Background. Peripheral Blood Stem Cells (PBSC) represent the most used source for stem cell in allogeneic transplantation. The collection of an adequate dose of HSC is crucial for the successful outcome of the transplant, normally equal to 4 - 6 x106 CD34+/kg, with a minimum quantity of at least 2 x 106 CD34+/kg. In turn, the main predictive factor of an adequate collection of HSCs is the number of CD34+ measured on day 5 from the start of mobilization by G-CSF: it is well known that some donors (up to 5%) are defined "poor mobilizer" when the number of 20 cells/μL is not reached after 5 days of therapy-CSF administration. The prediction of an inadequate collection of HSCs is important for the recipient (delayed/failed engraftment, increased risk of infections), but also for the donor, thus predicting additional risks associated with multiple collection procedures, the administration of an additional mobilizing agent (i.e. Plerixafor) or the need of a subsequent bone marrow harvest. The aim of this study was to find predictive factors of HSC mobilization for allogeneic transplantation through the retrospective analysis of clinical and laboratory data of 139 healthy adult donors undergoing leukapheresis for PBSC collection at the Therapeutic Apheresis Unit of the University Hospital of Padua in the period March 2008 - April 2023. Materials and methods. 139 procedures were evaluated, of wich 134 were considered for statistical analysis: 68 were performed on MUD donors and 66 on haploidentical family donors. G-CSF (Lenograstim) was administered (Sub-Q) for 5 days, in an adequate dose not exceeding the maximum dose of 10 μg/kg/day. The CD34+ count (ISHAGE protocol) was performed on the 4th day after the first administration of G-CSF, then on the 5th day just before the HSCs collection and finally on the stem cell product. The evaluated potentially predictive variables of mobilization were: gender, age, weight, BMI, blood volume, type of donation (haploidentical/MUD), dose of G-CSF, WBC, neutrophils, monocytes, lymphocytes, PLT, Hct (baseline and during stimulation days), LDH, ferritin, CD34+ on day +4. By bivariate analysis the impact of each variable on the amount of CD34+ cells mobilized on day +5 was calculated. We divided the donors into 3 groups based on the CD34+ cell count on day 5, i.e., “insufficient mobilizer (IM)” (< 40/μl), “good mobilizer (GM)” (40 – 100/μl), "very good mobilizer (VGM)" (> 100/μl), and evaluated the presence of statistically significant correlations between the degree of mobilization and the variables examined. Results. The collection goal was not achieved by the first leukapheresis procedure in 13% of donors, due to donor/recipient weight imbalance or poor donor mobilization. Numerical variables significantly correlated with the CD34+ cell value measured on day +5 were the CD34+ cell, WBC and neutrophil values measured on day +4, as well as the baseline ferritin and monocyte values. The "IM" were 13 (9.7%), the "GM" 81 (60.4%) and the "VGM" 40 (29.9%). Baseline donor characteristics that may have significantly affected the degree of mobilization (defined in the three categories) were gender, BMI, and baseline lymphocyte count. Instead, among the parameters evaluated during mobilization, the main predictive factors identified were the number of CD34+ cells and WBC measured on day +4. Conclusions. Female gender, low BMI value and iron reserves status can be considered negative predictive factors of adequate mobilization, which must be taken into account both during the work-up phase for donation. The high BMI, combined with high CD34+ and WBC values at day +4, represent the characteristics most associated with "VGM" donors.
Background. Le cellule staminali emopoietiche (CSE) circolanti nel sangue periferico dopo stimolazione con G-CSF rappresentano la sorgente più utilizzata per il trapianto allogenico di CSE. Cruciale per l’esito positivo del trapianto è la raccolta di una dose di CSE congrua al target richiesto dal Centro-Trapianti, pari normalmente a 4-6 x106 CD34+/kg, con una quantità minima di CD34+/kg pari ad almeno 2x106. A sua volta, il fattore predittivo principale di una raccolta adeguata è il numero di CD34+ misurato in 5a giornata dall’inizio della stimolazione con G-CSF, ed è noto che alcuni donatori (fino al 5%) sono definiti “poor mobilizer”, quando non viene raggiunto il numero di 20 cellule CD34+/µL dopo 5 giorni di stimolazione. Prevedere una raccolta di CSE inadeguata è importante nell’interesse del ricevente (ritardato/mancato attecchimento, aumentato rischio di infezioni), ma anche del donatore, preconizzando così rischi aggiuntivi associati a procedure multiple di raccolta, alla somministrazione di un ulteriore agente mobilizzante (es. Plerixafor) oppure al ricorso ad espianto midollare. Scopo dello studio è stato di ricercare fattori predittivi della mobilizzazione di CSE per trapianto allogenico attraverso l’analisi retrospettiva dei dati clinici e di laboratorio di 139 donatori adulti sottoposti a staminoaferesi presso l’Unità di Aferesi Terapeutica dell’Azienda Ospedale Università di Padova nel periodo marzo 2008–aprile 2023. Materiali e metodi. Sono state valutate 139 procedure, considerandone per l’analisi statistica 134: 68 da donatori MUD e 66 da donatori familiari. Il G-CSF (Lenograstim) è stato somministrato s.c. per 5 gg., in dose adeguata non eccedente la dose massima di 10 μg/Kg/die. La conta delle CD34+ è stata effettuata il 4°g. dalla prima somministrazione del G-CSF, quindi il 5°g. prima della donazione di CSE e infine sul prodotto cellulare. Le variabili valutate sono state: genere, età, peso, BMI,volemia, tipologia di donazione (aploidentico/MUD),dose di G-CSF/kg, WBC, neutrofili, monociti, linfociti, PLT, Hct (basali e durante le giornate di stimolazione), LDH, ferritina, CD34+ in 4a giornata. Tramite analisi bivariata è stato valutato l’impatto di ciascuna variabile sulla quantità di cellule CD34+ mobilizzate il 5°g. Dopo aver suddiviso i donatori in 3 gruppi sulla base della conta delle cellule CD34+ in 5a giornata, e cioè “insufficient mobilizer (IM)”(<40/μl), “good mobilizer (GM)”(40–100/μl), “very good mobilizer (VGM)”(>100/μl), è stata valutata la presenza di correlazioni significative tra il grado di mobilizzazione e le variabili prese in esame. Risultati. Il target di raccolta non è stato raggiunto nel 13% dei donatori, per lo squilibrio di peso donatore/ricevente o per la scarsa mobilizzazione del donatore. Le variabili numeriche correlate significativamente con il numero di cellule CD34+ misurato il 5°g. sono stati i valori delle cellule CD34+, dei WBC e dei neutrofili misurati il 5°g, ed i valori basali della ferritina e dei monociti. Gli “IM” sono stati 13 (9,7%), 81 (60,4%) i “GM”, e 40 (29,9%) i “VGM”. Le caratteristiche basali del donatore che possono aver influito significativamente sul grado di mobilizzazione (definito nelle tre categorie) sono state il genere, il BMI e il valore basale dei linfociti. Invece, tra i parametri valutati durante la mobilizzazione, i fattori predittivi principali individuati sono stati il numero di cellule CD34+ e di WBC misurati il 5°g. Conclusioni. Il genere femminile, il basso valore di BMI possono essere considerati fattori predittivi negativi di adeguata mobilizzazione, dei quali tenere conto, insieme all’assetto marziale, durante la fase del work-up di idoneità alla donazione. L’elevato BMI, unito a valori elevati di CD34+ e WBC al giorno +4, rappresentano, le caratteristiche maggiormente associate ai donatori “VGM”.
Studio dei fattori predittivi della mobilizzazione di Cellule Staminali da Sangue Periferico (PBSC) per Trapianto Allogenico in 139 donatori sani
COLLER, MARCO
2022/2023
Abstract
Background. Peripheral Blood Stem Cells (PBSC) represent the most used source for stem cell in allogeneic transplantation. The collection of an adequate dose of HSC is crucial for the successful outcome of the transplant, normally equal to 4 - 6 x106 CD34+/kg, with a minimum quantity of at least 2 x 106 CD34+/kg. In turn, the main predictive factor of an adequate collection of HSCs is the number of CD34+ measured on day 5 from the start of mobilization by G-CSF: it is well known that some donors (up to 5%) are defined "poor mobilizer" when the number of 20 cells/μL is not reached after 5 days of therapy-CSF administration. The prediction of an inadequate collection of HSCs is important for the recipient (delayed/failed engraftment, increased risk of infections), but also for the donor, thus predicting additional risks associated with multiple collection procedures, the administration of an additional mobilizing agent (i.e. Plerixafor) or the need of a subsequent bone marrow harvest. The aim of this study was to find predictive factors of HSC mobilization for allogeneic transplantation through the retrospective analysis of clinical and laboratory data of 139 healthy adult donors undergoing leukapheresis for PBSC collection at the Therapeutic Apheresis Unit of the University Hospital of Padua in the period March 2008 - April 2023. Materials and methods. 139 procedures were evaluated, of wich 134 were considered for statistical analysis: 68 were performed on MUD donors and 66 on haploidentical family donors. G-CSF (Lenograstim) was administered (Sub-Q) for 5 days, in an adequate dose not exceeding the maximum dose of 10 μg/kg/day. The CD34+ count (ISHAGE protocol) was performed on the 4th day after the first administration of G-CSF, then on the 5th day just before the HSCs collection and finally on the stem cell product. The evaluated potentially predictive variables of mobilization were: gender, age, weight, BMI, blood volume, type of donation (haploidentical/MUD), dose of G-CSF, WBC, neutrophils, monocytes, lymphocytes, PLT, Hct (baseline and during stimulation days), LDH, ferritin, CD34+ on day +4. By bivariate analysis the impact of each variable on the amount of CD34+ cells mobilized on day +5 was calculated. We divided the donors into 3 groups based on the CD34+ cell count on day 5, i.e., “insufficient mobilizer (IM)” (< 40/μl), “good mobilizer (GM)” (40 – 100/μl), "very good mobilizer (VGM)" (> 100/μl), and evaluated the presence of statistically significant correlations between the degree of mobilization and the variables examined. Results. The collection goal was not achieved by the first leukapheresis procedure in 13% of donors, due to donor/recipient weight imbalance or poor donor mobilization. Numerical variables significantly correlated with the CD34+ cell value measured on day +5 were the CD34+ cell, WBC and neutrophil values measured on day +4, as well as the baseline ferritin and monocyte values. The "IM" were 13 (9.7%), the "GM" 81 (60.4%) and the "VGM" 40 (29.9%). Baseline donor characteristics that may have significantly affected the degree of mobilization (defined in the three categories) were gender, BMI, and baseline lymphocyte count. Instead, among the parameters evaluated during mobilization, the main predictive factors identified were the number of CD34+ cells and WBC measured on day +4. Conclusions. Female gender, low BMI value and iron reserves status can be considered negative predictive factors of adequate mobilization, which must be taken into account both during the work-up phase for donation. The high BMI, combined with high CD34+ and WBC values at day +4, represent the characteristics most associated with "VGM" donors.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/53732