Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).
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PMID:Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO). 146 3

In this second part of the review the clinical significance of autologous bone marrow transplantation (ABMT) as treatment for acute leukemias (AL) and malignant lymphomas is described. In most adult patients with AL in complete remission treated with conventional maintenance therapy relapse usually occurs within one year. However, the results of ABMT, as an intensive consolidation treatment in patients with AL in remission show long-term disease-free survival in a proportion of 40% of patients. Even better results have been reported in patients with purged bone marrow, although the difference is not statistically significant. A major problem of ABMT is still the high percentage of relapse (50%), while the probability of treatment related mortality is relatively low (up to 10%). ABMT is also showing good results in the treatment of non-Hodgkin's lymphomas of intermediate and high-grade histology and in Hodgkin's disease in cases refractory to the first line therapy and in sensitive relapse. However, in refractory cases the results are poor. It is noteworthy, that in all disorders treated with ABMT, prospective randomised controlled trials are missing and current data are based on heterogenous groups of patients. In the majority of solid tumors, even escalated doses of radiochemotherapy with ABMT are not able to eradicate malignant disease. In contrast, the results are very good in neuroblastoma. Although ABMT is a relatively complex and aggressive method, it is being increasingly applied to the treatment of haematological malignant diseases and the results obtained so far, are encouraging and showing that ABMT, besides allogeneic BMT, represents a promising potentially curative treatment for selected group of patients.
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PMID:[Transplantation of autologous bone marrow--a new approach in the treatment of neoplastic hematologic diseases. II. Clinical results in acute leukemia, malignant lymphoma and solid tumors]. 236 22

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.
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PMID:Status of allogeneic bone marrow transplantation in childhood in the GDR. 248 Feb 79

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.
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PMID:Influence of allogeneic bone marrow transplantation on the endocrine system in children. 248 Mar 5

Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.
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PMID:A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases. 267 Feb 9

These studies suggest that intensive chemoradiotherapy (eg., VAMP-TBI), if given relatively soon after diagnosis and before development of progressive disease, improves long-term survival for patients with advanced neuroblastoma. Although this particular therapy is not useful for those who already have developed progressive disease, other intensive regimens may warrant testing in this latter group of patients. Our current study is testing aggressive induction chemotherapy, ex vivo purging of autologous marrow, and VAMP-TBI followed by BMT. Because of the increasing risk of progressive disease with time after diagnosis, we recommend beginning the BMT phase by 20 weeks after diagnosis. This should result in 85% of newly diagnosed patients entering the BMT phase without progressive disease; and, with fewer toxic deaths, 90% should survive the BMT phase. Thus, approximately 70% of patients could be disease-free survivors 8-9 months after diagnosis. Because a significant number of patients still develop progressive disease during induction or after BMT, efforts are being made to improve induction and pretransplant therapies and to identify prognostic factors. If modifications of the current regimens do not decrease the rate of progressive disease, it may be necessary to develop additional or different therapy for patients identified to be at high risk. Hopefully, new strategies will further increase the percentage of patients with tumor-free survival.
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PMID:Bone marrow transplantation for poor prognosis neuroblastoma. 304 48

Bone marrow transplantation improves the chances of survival in a variety of hematological malignancies. However, infectious complications during the post-transplant phase contribute significantly to morbidity and mortality. To reduce the duration of granulocytopenia, which is approximately 20 days after BMT, in this study patients with ALL, relapsed or high-grade NHL, relapsed or refractory HD, or Neuroblastoma stage III/IV, were given rh GM-CSF to assess the effects on hematological and immunological reconstitution after conditioning therapy and BMT. The results of 9 patients are presented. After autologous BMT and subsequent rh GM-CSF therapy, a peripheral blood neutrophil count of 500/microliters was reached within 8-12 days, i.e., between 7 and 10 days earlier than would have been expected without rh GM-CSF. Furthermore, it appeared that rh GM-CSF was useful in case of insufficient bone marrow regeneration post autologous transplant. The influence of rh GM-CSF after allogeneic BMT is not yet clear. Further studies will be necessary to evaluate the potential of this promising new drug after BMT.
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PMID:Recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) after bone marrow transplantation. 307 46

Using OKT3 monoclonal antibody as a mitogen, we have studied interleukin 2 (IL2) production and proliferation in peripheral blood mononuclear cells (PBMC) of 23 patients receiving bone marrow transplants. Twenty patients were recipients of allogeneic bone marrow for treatment of hematologic malignancies, aplastic anemias (AA), or severe combined immunodeficiencies (SCID). Three patients with Hodgkin's disease or neuroblastoma received autologous bone marrow. Endogenous IL2 production was not detectable (less than 0.2 U/mL) in PBMC of 18 patients and was very low in PBMC from five patients (0.5 to 1.5 U/mL), as compared to normal controls (median 3.5 U/mL) or pretransplant patients (median 1.5 U/mL). The low IL2 production was associated with defective OKT3-induced proliferation of PBMC in 19 of 23 patients studied. In the first 6 months after BMT, 14 of 15 patients (93%) showed defective proliferation of PBMC as compared to five of eight patients (63%) tested between 7 and 18 months after BMT (P less than .1). In all but three patients, addition of highly purified human lymphocyte IL2 (hpIL2) restored OKT3-induced proliferation of PBMC to within the normal range. This study demonstrates that PBMC in patients after BMT have a defect of IL2 production but are able to express IL2 receptors in response to OKT3 antibody and to proliferate normally upon addition of hpIL2. PBMC of all patients showed similar functional defects, whether or not they received additional therapy, including various conditioning regimens prior to BMT and immunosuppressive therapy after BMT. These observations suggest that T cell defects after BMT are most likely secondary to quantitative or qualitative defects of transplanted T lymphocytes or their precursors.
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PMID:Defective interleukin 2 production in patients after bone marrow transplantation and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2. 637 75

The use of new strategies for dose intensification using peripheral blood stem cell or autologous purged bone marrow rescue has raised expectations for cure in advanced neuroblastoma, although conflicting reports exist regarding the efficacy of these approaches. Using risk groups based on both biological and clinical staging, the Children's Cancer Group (CCG) has conducted a series of pilot studies to test new induction, consolidation and myeloablative regimens to attempt to improve outcome. We summarise below the outcome and prognostic factor analysis for the pilot chemotherapy trial, CCG-(CCG-321P2), and the use of high dose myeloablative chemoradiotherapy with allogeneic (CCG-321P1) or autologous purged bone marrow rescue (CCG-321P3) for high risk neuroblastoma patients who were progression-free at the end of induction chemotherapy. After autologous bone marrow transplantation (ABMT), progression-free survival (PFS) at 4 years was 38% (median follow-up 4 years). Prognostic factors for relapse after ABMT included pre-BMT disease status, bone marrow tumour content at harvest, extent of primary resection at diagnosis, and time to ABMT. MYCN amplification, age, stage, and pre-BMT myeloablative regimen were not significant. Allogeneic BMT did not have a better outcome than ABMT. In a retrospective, non-randomised comparison of ABMT and chemotherapy, there was a significant difference in PFS for stage IV patients. High risk subgroups possibly benefiting from ABMT could be identified, including those with tumour MYCN amplification, over 2 years at diagnosis, and those not in complete remission at the end of induction. A randomised prospective trial comparing myeloablative therapy with ABMT to continuous infusion consolidation chemotherapy is currently underway in CCG to determine the relative benefit.
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PMID:Role of myeloablative therapy in improved outcome for high risk neuroblastoma: review of recent Children's Cancer Group results. 757 71

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.
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PMID:High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma. 793 72


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