Cameron Tebbi

Children's Cancer Research Group Laboratory · Pediatric Hematology/Oncology

Certain viruses have been found to induce diverse biological pathways to carcinogenesis, evidenced by the presence of viral gene products in some tumors. Despite the fact that many fungal agents contain mycoviruses, until recently, their possible direct effects on human health, including carcinogenesis and leukemogenesis, had not been explored. In...

Carcinogenic effects of Aspergillus spp. have been well established and generally attributed to a variety of mycotoxin productions, particularly aflatoxins. It is known that most carcinogenic mycotoxins, with the exception of fumonisins, are genotoxic and mutagenic, causing chromosomal aberrations, micronuclei, DNA single-strand breaks, sister chro...

Sickle cell disease and its variants constitute the most common inherited blood disorders affecting millions of individuals worldwide. Significant information regarding the nature of the genetic mutations and modifier genes that result in increased or decreased severity of the disease are available. In recent years, detailed data regarding molecula...

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, e...

Importance Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SC...

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, e...

The etiology of acute lymphoblastic leukemia (ALL) remains unknown. A recent “two-hit” model for the occurrence of precursor B cell acute lymphoblastic leukemia propose that this disease arises through a two-step process, including predisposing genetic mutation and exposure to infections. While several genetic mutations are proposed, no infection c...

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus. This culture was subjected to electron microscopy, purification, and mass...

Currently, there are no known methods to predict of susceptibility to, and means for prevent Acute Lymphoblastic Leukemia (ALL). We have evaluated and patented a group of proteins dubbed Protein X from a certain strain of Aspergillus Flavus (AF) and developed methods for screening and identifying totally asymptomatic patients in remission of ALL, i...

A method is described using Aspergillus flavus fungal cultures, EBV or their combination to induce leukemic cell surface markers in mononuclear cells of former or current acute lymphoblastic leukemia/lymphoma patients. Detection of the leukemic transformation by methods known in the art identified patients who have or had acute lymphoblastic leukem...

Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes. Protocol P9426, a response-dependent and reduced treatment for low ris...

Hemoglobin (Hb) S and Hb E are the most common variant hemoglobins, but because of the geographical separation of the areas where they are prevalent, the combination of the 2 is uncommon. Approximately 46 cases of hemoglobin SE compound heterozygosity have been reported. No deaths from the condition have been reported previously, whereas death afte...

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study e...

To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs). Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lu...

A case of a premature infant with lactic acidosis and hepatic iron accumulation, born to a mother with multiple fetal demises, is presented and discussed by both clinician and pathologist, in this traditional clinico-pathologic conference. The discussion includes the differential diagnoses of lactic acidosis and hepatic iron accumulation in infants...

845 Background Transfusion therapy can effectively treat many complications associated with sickle cell disease (SCD), but iron overload will develop without iron chelation therapy. Despite long-term transfusion requirements, long-term data for iron chelation in SCD are limited. The oral iron chelator, deferasirox, effectively reduced iron burden...

4669 Two similarly designed prospective, uncontrolled, open-label clinical trials were planned to assess the safety and efficacy of a new intravenous immunoglobulin (IVIG), IGIV3I 10% Grifols, in subjects with chronic immune thrombocytopenia (ITP) in the USA, Canada and Europe (Spain, Russia and the United Kingdom). Subjects were candidates to be e...

1074 Poster Board I-96 Introduction For many patients, central venous catheters (CVCs) are the only option for vascular access. Thrombotic occlusion is a common complication of CVCs and can prevent delivery of treatment. The objectives of this phase III, open-label, single-arm study were to evaluate the safety and efficacy of the thrombolytic agen...

The incidence of central nervous system (CNS) involvement and effects of therapy were reviewed in 42 consecutive pediatric patients with acute nonlymphocytic leukemia (ANLL). The morphology of ileukemic cells was considered M1 in 13, M2 in 7, M3 in 5, M4 in 8, and M5 in 9. Two patients with M5 morphology presented with CNS disease at diagnosis. Sys...

Composite tumors are extremely rare. Such tumors in adrenal glands are usually of neuroendocrine-neural type and occur mostly in adults. Their pathogenesis remains elusive. We report a patient with composite neuroblastoma (NB), adrenocortical tumor (ACT), and Li-Fraumeni syndrome (LFS) with germline TP53 R248W mutation. LFS predisposes to the devel...

Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs). Treatment for low- and high-risk HD with doxorubic...

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with...

The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD). Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female,...

Introduction. To reduce protocol non-compliance as a confounding variable impacting trial outcome, Pediatric Oncology Group (POG) mandated pre-radiation quality assurance review in POG 9426, a trial in pediatric early stage Hodgkin’s disease (HD). This report documents the impact of this quality assurance program. Patients and Methods. POG 9426 inv...

In this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed. From 1984-1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials. Patients' ages ranged from 3.1-17.8 years (mean of...

PurposeIn this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed.Materials and Methods From 1984–1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials. Patients' ages ranged f...

Purpose In this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed. Materials and Methods From 1984–1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials. Patients' ages range...

There is mounting national and international evidence to support targeted improvements in cancer care services for adolescents and for young adults; an age group defined in Australia as those between 15 and 25 years. Both paediatric and adult oncology and haematology services currently provide cancer care for adolescents and young adults. There are...

Experience reveals that there is significant noncompliance with self-administered medication, especially in chronic conditions such as cancer. Noncompliance transcends the boundary of disease categories and age group. However, this is most prevalent during the adolescent years when the process of transition from parental dependency to autonomy prod...

History of Adolescent Oncology.- Epidemiology and Etiology of Cancer in Adolescents and Young Adults.- Access to Care Before and During Therapy.- Older Adolescents and Young Adults with Cancer, and Clinical Trials: Lack of Participation and Progress in North America.- Acute Lymphoblastic Leukemia.- Acute Myelogenous Leukemia.- Hodgkin Lymphoma.- No...

Amputations have been performed for centuries to treat a variety of disorders including cancer. Historically amputees often are geriatric patients with diabetes and peripheral vascular disease, or those receiving injuries as a result of an accident or war [1–3]. In fact, in 1866 after the Civil War in the United States, one-fifth of the entire reve...

We previously developed a homoharringtonine resistant C-1300 neuroblastoma cell line with cross-resistance to adriamycin and increased levels of p-glycoprotein, and showed that drug resistance could be reversed in this cell line by cyclosporin A. The present study shows that cremophor EL, a parenteral vehicle for cyclosporin A, can also completely...

The 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates 1-O-alkyl (ether) and 1-S-alkyl (thioether) phospholipids, being analogues of ara-CDP-sn-1,2-O-dipalmitoylglycerol (1), showed significant antitumor activity against L1210 and P388 leukemia in vivo. The more active conjugates include the 1-O-alkyl analogues, ara-CDP-rac-1-O-hexadecyl-2-O-palm...

The development of resistance accounts for therapy failure in the majority of advanced cases of neuroblastoma in children. A new transplantable murine C-1300 neuroblastoma cell line was developed in vitro, by repeated exposure of a sensitive cell line to increasing, but sublethal, doses of Homoharringtonine (HHT). The ED50 of the highly resistant c...

Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma...

The vocational experiences and general well-being of 58 young adult subjects (mean age 24.3 yr) with insulin-dependent diabetes mellitus (IDDM) diagnosed during their adolescence were compared with that of 55 healthy matched control subjects with linear logistic discriminant function analyses. Assessment measures included the Rand General Well-Bein...

Long-term vocational achievements of 40 survivors of cancer diagnosed during adolescence were examined and compared with 40 healthy sex-matched and age-matched controls. Patients' ages at diagnosis ranged from 13 to 19 years (mean, 16.15). Study subjects had survived cancer for over 5 years and were on no cancer therapy. Assessment measures include...

With increased patient survival, the psychosocial consequences of amputation in cancer patients has become increasingly important. The following study examined the psychosocial correlates of amputation in 16 male and 17 female Brazilian adolescent patients aged 10-20 years who had lost a limb to cancer. Interviews were conducted within 12 months of...

We studied a total of 143 patients with 231 assays of CFU-GM, of these, 45 patients were studied with 58 simultaneous assays of CFU-GEMM in an attempt to correlate progenitor colony growth with disease state. Blood and marrow leukocytes were cultured in a standard methylcellulose culture system using normal human leukocyte colony stimulating activi...

Attributions of responsibility have been shown to be important determinants of illness behavior in adults. This study examines the salience of attributional judgements among adolescents with cancer. Patients and their parents were categorized according to their attributions of responsibility for the cause of and solution to the adolescent's health...

Osteosarcoma is the most common bone tumor of children and adolescents. The peak incidence of the disease is in the 15 to 19 year age group. The disease is more commonly seen in males than females. While several factors, including exposure to radiation, genetic disorders such as retinoblastoma, and high rate of bone growth, have been associated wit...

In an attempt to examine factors affecting compliance with orally administered chemotherapy agents, we have examined the relation of agreement of parents and their adolescent children on various treatment-related issues and compliance with cancer chemotherapy. In a longitudinal study, 16 parent/cancer patient pairs were interviewed regarding their...

The prevalence of depression was studied, using the Beck Depression Inventory (BDI) and Schedule for Affective Disorders and Schizophrenia (SADS), in a sample of 30 adolescent cancer patients. BDI scores revealed that 26 patients (87%) were not depressed, 4 (13%) were moderately depressed and no one had severe depression. Similarly, SADS data indic...

Administered a religious beliefs scale by J. E. Faulkner and G. F. DeJong (see record 1967-04453-001) and the Nowicki-Strickland Locus of Control (LC) Scale to 28 adolescent cancer patients (aged 10–23 yrs). 17 Ss indicated that practicing their religion provided them with support by offering security in the face of death and helped them understan...

There have been several reports of the association between Down's Syndrome and acute megakaryoblastic (M7) leukemia (AMKL). The diagnosis of this rare form of leukemia has been better delineated by the use of the platelet peroxidase reaction and the antifactor VIII antibody immunoperoxidase test. In the past, the prognosis of patients with a combin...

Assessed the educational, vocational, and psychosocial status of 20 long-term survivors (aged 17–38 yrs) who had undergone amputation for cancer during adolescence or early adulthood. When they were interviewed, all Ss had survived their diagnosis for at least 5 yrs, were disease free, and were not receiving cancer-related therapy. Results indicate...

The toxicity of high dose cytosine arabinoside (Ara-C) in 23 leukemic children aged 1.5 years to 16 years 11 months was evaluated. The group included 11 children with acute lymphoblastic leukemia (ALL), nine with acute nonlymphoblastic leukemia (ANLL), two with chronic myelocytic leukemia (CML) in blastic crisis, and one with Burkitt's lymphoma. To...

The experience with the treatment of malignant histiocytosis has been disappointing. Despite modest treatment success with a combination of cyclophosphamide, Adriamycin (doxorubicin), vincristine and prednisone, the overall prognosis remains poor. There are only a few reports of prolonged complete remissions in pediatric patients. The following rep...

The production of granulocyte–macrophage colony-stimulating activity (CSA) by isolated murine femur shafts, non-dispersed bone marrow and spleens was assessed following administration of Vinblastine (VLB). These organs were removed from 2 h to 10 days post-VLB and allowed to condition endotoxin-free medium for 48 h. CSA activity was assessed using...

Compliance with self-administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age,...

An association between eosinophilia and neutropenia has been observed in a number of clinical conditions. To probe the role of eosinophils in granulopoiesis, marrow and peritoneal eosinophils, obtained from Schistosoma mansoni-infected mice, were separated and purified. Normal bone marrow cells were cultured in semisolid culture medium in concentra...

Compliance with self-administered therapy in pediatric and adolescent patients is not always complete. Noncompliance may result in erroneous conclusions about the efficacy of a given therapy and lead to unnecessary tests and alteration of treatment regimens. To examine the causes of noncompliance, 46 cancer patients aged 2.5 to 23 years (mean age,...

Three monoclonal antibodies (mAbs), termed SN2, SN2a and SN2b, were used in the present work to study a human T-cell leukemia-associated cell surface glycoprotein, GP37. Strong specificity of mAbs SN2, SN2a and SN2b for T leukemia cells was demonstrated by radioimmunoassay and fluorescence-activated cell sorter (FACS) analysis. GP37 was not detecte...

Two histologically benign adipose tumors were found to have clonal karyotypic changes. Del(4), del(6), and inv(13) were present in a fibrolipoma, and t(7;8) in a lipoblastoma. Additional studies are needed of the frequency and malignant potential of lipomas with cytogenetic abnormalities.

Using a plasma clot technique, we studied the comparative levels of in vitro erythroid colony forming units (CFU-E) of normal and W anaemic mice following intravenous (IV) injection of 6.25 mg/kg of vinblastine (VBL). Mice used in this study were C57Bl/6J, WBB6F1, (+/+,Wv/+ and W/Wv). CFU-E content was looked at on day 0, 1, 3, 5, 7 and 10 followin...

Twenty-two patients with newly diagnosed nonmetastatic osteosarcoma of the extremity were treated with an adjuvant chemotherapeutic regimen consisting of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin. Fourteen of the 22 patients remain continuously disease free for 65+ to 113+ months, with a median time on study of 70+ months. The 7...

Bone marrow is the commonest site of metastasis in neuroblastoma. This results in minimal to total bone marrow suppression. To establish the mechanism of neuroblastoma suppression of granulopoiesis, the effects of murine C-1300 neuroblastoma cells on granulopoietic activity of normal syngeneic mice was examined. Using a double layer agar system, in...

Tetraploid populations have been observed in various types of leukemia, but relatively few reports exist of triploid cell populations in acute or chronic leukemia. We report two cases of Ph-positive leukemia with a modal triploid cell population. Examination of peripheral blood from a 3-year-old boy with Ph-positive acute lymphoblastic leukemia (AL...

Amputation is often a component in the treatment of bone tumors such as osteogenic sarcoma, which is most prevalent in the adolescent age group. Adaptation to cancer and loss of a limb requires a significant multidimensional effort. To examine the role of social support systems, 27 adolescents who had undergone amputations for cancer were interview...

The specific cytotoxic activity of anti-human T cell leukaemia immunotoxins (IT) was investigated for their effects on in vitro colony formation of leukaemic cells and normal haematopoietic progenitors, i.e., CFU-GM, CFU-E and CFU-GEMM. These IT were prepared by conjugating ricin A chain with the monoclonal antibodies SN1 and SN2. These antibodies...

Near-tetraploid cell populations were observed in a case of T-cell acute lymphoblastic leukemia (T-ALL) and in one of acute myeloblastic leukemia (AML). In the ALL case, hyperdiploid chromosomal changes, characterized by an isochromosome 17q [i(17q)], as well as other changes, were seen at the onset of the disease. At the first relapse, hypertetrap...

Ten consecutive patients were entered on a pilot study--for the treatment of children with far-advanced Burkitt's lymphoma--which was conducted at the Roswell Park Memorial Institute (R.P.M.I.) and the University of Rochester Medical Center (U. of R.). With the use of high-dose cyclophosphamide (HDC), intermediate-dose methotrexate (IDM), vincristi...

Osteosarcoma is the commonest bone cancer seen in children and adolescents. Its peak incidence is during the adolescent growth spurt, and it occurs more frequently in taller individuals. The commonest site of occurrence is around the knee, ie, distal femur or proximal tibia. The classic presentation consists of pain and swelling at the tumor site....

Osteosarcoma is the commonest bone cancer seen in children and adolescents. Its peak incidence is during the adolescent growth spurt, and it occurs more frequently in taller individuals. The commonest site of occurrence is around the knee, ie, distal femur or proximal tibia. The classic presentation consists of pain and swelling at the tumor site....

We generated a monoclonal antibody, termed SN2, which defines a human T cell leukemia-associated cell surface glycoprotein, GP37, with an approximate m.w. of 37,000. This antibody was generated by using a human leukemia antigen preparation. The reactivity and specificity of SN2 were characterized by a sensitive radioimmunoassay against a variety of...

The past two decades have seen a marked improvement in the treatment and survival of adolescents and young adults with malignant disorders. For the physician who treats adolescents, this success has introduced a new challenge: to extend the treatment considerations to address the concerns of the individual who is at an age involving emancipation an...

A variant translocation, t(8;22) (q24;q12), was found in bone marrow (BM) and long-term cultured peripheral blood (PB) cells obtained from an American boy with Burkitt-type acute lymphoblastic leukemia (ALL-L3, French-American-British classification). Surface marker studies revealed a monoclonal immunoglobulin A (sIgA) with a lambda chain (74%) on...

We investigated the psychological effects of amputation on adolescent patients by interviewing 27 persons who had a limb amputation because of cancer during their adolescence and compared them to data obtained from eight patients with amputations due to trauma at similar ages. In cancer patients, mobility-related activities and social matters inclu...

During remission, patients with acute lymphoblastic leukemia (ALL) may develop fungal infections. We investigated the possible contribution of drug-induced neutrophil (PMN) dysfunction to such infections before and after a single dose of vin-cristine (VCR) in 9 leukemic children in remission. At the time of “pulse” therapy, PMN yeast phagocytosis w...

The role of eosinophils in granulopoiesis is unclear. In a variety of conditions, the level of eosinophils is inversely related to the level of neutrophils. The present report describes two patients with eosinophilia and neutropenia and examines the in vitro effects of eosinophils on the colony formation of their bone marrow in semisolid culture me...

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m2). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 wer...

The role of eosinophil in gramulopoiesis is unclear. In a variety of conditions, the level of eosinophils is inversesly related to the level of neutrophils. The present reports describes two patients with weosinophilia and neutropenia and examines the in vitro effects of eosinopils on the colony formation of their bone marrow in semisolid culture m...

Eight patients with recurrent medulloblastoma were treated with a chemotherapy regimen consisting of vincristine, BCNU, dexamethasone and intrathecal and intermediate dose intravenous methotrexate (500 mg/m²). Five also received local low dose radiotherapy (RT). All 8 patients responded to treatment; 6 completely and 2 partially. These latter 2 we...

Semi-solid culture techniques provide a useful means for studying the sensitivity of granulopoietic progenitors exposed to various chemotherapeutic agents. We have examined the effects of two phosphodiesterase inhibitors-PGI2 releasers, pentoxifylline and RA-233, on C57/BJ mice resulted in a decline in the number of leukocytes as well as mouse bone...

A 12 1/2-year-old female presented with Ewing's sarcoma of the manubrium sterni which extended into the anterior mediastinum. At presentation there was no evidence of metastatic disease. Her initial treatment consisted of radiation therapy and chemotherapy. The residual tumor was subsequently resected and the sternal defect was repaired with Marlex...