摘要:

We discuss the history and progress of treatment for acute myelogenous leukemia (AML) in children as it has evolved over the past decade. We review the results of clinical trails for children with AML and examine the major strategies that have contributed to progresss in the treatment of this disease.Prior to the 1970's, nearly every child with AML died. Modern intensive chemotherapy, bone marrow transplantation, and advanced supportive care of critically ill patients have improved the outlook for children with this fatal disease.ColclusionAlthough it represents only 15–20% of all childhood acute leukemias, >30% of deaths from leukemia are still a consequence of AML, and only 30–40% of children with newly diagnosed AML are expected to achieve a long-term remission. Greater advances in treatment are expected as headway is made in understanding the comples biology of this heterogenous disease.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Significant advances have occurred in the diagnosis, treatment, and long-term outcome of patients with acute promyelocytic leukemia (APL). The purpose of this review is to describe the molecular genetics of this disease, the use of all-trans retinoic acid (ATRA) in clinical trials of APL, and the clinical and basic research questions for future investigation. Findings of clinical studies in mainland China using ATRA as induction therapy for patients with APL concurrent with laboratory characterization of the molecular changes in APL have led to worldwide clinical trials of ATRA in the treatment of patients with APL. Major advances in understanding the molecular biology and genetics of APL have occurred over the past 5 years. These findings have been translated into novel treatment strategies using all-trans retinoic acid as a differentiation agent in the induction phase of therapy resulting in improved long-term outcome, reduced morbidity, and lower costs for patients with APL. Advanced molecular techniques are being employed for diagnosis and for monitoring of patient response to treatment.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This article reviews bone marrow transplantation (BMT) in acute myelogenous leukemia (AML) of children from adoption of allogeneic BMT for children in first complete remission to the present where autologous BMT, marrow purging, and alternative donors are the major issues. Match related BMT in first remission achieved long-term disease free survival in well over half the young patients. However, as only 25–30% of patients have a matched sibling donor, other options for BMT has been explored, including autologous BMT and unrelated donor BMT. There are many issues that require further study regarding autologous transplant, including the efficacy and benefits of marrow purging. Unrelated donor transplants offer encouraging results in suitable patients, but bring with them the increased risk of complications. BMT is also successful in some children in second remission or who have refractory disease. A recent development in the transplant of children with AML is the use of non-radiation-containing conditioning regimens to avoid potential long-term sequelae of total body irradiation. Nonradiation regimens appear to be as efficacious as radiation-containing regimens for these children. The superiority of BMT over chemotherapy has recently been challenged, as improved supportive care and extremely intensive therapy have resulted in −75% of children achieving a remission and 30–40% of patients surviving. Recent studies have focused upon answering the question regarding the role of BMT in children in first remission. Strategies to improve the outcome of BMT and comparison sequelae of BMT to those on high dose chemotherapy are issues that need to be addressed.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Over the past 15 years, daunorubicin, cytosine arabinoside and, to a lesser extent, 6-thioguanine and etoposide have become the standard agents used to treat patients with acute myelogenous leukemia (AML). These agents have been used in various combinations and schedules with only small improvements in overall outcome because few other agents with promise were available. This situation has changed over the past few years so that today there are a number of new agents that have the potential to supplement or replace the standard drugs. Idarubicin, mitoxantrone, amsacrine, homoharringtonine, 2-chlorodeoxyadenosine, fludarabine, carboplatin, retinoids, colony stimulating factors, and interleukin-2 are discussed.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The child with acute myelogenous leukemia (AML) is at high risk for infection, especially during the induction phase of therapy. Appreciation of special risk factors and the changing spectrum of infecting pathogens is critical to development of the most appropriate initial evaluation and therapy for these children.Based on the available data in pediatrics, and extrapolation from studies in adult populations, we make recommendations for the initial empiric management of the febrile child with AML, the proper use of vancomycin, and management of special infectious complications related to central venous catheter use.Fungal infections are rapidly becoming the single most serious supportive care problem for children with AML. Optimal initial empiric therapy, treatment of proven systemic infections, and current status of attempts at prophylaxis are reviewed.Finally, the issue of colony stimulating factor use in AML is broached. Hopefully, studies underway will demonstrate the benefits and risks of these agents in AML.The time is long past due for large, well designed studies of supportive care in AML. Therapeutic trials addressing this very important aspect of the total care of the child with AML need to accompany the advancing new anti-oncologic therapies of the disease.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Acute myelogenous leukemia (AML) is a costly disease to treat, as patients experience many hospital stays secondary to chemotherapy, the side effects of treatment, and bone marrow transplantation. The trend for some medical centers has been to reduce costs and increase quality through case management. The case manager uses critical pathways and one-on-one interaction to facilitate the patients' progress through the hospital system and to decrease delays and duplication.ConclusionCase management and critical pathways could become an indispensable tool for the management of pediatric patients with cancer.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeWe determined the complete response and survival rates for infants with disseminated (state D) neuroblastoma that followed therapy identical to that for regional disease. In those infants whose disease excluded cortical bone metastases (state DS), we determined complete response rates achieved either spontaneously or with stage D therapy.Patients and MethodsEight-eight patients with metastatic disease received induction chemotherapy followed by a second operation, the results of which determined additional therapy. Twenty-five patients were observed after diagnosis, without chemotherapy, until a second operation.ResultsThe complete response (CR) rates for patients with stage D discase after induction chemotherapy and postinduction surgery were 26% and 52%, respectively, and for immediately treated patients with stage DS disease 69% and 77%, respectively. Fifty-four percent of initially observed patients with stage DS disease achieved CR after a second operation; 44% were never treated beyond these two operations. Five-year actuarial survival rates for patients with stage D and for all those with stage DS disease were 60% (SE = 6%) and 90% (SE = 5%), respectively.ConclusionsImproved survival rates for patients with stage D disease were achieved on this protocol but remained considerably lower than those for infants with less extensive disease. Rates of survival for patients with stage DS disease were achieved with therapy less aggressive than in published series.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeThe fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Because the new born has hypoplasminogenemia and a possible existence of a dysfunctional plasminogen with normal adult levels of plasminogen activator inhibitor type 1 and α2-antiplasmin and elevated levels of plasminogen activator inhibitor type 2, it could be expected that the response to standard concentrations and doses of plasmonogen activators would be reduced.Patients and MethodsWe have studied the Kinetics of in vitro fibrinolysis after adding different concentrations of streptokinase(SK), urokinase (UK), and recombinant tissue plasminogen activator(rt-PA) by use of a microtiter clot lysis assay.ResultsGeometrical dilution rows showed characteristic dose response curves. After clot formation, a rapid lysis was seen with all plasminogen activators. The 50% lysis time correlated to the plasminogen activator dose and showed no diferences among normal adults, children aged 1–6 years, and children aged 7–14 years. Newborns demonstrated a significantly prolonged 50% lysis time with all urokinase concentrations. The 50% lysis time with recombinant tissue plasminogen activator and streptokinase was significantly prolonged only at high concentrations, whereas we could not see any differences at lower concentrations.ConclusionThe experience with thrombolytic agents in newborns is limited, and no controlled investigations have been reported. Our results of the fibrinolytic potential in a plasma milieu in vitro after adding different plasminogen activators can be helpful to establish dosage guidelines for thrombolytic therapy in newborns and older children.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeThe combination of ifosfamide (I) and etoposide (E) was useful in salvaging patients with recurrent/resistant malignant solid tumors of childhood. Carboplatin (C), active against a number of pediatric cancers, was added to I and E to form a three-drug combination called ICE to improve the response rate.Patients and MethodsICE, consisting of I 1.5 g/m2plus E 100 mg/m2i.v.q.d. × 3 plus C i.v. on day 3 only, was given in 21–28-day intervals. C was started at 300 mg/m2, and the dose was escalated in 25% increments, with three evaluable patients treated at each level.ResultsNinety-two patients were enrolled in this phase I/II study between July 1990 and April 1993. A total of 331 courses of ICE was administered. Median courses of ICE received were three (range, 1–16). The maximum tolerated dose (MTD) for C when used in combination was found to be 635 mg/m2. The response rate for ICE at teh MTD for C was complete response (CR) 26% and CR + partial response (PR) 53%. The response was even better in those who received C at the MTD: 32% achieving a CR and 63% a CR + PR. Pancytopenia was the dose-limiting toxicity. Thirteen episodes of bacterial infection were reported, none fatal. Only one patient developed a Fanconi-like syndrome.ConclusionThe MTD of C when used with I and E was found to be 635 mg/m2. The overall CR + PR rate for all patients treated at all C dose levels was 53%. Best responses were seen in non-Hodgkin's lymphoma, neuroblastoma, soft tissue sarcomas, and Wilms' and tumor. Myclosuppression was the predominant toxicity and was dose limiting.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

SummaryThis study assessed the clonality of hypoplastic and subsequent recovery phases before the development of overt leukemia by molecular genetic analysis. We describe a boy who had transient granulocytopenia and anemia before the development of acute lymphoblastic leukemia (ALL). Initially, his bone marrow was hypocellular with 23.6% of lymphoblastic cells, whereas subsequent marrow after the administration of granulocyte colony-stimulating factor (G-CSF) appeared almost normal without any lymphoblasts. At diagnosis, we found the rearrangement of T cell receptor (TCR) δ gene in the leukemic cell DNA by Southern bolt hybridization. The junctional sequence of the Vδ2-Dδ3 recombination of leukemic cells obtained by polymerase chain reaction (PCR) was used for a clonospecific probe. Using the probe, the presence of leukemic clone in the materials before and after diagnosis was examined. We found that the clonospecific probe could detect one leukemic cell in 10,000 normal cells, and we demonstrated the presence of the leukemic clone at the initial hypoplastic and the subsequent recovery phase. The PCR method is very useful to confirm the presence of leukemic clone even in a retrospective analysis using low-quality materials and may be helpful to understand the pathogenesis of a smoldering preleukemic phase.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID