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Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Zoltán Hajdú was born on May 4th, 1952 in Végardó. He completed his secondary school studies at the Rákóczi Secondary Grammar School in Sárospatak, and after his military service, he graduated from the Lajos Kossuth University of Debrecen in Geography and History. In 1976–1977, he was an assistant lecturer at the Technical University of Heavy Industry in Miskolc. He defended his doctoral dissertation at the Institute of Geography at the Lajos Kossuth University in 1977, and in 1977–1978, he became a scholarship researcher of the Central Office of the Hungarian Academy of Sciences in Pécs. Since 1978 he has been a research fellow at the Transdanubian Scientific Institute (and its successors) of the Hungarian Academy of Sciences. He defended his CSc dissertation in 1986 and became a Doctor of the Hungarian Academy of Sciences in 2002. His habilitation procedure was successfully completed in 2013 and he became a professor in 2017. The present semi-structured interview was conducted in March 2022 at the Institute of Regional Studies. The aim of the article is to help readers get acquainted with the most important stages of Zoltán Hajdú’s life, his relationship with geography, as well as the factors underlying the previous two and affecting his career.

Background: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy.Methods: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib.Results: The median follow-up from maintenance start was 44 months. Three-year progression-free survival (PFS) was 52% (48%-57%) for no EMD, 56% (44%-69%) for paraskeletal involvement, and 45% (22%-68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three-year overall survival (OS) was 81% (77%-84%), 88% (80%-96%), and 68% (47%-89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD.Conclusion: Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.

Electoral geography tends to focus on the impact of geographical context on electoral behavior recently and challenges the classical compositional approach. We analyze spatial contextual factors of the 2018 general elections of Bosnia and Herzegovina, where the linear regression models based on the fault line theory result in wrong estimations in several municipalities, not fitting into the national pattern. Using spatial modelling, it is confirmed that the strong territorial base of Bosnian parties is shaped by spatial dependence and spatial spillover effects. In addition to the spillover effect of individual party performance, the indirect neighbourhood role of ethnicity, sectoral structure and education was also shown in some cases.

Hungarian-Serbian relations have never been as cordial as they are now, and this is an opinion shared by the leadership of both countries in spite of the modern history of the two nations. In our paper, we seek explanation for this change and argue that it is a consequence of multiple factors: First, the geopolitical changes in the Western Balkans, which have resulted in a great power competition that has opened up space for small states, like Hungary, to assert their interests. Secondly, the changes in domestic politics in Hungary that have brought national interests into the foreground, resulting, among other outcomes, in more active foreign policy with regard to the Western Balkans region. In this paper, we attempt to give a different, critical view of these relations, discussing migration, economic cooperation and political maneuvers in particular.

Background In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response. Method We analysed 1,222 ASCT patients who were classified based on (1) the interval between induction and stem cell collection, (2) the type of induction regimen: BID (Bortezomib, IMiDs and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide and Dexamethasone), and (3) the time to best response (Early i.e. best response within 4 or 5 months, depending on the regimen vs Late; Good i.e. VGPR or better vs Poor) RESULTS: The length of induction treatment required to achieve a Good response did not affect PFS (p=0.65) or OS (p=0.61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (p=0.31), and median OS 81.7, 92.7, and 77.4 months, respectively (p=0.83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, p value = 0.02). However, achieving a Good response at induction was associated with a better response (≥ VGPR) post-transplant CONCLUSION: The kinetics of response did not affect outcomes.

Bosnia and Herzegovina has witnessed continuous depopulation since 1991. Depopulation was foreseen even without the emergence of war, but not nearly to that extent or that early. Bosnia and Herzegovina is in a worse demographic position than the European Union countries that show similar demographic trends. Very low birth rates, low fertility and low natural population growth have been recorded in the time of weaker economic development, which increasingly accelerates the emigration of the educated population in particular, and permanently adversely affects the reproductive potential of the country. This paper considers a hidden mutual relationship between the demographic situation (natural change, population ageing) in Bosnia and Herzegovina and its citizens' system of values. According to the survey conducted on 614 respondents, Bosnia and Herzegovina's citizens have fewer children than they would like.

Background: Post-transplant cyclophosphamide (PTCY) is increasingly used for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from an HLA-matched unrelated donor (MUD) as an alternative to the standard anti-thymocyte globulin (ATG) graft-versus-host disease (GvHD) prophylaxis. Following the demonstration that the use of PBSC haploidentical grafts results in more GvHD than bone marrow grafts, groups have attempted to reduce GvHD in haploidentical-PBSCT by adding ATG to PTCY. The experience of combined PTCY+ATG in the MUD allo-PBSCT is minimal and whether ATG brings any added value when PTCY is used in this setting is still unclear. Methods: In this registry-based study, we compared outcomes of 421 patients with PTCY and 151 patients with PTCY+ATG who underwent a first MUD allo-PBSCT for acute myeloid leukemia (AML) in complete remission. Results: Characteristics of PTCY and PTCY+ATG patients were well balanced, including the number of additional immunosuppressive drugs, with the only significant difference between the two cohorts being the median year of transplant, and the follow-up period (19.6 versus 31.1 months, respectively, pConclusions: To date, the question of the best combination of GvHD-preventing drugs in the MUD-PBSCT setting remains unanswered. Our results highlight that in PTCY-based MUD-PBSCT for AML, the addition of ATG does not provide any extra benefit in terms of further GvHD reduction, better GRFS or better survival.

Absztrakt: Bevezetés: Jelenleg nem áll rendelkezésünkre specifikus kuratív kezelés vagy vakcina az új koronavírus-2 (COVID–19, SARS-CoV-2) kezelésére. A súlyos citokinvihar-szindrómával társuló COVID–19-fertőzés kezelésére sürgősen szükséges alternatív kezelési megoldást találni. Célkitűzés: A convalescens plazmaterápia alkalmazása más, súlyos vírusfertőzések kezelésében a túlélés javulását eredményezte, és ígéretes terápiás megközelítés lehet súlyos COVID–19-betegek számára. Módszer: Két kritikus állapotú, COVID–19-fertőzött beteg convalescens friss fagyasztott plazmával történő kezelését mutatjuk be. Eredmények: A plazmaterápia megkezdésekor mindkét beteg gépi lélegeztetésre szorult, és antivirális kezelésben, valamint maximális szupportív ellátásban részesült. A COVID–19-fertőzésből nemrég felépült és a súlyos akut légúti distressz szindrómát okozó koronavírus-2 elleni immunglobulin-G-t termelő donorokból 3 × 200 ml convalescens plazma transzfúzióját alkalmaztuk. A convalescens plazma transzfúzióját követően mindkét betegnél javult az oxigénszaturáció, és a gyulladásos értékeket jelző paraméterek csökkenést mutattak. A convalescens plazma adását megelőző paraméterekhez viszonyítva növekedett a lymphocytaszám, és csökkent az interleukin-6-szint. Mindkét betegnél 2 héten belül megszüntethető volt a gépi lélegeztetés. Nem észleltünk a convalescens plazma adása során súlyos mellékhatást. Következtetések: Megfigyelésünk alapján a convalescens plazmával történő terápia jól tolerálható volt, és javíthatja a betegek gyógyulási arányát. A convalescens plazmával való kezelés optimális dózisának, időpontjának és klinikai előnyeinek meghatározására további nagy, kontrollált vizsgálatok szükségesek. Közleményünk megírásának célja az első két, hazánkban convalescens plazmával sikeresen kezelt, kritikus állapotú COVID–19-fertőzött beteg kórtörténetének bemutatása. Orv Hetil. 2020; 161(27): 1111–1121.

Absztrakt: A COVID–19 a SARS-CoV-2 vírus által okozott, járványosan terjedő, légúti kiindulású betegség. A kórokozó magas patogenitású, zoonotikus eredetű humán coronavírus, mely hatékonyan terjed emberről emberre cseppfertőzéssel és közeli kontaktussal. A vírusdiagnosztika a légutakból vett minta PCR-vizsgálatán alapul, melynek ismétlésére szükség lehet a fertőzés kizárására. A PCR-eredményt a klinikummal egybe kell vetni, mivel a preszimptomatikus beteg már vírust üríthet, a gyógyultak PCR-pozitivitása pedig hetekig elhúzódik. A terápiás stratégiák két ágát az antivirális gyógyszerek, valamint a hiperinflammációt gátló immunmodulánsok adják. Jelen összefoglalásunk a második azon két társközlemény közül, melyek célja a 2020. május 25-ig elérhető legfőbb nemzetközi és hazai betegséggel kapcsolatos eredmények ismertetése, elsősorban, de nem kizárólag hematológus kollégák számára.

Absztrakt: A COVID–19 a SARS-CoV-2 vírus által okozott, járványosan terjedő, légúti kiindulású betegség. A kórokozó magas patogenitású, zoonotikus eredetű humán coronavírus, mely hatékonyan terjed emberről emberre cseppfertőzéssel és közeli kontaktussal. A medián lappangási idő 5 nap, a maximum 14 nap. A COVID–19 kardinális tünetei a láz, dyspnoe és száraz köhögés. Az esetek 80%-a enyhe lefolyású, 5%-ban azonban intenzív terápiás ellátás és gépi lélegeztetés válik szükségessé. A COVID–19 akár súlyos, az egész szervezetre kiterjedő citokinvihart is kiválthat, mely gyors beavatkozás nélkül végzetes kimenetelű lehet. Jelen összefoglaló – melyet a diagnosztikai és terápiás szempontokat tárgyaló társközlemény követ – a betegséggel kapcsolatban 2020. május 25-ig elérhető legfőbb nemzetközi és hazai irodalmi eredményeket ismerteti; elsősorban, de nem kizárólag hematológus kollégák számára.

Absztrakt: Az elmúlt hónapokban pandémiához vezető, Kínából induló, új koronavírus okozta megbetegedés (COVID–19) rámutatott az emberiség kiszolgáltatottságára. Aktuálisan a COVID–19 kezelésére randomizált kontrollált vizsgálattal igazolt hatékonyságú, törzskönyvezett gyógyszer nem áll rendelkezésre. A súlyos akut légúti tünetegyüttest okozó koronavírus-2 (SARS-CoV-2) a jelen munka írásáig – a legóvatosabb becslések szerint is – közel 4 millió fertőzésért és megközelítőleg 300 000 halálesetért felelős. A patomechanizmus mélyebb megismerése fedte fel, hogy a fatális esetek hátterében az immunválasz diszregulációja, a citokinvihar-szindróma (CRS) áll. Eddigi ismereteink alapján a COVID–19-ben kialakuló citokinvihar sarkalatos szereplője az interleukin-6 (IL6). Esetleírások és kis betegcsoportokon végzett vizsgálatok eredményei alapján az IL6 monoklonális antitest gátló terápia (tocilizumab) eredményesnek mutatkozik a citokinvihar kezelésében. A szerzők egy eset leírása kapcsán foglalják össze a legfrissebb ismereteket a COVID–19 terápiájával kapcsolatosan. A jelen esetismertetés súlyos COVID–19-ben szenvedő betegben kialakult CRS sikeres terápiáját mutatja be, melynek során – a szerzők tudomása szerint – hazánkban elsőként került sor tocilizumab alkalmazására infektológiai osztályon. Orv Hetil. 2020; 161(26): 1070–1077.

Absztrakt: Bevezetés: Az autológ haemopoeticus őssejtek transzplantációja ígéretes kezelési lehetőség egyes malignus és nem malignus betegségek körében. A beavatkozás ugyanakkor szövődményekkel járhat, ezek közül kiemelkedő fontosságúak a korai, illetve késői poszttranszplantációs szakban fellépő infekciók. Célkitűzés: A korai (Módszer: A 2007 és 2014 között intézetünkben autológ haemopoeticus őssejtek transzplantációjával kezelt 699 beteg prospektíven gyűjtött adatait retrospektív módon vizsgáltuk és dolgoztuk fel. Eredmények: A 699 beteg medián életkora 56 (interkvartilis tartomány: 43–62) év, 54%-uk (376 fő) férfi. 25 pácienst más centrumba irányítottak vissza további gondozásra, 19 beteg utánkövetése pedig megszakadt. A betegek 69,8%-ában (488 fő) fordult elő neutropeniás láz. 96 betegben (13,7%) összesen 102 infekciós epizódot azonosítottunk. A leggyakrabban – összesen 49 epizódban – bacteriaemiát észleltünk. Ezek előfordulási mediánja 7 (5–11) nap volt a transzplantációt követően. A bacteriaemiák döntő többsége (33/49) a megtapadás előtt lépett fel. Incidenciájuk a malignus lymphomában szenvedő betegek esetében szignifikánsan magasabb volt, mint a plazmasejt-rendellenességekben szenvedő csoportban (p = 0,0005, OR: 2,41, 95% CI: 1,49–3,99). Vírusfertőzés 12, míg bizonyított vagy valószínű invazív gombainfekció 8 alkalommal következett be. A poszttranszplantációs +100 napig követett 655 páciensnél a kórházi halálozás 2,4% (16 fő) volt, amelyből 8 haláleset infekciós szövődménnyel állt összefüggésben. A korai infekciók kedvezőtlenül befolyásolták a túlélést (p = 0,0001). Következtetés: Autológőssejt-transzplantáltakban az ismeretlen eredetű, neutropeniás láz gyakori. A dokumentált bacteriaemiák aránya azonban alacsony. A plazmasejtes alapbetegség miatt kezeltekhez képest a lymphomás betegekben nagyobb valószínűséggel lép fel bacteriaemia. A korai infekciók rontják a túlélés esélyeit, így megelőzésük és hatékony kezelésük továbbra is kiemelt fontosságú. Orv Hetil. 2020; 161(3): 103–109.

Contains fulltext : 248798.pdf (Publisher’s version ) (Open Access) Allogeneic hematopoietic cell transplantation (allo-HCT) remains a treatment option for patients with chronic myeloid leukemia (CML) who fail to respond to tyrosine kinase inhibitors (TKIs). While imatinib seems to have no adverse impact on outcomes after transplant, little is known on the effects of prior use of second-generation TKI (2GTKI). We present the results of a prospective non-interventional study performed by the EBMT on 383 consecutive CML patients previously treated with dasatinib or nilotinib undergoing allo-HCT from 2009 to 2013. The median age was 45 years (18-68). Disease status at transplant was CP1 in 139 patients (38%), AP or >CP1 in 163 (45%), and BC in 59 (16%). The choice of 2GTKI was: 40% dasatinib, 17% nilotinib, and 43% a sequential treatment of dasatinib and nilotinib with or without bosutinib/ponatinib. With a median follow-up of 37 months (1-77), 8% of patients developed either primary or secondary graft failure, 34% acute and 60% chronic GvHD. There were no differences in post-transplant complications between the three different 2GTKI subgroups. Non-relapse mortality was 18% and 24% at 12 months and at 5 years, respectively. Relapse incidence was 36%, overall survival 56% and relapse-free survival 40% at 5 years. No differences in post-transplant outcomes were found between the three different 2GTKI subgroups. This prospective study demonstrates the feasibility of allo-HCT in patients previously treated with 2GTKI with a post-transplant complications rate comparable to that of TKI-naive or imatinib-treated patients.

Introduction: Cellular composition of grafts is believed to be one of the significant determinants of outcomes of reduced-intensity conditioning (RIC) allogenic hematopoietic cell transplantation (allo-HCT). However, inconsistent results of the influence of CD34+ cells dose on the incidence of graft-versus-host disease (GVHD), disease control and survival have been reported in studies published thus far. Allo-HCT remains the only potentially curative treatment modality for eligible patients with myelofibrosis (MF). As patients with this diagnosis were underrepresented or not included in the above mentioned analyses, this EBMT registry study aimed to determine impact of CD34+ cell counts on allo-HCT results in this population. Methods: Six hundred and fifty seven patients with primary or secondary MF transplanted with use of peripheral blood (PB) as a source of stem cells after RIC regimen (Fludarabine/Melphalan, N=536 (82%); Fludarabine/Busulphan, N=121 (18%)) between 2000 and 2016 were included. Stem cell donor type was HLA-identical sibling (MSD; N=249, 38%) or unrelated (UD; N=408, 62%). Use of ex vivo T-cell depletion and post-transplant cyclophosphamide to prevent GVHD were the exclusion criteria. Median patient age was 58 (range, 22-76) years. In-vivo T-cell depletion was used in 526 (80%) of cases. Median transplanted CD34+ dose was 6.6 (2-29) x 10^6 per kg of recipient body weight. Median follow-up was 46 (2-194) months. Patient and transplant characteristics are summarized in Table 1. Results: We did not observe any impact of CD34+ cells dose on outcome variables in the whole study group. However, in an analysis adjusted for donor type, among patients transplanted from a MSD, the 2yr overall survival (OS) probability was 77% for those transplanted with higher doses of CD34+ cells (defined as >7.0 x 10^6/kg) compared to 60% for lower CD34+ counts (below 7.0 x 10^6/kg), P=0.007 (Figure 1). The corresponding probabilities of 2yr non-relapse mortality (NRM) were 16% and 29% (P=0.04), respectively (Figure 2). In multivariate analysis, for patients transplanted from a MSD, higher CD34+ dose was an independent predictor for better survival (HR 0.56; P=0.01) and lower risk of NRM (HR 0.54; P=0.02). We did not find any association between CD34+ counts with probability of engraftment, the incidence of acute (aGVHD) and chronic (cGVHD) nor disease relapse. The effect of cell dose was not seen in the UD cohort. Factors associated independently with an unfavorable outcome in the whole study group were: older patient age and transplantation from CMV seronegative donors to seropositive recipients for OS and NRM and use of an UD and female donor for NRM. Allo-HCT from UD was also an independent predictor for higher incidence of aGVHD and lower probability of engraftment. Use of in vivo T-cell depletion was a protective factor for aGVHD. It was in turn associated with higher risk of relapse. Conclusions: Our analysis suggests a potential survival benefit for MF patients treated with RIC PB-allo-HCT from MSD with higher doses of CD34+ cells (threshold > 7.0 x 10^6/kg). We suggest that this factor should be taken into consideration when planning and performing hematopoietic cell apheresis. Disclosures Kröger: Celgene: Honoraria, Research Funding; DKMS: Research Funding; JAZZ: Honoraria; Medac: Honoraria; Neovii: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Research Funding; Sanofi-Aventis: Research Funding. Robin:Novartis Neovii: Research Funding. Chevallier:Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria. Mielke:Bellicum: Consultancy, Honoraria, Other: Travel (via institution); EBMT/EHA: Other: Travel support; Miltenyi: Consultancy, Honoraria, Other: Travel and speakers fee (via institution), Speakers Bureau; IACH: Other: Travel support; Jazz Pharma: Honoraria, Other: Travel support, Speakers Bureau; ISCT: Other: Travel support; GILEAD: Consultancy, Honoraria, Other: travel (via institution), Speakers Bureau; Celgene: Honoraria, Other: Travel support (via institution), Speakers Bureau; DGHO: Other: Travel support; Kiadis Pharma: Consultancy, Honoraria, Other: Travel support (via institution), Speakers Bureau. Snowden:Janssen: Honoraria; Mallinckrodt: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; IDMC: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Blaise:Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria. Hernandez Boluda:Incyte: Other: Travel expenses paid. McLornan:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Novartis: Honoraria.

Contains fulltext : 251609.pdf (Publisher’s version ) (Open Access) BACKGROUND: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). METHODS: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0-100 days, 101 days-1 year, and >1 year after the first transplant. RESULTS: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4-108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and

Large randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.

Absztrakt: Az izocitrat dehidrogenaz 1 es 2 szomatikus mutaciok az akut myeloid leukemia visszaterő genetikai elteresei, tagabb ertelemben vett epigenetikus hatasmoddal. Az irodalomban ellentmondo ...

Absztrakt: Bevezetes: Hematologiai es őssejt-transzplantalt betegek veraram-infekcioirol keves adat all rendelkezesre. Epidemiologiajuk naprakesz ismerete ugyanakkor elengedhetetlen a hatekony terapia megvalasztasahoz. Celkitűzes: Jelen kutatas celja a veraram-infekciok gyakorisaganak, a korokozok megoszlasanak es rezisztenciajanak elemzese, a 7 es 30 napos halalozas, illetve az ezt befolyasolo rizikofaktorok vizsgalata volt. Modszer: 2016. januar es 2017. julius kozott a Hematologiai es Őssejt-transzplantacios Osztalyon apolt betegek veraram-infekcioira vonatkozo adatok kerultek feldolgozasra. Az adatokat, az intezmenyi adatbazisokbol gyűjtottuk ossze es retrospektiv modon elemeztuk, leiro statisztikai modszerek alkalmazasaval. A rezisztenciara vonatkozo adatokat osszevetettuk az Orszagos Epidemiologiai Kozpont 2016-os adataival. Eredmenyek: Osszesen 362 beteg 624 pozitiv vermintajabol 216 kontaminacionak bizonyult. A 408 nem kontaminans izolatumhoz kapcsolodo epizodok szama 353 volt. A monomikrobas (N =...

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n=287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P=0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versus-host disease without increasing the risk of relapse. ispartof: HAEMATOLOGICA vol:104 issue:6 pages:1230-1236 ispartof: location:Italy status: published

Rituximab (R) is increasingly incorporated in reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic cell transplantation (alloHCT) in patients with B-cell malignancies, not only to improve disease control, but also to prevent graft-versus-host disease (GVHD). There are no randomized prospective data to validate this practice, although single center data and the CIBMTR analysis have shown promising results. We aimed at validation of these findings in a large registry study. We conducted a retrospective analysis using the EBMT registry of 3,803 adult patients with B-cell malignancies undergoing alloHCT (2001-2013) with either rituximab (R-RIC-9%) or non-rituximab (RIC-91%) reduced intensity regimens respectively. Median age and median follow up were 55 years (range 19.1-77.3) and 43.2 months (range 0.3-179.8), respectively. There was no difference in transplant outcomes (R-RIC vs RIC), including 1-year overall survival (69.9% vs 70.7%), 1-year disease-free survival (64.4% vs 62.2%), 1-year non-relapse mortality (21% vs 22%), and day-100 incidence of acute GVHD 2-4° (12% vs 12%). In summary, we found that addition of rituximab in RIC regimens for B-cell malignancies had no significant impact on major transplant outcome variables. Of note, data on chronic GVHD was not available, limiting the conclusions that can be drawn from the present study. ispartof: FRONTIERS IN IMMUNOLOGY vol:11 ispartof: location:Switzerland status: published

The role of spleen size and splenectomy for the prediction of post-allogeneic hematopoietic stem cell transplant (allo-HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000-2017 after either fludarabine-busulfan or fludarabine-melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000-2009 vs 14.1% in 2010-2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44-0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01- 2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67-1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28-0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14- 0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87-2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.

Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25–3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09–7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers.

Background: Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. Methods: We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18–70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts

This study sought to identify novel CD8+ T cell homing markers by studying acute graft versus host disease (aGvHD), typically involving increased T cell homing to the skin and gut. FACS-sorted skin-homing (CD8β+ /CLA+ ), gut-homing (CD8β+ /integrinβ7+ ), and reference (CD8β+ /CLA- /integrinβ7- ) T cells were compared in patients affected by cutaneous and/or gastrointestinal aGVHD. Microarray analysis, qPCR, and flow cytometry revealed increased expression of peptidase inhibitor 16 (PI16) in skin-homing CD8+ T cells. Robust association of PI16 with skin homing was confirmed in all types of aGvHD and in healthy controls, too. PI16 was not observed on CLA+ leukocytes other than T cells. Induction of PI16 expression on skin-homing T cells occurred independently of vitamin D3. Among skin-homing T cells, PI16 expression was most pronounced in memory-like CD45RO+ /CD127+ /CD25+ /CD69- /granzyme B- cells. PI16 was confined to the plasma membrane, was GPI-anchored, and was lost upon restimulation of memory CD8+ T cells. Loss of PI16 occurred by downregulation of PI16 transcription, and not by Phospholipase C (PLC)- or Angiotensin-converting enzyme (ACE)-mediated shedding, or by protein recycling. Inhibitor screening and pull-down experiments confirmed that PI16 inhibits cathepsin K, but may not bind to other skin proteases. These data link PI16 to skin-homing CD8+ T cells, and raise the possibility that PI16 may regulate cutaneous cathepsin K.