Čimbenici koji utječu na mobilizaciju perifernih krvotvornih matičnih stanica kod bolesnika s limfomima i multiplim mijelomom

master's thesis

• Title (english): Factors affecting peripheral hematopoietic stem cell mobilization in patients with lymphoma and multiple myeloma
• Author: Marko Matašin
• Mentor: Ozren Jakšić (mentor)
• Committee member: Radovan Vrhovac (predsjednik povjerenstva)
• Committee member: Maja Čikeš (član povjerenstva)
• Committee member: Ozren Jakšić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2016-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Intenzivna kemoterapija uz potporu autologne transplantacije krvotvornih matičnih stanica dobro je utvrđena terapijska opcija u liječenja hematoloških maligniteta, uključujući multipli mijelom i limfom. Za provođenje autologne transplantacije potreban je adekvatan broj perifernih krvotvornih matičnih stanica. Kako se one fiziološki u perifernoj krvi ne nalaze u dovoljnoj količini, potrebno je potaknuti prelazak dodatnog broja matičnih stanica iz koštane srži u perifernu krv. Taj postupak se naziva mobilizacijom krvotvornih matičnih stanica. Ona se danas kod većine bolesnika provodi jednim od dvaju standardnih protokola – kemomobilizacijom ili mobilizacijom faktorima rasta („steady-state“), a kod odabrane skupine bolesnika koji slabo mobiliziraju matične stanice uz dodatnu primjenu novog mobilizacijskog lijeka pleriksafora.
Mobilizacija može biti otežana činjenicom da su bolesnici često prethodno podvrgnuti modalitetima terapije koji smanjuju sposobnost mobiliziranja matičnih stanica, kao i konstitucijskim čimbenicima koji otežavaju mobilizaciju. Mnogobrojne studije su identificirale najvažnije negativne prediktore u koje ubrajamo: dob, spol, dijagnozu, dulje vrijeme od postavljene dijagnoze, zahvaćenost koštane srži, radioterapiju, dulje vrijeme od posljednje kemoterapije do mobilizacije, veći broj prethodnih terapijskih linija, prethodne autologne transplantacije, fludarabin, melfalan, lenalidomid, alkilirajuće agense, kemoterapeutike bazirani na platini, leukopeniju, trombocitopeniju. Stoga je za kliničare veoma bitno prepoznati bolesnike iz rizične skupine kako bi pravovremenom intervencijom spriječio mogući neuspjeh mobilizacije kako bi osigurali najbolji tretman za bolesnika uz minimiziranje troškova ove skupocjene procedure.
Ova restrospektivna analiza uključila je bolesnike kojima je učinjena mobilizacija i prikupljanje perifernih krvotvornih matičnih stanica kao priprema za visokodoznu kemoterapiju i autolognu transplantaciju krvotvornih matičnih stanica u liječenju limfoma i multiplog mijeloma. Pacijenti su liječeni na Zavodu za hematologiju Klinike za unutarnje bolesti Kliničke bolnice Dubrava, u razdoblju od 2007. do 2016. godine. Na uzorku od 133 pacijenta koji su podvrgnuti 144 postupaka mobilizacije su istražene značajke samih pacijenata, prethodne terapije i intramobilizacijski faktori koji predviđaju uspjeh postupka te su dobiveni rezultati uspoređeni s podatcima iz do sada publiciranih radova.

Abstract (english)

High dose chemotherapy with the support of autologous haematopoietic stem cell transplantation is a well established treatment course in therapy of haematologic malignancies, including multiple myeloma and lyphoma. It is needed to collect an adequate ammount of haemotopoietic stem cells in order to commence autologous stem cell transplantation procedure. Since the number of these cells in the periphery bloodstream is physiologically not high enough, a procedure is needed to stimulate the translocation of additional stem cells from the bone marrow into the periphery blood. This procedure is called haematopoietic stem stem cell mobilization. In today's practices it is done with one of two standard approaches for most of the patients – with chemomobilization or mobilization by growth factors („steady-state“), and in selected group of patients called who mobilize stem cells poorly with additional help of a novel mobilization agent plerixafor.
Mobilization can be complicated by the fact that patients undergoing it often have a history of mobilization impairing therapy, as well as constitutional factors which reflect negatively on ability to mobilize stem cells. Numerous studies have identified relevant negative predictors which include: age, sex, diagnosis, longer time since diagnosis, bone marrow involvement, radiotherapy, longer time since last chemotherapy to mobilization, numerous lines of chemotherapy, previous autologous haematopoietic stem cell transplantation, fludarabine, melphalan, lenalidomide, use of alkylating agents, platinum based chemotherapy, leukopenia, thrombocytopenia. Thus it is very important for the clinician to recognize a patient belonging the high-risk group so he could apply a timely intervention which will not only provide the best possible benefit for the patient, but also minimize the price of this costly procedure.
This retrospective analysis includes patients which have been subjects to haematopoietic stem cell mobilization and apheresis as a part of high dose chemotherapy and autologous haematopoietic stem cell transplantation treatment course in lymphoma and multiple myeloma therapy. Patient were treated in the Hematology department of Internal medicine clinic of University hospital Dubrava during the period between year 2007. and 2016. In a sample of 133 patients undergoing 144 mobilization procedures we have investigated patient characteristics, previous therapy and intramobilization factors which predict successfulness of the procedure and we compared our results to available published data.

• Keywords: mobilizacija; matične stanice; limfom; multipli mijelom
• Keywords (english): mobilization; stem cells; lymphoma; multiple myeloma
• Language: croatian
• URN:NBN: urn:nbn:hr:105:003350
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-08-10 09:46:32