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Behandling av kronisk myeloisk leukemi med tyrosinkinasinhibitorer i samband med graviditet
Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
2019 (Swedish)Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Abstract [sv]

Bakgrund: Vid kronisk myeolid leukemi (KML) överproducerar blodstamceller omogna granulocyter som kan öka risken för infektioner, anemi och lätta blödningar. Ifall sjukdomen inte åtgärdas i tidigt skede så kan cancercellerna konkrurera ut friska blodceller vilket kan leda till ett livshotande tillstånd. KML drabbar främst vuxna över 55 år. Orsaken till KML är nästan alltid en somatisk mutation i blodcellerna som leder till förändring i karyotypen, den abnormala kromosomen kallas för Philadelphia kromosomen. De olika behandlingalternativ som finns mot KML inkluderar kemoterapi (låg dos/hög dos med stamcellstransplantation), interferon alfa, donator lymfocytinfusion och tyrosinkinasinhibitor (TKI). TKI är standardbehandling vid KML och TKIs inlkluderar imatinib, dasatinib, nilotinib, bosutinib och ponatinib. Studier har visat att TKI administrerat på friska råttor och möss har en teratogen effekt.

Syfte: Syftet med arbetet var att utvärdera risker och fördelar vid behandling av kronisk myeloid leukemi med tyrosinkinasinhibitor i samband med graviditet.

Metod: Arbetet är en litteraturstudie baserat på 13 caserapporter därav 4 studier om imatinib, 4 om nilotinib, 4 om dasatinib och 1 studie om imatinib, nilotinib och dasatinib. Bosutinib och ponatinib exkluderades eftersom det fanns inga studier om exponering av dessa läkemedel under graviditet.

Resultat: Från studierna om imatinib var det totalt 23 av 163 patienter som fick missfall och 14 av 90 födsel slutade med foster abnormiteter. Totalt hade 49 fall rapporterats om exponering med nilotinib under graviditet därav 46 fall resulterade i normal födsel och 3 spädbarn fick fetala abnormiteter som resulterade till dödlighet. Av de fyra fall som rapporterades om Dasatinib var det ett som slutade med abort efter vecka 17 på grund av fostrets dåliga perinatala prognos. Alla patienter behandlades inte med TKIs under graviditeten. Vissa patienter hade kombinationer av läkemedel.

Slutsats: Det finns fortfarande inte bekräftade risker med TKI behandling i samband med graviditet då statistiskt underlag saknas. Fördelen med att behandlas med TKI under graviditet är att risken för återfall och försämrad sjukdomprognos förminskas. Läkaren ska alltid diskutera med patienten om eventuella risker och möjligheter. Behandling för varje patient individualiseras utifrån patienens önskemål.

Abstract [en]

Background

Chronic myeloid leukemia (CML) is a type of leukemia that affects bone marrow and blood cells. In CML, the blood stem cells produce an excessive number of immature granulocytes which leads to a high count of white blood cells in patients. Consequently, the risk of acquiring infections, anemia and hemorrhage, is increased. If not successfully treated the leukemia cells will eventually crowd out platelets and healthy blood cells and ultimately lead to death. Generally, CML occurs in adults aged 55 years or older. The cause of CML is in most cases a somatic mutation that is referred to as the Philadelphia chromosome. There are various treatments for CML, I.e., chemotherapy, interferons-alpha, high-dose chemotherapy combined with a stem cell transplantation, donor lymphocyte infusion (DLI), and tyrosine kinase inhibitors (TKI). TKI are the standard treatment for CML. There are several types of TKI, namely: Imatinib, nasatinib, nilotinib, bosutinib and ponatinib. Although considered the most effective treatment for CML, there are several animal studies indicating that TKI has a teratogenic effect.

Purpose

The objective of this study was to evaluate the risks and benefits of TKI treatment in connection with pregnancy.

Method 

A literature review based on 13 case reports, among them four reports about imatinib, four reports about nilotinib, four reports about dasatinib and one report describing several patients treated with imatinib, nilotinib and dasatinib. Studies about bosutinib and ponatinib are excluded from this study due to the lack of scientific research regarding their impact on pregnant women.

Result

The studies about Imatinib showed that 23 of 163 patients had miscarriage. Furthermore, 14 of the 90 live births resulted in foster abnormalities. There were totally 49 cases in which Nilotinib was administered to pregnant women. In 46 cases the patients gave birth to healthy children. However, in three cases the fetuses were abnormal and in one of these cases the child was stillborn. Moreover, there were four case studies in which the patients were treated with dasatinib. In one case the treatment lead to an abortion after week 17 due do the fetus poor perinatal prognosis. All patients were not treated with TKIs during pregnancy. Some patients had combinations of drugs. 

Conclusion 

There are still no confirmed risks with TKI treatment in connection with pregnancy because statistical evidence is missing. The benefit of being treated with TKI during pregnancy is that the risk of relapse and impaired disease prognosis is reduced. The doctor should always discuss with the patient about risks and opportunities. Treatment for each patiens is individualized based on the patients wishes.

Place, publisher, year, edition, pages
2019. , p. 27
Keywords [en]
TKI
Keywords [sv]
tyrosinkinashämmare, KML
Keywords [la]
imatinib, nilotinib, dasatanib, bosutinib, ponatinib
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-82635OAI: oai:DiVA.org:lnu-82635DiVA, id: diva2:1317137
Subject / course
Pharmacy
Educational program
Bachelor of Science Programme in Pharmacy, 180 credits
Supervisors
Examiners
Available from: 2019-05-22 Created: 2019-05-21 Last updated: 2019-05-22Bibliographically approved

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