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Biomedical subjects

C K Tebbi

Publications and source records attributed to C K Tebbi.

At least 37 records · Page 2Linked to original sources

The role of parent-adolescent concordance in compliance with cancer chemotherapy.

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 knowledge and understanding of illness, medications, and treatment, and their medication compliance. Adolescent responses matched closely those of parents on topics pertaining to medication dose, frequency, number, and purpose. Age was positively correlated with agreement for medication instructions. Disagreements were more commonly found in patients under 17 years of age. Compliance was greater when parents and patients agreed on who was responsible for medication administration, and on their understanding of medication instructions, number, and effectiveness. Treatment of the adolescent oncology patient should include consideration of psychosocial developmental factors, encourage parent-child communication, and place less reliance on self-administered therapy.

Adolescent↗

Acute megakaryoblastic leukemia associated with mosaic Down's syndrome.

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 combination of Down's Syndrome and AMKL has been extremely poor, with a median survival of 6.9 months for 11 reported cases in the literature. The present report reviews the previously reported cases and describes a unique patient with mosaic Down's syndrome and AMKL with favorable response to therapy.

Amsacrine↗

Toxicity of high dose Ara-C in children and adolescents.

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. Toxicity consisted of bone marrow suppression in all patients, with a mean nadir time of 11 days for platelets and granulocytes. All patients experienced nausea and vomiting; 12 of 23 had drug induced fever; seven of 23 conjunctivitis; five of 23 mucositis; four of 23 diarrhea, and one of 23 elevated transaminase with hyperbilirubinemia. Adverse reactions were mild and reversible in all patients. No serious neurologic toxicity was seen. The toxicity observed in four patients with prior cranial irradiation was not any different from nonirradiated patients. The only life-threatening effect was neutropenia, the consequences of which were generally well controlled with antibiotic therapy. While this agent was effective in induction of remission in AML patients resistant to standard doses of Ara-C, it had no significant effect in a very small number of patients with relapsed ALL and CML in blast crisis. Side effects of high dose Ara-C though relatively substantial are manageable enough to warrant wider scale efficacy trials of this agent in childhood leukemias and solid tumors.

Adolescent↗

Malignant histiocytosis. Complete remission in two pediatric patients.

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 report describes two children who have had long-term remission with an aggressive combination chemotherapy program that included intrathecal prophylaxis. The chemotherapeutic regimen described merits further evaluation in a larger number of patients.

Adolescent↗

Compliance of pediatric and adolescent cancer patients.

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, 6.85 years) and 40 parents were extensively interviewed at 2 weeks, 20 weeks, and 50 weeks post-diagnosis. The results of self-reported compliance were corroborated by serum bioassay of the prescribed medications. A significant correlation between the age of patient and compliance with chemotherapeutic agents and nonchemotherapeutic medications was found (P less than 0.05 and P less than 0.02, respectively), with adolescent patients being compliant less often. Over the course of therapy, compliance among patients decreased, but not significantly. A significant negative correlation was found between compliance and the number of children in the family. Compliers and noncompliers did differ significantly in how well they understood instructions concerning how to take their medication (P = 0.04). No significant correlations between compliance and stage of the disease, number or type of drugs used, complexity of the regimen, degree of satisfaction with information given to the patient, understanding of disease, treatment, or belief in medication efficacy were found. The main reasons given for noncompliance were forgetfulness, busy schedules, and nonavailability of medication. More compliers than noncompliers were in agreement with their parents regarding who was responsible for the administration of the medication. Compliance is a complex and multifaceted issue which interrelates with a large number of medical and social factors.

Administration, Oral↗

Human T-cell leukemia-associated cell surface glycoprotein GP37: studies with three monoclonal antibodies and a rabbit antiserum.

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 detected on normal human peripheral blood lymphocytes, purified normal T-cells, normal thymocytes nor normal bone marrow cells. Furthermore, GP37 was barely detectable on phytohemagglutinin (PHA)- and Concanavalin A (Con A)-activated T-cells. The results indicate clinical utility of these mAbs. Competitive binding experiments show that the epitopes recognized by SN2 and SN2a are sufficiently close to each other to allow complete reciprocal inhibition of binding whereas the epitopes recognized by SN2 and SN2b are less close to allow only partial reciprocal binding inhibition. The biochemical nature of antigenic determinants defined by these mAbs was studied by treating T leukemia cells with trypsin, chymotrypsin, thermolysin, neuraminidase and mixed glycosidases. The results suggest that the antigenic determinants defined by these mAbs all consist of the protein moiety of the glycoprotein GP37. No significant antigenic modulation was observed when T leukemia cells were reacted with SN2. In a sequential immunoprecipitation experiment, a 125I-labeled leukemia antigen preparation was first treated with a rabbit anti-T leukemia antiserum. The latter had been prepared by immunizing a rabbit with a partially purified human T leukemia antigen preparation and showed a good specificity for T leukemia cells. Subsequent treatment of the labeled antigen preparation with SN2 showed that SN2 antigen had been precleared. Thus, both mouse mAb SN2 and the rabbit anti-T leukemia antiserum react with the same GP37 molecule.

Animals↗

Chromosome abnormalities in two benign adipose tumors.

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.

Child, Preschool↗

Adjuvant adriamycin and cisplatin in newly diagnosed, nonmetastatic osteosarcoma of the extremity.

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 72-month disease-free survival estimate is 64%. Pulmonary metastases occurred in six patients, an isolated stump recurrence was seen in one patient, and one patient had a local recurrence following a limb-salvage procedure. For those patients in whom pulmonary metastases developed, the onset was late in three of six, and the number of metastases was three or fewer in all patients. Two patients with pulmonary metastases and one with a stump recurrence have apparently been salvaged, thus resulting in a 77% 72-month survival. Toxicity observed in patients treated with this regimen was in keeping with previous reports. This chemotherapeutic regimen is effective in the adjuvant therapy of nonmetastatic osteosarcoma of the extremity. It should be incorporated into other adjuvant protocols in an effort to continue to improve the outcome in patients with osteosarcoma.

Adolescent↗

Suppressive effects of neuroblastoma cells and conditioned media on in vitro granulopoiesis.

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, intact tumor cells, media conditioned by the culture of neuroblastoma cells (NCM) and homogenate of these cells were found to have significant suppressive effects on granulocyte macrophage colony formation (CFU-GM). The rate of production of the NCM was gradual, reaching a plateau by day 4 of the culture. No cell-cell contact was necessary to elicit the CFU-GM depression i.e. regardless of the location of the intact tumor cells or their homogenate in the same or separate layer of the culture, there was a significant linear suppression of CFU-GM (p less than .0005). This suppression proved to be dose dependent. NCM also caused a similar decline in colony formation (p less than 0.005) indicating the suppression is due to diffusible factor(s). The CFU-GM suppressive factor(s) are not dialyzable and cannot withstand 56 degrees C for 15 min. The granulopoietic suppression seen in neuroblastoma may be, at least in part, due to the suppressive effects of these factor(s).

Animals↗

The role of social support systems in adolescent cancer amputees.

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 interviewed. Inquiries were made regarding patients' perceived social support providers and the impact of amputation upon their lives and independence. Parents, especially mothers, were perceived as realistic and most helpful at the time of surgery (80%), followed by professional hospital staff (59.3%), and siblings (59.3%). Friends of patients were less helpful, as many reported their friends felt sorry for them (65.4%), avoided them (33.3%), or drifted away (40%). Only 7.4% of the patients had a clear preference to be associated with other amputees. This study details other preferences and difficulties encountered by the adolescent amputees and the role of support systems in their adaptation to their disease and amputation.

Adolescent↗

Chromosomes and causation of human cancer and leukemia. LIV. Near-tetraploidy in acute leukemia.

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, hypertetraploid cells appeared in about 10% of the mitoses in the bone marrow (BM), and by the second and third relapses, the hypertetraploidy was present in more than 90% of the mitoses in the BM. Even though karyotypic instability was evident, all abnormal karyotypes contained one or two i(17q) at every sampling. In spite of karyotypic instability at each relapse, karyotypic evolution was observed whenever relapse occurred. A normal female karyotype was confirmed in the BM of each period. Immunologic examinations performed at each sampling revealed no recognizable changes before and after the appearance of tetraploidy. In the AML case, which was classified as FAB M2, cytogenetic examination was performed at diagnosis and relapse. In both, hypotetraploid cells were observed in over 60% of the BM cells; the modal chromosome number was 90. Banding analysis was successful at relapse, and a pseudodiploid clone characterized by t(8;21) and a hypotetraploid clone with two t(8;21) and a loss of two Y chromosomes were observed in the same BM sample. A normal male karyotype was also observed in BM cells. In both cases, giant and bizarre blasts were seen in the BM. A close correlation between near-tetraploid mitoses and giant and bizarre blast cells in BM smears of the same samples was observed. Previously published tetraploid acute leukemia cases analyzed with banding methods were accumulated and compared with our two cases.

Adolescent↗

Near-triploid Ph-positive leukemia.

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 (ALL) and a 68-year-old male with Ph-positive chronic myelocytic leukemia (CML) in blastic crisis revealed modal populations of 72 and 63 chromosomes, respectively. G-banding analysis of both cases revealed the following: karyotypic instability (no clonality), dominant trisomy, and the random association of the Ph chromosome with gains and losses of chromosomes involved in this translocation. The cytogenetic evidence obtained suggests that the triploid cell populations were not derived from a duplication of a hypodiploid cell population, but resulted from random loss of chromosomes from tetraploid cell populations derived from duplication of pseudodiploid cells.

Aged↗

High-dose cyclophosphamide and intermediate-dose methotrexate for the treatment of far-advanced Burkitt's lymphoma.

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), vincristine (VCR), prednisone (PRED), and intrathecal (IT) chemotherapy, nine of these 10 children achieved a complete remission (CR), and six of these nine children have remained in CR for more than 3 years and are likely cured of their disease. This regimen had significant, but generally manageable, toxicity. A single patient with ataxia-telangiectasia died during induction therapy of pneumonia and a gastrointestinal hemorrhage. A single patient with severe hemorrhagic cystitis required the substitution of cytosine arabinoside for cyclophosphamide (Cytoxan) in the regimen. One of five children presenting with bone marrow involvement survives. Such involvement appears to place patients at greater risk for developing meningeal disease. Attempts at more aggressive methods of central nervous system (CNS) prophylaxis should be employed in this group of patients.

Adolescent↗

Effect of specific anti-human leukaemia immunotoxins on the colony formation by human haematopoietic progenitors and by human leukaemia cells.

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 define two unique human T cell leukaemia antigens. This study reveals that while these IT are only marginally cytotoxic to normal haematopoietic progenitors, they strongly suppress colony formation of human T leukaemia cells. The latter suppression is augmented by the presence of 10 mM NH4Cl which results in total suppression. The present results indicate the therapeutic usefulness of these IT for in vitro eradication of leukemia cells in the bone marrow of patients with T cell leukaemia. Potentially, such a purged bone marrow can be used in autologous transplantation in leukaemia patients.

Antibodies, Monoclonal↗

Monoclonal antibody SN2 defining a human T cell leukemia-associated cell surface glycoprotein.

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 cultured and uncultured human cells. In selected cases, the cell specimens were tested further by indirect immunofluorescence staining. Among the various cultured malignant and nonmalignant human cell lines tested, SN2 reacted only with leukemic T cell lines, with one exception. It reacted with 10 of 11 leukemic T cell lines tested; the 10 reactive cell lines are PEER, JM, MOLT-4, CCRF-CEM, CCRF-H-SB2, RPMI 8402, DND-41, HPB-ALL, SKW-3, and HPB-MLT; the unreactive line was HUT 78. The reactive cell lines were derived from patients either with T cell-type acute lymphoblastic leukemia (the first eight cell lines), with T cell chronic lymphocytic leukemia (SKW-3), or with Japanese adult T cell leukemia-lymphoma (HPB-MLT). The unreactive cell line, HUT 78, was from a patient with Sezary syndrome. Results consistent with the above were obtained from studies in which uncultured malignant cell specimens from different cancer patients were tested against SN2; SN2 reacted only with T leukemia cells. Among various uncultured normal cell specimens tested, SN2 did not react with thymocytes, bone marrow cells, peripheral blood lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, or erythrocytes. It did, however, react with platelets.

Animals↗