I-Jakafi imela iparadim yeentuthuko kwi-pharmacology.
Siphila kumaxesha amangalisa apho singayiqondi kakuhle ngakumbi iindlela zesifo kodwa nendlela yokujolisa ezi ndlela ngezilwanyana ezisanda kufunyanwa. Ngokomzekelo, i-Jakafi (i-ruxolitinib) yaba yiyayisisigqibo sokuqala se-FDA sokuphatha i- polycythemia vera , kwaye isebenza ngokuvimbela ama-enzymes uJanus Associated Kinase 1 (JAK-1) kunye noJanus Associated Kinase 2 (JAK-2).
Kanye nezinye iinguqu zamaselula, ezi enzyme ziya ku-haywire kubantu abane polycythemia vera.
Yintoni iPolycythemia Vera?
I-Polycythemia vera yintlungu engavamile yegazi. Isifo esibangelisayo esivame ukunikela emva koko ebomini (abantu kwiminyaka yabo engama-60) kwaye ekugqibeleni kubangela i-thrombosis (cinga ukuphazamiseka) kwisinye kwisithathu kubo bonke abantu abachaphazelekayo. Njengoko sonke sisazi, ukuphazamiseka kungabulala ngoko ukuxilongwa kwe-PV kunzima kakhulu.
Ibali lendlela u-PV uqala ngayo kwintolongo yethambo. Umongo wethu wethambo uxanduva lokwenza iiseli zethu zegazi. Iindidi ezahlukeneyo zeeseli zegazi emzimbeni wethu zineendima ezahlukileyo. Iiseli zegazi ezibomvu zihambisa i-oksijini kwiisisu kunye namalungu ethu, amangqamuzana egazi ezimhlophe anceda ukulwa nokusuleleka kunye neeplatelets ukuyeka ukuphuma. Kubantu abanePV, kukho utshintsho kwiiseli ezininzi ze-hematopoietic ezenza umkhiqizo ogqithiseleyo weeseli ezibomvu zegazi, iiseli zegazi ezimhlophe kunye neeplatelet. Ngamanye amagama, kwi-PV, iiseli zangaphambili, ezahlula kwiiseli ezibomvu zegazi, iiseli zegazi ezimhlophe kunye neeplatelets, ziphonswa kwi-overdrive.
Uninzi lwento nayiphi na into engekho nto, kwaye kwimeko yePV, ezininzi iiseli zegazi zinokuthi zidibanise imilambo yethu yegazi ebangela zonke iintlobo zeengxaki zeklinikhi kubandakanywa oku kulandelayo:
- intloko
- ubuthathaka
- i-pruritis (ukucheka okwenziwa ngokuqhelekileyo emva kweshafa eshushu okanye ibhegi)
- ukungcola
- ukuthuka
- i-thrombosis okanye ukugqithisa kwegazi ngokugqithiseleyo (iingubo zamagazi zinokuvala iireyriyiti kwaye zenze i-stroke, i-heart attack, kunye ne-pulmonary embolism, okanye i-vegg veins njenge-portal vein esondla isibindi esabangela ukulimala kwesibindi.)
- ukuphuma (amaninzi amangqamuzana egazi-amaninzi awo aneeplatelet ezingaphili-angabangela ukuphuma kwegazi)
- i-splenomegaly (I-spleen, ehlengahlengayo iiseli ezibomvu zegazi, ezikhukhulayo ngenxa yenani elikhulayo lamaseli e-PV.)
- I-erythromelalgia (Ubuhlungu kunye nokufudumala kwiidijithi kubangelwa iiplatelet ezininzi ezinqanda ukugeleza kwegazi kwiminwe kunye neenzwane ezingakhokelela ekufakeni idijithi nokufa.)
I-PV inokukhuphaza nezinye izifo ezifana nesifo senhliziyo nesifo sengqondo segazi ngokubakho kwinani elongeziweyo leeseli zegazi ezijikeleza ukujikeleza kunye ne-muscular smooth hyperplasia okanye ukugqithisa okuqhubekayo kwandisa ukuhamba kwegazi. (Imisipha yomzimba yenza iindonga zemithambo yethu yegazi, kwaye inani elinyukayo yeeseli zegazi mhlawumbi likhupha izinto ezininzi zokukhula ezibangela ukuba i-muscle evulekileyo ikhule.)
Incinci yabantu abanePV iyaqhubeka nokuphuhlisa i-myelofibrosis (apho umongo wethambo usichithwa okanye "uphelelwe" kwaye uzaliswe nge-fibroblasts engenamsebenzi kunye ne-filler-like aemia) kwaye ekugqibeleni i-leukemia. Gcina ukhumbula ukuba i-PV idla ngokubizwa ngokuba yi- myeloproliferative neoplasm okanye umdlavuza ngoba njengamanye amagciwane angabangela ukunyuka kwamathambo kwiinombolo zeeseli. Ngelishwa, kwabanye abantu abanePV, i-leukemia imele ukuphela komgca ngokuqhubeka komhlaza.
Jakafi: Imithi edibanisa i-Polycythemia Vera
Abantu kwisigaba se-plethoric se-PV okanye isigaba esibonakaliswe yinani elongeziweyo lamaseli egazi liphathwa ngamanyathelo angenelelo okunciphisa iimpawu kunye nokuphucula umgangatho wobomi. Ininzi eyaziwayo phakathi kwezi zonyango mhlawumbi i- phlebotomy okanye igazi lokunciphisa ukubalwa kweeseli zegazi.
Iingcali ziphinda ziphathe i-PV kunye ne-myelosuppressive (cinga i-chemotherapeutic) i-agents-hydroxyurea, i-busulfan, i-32p kwaye, ngoku kutshanje, i-interferon-leyo inqanda ukuveliswa okweqile kweeseli zegazi. Ukwelashwa kwe-Myelosuppressive kwandisa ingqondo yesigulane kwaye kucinga ukuba kunceda abantu abanePV baphile ixesha elide.
Ngelishwa, ezinye zeziyobisi ezifana ne-chlorambucil zithatha umngcipheko wokubangela i-leukemia.
Kwabantu abanePV abanenkathazo yokunyamezela okanye abangayiphenduliyo kwi-hydroxyurea, ummeli wokuqala we-myelosuppressive, uJakafi uvunyiwe yi-FDA ngoDisemba 2014. I-Jakafi isebenza ngokuvimbela i-JAK-1 ne-JAK-2 enzyme eguqulwa ngabantu abaninzi nePV. Ezi enzyme zibandakanyeka kwigazi kunye nokusebenza kwe-immunological, iinkqubo ezingavamile kubantu abanePV.
Kwimizuzu engama-21 yabantu abangenakuxhaswa okanye abangayithobeli i-hydroxyurea, uphando lubonisa ukuba i-Jakafi iyanciphisa ubukhulu be-spleen (iyanciphisa i-splenomegaly) kwaye iyanciphisa imfuno ye-phlebotomy. Uphando lubonisa ukuba nangona unyango olungcono lunokufumaneka, i-1 pesenti yabantu abanjalo babeya kufumana inzuzo enjalo. Ingqalelo, uJakafi wayevunywe ngaphambili ngu-FDA kunyango lwe-myelofibrosis ngo-2011. Iimpembelelo eziqhelekileyo eziqhelekileyo zikaJakafi (apho i-FDA ihambelana "nemiphumo emibi") ibandakanya i-anemia, ukubalwa kweeplatelet zegazi, ukuxakeka, ukutywina, kunye nokukhwabanisa.
Kufuneka kuqatshelwe ukuba njengokuba kunjalo nangonyango oluthile lwe-myelosuppressive, akucaci nokuba uJakafi uza kunceda abantu baphile ixesha elide.
Ukuba wena okanye umntu omthandayo unempembelelo engaphenduliyo kwi-hydroxyurea, i-Jakafi imela unyango olutsha oluthembisayo. Konke thina, i-Jakafi imela iparadiym yokubaluleka kokusetyenziswa kwamachiza okuya phambili. Abaphandi bahamba bhetele ekuqaliseni ukuba zeziphi iindlela eziphazamiseka zizifo kwaye zijolise kule ngozi.
Imithombo:
"Unyango lwe-syeloproliferative neoplasms: nini, yiphi i-agent, kwaye njani?" nguHL Geyer kunye ne-RA Mesa epapashwe ngeGazi ngo-12/4/2014.
Prchal JT, Prchal JF. Isahluko 86. Polycythemia Vera. Ku: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT. eds. Williams Hematology, 8e . New York, NY: McGraw-Hill; 2010.