摘要:

PurposeNeuroblastomas have a variety of clinical behaviors, from spontaneous regression or differentiation to early metastasis and death. We have examined a variety of genetic variables that might explain or predict the clinical behavior.Patients and MethodsWe have studied DNA or RNA from a number of children enrolled in clinical trials with the major pediatric oncology cooperative groups.ResultsWe propose that neuroblastomas may be classified into three subsets with distinct biological features and clinical behavior. The first subset consists of those tumors with hyperdiploid modal karyotypes and highTRK-Aexpression. Patients with these tumors are usually infants with low stages of disease and a very favorable outcome. The second group consists of tumors that have a near-diploid DNA content, usually with 1p allelic loss or other structural changes, but they lackMYCNamplification, andTRK-Aexpression is low. The patients are generally older, with advanced stages of disease and an intermediate outcome. The third group is characterized by tumors withMYCNamplification, 1p allelic loss, and low or absentTRK-Aexpression. The patients are 1-5 years of age and have advanced stages of disease, rapid tumor progression, and a very poor prognosis. Current evidence suggests the tumor types are genetically distinct, and one type seldom if ever evolves into another.ConclusionsIdentification of these genetic and clinical subsets permits a more accurate prediction of outcome. This, in turn, allows more appropriate selection of therapeutic intensity to minimize side effects in those with a favorable outcome but optimize the chance of cure in those requiring aggressive treatment.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeTo study the risk of non-B-cell acute lymphoblastic leukemia (ALL) relapse in relation to the routines of administration of oral methotrexate (MTX) and 6-mercaptopurine (6MP) and to the erythrocyte (E) levels of the intracellular cytotoxic metabolites, that is, MTX polyglutamates and 6-thioguanine nucleotides (E-MTX and E-6TGN).Patients and MethodsE-MTX and E-6TGN levels were measured at least three times (medians, eight and nine) in 294 children with non-B-cell ALL during oral MTX and 6MP therapy. For each patient, we registered (a) the individual circadian schedule of drug administration and (b) the coadministration of food, and (c) calculated a mean (m) of all E-MTX and E-6TGN measurements and (d) the product of mE-MTX and mE-6TGN (mE-MTX*6TGN), due to their synergistic action.ResultsA total of 42 patients were on a morning schedule, 219 were on an evening schedule, and 33 had miscellaneous routines. A total of 149 patients took the drugs with meals, 106 took the drugs between meals, and 39 had varying routines. With a median follow-up of 78 months, ALL has recurred in 66 patients. The patients on an evening schedule had a superior outcome [probability of event-free survival (pEFS) = 0.82 ± 0.03 vs. 0.57 ± 0.08;p= 0.0002], whereas the coadministration of food did not significantly influence outcome. Patients with a mE-MTX*6TGN < 813 [product of median mE-MTX (4.7 nmol/mmol Hb) and mE-6TGN (173 nmol/mmol Hb)] had an inferior outcome (pEFS = 0.70 ± 0.04 vs. 0.85 ± 0.03;p= 0.003), even if only patients on an evening schedule were analyzed. Thus, 109 patients on the MTX/6MP evening schedule with an mE-MTX*6TGN ≤ 813 (nmol/mmol Hb)2had a pEFS of 0.89 ± 0.03 and a probability of continuous hematopoietic remission of 0.91 ± 0.03.ConclusionsAn evening schedule should be recommended for oral MTX/6MP maintenance therapy. The value of individual dose adjustments by E-MTX and E-6TGN remains to be determined in prospective randomized trials.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeThe aim of the therapeutic trials was to optimize the treatment of severe aplastic anemia (SAA) and moderate aplastic anemia in children who lack a suitable bone marrow donor, using immunosuppressive therapy in the most effective combination and dose.Patients and MethodsTwo sequential therapeutic trials for the treatment of severe and moderate aplastic anemia in children were conducted by 10 institutions. The treatment protocols included antithymocyte globulin (ATG), prednisone, and cyclosporine A (CSA); patients entered on the first protocol, 0190 (ATG × 2), were given two courses of ATG, and those enrolled on the second protocol, 0190B (ATG × 1), were given only one course of ATG. Ten patients were evaluable on ATG × 2. All patients had SAA; three had hepatitis-induced severe aplastic anemia (HI-SAA). Twelve patients were evaluable on ATG × 1; all had SAA, one of whom had HI-SAA.ResultsSeven of 10 patients on ATG × 2 responded, and eight of 12 patients treated on ATG × 1 responded.ConclusionTreatment with immunosuppressive therapy using ATG, CSA, and prednisone was very well tolerated. The response rates in both protocols were similar, and results compare favorably with those of previous therapeutic trials, suggesting that a second course of ATG is not necessary.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeCurrently bone marrow transplantation (BMT) with an HLA-identical sibling donor is recommended as optimal therapy for children with acquired severe aplastic anemia (SAA). Immunosuppressive therapy (IST) has become a very successful initial therapy for SAA in children lacking a related bone marrow donor. We wished to evaluate whether current IST regimens may be as efficacious as BMT.Patients and MethodsA retrospective review identified children treated for SAA over a 12-year period. Children with a related donor received a BMT. Children lacking a donor were treated with IST followed by a “rescue” BMT if IST was ineffective. IST consisted of anti-thymocyte globulin and steroid ± cyclosporine A. Transfusion independence and survival rates were compared between the two groups.ResultsTwenty-seven children were identified. Nine received a related BMT; seven of these survive and are transfusion independent (median follow-up 54 months). Sixteen of 18 patients who received IST are transfusion-independent survivors, including three of four patients who received a rescue BMT (median follow-up 33.5 months). Actuarial survival is 75% (95% CI = 45%, 105%) and 92% (95% CI = 78%, 107%) for the BMT and IST groups, respectively (p= 0.15). Severe toxicity was not experienced by any patient as a result of IST.ConclusionsEquivalent rates of transfusion independence and survival were experienced by patients receiving BMT and IST. We propose that a prospective trial be undertaken to evaluate IST as initial therapy in all children with SAA, to be followed by BMT if there is inadequate response.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeThe purpose of this study was to determine the feasibility, toxicity, and early response of patients with clinical group III rhabdomyosarcoma (RMS) to a chemotherapy regimen of etoposide (ETOP), ifosfamide (IFOS), and vincristine (VCR) with hyperfractionated radiation therapy (XRT).Patients and MethodsSixty-eight patients aged <21 years, previously untreated, with clinical group III RMS or undifferentiated sarcoma with normal organ function were eligible for this study. Chemotherapy was as follows: weeks 0-8: IFOS 1.8 g/m2/day × 5 days every 3 weeks × 3 (with mesna), ETOP 100 mg/m2/day × 5 days every 3 weeks × 3, and VCR 1.5 mg/m2/week × 9; weeks 9-16: hyperfractionated XRT (except patients with parameningeal tumors with meningeal extension, who received XRT on day 0), IFOS/mesna weeks 9, 12, 16, and VCR weeks 9, 10, 11, 12, 16; weeks 20-99: IFOS/mesna q 3 weeks × 2, ETOP q 3 weeks × 2, and VCR weekly × 6 weeks. Four drug cycles were repeated every 9 weeks, beginning at week 29. In January 1991, the duration of therapy was reduced to 12 courses due to emerging evidence of IFOS-induced renal tubular dysfunction.ResultsOf the 62 patients evaluable for response, 45 (73%) achieved a complete response. There were three fatal toxicities due to infection. Life-threatening neutropenia was seen in 55 of 60 patients, and life-threatening infections occurred in 27 of 60 patients. Twenty-five patients (42%) developed some degree of neurotoxicity from vincristine. Eleven patients (18%) developed nephrotoxicity, 7 cases of which were severe; 6 of the 11 patients who developed nephrotoxicity were <2 years old.ConclusionsThis pilot study had toxicity and response rates comparable to the other two Intergroup Rhabdomyosarcoma Study (IRS)-IV pilot trials of vincristine-actinomycin-cyclophosphamide and vincristine-actinomycin-ifosfamide and is, therefore, being evaluated in the current IRS randomized trial. Due to the high incidence of life-threatening neutropenia and infections, the use of growth factors is now routine. Five of 11 patients who developed nephrotoxicity did so after more than eight courses of IFOS; therefore, the current randomized trial limits IFOS to a total of eight courses.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeNoonan syndrome (NS) is a congenital disorder characterized by various phenotypic features and congenital anomalies. Bleeding disorders are among the more serious, common, yet poorly defined complications associated with NS. As a means of focusing on these complications, we report three patients with stigmata of NS, each of whom had a combination of different hemostatic disorders, and review the literature on bleeding disorders in NS.Patients and MethodsThe clinical course and hemostatic abnormalities in three patients with NS were studied, and a literature review on NS was undertaken.ResultsThe three patients we report had decreased coagulation factor levels (factors XI and II), von Willebrand disease, various levels of thrombocytopenia, and abnormal platelet function. The literature review on NS discloses multiple types of hemostatic abnormalities and a wide range of clinical presentations. A low level of coagulation factor XI is the most frequently described; thrombocytopenia and abnormal platelet function are also common.ConclusionsThe existence of various types of bleeding disorders within one syndrome is unusual and requires further investigation. Recognition of this common complication in children with NS would aid both clinical management and understanding of the spectrum, the frequency, and perhaps even the basis of the hematostatic defects in this syndrome. We recommend performing coagulation screening tests in every patient with NS.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeA case of primary Burkitt's cell lymphoma of the liver is reported.PatientA 14-year-old Chinese boy presented with a 10-day history of postprandial epigastric pain and weight loss.ResultsPreoperative imaging studies revealed a large solid mass confined to the right lobe of the liver; there was no evidence of involvement of other sites. There was serological and immuno-histochemical evidence of asymptomatic hepatitis B virus infection. Complete removal of the mass was achieved by right hepatic lobectomy. Histological examination revealed a small noncleaved cell lymphoma of Burkitt's type that immunostained positively for B-cell markers. The patient remains well, with no evidence of disease >8 years after surgical resection and combination chemotherapy.ConclusionsOnly five cases (two children and three adults) of primary small noncleaved cell lymphoma of the liver have been reported. We believe this is the second reported case of childhood hepatic lymphoma with long-term disease-free survival. Further work is needed to elucidate the relationship between hepatitis B virus infection and the development of a primary small noncleaved lymphoma of the liver.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeWe report a reversible sensorimotor neurotixicity that developed in two β-thalassemic patients treated with high-dose deferoxamine (DFO) for iron overload.MethodsTwo patients were treated with high-dose (120 mg/kg/day) intravenous DFO for iron overload.ResultsSensorimotor toxicity developed after 5 and 6 months of treatment, respectively. The development of the neurotoxicity did not correlate with the serum ferritin or the ratio of DFO dose to serum ferritin. Symptoms resolved in both patients with discontinuation of DFO treatment. In 1 patient, symptoms recurred with resumption of DFO treatment.ConclusionsThese cases demonstrate that a reversible sensorimotor neurotoxicity, a previously unreported toxicity, may complicate DFO therapy; this complements the previously reported auditory and visual neurotoxicity associated with DFO therapy. Discontinuation of therapy at the time of onset of neurotoxicity is recommended, with possible resumption at lower doses.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeThis study evaluated the feasibility of performing haploidentical CD34+selected transplants for children with Down's syndrome (DS) and recurrent leukemia.Patients and MethodsWithin a cohort of 15 children, two patients had DS. Transplantation of CD34+cells from haploidentical parents was performed after the children were conditioned with fractionated total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate.ResultsThe preparative regimen was well tolerated, and engraftment of polymorphonuclear cells and platelets took place promptly (by day 20) in both patients with DS. However, both patients with DS experienced severe grade IV GVHD that was limited to the skin and was refractory to salvage with high-dose methylprednisolone therapy. In one patient, GVHD responded to second-line salvage therapy with ATG, but the patient died on day 234 from leukemic relapse. The second patient had GVHD that did not respond to ATG and died of multisystem organ failure and refractory GVHD on day 44. Two of two DS patients had steroid refractory severe acute GVHD of the skin, while only one of 11 evaluated and identically treated non-DS patients had severe GVHD (P< 0.05).ConclusionThese observations in patients who underwent mismatched bone marrow transplantation suggests that patients with DS have an increased risk of severe acute GVHD of the skin in this context.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

PurposeBone marrow transplantation (BMT), particularly preparative regimens, may have a significant impact on the developing nervous system. However, the effects of various BMT regimens on children's growth and development have been poorly documented to date. Twins serve as ideal subjects to study the impact of medical treatment, since they control for nonmedical (genetic and environmental) influences upon neurodevelopmental outcome.Patients and MethodsTwo cases of monozygotic twins are presented to illustrate the impact of BMT regimens. Growth data and neurocognitive testing are presented for each patient (affected twin) in relation to his/her syngeneic BMT donor and case control (control twin).ResultsThese two cases illustrate the growth retardation that has been reported after BMT. However, changes in growth trends across twins appear to have begun after diagnosis, rather than after BMT per se. Comparisons of cognitive test results within these twin pairs illustrate learning problems in the affected twins. However, there was also evidence of learning anomalies in the unaffected twins.ConclusionsResults underscore the importance of longitudinal assessment in order to identify the side effects of BMT regimens for children. Differences across the two cases highlight important research questions regarding variables associated with patients, disease, and treatment (e.g., age at the time of BMT, previous neurotoxic treatments, underlying disease) and emphasize the importance of controls in this line of research.

ISSN:1077-4114    

出版商:OVID    

年代:1997

数据来源: OVID