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)

The frequency and pattern of obesity in survivors of acute lymphoblastic leukaemia (ALL) was examined in a retrospective analysis of height and weight at zero, two, and four years from diagnosis in 40 children (19 boys and 21 girls). The children had been treated according to the Medical Research Council protocols UKALL VIII and X, both of which included cranial radiotherapy at a dose of 1800 cGy. Body mass index (BMI), determined as weight/height, was used as a measure of fatness. The BMI Z scores were calculated for each patient from standard tables. The ALL group was compared with a control group of 18 age matched children who had received chemotherapy but no radiotherapy. Changes in BMI between diagnosis and two and four years later were analysed by paired t tests. Mean BMI Z scores at diagnosis were similar between ALL boys, ALL girls, and the control group. Two years after diagnosis the ALL group, particularly the girls, showed a significant increase in BMI. By four years BMI had decreased slightly in the ALL boys, but had increased still further in the ALL girls with 57% having BMI Z scores greater than 2. In the control group BMI increased, but not significantly, at two and four years. It is concluded that the obesity seen in patients treated for ALL is more pronounced in girls than boys, and that cranial irradiation is an important factor.
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PMID:Patterns of obesity in boys and girls after treatment for acute lymphoblastic leukaemia. 771 53

Spicamycin, a nucleoside antibiotic containing fatty acids with a variety of chain lengths (C12-C18), showed potent antitumor activity against human gastric cancer SC-9 and human breast cancer MX-1 in a xenograft model. We have made several semi-synthetic spicamycin analogues (SPMs) which differed in the chain length of the fatty acid moiety, and examined their structure-antitumor activity relationship. The cytotoxic activities of SPMs depended on the chain length of the fatty acid moiety, with dodecanoyl, tetradecanoyl, hexadecanoyl and icosanoyl analogues (SPM VIII, SPM X, SPM XII and SPM XVI) exhibiting the most potent cytotoxic activity against P388 murine leukemia cells. SPM VIII showed the most activity against SC-9 in the human tumor xenograft model with the highest therapeutic index among SPMs. The antitumor activity of SPM VIII was superior to that of mitomycin C.
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PMID:Structure-antitumor activity relationship of semi-synthetic spicamycin analogues. 822 22

Concern about the reproductive potential of long-term survivors of acute lymphoblastic leukaemia (ALL) prompted an investigation into the impact of the disease on spermatogenic cells. Using rats as a model, histological, immunocytochemical and electron microscopic analysis was applied to investigate changes in the seminiferous epithelium. In rats transplanted with leukaemic cells at early puberty, degenerate primary spermatocytes and spermatids were prevalent within stage VIII tubules. Electron microscopically, step 8 spermatids showed acrosomal abnormalities and nuclear contour distortion. In the distorted step 9 spermatids, the microtubules of the manchette were abnormally oriented or deficient. Antitubulin antibody staining was reduced in elongating spermatids in the group transplanted with leukaemic cells at early puberty but was not observed in the older leukaemic group. Step 13 spermatids showed extracted chromatin and degenerate step 19 spermatids were occasionally found. Similar but less severe changes were seen in the group of rats transplanted with leukaemic cells at late puberty. We conclude that germinal cell damage induced by ALL is dependent on the developmental maturity of the seminiferous epithelium. The present findings are of particular importance when interpreting the impact of anticancer chemotherapeutics on germinal cells in patients with ALL.
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PMID:Acute lymphoblastic leukaemia in rats induces pathomorphological changes in germ cells. 865 5

Twelve dogs suffering from acute lymphoblastic leukaemia were investigated concerning the following tests: platelet count, prothrombin time (PT, standard test, modified test), activated partial thromboplastin time (APTT), activity of the individual coagulation factors II, V, VII, X, VIII:C, IX, XI, XII, prekallikrein, and high-molecular weight kininogen, the activity of antithrombin III (AT III), protein C, plasminogen, and alpha 2-antiplasmin as well as concentration of fibrinogen, soluble fibrin and fibrin(ogen) degradation products (FDP). All patients showed a decreased platelet count due to suppression of megakaryopoesis by infiltration of the bone marrow with leukaemic cells. In addition, in most of the patients a moderate activity decrease of one or more individual coagulation factors has been found, especially regarding factor II (median, x0.50 = 51%, p = 0.0001), but also factors X (x0.50 = 71%, p = 0.0003) and XI (x0.50 = 68%, p = 0.0006). This was reflected by the APTT and the PT activity (modified test), which were prolonged or decreased, respectively, in the majority of the cases. Furthermore, the activity of AT III and of plasminogen was distinctly diminished (p < 0.001). Like the concentration of FDP, the plasma level of soluble fibrin was significantly higher than in normal dogs (p < 0.001). This indicates that besides thrombocytopenia disseminated intravascular coagulation occurs frequently in dogs with acute lymphoblastic leukaemia and is a main cause for the decreased activity of several plasmatic components of the haemostatic system. The lack of correlation between the concentration of soluble fibrin as an indicator of intravascular coagulation and the total blast cell count (rS = 0.011) shows the importance of other factors like degree of cell lysis as well as participation of organs such as the liver for generation of consumption coagulopathy in dogs with acute lymphoblastic leukaemia.
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PMID:[Changes in hemostasis of dogs with acute lymphoblastic leukemia]. 951 98

A 16 year old boy with epilepsy and learning difficulties is reported. At 3 years of age he was diagnosed with common acute lymphoblastic leukaemia, and received therapy according to the UK protocol, UKALL VIII. This included prophylactic CNS radiotherapy and chemotherapy. He did not develop CNS leukaemia, and complete remission was achieved. At age 7, he began to experience lethargy and learning difficulties, especially problems with hand-writing, concentration and memory. Furthermore, he began experiencing atypical absence seizures, which were provoked by concentration at times of tiredness. EEG showed bilateral non-specific abnormalities, with some epileptiform features. Over the following 9 years, several anti-epileptic drugs were prescribed. Although with the changes in therapy initial remissions have been achieved, the seizures have, each time, continued to relapse. At age 12, EEG was very abnormal, showing frequent generalized slow or sharp waves. At age 13, MRI revealed multiple discrete small high-intensity lesions in the subcortical white matter of both hemispheres. Problems with lethargy, concentration and memory persist and although multiple anti-epileptic drugs have been prescribed, seizures continue to occur almost daily.
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PMID:Leukoencephalopathy after CNS prophylaxis for acute lymphoblastic leukaemia. 966 10

Among 379 patients with AML with FAB type M1, 2 and M4-7 diagnosed between 1978 and 1997 in our institution, 19 (5%) had hypofibrinogenemia (HF), ie a fibrinogen level <180 mg/dl. Compared to patients with normal fibrinogen (n = 360) patients with HF had significantly elevated markers of activation of coagulation (TAT, F1.2, FPA) and fibrinolysis (D-dimer, FDP) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia. Patients with HF had significantly longer prothrombin times, thrombin clotting and reptilase times. Factor X and VIII were significantly lower than in patients without HF. With the exception of M7, HF occurred in all FAB subtypes, but was most common in M5 (12.1%). Patients with HF did not differ from those with normal fibrinogen with regard to age, sex, leukocyte count and other hematological parameters. During induction chemotherapy fibrinogen normalized rapidly (median 5 days) and there was no increased incidence of early hemorrhagic death. The overall and disease-free survival was similar to that of patients without HF.
Leukemia 1998 Aug
PMID:Hypofibrinogenemia in non-M3 acute myeloid leukemia. Incidence, clinical and laboratory characteristics and prognosis. 969 71

Immunohistochemistry of acute leukaemias in bone-marrow paraffin sections is commonly thought to be useless because of the poor preservation of many lineage-related markers. The recent development of antibodies against fixative-resistant epitopes and of new antigen retrieval techniques, however, has expanded the possibility of accurately testing routine samples. To assess the relevance of paraffin section phenotyping in lineage determination, 110 examples of acute leukaemia were studied by specific antibodies against CD1a, CD3, CD15, CD20, CD34, CD68, CD79a, TdT, myeloperoxidase, glycophorin A, and factor-VIII-related antigen. The cases included 59 acute myeloid leukaemias, classified according to the FAB cooperative group criteria, 39 precursor B-cell acute lymphoblastic leukaemias (ALLs), seven T-ALLs, and five mixed precursor B-cell/myeloid acute leukaemias. The combination of the markers employed always allowed the identification of the cell lineage (myeloid, lymphoid or mixed) and, in some instances, of phenotypic profiles characteristic of distinct acute leukaemia subtypes. According to the results obtained, bone-marrow biopsy may be regarded as a reliable tool for acute leukaemia diagnosis; this observation is of practical relevance especially for the classification of cases which lack circulating blasts in the peripheral blood or showing dry tap at bone-marrow aspiration.
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PMID:Acute leukaemia immunophenotyping in bone-marrow routine sections. 1023 10

Immunofluorescence stainings for the CD10 antigen and terminal deoxynucleotidyl transferase (TdT) can be used for the detection of leukemic blasts in CD10+ precursor-B-acute lymphoblastic leukemia (precursor-B-ALL) patients, but can also provide insight into the regeneration of normal precursor-B-cells in bone marrow (BM). Over a period of 15 years, we studied the regeneration of CD10+, TdT+, and CD10+/TdT+ cells in BM of children with (CD10+) precursor-B-ALL during and after treatment according to three different treatment protocols of the Dutch Childhood Leukemia Study Group (DCLSG) which differed both in medication and time schedule. This study included a total of 634 BM samples from 46 patients who remained in continuous complete remission (CCR) after treatment according to DCLSG protocols VI (1984-1988; n = 8), VII (1988-1991; n = 10) and VIII (1991-1997; n = 28). After the cytomorphologically defined state of complete remission with CD10+ and CD10+/TdT+ frequencies generally below 1% of total BM cells, a 10-fold increase in precursor-B-cells was observed in protocol VII and protocol VIII, but not in protocol VI. At first sight this precursor-B-cell regeneration during treatment resembled the massive regeneration of the precursor-B-cell compartment after maintenance treatment, and appeared to be related to the post-induction or post-central nervous system (CNS) therapy stops in protocols VII and VIII. However, careful evaluation of the distribution between the 'more mature' (CD10+/TdT-) and the 'immature' (CD10+/TdT+) precursor-B-cells revealed major differences between the post-induction/post-re-induction precursor-B-cell regeneration (low 'mature/immature' ratio: generally <1.0), the post-CNS treatment regeneration (moderate 'mature/immature' ratio: 1.2-2.8), and the post-maintenance regeneration (high 'mature/ immature' ratio: 5.7-7.6). We conclude that a therapy stop of approximately 2 weeks is already sufficient to induce significant precursor-B-cell regeneration even from aplastic BM after induction treatment. Moreover, differences in precursor-B-cell regeneration patterns are related to the intensity of the preceding treatment block, with lower 'mature/immature' ratios after the highly intensive treatment blocks. This information is essential for a correct interpretation of flow cytometric immunophenotyping results of BM samples during follow-up of leukemia patients. Particularly in precursor-B-ALL patients, regeneration of normal precursor-B-cells should not be mistaken for a relapse.
Leukemia 2000 Apr
PMID:Regeneration pattern of precursor-B-cells in bone marrow of acute lymphoblastic leukemia patients depends on the type of preceding chemotherapy. 1076 56

We present a case of 39 year old woman who developed malignant external otitis (m.e.o.) of Pseudomonas aeruginosa aetiology during pancytopenia after autologous bone marrow transplantation (ABMT). The infection was probably of endogenous origin. 7 days before ABMT otolarygological examination including otoscopy and external ear lavage was performed. Slight inflammatory reaction of external ear was accompanied by the massive involvement of middle ear followed by infiltration of petrous pyramid and mastoid process and finally facial and vestibulocochlear nerve paralysis. Initially the symptoms indicated subarachnoid haemorrhage. Mononuclear cells detected in cerebrospinal fluid as well as CT scan were suggestive of leukaemic infiltration. The latter was negated by immunophenotyping of cerebrospinal fluid cells and MR imaging. Antibiotic therapy resulted in clinical improvement. Life-threatening complications are not frequent after ABMT (transplant related mortality--14/310 (4.5%) in our center). We have met m.e.o. for the first time. At present--13 months after ABMT the patient shows slight symptoms of nerve VII and VIII paresis and remains in complete remission of acute leukaemia. We emphasize the importance of proper preparation of patients for high dose chemotherapy followed by bone marrow transplantation as well as diagnostic difficulties related to pancytopenia.
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PMID:[Malignant external otitis: a rare complication after autologous bone marrow transplantation]. 1094 11

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles.
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PMID:Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI). 1116 21


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