Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy and irradiation to the hypothalamic-pituitary-gonadal axis given for childhood cancer carry with them a risk of endocrine late effects. These treatment modalities are part of the treatment of common oncological diseases in childhood such as acute lymphoblastic leukaemia, brain tumours, Hodgkins lymphoma and solid tumours outside the central nervous system. Cranial irradiation of a prepubertal child can induce early or even precocious puberty, particularly in girls. Hypogonadotrophic hypogonadism may develop at a later stage. Irradiation of the gonads, as e.g. part of total body irradiation before bone marrow transplantation, will most likely cause gonadal failure and late, incomplete or absent puberty in girls. Many boys will experience a normal pubertal development except for small testes. Alkylating agents given for a variety of childhood cancers, are gonadotoxic. After high doses of these drugs, girls are at great risk of developing ovarian failure, whereas boys will usually go through puberty normally. Many children receive a combination of several treatment modalities, which complicates the prediction of pubertal development. Control and management of children with cancer at risk of having a disturbance of puberty is difficult and requires detailed knowledge of endocrinology as well as oncology. This chapter reviews the common treatments for the most frequent childhood cancers, the known effects of the therapy on pubertal development and provides outlines of control and management.
Best Pract Res Clin Endocrinol Metab 2002 Mar
PMID:Disturbance of pubertal development after cancer treatment. 1198 1

In children with acute lymphoblastic leukaemia (ALL), measurements of minimal residual disease (MRD) during therapy provide crucial information about the response to treatment and the risk of relapse. Flow cytometry is a practical and widely applicable tool for monitoring MRD in patients with ALL. This approach is based on the identification of immunophenotypes expressed by leukaemic cells but not by normal lympho-haematopoietic cells in bone marrow and peripheral blood. These phenotypes can identify one leukaemic cell among 10 000 normal cells and are currently applicable to at least 90% of patients with ALL. A strong correlation between flow cytometric measurements of MRD during clinical remission and treatment outcome has been demonstrated, suggesting that these assays should be incorporated into treatment protocols.
Best Pract Res Clin Haematol 2002 Mar
PMID:Advances in the immunological monitoring of childhood acute lymphoblastic leukaemia. 1198 13

Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are assumed to be unique 'fingerprint-like' sequences for each acute lymphoblastic leukaemia (ALL). Various clonal Ig/TCR gene rearrangements can be identified at diagnosis in virtually all childhood ALL patients, representing molecular targets for detection of minimal residual disease (MRD) during follow-up analysis. The usage of at least two MRD-PCR targets per patient generally ensures high sensitivity (</=1:10(4) normal cells) and prevents false-negative results owing to ongoing or secondary rearrangements.MRD monitoring in childhood ALL employing Ig/TCR gene rearrangements as PCR targets has significant prognostic value. This is particularly powerful for evaluation of early treatment response and consequently can be used for improved therapy stratification. Prolonged continuous MRD monitoring might be important for patients at intermediate or high risk of relapse. MRD monitoring in second complete remission identifies patients with excellent drug sensitivity and predicts outcome after stem cell transplantation.
Best Pract Res Clin Haematol 2002 Mar
PMID:Molecular monitoring of residual disease using antigen receptor genes in childhood acute lymphoblastic leukaemia. 1198 15

Despite intensive chemotherapy and stem cell transplantation (SCT) programmes, overall survival in adult acute lymphoblastic leukaemia (ALL) remains poor compared to that in childhood ALL. Despite clinical and morphological remission being achieved by over 80% of patients, 5-year survival is limited to 40% of patients, clearly indicating that morphology is insufficient in predicting future outcome. Molecular assessment of residual disease in bone marrow using immunoglobulin genes as markers of clonality has recently been evaluated in a large adult ALL study in our institution. Analysis of disease-free survival (DFS) rates for minimal residual disease-(MRD-) positive and -negative patients established that MRD positivity was associated with increased relapse rates at all times, being most significant at 3-5 months post-induction and beyond. Pre-autologous SCT tests are predictive of outcome, but for allogeneic SCT outcome is related to results of the tests after the procedure rather than before. The association of MRD test results and DFS was independent of, and greater than, other standard predictors of outcome and is therefore important in determining treatment for individual patients.
Best Pract Res Clin Haematol 2002 Mar
PMID:Molecular analysis of minimal residual disease in adult acute lymphoblastic leukaemia. 1198 17

The Philadelphia chromosome (Ph) is found in approximately 5-25% of acute lymphoblastic leukaemia (ALL) cases and is the harbinger of a poor outcome. Polymerase chain reaction (PCR) assays can detect leukaemia-specific genetic lesions down to a sensitivity approaching one leukaemia cell in a background of a million normal cells. In Ph(+) ALL, the unique BCR-ABL translocation is thus a specific target for the detection of minimal residual disease (MRD). After chemotherapy or transplantation the detection of residual BCR-ABL transcripts is associated with a high risk of subsequent relapse. With the advent of novel therapeutics that target the structure and function of BCR-ABL, the detection of MRD may allow for targeted therapy that could abort a potential relapse.
Best Pract Res Clin Haematol 2002 Mar
PMID:Molecular measurement of minimal residual disease in Philadelphia-positive acute lymphoblastic leukaemia. 1198 18

Immunophenotypic analysis of leukaemic cells using multiparametric flow cytometry has proved to be an attractive approach for MRD investigation in acute lymphoblastic leukaemia (ALL); by contrast, information on acute myeloid leukaemia (AML) is still scanty. Here, we first review the methodological strategies for these studies. Triple or quadruple antigenic combinations, analysed by multiparametric flow cytometry, have shown that in 80% of AML patients it is possible to identify aberrant or uncommon phenotypic profiles on blast cells, thereby allowing their distinction from normal cells and their use as leukaemia-associated phenotypes (LAP). We also focus on technical aspects that are important in the definition of LAP. We then review pitfalls that could potentially affect results using this approach. Finally, we review available information concerning the clinical value of these studies. Although reported data in the literature are still scanty, several authors have shown that this technique could be used for the prognostic evaluation of AML patients, when immunophenotypic evaluation is applied after induction therapy.
Best Pract Res Clin Haematol 2002 Mar
PMID:Immunological evaluation of minimal residual disease (MRD) in acute myeloid leukaemia (AML). 1198 19

Over the past decade considerable advances have been made in the sensitivity of detection of residual lymphoma and leukaemia cells. Assays based on the polymerase chain reaction (PCR) can detect one tumour cell in up to 10(5) to 10(6) normal cells. The identification and cloning of breakpoints associated with specific chromosomal translocations has made possible the application of these techniques to a variety of lymphoid malignancies. In parallel, B cell malignancies exhibit rearrangements of their immunoglobulin genes that are also suitable targets for PCR amplification to identify residual cells. Although these techniques provide a useful adjunct to standard methods of detection and diagnosis, their role in determining disease outcome remains investigational. There is confusion as to whether it is necessary to eradicate PCR-detectable lymphoma cells for cure, so it is not yet possible to determine whether the detection of residual lymphoma cells by PCR is an indication to continue therapy.
Best Pract Res Clin Haematol 2002 Mar
PMID:Monitoring disease in lymphoma and CLL patients using molecular techniques. 1198 23

The study of minimal residual disease (MRD) as a 'surrogate' marker of molecular response to treatment has drawn great interest because of the potential of tailoring treatment and the possibility of gaining insight into the nature of a cure. Polymerase chain reaction-based (PCR-based) detection of MRD by immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements can be applied in more than 90-95% of cases of childhood acute lymphoblastic leukaemia (ALL). Accordingly, several retrospective studies of MRD in childhood ALL have used one of the different PCR approaches for the detection of antigen-receptor gene rearrangements. The promising results on the predictivity of MRD evaluation at the end of induction treatment has raised the need of a new definition of remission. Until now, most PCR-based MRD studies have used semiquantitative methods for the detection of Ig and TCR gene rearrangements. The introduction of real-time quantitative PCR (RQ-PCR) has resulted in the improvement of sensitivity and specificity and has given better quality control of the MRD data. There is an urgent need to incorporate MRD data in clinical studies, properly designed to address treatment questions. In this context several ongoing co-operative study groups have adopted an MRD-based risk group classification to explore whether a better tailored treatment would result in further improvement in cure rates for children with ALL.
Best Pract Res Clin Haematol 2002 Dec
PMID:Results of minimal residual disease (MRD) evaluation and MRD-based treatment stratification in childhood ALL. 1261 67

The prognosis for adult acute lymphoblastic leukaemia (ALL) is poor. Only 20-30% of patients will be cured with conventional chemotherapy. Haematopoietic progenitor transplantation is thus an attractive option in these patients. Even if allogeneic transplantation allows a better control of the disease, autologous transplantation remains an important alternative for patients lacking a suitable donor or when allogeneic transplants imply excessive risk. Relapse is the main drawback of autologous transplants, but many strategies are being explored to overcome this problem. We focus here on transplant modality, the source of haematopoietic progenitors, and the best timing to apply the procedure. Also reviewed are the current situation and future strategies for improving results in this setting, such as ex vivo purging; immunotherapy and maintenance chemotherapy.
Best Pract Res Clin Haematol 2002 Dec
PMID:Autologous stem cell transplantation and purging in adult acute lymphoblastic leukaemia. 1261 70

Lymphoblastic lymphoma (LBL) is a rare subtype of non-Hodgkin's lymphoma (NHL) with biological features similar to those of acute lymphoblastic leukaemia. In the majority of cases LBL shows a T-cell phenotype, and mediastinal tumours are the most frequent manifestation. Outcomes of LBL patients treated according to NHL or ALL-type regimens are reviewed. Since prophylaxis of CNS relapse and local recurrence emerged as important issues in the treatment of LBL the different options are discussed. Several studies have used autologous stem cell transplantation (SCT) in the primary treatment of LBL and results are reviewed. The analysis of published prognostic factors and models in LBL demonstrates that, at present, no convincing risk model is available for LBL treated according to contemporary intensive chemotherapy protocols. Therefore indications for SCT in first complete remission (CR) cannot be defined. Future prospects for improvement of treatment results in LBL include intensification of chemotherapy, definition of prognostic factors, evaluation of minimal residual disease and SCT in high-risk patients.
Best Pract Res Clin Haematol 2002 Dec
PMID:Treatment of lymphoblastic lymphoma in adults. 1261 72


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