PubMed Health⌕ Search

Biomedical subjects

J Laver

Publications and source records attributed to J Laver.

At least 19 recordsLinked to original sources
PubMed2000

Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease.

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.

Acute Disease↗
PubMed2000

Burkitt lymphoma is immunophenotypically different from Burkitt-like lymphoma in young persons.

INTRODUCTION: Burkitt-like lymphoma (BLL) is a provisional category of B-cell lymphoma which is morphologically intermediate between Burkitt lymphoma (BL) and large B-cell lymphoma (LBCL). The clinical significance of this morphology is controversial. PATIENTS AND METHODS: We examined 41 cases of pediatric B-cell lymphoma by immunohistochemistry for proteins associated with proto-oncogenes c-myc, BCL-2 and BCL-6 and a subset of cases (with adequate slides) for a proliferation-associated marker (Ki-67) and for apoptosis (Apop-Tag). Sixteen cases of BLL, thirteen cases of BL and twelve cases of LBCL were examined. RESULTS: Our results showed BCL-6 expression in 16 of 16 BLL, 4 of 13 BL, and 9 of 12 LBCL; c-myc expression in 14 of 15 BLL, 9 of 13 BL, and 12 of 12 LBCL; and BCL-2 expression in 2 of 16 BLL, 9 of 13 BL, and 6 of 12 LBCL. Mean apoptotic index for BLL was 10.3% (n = 6); for BL was 17.1% (n = 5); and for LBCL was 10.9% (n = 6). Ki-67 was diffusely reactive in all cases tested. There was a significantly higher proportion of BLL than BL which expressed BCL-6 (P = 0.0001). CONCLUSIONS: Labeling for BCL-6 distinguishes BLL from BL. It is likely that in children in North America, BLL is biologically distinct from BL and more closely resembles a subset of LBCL.

Adolescent↗
PubMed1999

Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study.

This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

Adolescent↗
PubMed1998

Survival with combined modality therapy after intracerebral recurrence of pleuropulmonary blastoma.

BACKGROUND: We present and discuss the successful treatment of pleuropulmonary blastoma metastatic to the brain using a multimodality regimen with surgery, high-dose chemotherapy and radiation therapy. PROCEDURE: A 3-year-old boy referred to our institution with bilateral pulmonary cysts was diagnosed with pleuropulmonary blastoma (PPB). Initial treatment included surgery and multiagent chemotherapy with vincristine, dactinomycin, cyclophosphamide, cisplatin, and doxorubicin. One year after the completion of therapy, his PPB recurred as an intracerebral metastasis, and required further treatment with a multimodality salvage regimen. The child was successfully treated with a subtotal surgical resection, followed by high-dose cyclophosphamide, and radiation therapy. He is now disease-free 24 months later. RESULTS: Intracerebral metastases of PPB have been a uniformly fatal complication of this tumor. Postsurgical chemotherapy and radiation therapy appear to have contributed to the prolonged survival and potential for cure in our patient. CONCLUSIONS: The use of this multimodality regimen may be warranted in other patients with recurrent PPB metastatic to the brain.

Brain Neoplasms↗
PubMed1998

Randomized trial of r-metHu granulocyte colony-stimulating factor in an intensive treatment for T-cell leukemia and advanced-stage lymphoblastic lymphoma of childhood: a Pediatric Oncology Group pilot study.

PURPOSE: Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL). PATIENTS AND METHODS: This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C). RESULTS: Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy. CONCLUSION: r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.

Adolescent↗
PubMed1997

Successful treatment of relapsed infant acute lymphoblastic leukemia with intensive antimetabolite-based chemotherapy.

PURPOSE: The treatment of infant acute lymphoblastic leukemia (ALL) continues to be a significant challenge for pediatric oncologists due to the high incidence of early relapses. Salvage regimens used to date have met limited success. We describe two cases of relapsed infant ALL who have achieved long-term survival with an intensive antimetabolite-based salvage regimen. PATIENTS AND METHODS: Two consecutive infants with relapsed ALL presented at our institution and were treated with an antimetabolite-based regimen. Both cases exhibited clinical and biological phenotypes previously associated with infantile ALL. RESULTS: Both patients have achieved prolonged and sustained remissions 48 and 30 months EFS respectively following therapy with intensive antimetabolite-based salvage regimen. CONCLUSIONS: An intensive multiagent antimetabolite based salvage regimen resulted in prolonged EFS in two cases of relapsed infant ALL. Dose intensification was achieved by administering repeated cycles of the same treatment schema using high dose chemotherapy throughout therapy. These infants were spared prophylactic cranial irradiation without a negative impact on outcome. The use of L-asparaginase, timed after high-dose Cytarabine (ARA-C) throughout therapy, might have contributed to their cure.

Antimetabolites, Antineoplastic↗
PubMed1997

A pilot study of continuous infusion Ara-C in combination with rhG-CSF in relapsed childhood acute myeloid leukemia.

Relapse in acute myeloid leukemia (AML) following intensive chemotherapy bears a bad prognosis. We treated 18 children with relapsed AML on two separate protocols that included continuous infusion (CI) of cytosine arabinoside (ara-C) (total dose 4gr-6gr/m2) over 96-120 hours. In an attempt to increase the fraction of blasts in S-phase and render them more sensitive to cell-cycle specific agents such as ara-C, 10 patients received 5mcg/kg rhG-CSF twice daily beginning 48 hours before and continuing through the duration of the CI ara-C (POG #9192 study). The percentage of cells is S phase before and after G-CSF administration was determined. In a second group of patients (n = 8) who received ara-C alone, endogenous concentrations of G-CSF and serial blood counts were measured (St Jude's R4 study). The rationale of the St Jude's R4 was to optimize the schedule of the second course of ara-C at a time when the patient's endogenous G-CSF concentration was increased and thus maximize the percent of cells captured in S phase. Four out of 8 patients receiving CI ara-C alone and 4 out of 10 patients receiving CI ara-C with rhG-CSF achieved a complete remission (CR) after 1 cycle of therapy. Four patients in CR underwent marrow transplantation (2 allogeneic and 2 autologous). Cell cycle analysis of blast cells cultured in vitro with or without G-CSF showed a two fold increase in the percentage of cells in S phase (P = 0.03) whereas cells obtained from patients before and after G-CSF administration showed no difference in cell cycling. Correlation between G-CSF concentrations and ANC showed a negative association indicating that the regulatory mechanisms for G-CSF production remained intact. In our relatively small series, CI ara-C achieved a CR rate of 44% with rhG-CSF having no effect on the remission rate. Although in vitro rhG-CSF increased the percentage of blasts in S phase significantly, in vivo effects were not observed. Larger studies with combinations of different hematopoietic growth factors and cell-cycle active drugs are needed to evaluate the role of these cytokines in the therapy of recurrent AML.

Acute Disease↗
PubMed1997

Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood.

BACKGROUND: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase inappropriately expressed in lymphoid tissue involved by CD30+ anaplastic large-cell lymphoma (ALCL) with the translocation t(2;5)(p23;q35)(, which juxtaposes the nucleophosmin gene (NPM) with that encoding ALK, resulting in a hybrid (NPM-ALK) message. PATIENTS AND METHODS: A polyclonal antibody against residues of the kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL) and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase method. RESULTS: Nineteen of 20 CD30+ cases (the majority exhibiting anaplastic morphology) labeled with anti-ALK 11, and 5/28 CD30- cases were also ALK+ (3 T cells, 1 null cell, and 1 B cell). Sixteen of 17 B-cell pediatric LCLs were negative, as were 6/6 cases of Hodgkin's disease and 7/7 cases of adult B-cell lymphoma. In pediatric LCLs with adequate follow-up (24/44 ALK+), there was no significant association between ALK expression and two-year event-free survival, similar to the finding reported previously for CD30 expression in these cases. CONCLUSION: We conclude that the majority of pediatric CD30+ ALCLs show ALK overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK fusion, but that the clinical significance of this entity remains unproven.

Adult↗
PubMed1997

Comparison of long-term outcome of children with severe aplastic anemia treated with immunosuppression versus bone marrow transplantation.

Children with severe aplastic anemia (SAA) are treated with bone marrow transplantation (BMT) if a human leukocyte antigen (HLA) compatible sibling donor is available, or alternatively with immunosuppressive therapy (IST). Three retrospective trials examining BMT vs IST in pediatric patients treated from 1970-1988 found BMT resulted in a superior survival rate. Advances have been made in general supportive care and in the approach to each of these treatment modalities in the last decade. To compare survival following BMT and IST in a more recent era, we retrospectively analyzed the results of 48 consecutively treated children with SAA presenting to Memorial Sloan-Kettering Cancer Center (MSKCC) between 1983 and 1992. In contrast to the previous studies, the estimated survival of the BMT and IST groups at 120 months are equivalent, 75.6% and 73.8%, respectively. The IST results in our series are superior to the 42-48% (2-10 year) survival previously published, but similar to survival data observed in more recent IST trials employing more intensive immunosuppression (antithymocyte globulin and cyclosporine). The overall BMT survival rates are similar to those previously published, although BMT results improved dramatically during the latter five years of this analysis, with all 11 patients transplanted surviving with a minimum follow-up of 3 years. No surviving BMT patient has extensive chronic graft-versus-host disease (GvHD), a major cause of long-term mortality post-BMT. Therefore, it is likely the BMT survival curve will remain stable. In contrast, the survival curve of the IST patients is likely unstable, since patients are still at risk for relapse or development of clonal disease. Thus, despite overall similar survival rates, we continue to recommend BMT as first-line therapy in pediatric SAA patients with matched sibling donors.

Adolescent↗
PubMed1996

Serum levels of GM-CSF are elevated in patients with thrombocytopenia.

Serum levels of GM-CSF, IL-3 and IL-6 were measured in patients with immune thrombocytopenia (ITP), non-immune thrombocytopenia (NIT), autoimmune haemolytic anaemia (AIHA) and neutropenia. 8/10 children with ITP had elevated serum levels of GM-CSF (mean 18.4 pg/ml) while thrombocytopenic, but only two had detectable levels (mean 4.5 pg/ml) after normalization of the platelet count. In patients with NIT a significant inverse correlation between platelet count and serum levels of GM-CSF was observed. IL-3 and IL-6 levels were not significantly elevated in thrombocytopenic patients and only two of the nine patients with either AIHA or neutropenia had detectable levels of GM-CSF. Thus, GM-CSF may play a role in the response of severe thrombocytopenia.

Adolescent↗
PubMed1996

Myelodysplasia associated with Turner syndrome.

PURPOSE: This study reports the association of myelodysplasia with Turner syndrome. PATIENT AND METHODS: An 11-year-old girl with Turner syndrome was found to have mild macrocytic anemia that persisted during 2 years. RESULTS: Examination of the bone marrow revealed dyserythropoietic features with multinucleation consistent with refractory anemia. Levels of hemoglobin F were also markedly elevated (57%). She also had transient neutropenia and thrombocytopenia, as well as abnormal platelet function studies. The hematopoietic abnormalities were mild and may have been missed were she not followed for her hypertension and aortic coarctation. CONCLUSIONS: Myelodysplastic syndromes in children are frequently associated with chromosomal abnormalities, but an association with Turner syndrome has not been previously described. This could be due to the fact that mild hematopoietic abnormalities in these patients may not be investigated.

Anemia↗
PubMed1996

Neurologic complications following bone marrow transplantation for sickle cell disease.

A boy with sickle cell anemia underwent bone marrow transplantation (BMT). He was normal on neurological examination, but had radiologic evidence of an old left frontal lobe infarct, multiple cerebral vascular stenoses and moyamoya collaterals. After BMT he developed seizures with extension of the infarct and subarachnoid hemorrhage. One year later angiography revealed worsening stenosis of the M1 segments of both middle cerebral arteries. At that time an increase in von Willebrand's factor with decreased large molecular weight multimers (LvWF) was observed. We speculate that LvWF dependent, shear-induced platelet aggregation, together with endothelial damage may have contributed to the development of neurologic complications in this patient.

Anemia, Sickle Cell↗
PubMed1996

Progressive autologous graft-versus-host disease induced by cyclosporin A.

The development of graft-versus-host disease (GVHD) in patients undergoing allogeneic bone marrow transplantation for leukemias and lymphomas has been associated with a lower incidence of relapse. This phenomenon is thought to be secondary to the anti-tumor effect of adoptively transferred cells. Cyclosporin A (CsA) therapy is known to cause autologous and syngeneic GVHD in experimental models and humans, and has been used in patients undergoing autologous bone marrow transplantation. It has been the consensus to date that CsA-induced autologous GVHD is generally mild, confined to the skin, self-limiting and non-life-threatening. We report by case of severe and progressive GVHD induced by CsA in a child following autologous bone marrow transplantation for acute lymphoblastic leukemia in second remission.

Bone Marrow Transplantation↗
PubMed1995

Adult Wilms' tumor: prognostic and management considerations.

Wilms' tumor is the most common malignant tumor of the urinary tract in children but is rare in adults. Although histologically the tumors appear to be the same, successful treatment with multimodal therapy is much more common in childhood. We report on 2 patients with adult, anaplastic, Stage IV Wilms' tumor, one of which was discovered during pregnancy and was managed successfully with chemotherapy, including ifosfamide, carboplatinum, and etoposide. As more patients are properly identified and treatment outcomes with chemotherapeutic regimens documented, better therapeutic approaches in adult Wilm's tumor will be developed, resulting in improved survival.

Adult↗
PubMed1995

Cost analysis of immunomagnetic marrow purging for neuroblastoma: in-house purging versus submission to purging centers.

High-dose chemoradiotherapy in conjunction with autologous bone marrow transplantation has been used in the treatment of advanced stage neuroblastoma. Because of frequent marrow involvement, marrow purging methods, such as the immunomagnetic technique, have been developed. Current cost constraints force institutions to consider in-house purging versus submission of marrow to purging centers. Our analysis demonstrates that 15 procedures per year are needed to justify an up-front investment in equipment and supplies with a break-even period of 5 years. This number is also required to keep technical proficiency current without frequent retraining of personnel. The analysis includes start-up costs for institutions without a bone marrow processing laboratory, as well as for institutions already processing marrow or peripheral blood stem cells. For institutions performing fewer procedures per year, submission of marrow to purging centers is more cost effective than in-housing purging.

Bone Marrow Purging↗
PubMed1995

Phenotypic analysis of early hematopoietic progenitors in cord blood and determination of their correlation with clonogenic progenitors: relevance to cord blood stem cell transplantation.

Human cord blood (CB) can be utilized as a source of transplantable stem cells. In the clinical setting, the numbers of clonogenic progenitors and nucleated cells are used as indirect measures of the stem cell content of CB samples. In an attempt to define other parameters of engraftment potential, we have determined the numbers of CD34+ cells, and of CD34+ cells co-expressing CD38 and/or HLA-DR in 17 CB samples. At the same time, clonogenic progenitors were assayed in the presence of erythropoietin and different combinations of rhIL-3, rhG-CSF, rhGM-CSF, rh-Steel Factor and medium conditioned by the PU34 primate cell line. Unseparated CB contained a mean of 14.8 x 10(4) CD34+ cells/mL. CD34+CD38-, CD34+DR+ and CD34+DR+ CD38- cells represented 12.2%, 91% and 10% of all CD34+ cells, respectively. Linear regression analysis demonstrated that the total number of CD34+ cells, as well as the different subsets, correlated positively with the numbers of total colonies and day 14 CFU-GM. Furthermore, the proportion of CD34+CD38- cells was significantly higher than has been reported for adult marrow. Cord blood CD34+CD38- and CD34+DR+ cells have a high proliferative potential and are enriched for primitive hematopoietic progenitors. Thus, we conclude that a single collection of CB could be sufficient to engraft an adult recipient, and that quantitation of CD34+ cells and their subsets may be useful in determining the engraftment potential of CB samples.

ADP-ribosyl Cyclase↗
PubMed1995

Effects of CD34+ selection and T cell immunodepletion on cord blood hematopoietic progenitors: relevance to stem cell transplantation.

Cord blood (CB) has been used recently for stem cell transplantation. We have investigated two different approaches to deplete CB samples of T cells capable of mounting graft-vs.-host disease (GVHD). The methods used were selection of CD34+ cells using avidin-biotin columns (CellPro) and T cell immunodepletion with T10B9 monoclonal antibody (mAb) plus complement. Using the avidin-biotin columns, 10.3% of the original CD34+ cells were recovered. Although this technique yielded a population containing 60 +/- 5.5% CD34+ cells, about 1 log of CFU-GM progenitors were lost. In contrast, after the T10B9 mAb and complement immunodepletion, 75 +/- 19% and 62 +/- 7% of the CD34+ cells and CFU-GM were recovered, respectively. T cell depletion was 3.6 logs using the CellPro columns and 2.2 logs after immunodepletion. To investigate whether cell losses following T cell depletion could be overcome by ex vivo expansion, cells were cultured in the presence of recombinant human interleukin-3 (rhIL-3) and recombinant human c-kit ligand (stem cell factor [rhSCF]) for 7 days. There were 14- and six-fold expansions in the number of progenitors recovered after CellPro and immunodepletion, respectively. To asses the engraftment potential of expanded cells, we used a murine transplantation model in which the presence of human cells was identified by the anti-CD45 mAb. Cells expanded in vitro engrafted in irradiated BNXid mice as efficiently as nonexpanded cells, suggesting that expansion did not affect their transplantability. This study shows that both techniques resulted in significant T cell depletion of CB. Furthermore, in vitro expansion could overcome cell losses sustained during the separation techniques without impairing the engraftment potential of the expanded cells.

Animals↗