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Chemotherapy induced pediatric oncologic emergencies

Chemotherapy induced pediatric oncologic emergencies . Prof : Mohamed A. Badr Hematology unit Zagazig university. pharmacologic treatment modalities have quite unique effects on both the patient and the disease

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Chemotherapy induced pediatric oncologic emergencies

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  1. Chemotherapy induced pediatric oncologic emergencies Prof : Mohamed A. Badr Hematology unit Zagaziguniversity

  2. pharmacologic treatment modalities have quite unique effects on both the patient and the disease • Tumour destruction potential and drug toxicity typically correlate with drug dosage .

  3. Factors affecting the incidence of the adverse effects of the antineoplastic drugs : • A. Age : the extremes of age . • B. The multiple drug policy . • C. The multiple drug interactions caused by the mutual effect, of the various drugs on one another .

  4. The antineoplastic drugs used in the treatment of malignant diseases may cause a pediatric oncologic emergency by two ways :- • I. Direct effect: mainly on the bone marrow ; blood and blood vessels . • II. Indirect effect: through drug interactions.

  5. *Most cancer patients have episodes of LEUKOPENIA (WBC < 1500/ml) after chemotherapy , mainly due to mylosuppression . • Especially when febrile,all pediatrics patients with neutropenia (ANC<500/ml3) need prompt attention because there is a risk of bacterial , viral and Opportunisticinfection .

  6. On the other hand ; LYMPHOPEN1A ( ALC < 1OOO/ml3) and defective cell-mediated immunity places patients at risk of opportunisticfungal and protozool infections, some of these infections are emergencies .

  7. Chemotherapy induced coagulopathy may appear as : a) thrombocytopenia with hemorrhagic problems like petichea, purpura ,ecchymosis and epistaxis . When the platelet count. is below 10.000 /ml internal hemorrhage may occur with pediatric oncologic emergency . b) Reduced coagulation factors which may cause ecchymosis , bleeding from punctuate sites and cerebrovascular accidents

  8. 30% of the cerebrovascular accidents in pediatric patients with malignancy are caused directly by chemotherapy . Drugs which may cause CVA : 1- Asparaginasecoagulopathy either due to hemorrhage or thrombosis , 2- Cisplatin can lead to cerebral ischemia as result of: a- Renal wasting of solutes with subsequent hypomagnesemic arterial spasm. Or , b-A direct thrombotic endothelial injury .

  9. Hemorrhagic complication of treatment of acute lymphoblastic leukemia with l-asparaginase. Nonenhanced CT shows a right frontal intraparenchymal hematoma resulting from cortical vein thrombosis. Note clot within the superior sagittal sinus (arrow).

  10. Left lateral sinus thrombosis demonstrated on MR venography [left image]. This patient on combined chemotherapy presented with sudden onset of headache. One week after treatment with heparin, [right image] the MR venogram of the patient displayed increased flow in the left lateral sinus consistent with early recanalization of the sinus; headache had resolved at this point.

  11. 3* Methotrexate : after high dose IV or IT Methotrexate: an acute stroke like syndrome may occur due to vascular or embolic cause. The syndrome includes behavioral abnormalitis , focal sensorimotor signs and abnormal reflexes . Cerebrovascular accidents present with sudden change in motor function or speech Convulsions may also be observed . Immediate C.T scan may reveal evidence of bleeding or progressive tumor . MRI may identify the CVA .

  12. The acute syndrome of Inappropriate secretion of the anti-diuretic hormone (ISADH) with hypo-osmolality and water intoxication may be caused by vincristinc and cyclophosphamide .

  13. Abdominal emergencies in the form of hemorrhagic pancreatitis may be a side effect of Asparaginase therapy.

  14. CT abdomen showing diffusely enlarged pancreas with low density from edema

  15. Mechanisms of drug interactions: Drug effects are basically due to : 1- inhibition of metabolic process(Antagonistic action ) 2-Stimulation of the metabolic processes(Agonistic action ) 3- Modulation So, the consequences of drug interaction may be: overadditive, synergistic, potential effect Or antagonistic effect

  16. Examples of Drug-interactions that may cause pediatric emergency : I-Cyclophosphamide: • In combination with allopurinol, severe myelosuppression occurred in 58% of patients. • In combination with doxorubicin bladder injury with hematuria may occur.

  17. 2-Doxorubicin: A high incidence of cardiotoxicity was observed with doxorubicin and concomitant cyclophosphamide ,ifosfamide and radiotherapy . These combinations seem to have additive toxicity which might become clinically important before reaching the cumulative toxic dose of 450mg/m2.

  18. 3-Methotrexate : • A high incidence of pulmonary toxicity with interstitial pneumonitis Appears to represent the clinical manifestation of a known drug interaction between Methotrexateand Etoposide. • In combination with Nonsteroidal Anti inflammatory drugs , the interaction include leucopenia , thrombocytopenia , acute renal failure . mucositis , nausea , vomiting and jaundice

  19. The mechanism of this interaction still unclear. One explanation is that there might be a competition of excretion in the renal tubule . In a Swedish study with low dose methotrexate and aspirin, glomular filtration ratedecreased in all patients .

  20. • Several reports describing severeinteractions between trimethoprim- sulfamethoxazol and methotrexate . Even at low concentration of MTX , severe bone marrow depression may occur due to an increase in systemic exposure to MXT .

  21. 4- Vincristine : * Severe hepatic injury with ascites occurred insome patients with Wilms' tumour with singledose Vincristine and Dactinomycin - The combination of potentially neurotoxic drugs with vinca alkaloids may increase the neurotoxicity of the latter .

  22. This neurotoxicity presents with severe parathesia muscle weakness and atrophy of nerve fibers when , vincristine is combined with Asparaginase , The concomitant use of vincristine and Metronidazole is believed to increase neurotoxicity of vincristine with painful legs.

  23. Severe drug-induced acute lung injury. A. Day 15: after intensive alkylating agent chemotherapy (cyclotherapy (cyclophosphamide-cisplatin-carmustine (BCNU). B. Day 20: partial resolution on corticosteroids. C. Day 24: residual small septal lilnes; corticosteroids continue. D. Day 28: resolution of radiographic abnormalities.

  24. THANK YOU

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