Zaburzenia genetyczne w ostrej białaczce limfoblastycznej u dzieci i ich wykorzystanie w praktyce klinicznej

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood anda heterogeneous disorder characterized by excessive proliferation and differentiation block. Thebasis of this process is formed by genetic aberrations: a large spectrum of mutations andrearrangements affect essential cellular transduction pathways, genes assuring proper courseof the hematopoiesis, oncogenes, tumor suppressors and apoptosis regulators. Application ofnovel molecular technologies and research methods allow to understanding the biology ofleukemogenesis, identified new diagnostic and prognostic markers based on gene expressionand used to stratify patients and to individualize therapy and improve the determination ofrisk factors in each age group. This review presents the current status of knowledge on geneticaberrations in both pediatric B-cell precursor and T-cell ALL.Ostra białaczka limfoblastyczna (ALL) jest najczęstszym nowotworem układu krwiotwórczegowieku dziecięcego oraz heteregenną chorobą charakteryzującą się nadmierną proliferacjąi zahamowaniem różnicowania. U podstaw ALL leżą zaburzenia genetyczne o charakterzeróżnego rodzaju mutacji i rearanżacji w obrębie kluczowych sygnałów przekaźnictwa komórkowego,genów warunkujących prawidłowy przebieg hematopoezy, onkogenów, genów supresorowychi regulatorów apoptozy. Zastosowanie nowych technologii molekularnych i metod badawczychpozwala na coraz dokładniejsze poznanie biologicznego podłoża leukemogenezy, poszukiwanienowych markerów o znaczeniu diagnostycznym i prognostycznym, o wartościprzydatnej w reklasyfikacji pacjentów do grup ryzyka, a także na odkrywanie nowych cząstekdocelowych dla zindywidualizowanych terapii. W prezentowanej pracy przedstawiono obecnypoziom wiedzy na temat zaburzeń genetycznych występujących w dziecięcej ALL

Mixed phenotype acute leukemia – how to diagnose, how to treat?

In 2009, the World Health Organization has published an updated classification of proliferative diseases, whereby biphenotypic acute leukemia and acute bilineal leukemia, which previously were two separate diseases, were replaced by a single name, mixed phenotype acute leukemia (MPAL). Incidence of MPAL is not exactly known and varies in different publications from 0.5 to 5% of all leukemias in children. In these patients genetic disorders are particularly important for both diagnosis and prognosis. However, due to the still unsatisfactory outcome, the main problem remains optimal therapeutic strategy of patients with MPAL. The majority of research points to better outcomes of MPAL treatment with usage of therapeutic programs for the treatment of acute lymphoblastic leukemia (ALL), although the results are worse than in patients with ALL. An attempt to standardize the therapeutic approach and further improve is the project iBFM AMBI2012

Porównanie wyników leczenia u dzieci z ostrą białaczką limfoblastyczną leczonych w latach 1994–2001 i 2002–2007

Cel. Celem niniejszej pracy była jednoośrodkowa retrospektywna analiza porównawcza wyników leczenia ostrejbiałaczki limfoblastycznej (ALL) u dzieci w latach 1994–2001 według protokołu ALL BFM-90/New York oraz w latach2002–2007 według programu ALL IC-BFM 2002.Pacjenci i metoda. W latach 1994–2001 leczonych było 103 dzieci chorych na ALL w wieku 1–17 lat, w tym 69 dziecizostało zakwalifikowanych do grupy standardowego ryzyka (SR) (Grupa. I-1) i było leczonych według programu ALLBFM-90, zaś 34 zakwalifikowano do grupy wysokiego ryzyka (HR) (Grupa II-1) i leczono wg programu New York. W latach2002–2007 zgodnie z programem ALL IC–BFM 2002 leczono 96 dzieci z ALL w wieku 1–18 lat, w tym 60 dzieciz grupy SR i IR (pośrednie ryzyko; Grupa I-2) oraz 36 dzieci z grupy HR (Grupa II-2). Mediana okresu obserwacji w obugrupach — 50 miesięcy.Wyniki. I całkowitą remisję (I CR) o czasie osiągnęło w Grupie I-1 — 94,2% dzieci i 98,3% w Grupie I-2 (p = 0,225),podczas gdy w Grupie II-1 — 87,9% i 91,4%, w Grupie II-2 (p = 0,632). Obserwowano następujące niepowodzeniaterapii: zgony spowodowane powikłaniami leczenia 1,7% — w Grupie I-2, 6,5% w Grupie II-1, 8,6% w Grupie II-2,podczas gdy nie obserwowano zgonów spowodowanych powikłaniami w Grupie I-1 (p = 0,944 dla grup SR/SR+IR;p = 0,945 dla grupy HR); zgony spowodowane ALL oporną na leczenie wystąpiły u 2,9% dzieci w Grupie II-1 oraz 2,8%w grupie II-2; wznowa choroby wystąpiła u 9,2% dzieci w Grupie I-1 i 10,1% w Grupie I-2 (p = 0,693) oraz w 24,1%dzieci w Grupie II-1 i 12,5% w Grupie II-2 (p = 0,046). U dzieci leczonych wg ALL BFM-90/New York przeważały wznowyszpikowe, tj. 83,3% w grupie SR i 71,4% w grupie HR. Natomiast u dzieci leczonych według ALL IC-BFM 2002 wznowyszpikowe stanowiły 50% i 50% wznowy szpikowo-mózgowe w grupie SR+IR oraz 50% wznowy szpikowe i 50%wznowy mózgowe w grupie HR.Prawdopodobieństwo przeżycia wolnego od niekorzystnych zdarzeń po 4 latach wynosi w Grupie I-1 — 86,6%i w Grupie I-2 — 85,6% (p = 0,237) (grupy standardowego ryzyka), a w Grupie II-1 — 61,6% i w Grupie II-2 — 78,3%(p = 0,047) (grupy wysokiego ryzyka).Wnioski. 1. Odsetki remisji o czasie, zgonów z powodu powikłań leczenia oraz zgonów z powodu ALL opornej naleczenie są porównywalne w obu analizowanych grupach. 2. Obserwowano istotnie mniejszą liczbę wznów ALLwśród pacjentów zakwalifikowanych do grupy HR leczonych wg ALL IC-BFM 2002, niż wśród pacjentów leczonych wgprogramu New York (p = 0,046). 3. W grupie dzieci leczonych wg ALL BFM-90 spostrzegano istotnie mniej nawrotówmózgowych i nie obserwowano nawrotów jądrowych. 4. Prawdopodobieństwo przeżycia wolnego od niekorzystnychzdarzeń było porównywalne w grupach SR, natomiast w grupach HR było istotnie wyższe u pacjentów leczonych wgALL IC-BFM 2002 niż u pacjentów leczonych wg New York (p = 0,047). 5. Dzięki ALL IC-BFM 2002 uzyskano istotnąpoprawę wyników leczenia pacjentów z grupy HR

Quality of life assessment in patients with a stoma due to rectal cancer

The AimThe aim of the study was to assess the quality of life in patients with a stoma, created for various reasons in the course of rectal cancer treatment.Material and MethodsThe study included 50 patients in the early post-surgery follow-up period, visiting the Stoma Outpatient Clinic in the Great Poland Centre in Poznań. All patients underwent surgery due to rectal cancer. Quality of life was assessed using anonymous questionnaires. Participation in the study was voluntary, and patients were informed about the proceedings. Standardized EORTC QLQ-C30 questionnaire for quality of life assessment in cancer patients and QLQ-CR38 module for colorectal cancer patients were used.ResultsIn all domains assessed, stoma patients showed significant impairment of functioning, which negatively influenced their quality of life. In our study group scores in all functional scales (physical – 70.6, role – 71.0, emotional – 61.8, cognitive – 75.6, social – 65) differed significantly from the reference values for the healthy population. QLQ-CR38 questionnaire was used to assess which symptoms were most disturbing for the patients. Negative influence of stoma on sexual functioning in men (mostly erectile and ejaculation dysfunctions) turned out to be the most significant (54.6). In women sexual dysfunctions were significantly less expressed (26.8). Another large group of symptoms having an unquestionable influence on level of functioning comprised direct stoma-related symptoms (47.8).ConclusionsCreation of a stoma still has a large negative impact on patients' quality of life. Influence of the stoma is most pronounced in the area of social functioning. In spite of improvement in support, the problems pertaining directly to the fact of having a stoma bag remain significant for this group of patients

Viral infections in children undergoing hematopoietic stem cell transplantation

BackgroundDue to clinical reasons, in stem cell transplant setting viral infections are divided as latent (herpesviruses, BKV) and sporadic (adenovirus – ADV, rotavirus – RV, influenza – INFL and others).ObjectiveThe aim of this study was the analysis of incidence and outcome of viral infections in 5 Polish pediatric hematopoietic stem cell transplantation (HSCT) centers.Patients and methodsA total number of 308 HSCTs (allo – 232, auto – 76) performed over a period of 24 months in children and adolescents in participating centers were analyzed retrospectively.ResultsIn the period under analysis, 205 viral infections were diagnosed (197 after allo-HSCT, and 8 after auto-HSCT). After allo-HSCT, infections occurred in 119 (51.3%) patients, of which 51.2% were one of multiple infections: 58 patients were infected with one virus, 29 with two, 16 with three and 16 with four or more viruses. Cumulative incidence of viral infections after allo-HSCT was: CMV – 28.0%, BKV – 18.5%, EBV – 15.5%, ADV – 9.5%, RV – 9.1%, VZV – 2.6%, INFL – 0.9%, HHV6 – 0.9%. In 8 (10.5%) auto-HSCT patients following infections were diagnosed: RV – 4, CMV – 2, ADV – 1, BKV – 1. With respect to specific virus, there were no differences between patients’ age and time from HSCT to beginning of infection (medians: 0.8–2.4 month), except for late VZV infection occurring at median time of 6.5 month after HSCT. Cure rates were lowest for: EBV (90,7%), ADV (93,8%), BKV (94,2%), CMV (94,6%), and reached 100% in case of INFL, HBV, VZV, HHV6 and RV.ConclusionsViral infections in children after HSCT occur in over 50% of the patients after allo-HSCT and 10% after auto-HSCT. Mixed and multiple infections occur frequently. Infections with CMV, EBV, BKV or ADV contribute to deaths in 5–10% patients

Viral infections in children undergoing hematopoietic stem cell transplantation: report 2016 of Polish Pediatric Infectious Working Group of Polish Society of Pediatric Oncology and Hematology

BackgroundPolish Pediatric Infectious Working Group of Polish Society of Pediatric Oncology and Hematology continues from 2012 the infections monitoring program in pediatric hematopoietic stem cell transplant (HSCT) and onco-hematology centers.ObjectiveEpidemiological analysis of viral infections in children and adolescents undergoing HSCT in pediatric centers in 2012–2013 and 2014–2015.MethodsRetrospective analysis of viral infections after 650 HSCT in children and adolescents.ResultsAn increase in incidence in 2014–2015 was observed (60.6% vs 51.3%; OR=1.5; p=0.035) after allo-HSCT. Cumulative incidence after allo-HSCT (2012–2013 vs. 2014–2015) was: CMV – 28.0% vs. 29.2%, BKV – 18.5% vs. 22.8%, EBV – 15.5% vs. 24.3%, ADV – 9.5% vs. 5.2%, rotavirus – 9.1% vs. 5.6%, VZV – 2.6% vs. 1.1%, influenza – 0.9% vs. 3.4%, HHV6 – 0.9% vs. 1.5%, norovirus – 0% vs. 2.2%, RSV – 0% vs. 1.5%, parainfluenza – 0% vs. 0.7%, and MPV – 0% vs 0.4%. Infections after auto-HSCT occurred in 8 (10.5%) patients between 2012 and 2013 vs. 2 (2.6%) between 2014 and 2015. Cure rate after viral infections has increased (2012–2013 vs. 2014–2015) for: EBV – 90.7% vs. 100%, ADV – 93.8% vs. 100%, BKV – 94.2% vs. 96.8%, CMV – 94.6% vs. 98%, and remained 100% in infections with influenza, VZV, HHV6, rotavirus as well as in parainfluenza, RSV, and MPV. Decrease of deaths rate attributed to viral infections from 6.5% (2012–2013) to 0.7% (2014–2015) was observed after allo-HSCT.ConclusionsWe found epidemiological trends in viral infections after HSCT in children: increase in incidence after allo-HSCT (increase EBV, appearance of CARV) and decrease after auto-HSCT. Decrease of deaths attributed to viral infections was observed in the last period of time

Viral infections after hematopoetic stem cell transplantation in children with acute lymphoblastic leukemia: the Polish experience

Introduction: Allogeneic hematopoetic stem cell transplantation (allo-HSCT) is one of the therapeutic options in pediatric acute lymphoblastic leukemia (ALL). Most previous analyses have concerned the reactivation of viruses in the entire population of children after allo-HSCT, regardless of the disease entity being an indication for transplantation. In our report, we aimed to evaluate the occurrence, etiology, risk factors and clinical outcome of viral infections in pediatric patients with ALL. Material and methods: 83 post-HSCT ALL patients from 2020 through 2021 were analyzed for infections with polioma BK virus (BKV), cytomegalovirus (CMV), Epstein-Bárr virus, severe acute respiratory syndrome coronavirus 2, adenovirus, respiratory syncytial virus, norovirus, rotavirus, influenza, human herpes virus-6, parainfluenza and rhinovirus. Results: Viral infections were detected after 41% of the transplantations. The viruses most commonly detected were BKV (26.2%) and CMV (23.8%). The analyzed potential risk factors for viral infections were total body irradiation (TBI), graft-versus-host disease, complete remission status, and donor type. Overall survival in the investigated group was 0.815. Conclusions: Complications occurred more frequently in patients without TBI and we did not confirm the impact of other factors. Viral infections in children with ALL after allo-HSCT remain a significant problem. Our results highlight the importance of frequent monitoring and anti-viral prophylaxis