent somatic variant encoding p.Lys66Arg in the transcription factor interferon regulatory factor 8 (IRF8) in 3 of 6 cases (50%) of pediatric-type follicular lymphoma. This specific point mutation was not detected in pediatric marginal zone lymphoma or in adult-type follicular lymphoma. Additional somatic point mutations in pediatric-type follicular lymphoma were observed in genes involved in transcription, intracellular signaling, and cell proliferation. In pediatric marginal zone lymphoma, no recurrent mutation was identified; however, somatic point mutations were observed in genes involved in cellular adhesion, cytokine regulatory elements, and cellular proliferation. A somatic variant in AMOTL1, a recurrently mutated gene in splenic marginal zone lymphoma, was also identified in a case of pediatric marginal zone lymphoma. The overall non-synonymous mutational burden was low in both pediatric-type follicular lymphoma and pediatric marginal zone lymphoma (4.6 mutations per exome). Altogether, these findings support a distinctive genetic basis for pediatric-type follicular lymphoma and pediatric marginal zone lymphoma when compared with adult subtypes and to one another. Moreover, identification of a recurrent point mutation in IRF8 provides insight into a potential driver mutation in the pathogenesis of pediatric-type follicular lymphoma with implications for novel diagnostic or therapeutic strategies.Modern Pathology advance online publication, 24 June 2016; doi:10.1038/modpathol.2016.102.
View details for DOI 10.1038/modpathol.2016.102
View details for PubMedID 27338637
Safety Report of Ferumoxytol for Magnetic Resonance Imaging in Children and Young Adults INVESTIGATIVE RADIOLOGY 2016; 51 (4): 221-227
The aim of this study was to assess the safety profile of ferumoxytol as an intravenous magnetic resonance imaging contrast agent in children.We prospectively evaluated the safety of ferumoxytol administrations as an "off-label" contrast agent for magnetic resonance imaging in nonrandomized phase 4 clinical trials at 2 centers. From September 2009 to February 2015, 49 pediatric patients (21 female and 28 male, 5-18 years) and 19 young adults (8 female and 11 male, 18-25 years) were reported under an investigator-initiated investigational new drug investigation with institutional review board approval, in health insurance portability and accountability act compliance, and after written informed consent of the child's legal representative or the competent adult patient was obtained. Patients received either a single dose (5 mg Fe/kg) or up to 4 doses of ferumoxytol (0.7-4 mg Fe/kg) intravenously, which were approximately equivalent to one third of the dose for anemia treatment. We monitored vital signs and adverse events directly for up to 1 hour after injection. In addition, we examined weekly vitals, hematologic, renal, and liver serum panels for 1 month after injection in over 20 pediatric patients. At fixed time points before and after ferumoxytol injection, data were evaluated for significant differences by a repeated measures linear mixed model.Four mild adverse events, thought to be related to ferumoxytol, were observed within 1 hour of 85 ferumoxytol injections: 2 episodes of mild hypotension and 1 case of nausea in 65 injections in pediatric patients without related clinical symptoms. One young adult patient developed warmness and erythema at the injection site. All adverse events were self-resolving. No spontaneous serious adverse events were reported. At a dose of 5 mg Fe/kg or lower, intravenous ferumoxytol injection had no clinical relevance or statistically significant effect (P > 0.05) on vital signs, hematological parameters, kidney function, or liver enzymes within 1 month of the injection.Ferumoxytol was overall well tolerated among 49 pediatric and 19 young adult patients experiencing various tumors or kidney transplants without major adverse events or signs of hematologic and kidney impairment or liver toxicity. Larger studies are needed to determine the incidence of anaphylactic reactions.
View details for DOI 10.1097/RLI.0000000000000230
View details for Web of Science ID 000372451200002
Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary? Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2016; 57 (1): 70-77
With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images.First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging.There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors.Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions.
View details for DOI 10.2967/jnumed.115.161646
View details for PubMedID 26471690
Progressing Toward a Cohesive Pediatric F-18-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary? JOURNAL OF NUCLEAR MEDICINE 2016; 57 (1): 70-77
The utility of IgM, CD21, HGAL and LMO2 in the diagnosis of pediatric follicular lymphoma HUMAN PATHOLOGY 2015; 46 (4): 629-633
Pediatric follicular lymphoma (pFL) is a rare neoplasm with features differing from follicular lymphoma arising in adults. Here, we describe a rare case of pFL that showed morphologic features partially overlapping with progressive transformation of germinal centers and reactive follicular hyperplasia. As typical of pFL, neoplastic B cells within follicles did not express B-cell leukemia/lymphoma 2 (BCL2). However, this case showed additional distinctive abnormal findings, which contributed to the diagnosis: (1) diffuse and uniform staining of immunoglobulin M (IgM) on cells within and outside of follicles, (2) abnormally dim expression of CD21 on follicular dendritic cells, and (3) expression of human germinal center-associated lymphoma (HGAL) and LIM domain only 2 (LMO2) on B cells in interfollicular and follicular areas. This case demonstrates the utility of these abnormal features, which can be seen in adult- or usual-type follicular lymphoma, in the diagnosis of pFL. Further studies are necessary to evaluate the significance of these findings in other cases of pFL.
View details for DOI 10.1016/j.humpath.2014.12.016
View details for Web of Science ID 000352117000020
Improved Outcomes after Autologous Bone Marrow Transplantation for Children with Relapsed or Refractory Hodgkin Lymphoma: Twenty Years Experience at a Single Institution BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 2015; 21 (2): 326-334
The purpose of this study is to evaluate the survival of pediatric patients undergoing autologous bone marrow transplantation (auBMT) for relapsed or refractory Hodgkin lymphoma (rrHL) and to identify factors that might contribute to their outcome. We reviewed the records and clinical course of 89 consecutive rrHL patients 21 years old who underwent auBMT at Stanford Hospitals and Clinics and the Lucile Packard Children's Hospital, Stanford between 1989 and 2012. We investigated, by multiple analyses, patient, disease, and treatment characteristics associated with outcome. Endpoints were 5-year overall and event-free survival. Our findings include that cyclophosphamide, carmustine, and etoposide (CBV) as a conditioning regimen for auBMT is effective for most patients 21 years old with rrHL (5-year overall survival, 71%). Transplantation after the year 2001 was associated with significantly improved overall survival compared with our earlier experience (80% compared with 65%). Patients with multiply relapsed disease or with disease not responsive to initial therapy fared less well compared with those with response to initial therapy or after first relapse. Administration of post-auBMT consolidative radiotherapy (cRT) also appears to contribute to improved survival. We are able to conclude that high-dose chemotherapy with CBV followed by auBMT is effective for the treatment of rrHL in children and adolescents. Survival for patients who undergo auBMT for rrHL has improved significantly. This improvement may be because of patient selection and improvements in utilization of radiotherapy rather than improvements in chemotherapy. Further investigation is needed to describe the role of auBMT across the entire spectrum of patients with rrHL and to identify the most appropriate preparative regimen with or without cRT therapy in the treatment of rrHL in young patients.
View details for DOI 10.1016/j.bbmt.2014.10.020
View details for Web of Science ID 000348632700018
Evaluation of Febrile, Nonneutropenic Pediatric Oncology Patients with Central Venous Catheters Who Are Not Given Empiric Antibiotics JOURNAL OF PEDIATRICS 2015; 166 (1): 157-162
To evaluate the practice of empiric antibiotics for febrile, nonneutropenic pediatric oncology patients with a central venous catheter (CVC) in place.Episodes of fever without neutropenia (absolute neutrophil count [ANC] 500 cells/mm(3)) were reviewed retrospectively in pediatric oncology patients with a CVC undergoing chemotherapy. Characteristics and symptoms were compared between patients with bacteremia and patients without bacteremia.A total of 392 episodes of nonneutropenic fever in 138 subjects (52 females; 38%) were reviewed. In this cohort, the median age at an episode was 7years, and the majority of patients had a diagnosis of acute leukemia (54%). Median ANC was 3100 cells/mm(3) (IQR, 1570-5980 cells/mm(3)). Median temperature was 38.7C (IQR, 38.3-39.2C). Twenty-four infectious episodes (6%) occurred in 18 subjects, and 5 CVCs required removal; all patients requiring removal admitted and received antibiotics owing to chills. There were no significant difference in age, sex, or ANC between patients with bacteremia and those without bacteremia; however, mean temperature was higher in the patients with bacteremia (39.4C vs 38.7C; P=.003). No deaths due to sepsis occurred, and no CVCs were removed because antibiotics were not administered empirically.Our practice of observing pediatric oncology patients undergoing chemotherapy with CVCs who are not neutropenic does not appear to lead to increased serious adverse outcomes and avoids antibiotic exposure for >90% of patients without a bacterial infection.
View details for DOI 10.1016/j.jpeds.2014.09.008
View details for Web of Science ID 000346584000032
View details for PubMedID 25444524
Hodgkin Lymphoma Following Adalimumab for the Treatment of Crohn's Disease in an Adolescent DIGESTIVE DISEASES AND SCIENCES 2014; 59 (10): 2403-2405
Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala CANCER LETTERS 2014; 351 (1): 59-63
Analysis of 327 consecutive cases at a pediatric referral hospital of Guatemala reveals that retinoblastoma accounts for 9.4% of all cancers and the estimated incidence is 7.0 cases/million children, higher than the United States or Europe. The number of familial cases is low, and there is a striking disparity in indigenous children due to late diagnosis, advanced disease, rapid progression and elevated mortality. Nine germline mutations in 18 patients were found; two known and five new mutations. Hypermethylation of RB1 was identified in 13% of the tumors. An early diagnosis program could identify cases at an earlier age and improve outcome of retinoblastoma in this diverse population.
View details for DOI 10.1016/j.canlet.2014.04.023
View details for Web of Science ID 000339775300008
View details for PubMedID 24814393
SIOP PODC Adapted Treatment Recommendations for Standard-Risk Medulloblastoma in Low and Middle Income Settings PEDIATRIC BLOOD & CANCER 2014; 62 (4): 553-564
Ionising radiation-free whole-body MRI versus F-18-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study LANCET ONCOLOGY 2014; 15 (3): 275-285
Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent.We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879.22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 125 mSv (SD 41) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 937% (95% CI 890-968) versus 908% (855-947); specificities 977% (95% CI 967-985) versus 995% (989-998); and diagnostic accuracies 972% (936-994) versus 983% (974-992). Tumour staging results showed very good agreement between both imaging modalities with a of 093 (081-100). No adverse events after administration of ferumoxytol were recorded.Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures.Thrasher Research Fund and Clinical Health Research Institute at Stanford University.
View details for DOI 10.1016/S1470-2045(14)70021-X
View details for Web of Science ID 000332399900038
SIOP-PODC recommendations for graduated-intensity treatment of retinoblastoma in developing countries PEDIATRIC BLOOD & CANCER 2013; 60 (5): 719-727
Retinoblastoma remains incurable in many regions of the world. The major obstacles to cure are delayed diagnosis, poor treatment compliance, and lack of evidence-based recommendations for clinical management. Although enucleation is curative for intraocular disease, in developing countries retinoblastoma is often diagnosed after the disease has disseminated beyond the eye. A SIOP-PODC committee generated guidelines for the clinical management of retinoblastoma in developing countries and developed a classification system based on the resources available in those settings. Recommendations are provided for staging and treatment of unilateral and bilateral retinoblastoma and counseling of families for whom compliance is an issue.
View details for DOI 10.1002/pbc.24468
View details for Web of Science ID 000316291700003
View details for PubMedID 23335388
Retinoblastoma in Central America: Report from the Central American Association of Pediatric Hematology Oncology (AHOPCA) PEDIATRIC BLOOD & CANCER 2012; 58 (4): 545-550
Retinoblastoma is highly curable in high income countries. Low income countries have poor results due to advanced disease and lack of resources. Central American Association of Pediatric Hematology Oncology (AHOPCA) aimed to standardize the approach and to improve outcomes of patients with retinoblastoma.One hundred seventy-one patients, age <18 years newly diagnosed with retinoblastoma were treated according to laterality and stage. Therapeutic modalities were: surgery (enucleation), local control (laser therapy, cryotherapy), chemotherapy, and radiation therapy. Chemotherapy consisted of vincristine, etoposide, and carboplatin (6 cycles). Outcomes were measured by overall survival. Events were abandonment of therapy and death.One hundred seventy-one patients (129 unilateral, 42 bilateral) were treated. Median age was 2 years 4 months; 112 (66%) were diagnosed before 3 years of age. 119 (92%) eyes in patients with unilateral disease were Reese-Ellsworth IV or V versus 52 (62%) eyes in patients with bilateral disease. Extraocular disease was more prevalent in unilateral disease (65% vs. 50%). Older age at diagnosis correlated with higher stage. Estimated overall survival at 60 months was 0.48??0.04. Outcome of patients with bilateral disease was significantly better than unilateral (62%??0.09 vs. 42%??0.05, P?=?0.0006). Thirty-eight patients (22%) refused or abandoned therapy.Protocol-directed therapy for retinoblastoma in Central America is possible. Patients present with advanced disease and outcome is significantly worse than in middle and high-income countries. Refusal and abandonment of therapy are societal events that affect outcome. Initiatives aimed at improving early diagnosis, while dedicated treatment centers are developed, are critical.
View details for DOI 10.1002/pbc.23307
View details for Web of Science ID 000300502800013
View details for PubMedID 21910211
Abandonment of Treatment for Childhood Cancer: Recommendations of the SIOP Pediatric Oncology in Developing Countries Abandonment of Treatment Working Group. 2011; In press
Retinoblastoma en Guatemala: Diagnstico Temprano Salva Vidas. Retinoblastoma en Guatemala: Diagnstico Temprano Salva Vidas. 2010
Neuroblastoma Involvement of the Falx Cerebri PEDIATRIC BLOOD & CANCER 2009; 53 (7): 1337-1339
Involvement of the falx cerebri in infants with stage 4 neuroblastoma is thought to be rare. The falx is derived from the neural crest and thus may be a location for primary neuroblastoma. Its propensity for metastasis is unknown. Management of neuroblastoma in this location is potentially challenging. We describe two children less than 18 months of age who were successfully managed with chemotherapy alone (without radiation or surgery) for falx involvement with neuroblastoma.
View details for DOI 10.1002/pbc.22192
View details for Web of Science ID 000271363800033
View details for PubMedID 19821537
Development of Retinoblastoma Programs in Central America PEDIATRIC BLOOD & CANCER 2009; 53 (1): 42-46
Retinoblastoma, a curable eye tumor, is associated with poor survival in Central America (CA). To develop a retinoblastoma program in El Salvador, Guatemala, and Honduras, twinning initiatives were undertaken between local pediatric oncology centers, nonprofit foundations, St. Jude Children's Research Hospital, and the University of Tennessee Hamilton Eye Institute.The retinoblastoma program focused on developing early diagnosis programs in Honduras with national vaccination campaigns, developing treatment protocols suited to local conditions, building local networks of oncologists and ophthalmologists, training local healthcare providers, using modern donated equipment for diagnosis and treatment, and the ORBIS Cybersight consultation program and Internet meetings to further education and share expertise. Pediatric ophthalmologists and oncologists worked with foundations to treat patients locally with donated equipment and Internet consultations, or at the center in Guatemala.Number of patients successfully treated increased after the program was introduced. For 2000-2003 and 2004-2007, patients abandoning/refusing treatment decreased in Guatemala from 20 of 95 (21%) to 14 of 123 (11%) and in Honduras from 13 of 37 (35%) to 7 of 37 (19%). Survival in El Salvador was good and abandonment/refusal low for both periods. Of 18 patients receiving focal therapy for advanced disease, 14 have single remaining eyes.Development of the program in CA has decreased abandonment/refusal and enabled ophthalmologists at local centers to use modern equipment to provide better treatment. This approach might serve as a guide for developing other multispecialty programs.
View details for DOI 10.1002/pbc.21984
View details for Web of Science ID 000266186200010
View details for PubMedID 19326423
Treating Pediatric Soft Tissue Sarcomas in a Country With Limited Resources: The Experience of the Unidad Nacional de Oncologia Pediatrica in Guatemala PEDIATRIC BLOOD & CANCER 2008; 51 (6): 760-764
About 250-300 children with newly diagnosed cancer are treated each year at the Unidad Nacional de Oncologia Pediatrica in Guatemala City; less than 5% of them have soft tissue sarcomas (STS). The aim of the article was to evaluate whether the therapeutic standards achieved in STS in developed countries could be reproduced in a low-income country.We reviewed the clinical data, treatment and outcome of 80 patients, 47 cases of rhabdomyosarcoma (RMS) and 33 of non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), treated between January 2000 and October 2007.Most of the RMS patients had advanced disease at diagnosis (87% groups III-IV). Their 3-year event-free survival rate (EFS) was 26.4% if abandoning the treatment was considered as an event, or 32.4% if it was censored (14 patients abandoned the treatment), and the 3-year overall survival rate (OS) was 43.5%. Local progression/relapse was the main cause of treatment failure. Among the patients with NRSTS, the EFS at 3 years was 36.4% (when abandoning the treatment was considered as an event) or 43.3% (when it was censored), and the OS was 44.2%. Outcome was satisfactory for synovial sarcoma patients, those with tumors < or =5 cm, and those with localized disease.Overall results were unsatisfactory compared to results reported from developed countries. Late diagnosis and the consequently high proportion of cases of advanced disease at diagnosis, the large number of patients failing to complete the treatment, and the poor quality of local control (in RMS) adversely influence outcome.
View details for DOI 10.1002/pbc.21699
View details for Web of Science ID 000260289300009
View details for PubMedID 18680154
Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group BLOOD 2008; 111 (3): 1044-1053
CCG-2961 incorporated 3 new agents, idarubicin, fludarabine and interleukin-2, into a phase 3 AML trial using intensive-timing remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification. Among 901 patients under age 21 years, 5-year survival was 52%, and event-free survival was 42%. Survival improved from 44% between 1996 and 1998 to 58% between 2000 and 2002 (P = .005), and treatment-related mortality declined from 19% to 12% (P = .025). Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88%, similar to historical controls. Postremission survival was 56% in patients randomized to either 5-drug reinduction or fludarabine/cytarabine/idarubicin. For patients with or without a related donor, respective 5-year disease-free survival was 61% and 50% (P = .021); respective survival was 68% and 62% (P = .425). Donor availability conferred no benefit on those with inv(16) or t(8;21) cytogenetics. After cytarabine intensification, patients randomized to interleukin-2 or none experienced similar outcomes. Factors predictive of inferior survival were age more than 16 years, non-white ethnicity, absence of related donor, obesity, white blood cell count more than 100 000 x 10(9)/L, -7/7q-, -5/5q-, and/or complex karyotype. No new agent improved outcomes; experience may have contributed to better results time.
View details for DOI 10.1182/blood-2007-04-084293
View details for Web of Science ID 000252792900022
View details for PubMedID 18000167
Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I. Pediatric blood & cancer 2007; 48 (3): 364-369
The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociacin de Hemato-Oncologa Peditrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.
View details for PubMedID 16883601
Poliovirus excretion in Guatemalan adults and children with HIV infection and children with cancer BIOLOGICALS 2006; 34 (2): 109-112
More than 20 patients with persistent poliovirus infections have been identified and reported to WHO. To date, almost all of these patients have had B-cell immune deficiency disorders. Since there are limited data on patients with HIV infection who have received oral poliovirus vaccine (OPV), we studied adults and children to determine if persons with acquired immunodeficiency due to HIV infection or cancer chemotherapy in a developing country setting had prolonged excretion of polioviruses. Stool samples from 94 HIV-infected children and 101 adults and 50 children surviving cancer in Guatemala City were cultured for polioviruses. No polioviruses were detected in any of the 195 persons with HIV infection or the 50 with cancer. The evidence from this and other studies indicates that the persistent poliovirus excretion in HIV-infected individuals is an unlikely event.
View details for DOI 10.1016/j.biologicals.2006.03.002
View details for Web of Science ID 000238304800007
View details for PubMedID 16682223
Myelodysplastic and myeloproliferative disorders of childhood: A study of 167 patients BLOOD 1999; 93 (2): 459-466
Myelodysplastic syndromes (MDS) and myeloproliferative syndromes (MPS) of childhood are a heterogeneous group of clonal disorders of hematopoiesis with overlapping clinical features and inconsistent nomenclature. Although a number of genetic conditions have been associated with MDS and MPS, the overall contribution of inherited predispositions is uncertain. We report a retrospective study examining clinical features, genetic associations, and outcomes in 167 children with MDS and MPS. Of these patients, 48 had an associated constitutional disorder. One hundred one patients had adult-type myelodysplastic syndrome (A-MDS), 60 had juvenile myelomonocytic leukemia (JMML), and 6 infants with Down syndrome had a transient myeloproliferative syndrome (TMS). JMML was characterized by young age at onset and prominent hepatosplenomegaly, whereas patients with A-MDS were older and had little or no organomegaly. The most common cytogenetic abnormalities were monosomy 7 or del(7q) (53 cases); this was common both in patients with JMML and those with A-MDS. Leukemic transformation was observed in 32% of patients, usually within 2 years of diagnosis. Survival was 25% at 16 years. Favorable prognostic features at diagnosis included age less than 2 years and a hemoglobin F level of less than 10%. Older patients tended to present with an adult-type MDS that is accommodated within the French-American-British system. In contrast, infants and young children typically developed unique disorders with overlapping features of MDS and MPS. Although the type and intensity of therapy varied markedly in this study, the overall outcome was poor except in patients with TMS.
View details for Web of Science ID 000077970900006
View details for PubMedID 9885207
Langerhans cell histiocytosis diagnosed by fine needle biopsy ARCHIVES OF OPHTHALMOLOGY 1997; 115 (9): 1212-1213
CHILDHOOD MONOSOMY-7 - EPIDEMIOLOGY, BIOLOGY, AND MECHANISTIC IMPLICATIONS BLOOD 1995; 85 (8): 1985-1999
HUMAN CYTOTOXIC LYMPHOCYTES-T SPECIFIC FOR AUTOLOGOUS FOLLICULAR LYMPHOMA RECOGNIZE IMMUNOGLOBULIN IN A MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTED FASHION CANCER 1992; 70 (8): 2181-2186
Previously, autologous Burkitt lymphoma-specific cytotoxic T-lymphocytes (CTL) were found to express the gamma and delta T-cell receptor and recognize tumor idiotype in a major histocompatibility complex (MHC) unrestricted fashion.In this study, the authors established autologous CTL lines and clones specific for a B-cell follicular lymphoma.These CTL are tumor specific and inhibited by antiimmunoglobulin monoclonal antibodies, but unlike the Burkitt lymphoma-specific CTL, they are MHC restricted and express the alpha and beta T-cell receptor.These studies suggest that different B-cell lymphomas can induce CTL of different phenotypes and MHC restriction.
View details for Web of Science ID A1992JT85900027
View details for PubMedID 1394049
INTERLEUKIN-3 IS A GROWTH-FACTOR FOR HUMAN FOLLICULAR B-CELL LYMPHOMA JOURNAL OF EXPERIMENTAL MEDICINE 1992; 175 (2): 371-376
More than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in close association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding cells may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. IL-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on IL-3 and that therapies directed against IL-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.
View details for Web of Science ID A1992HB06100007
View details for PubMedID 1732410
CORTICOSTEROID PRETREATMENT FOR POTENTIAL CONTRAST REACTIONS IN CHILDREN WITH LYMPHORETICULAR CANCER - A WORD OF CAUTION AMERICAN JOURNAL OF ROENTGENOLOGY 1990; 155 (2): 357-358