Papers by Jan Maciej Zaucha
Hematological Oncology, 2019
Background: There is still no clear therapeutic algorithm for MALT lymphoma patients beyond H. py... more Background: There is still no clear therapeutic algorithm for MALT lymphoma patients beyond H. pylori eradication and while recent data on chemotherapy based regimens +/-rituximab (R) have potentially set new standards for patients in need of systemic treatment, it appears of interest to investigate also chemotherapy-free strategies. Methods: We have retrospectively assessed all patients with histologically verified MALT lymphoma treated at the Medical University Vienna 1999-2019, and identified patients receiving first line systemic
Blood, Dec 6, 2014
Elderly patients with Hodgkin lymphoma (HL) have poor prognosis. The inferior outcome has been at... more Elderly patients with Hodgkin lymphoma (HL) have poor prognosis. The inferior outcome has been attributed to a variety of factors including histologic differences, higher incidence of advanced stages, presence of comorbidities, poor performance status, inability to tolerate chemotherapy at full dose and increased treatment-related toxicity and mortality. ABVD is recommended and widely used for elderly patients (pts) although no prospective studies exist to justify this guideline. Moreover there are only few studies, yet most limited in numbers of pts, evaluating the results of HL treatment in elderly population. Here we present the retrospective analysis of outcome of 414 elderly HL pts treated by PLRG allied centers between 2003-2013. Group consisted of 237 men and 177 women. Their median age was 60,5 (50-93) years with the following age ranges:50-59 years-50%, 60-69 years-27%, ≥ 70 years-23%. Histology subtype showed predominance of nodular sclerosis 56%, followed by mixed cellularity 30%. 168 (41%) pts presented with early stage (I,II Ann Arbor) and 246 (59%) with advanced stage (III, IV Ann Arbor). 384 patients were treated with ABVD or ABVD-like regimen, few with CHOP-like(14), BEACOPP(9), PVAG (5) or with corticosteroids only(2). The median follow-up was 28,7 months. The response rates according to age groups are shown in Table 1. Progression free survival (PFS) and overall survival (OS) for all pts were 21 months and 39,5 months, respectively. Median PFS in group 50-59yrs and group 60-69yrs was similar 21,3 months and 22months respectively but was statistically significantly longer than in pts≥70 years old (16 months) (p<0,05). Median OS in group 50-59, 60-69 and ≥ 70 years old was 50,5 months, 35,2 months, 21,5 months, respectively (p<0.05) . Comorbidities were evidently more common in older patients: 30% in 50-59 yrs old, 65% in 60-69 yrs old, 85% in ≥70 yrs old. However, irrespective of age, patients with high burden of cardiovascular disease showed significantly poorer OS and PFS than those with comorbidities other than cardiovascular (OS 29 months vs 41 months, PFS 9 months vs 21 months, respectively, p <0.05). Univariate analysis with Cox regression model including age ≥60, clinical stage >II, presence of B symptoms, IPS>2, serum albumin level below normal, ECOG>1, male sex, erythrocyte sedimentation rate ESR>10 and white blood cells count above…
Blood Advances
Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use facto... more Aggressive large B-cell lymphoma (LBCL) has variable outcomes. Current prognostic tools use factors for risk stratification that inadequately identify patients at high risk of refractory disease or relapse before initial treatment. A model associating 2 risk factors, total metabolic tumor volume (TMTV) >220 cm3 (determined by fluorine-18 fluorodeoxyglucose positron emission tomography coupled with computed tomography) and performance status (PS) ≥2, identified as prognostic in 301 older patients in the REMARC trial (#NCT01122472), was validated in 2174 patients of all ages treated in 2 clinical trials, PETAL (Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas; N = 510) and GOYA (N = 1315), and in real-world clinics (N = 349) across Europe and the United States. Three risk categories, low (no factors), intermediate (1 risk factor), and high (2 risk factors), significantly discriminated outcome in most of the series. Patients with 2 risk factors had wor...
Leukemia & Lymphoma, 2019
Abstract Cereblon (CRBN) is crucial for antiproliferative and immunomodulatory properties of immu... more Abstract Cereblon (CRBN) is crucial for antiproliferative and immunomodulatory properties of immunomodulatory drugs. The objective of this study was to verify whether germline single nucleotide polymorphisms (SNPs) in the CRBN gene may influence response to lenalidomide in multiple myeloma (MM). Fourteen tagging SNPs covering the genetic variability in the CRBN gene region were genotyped in 167 Polish patients with refractory/relapsed MM treated with lenalidomide-based regimens. We found that carriers of minor alleles of two studied CRBN SNPs rs1714327G > C (OR = 0.26; 95% CI = 0.1–0.67; p = .0055, Bonferroni corrected p = .033) and rs1705814T > C (OR = 0.22; 95% CI = 0.07–0.65; p = .0063, Bonferroni corrected p = .037) were significantly associated with lower probability of achievement at least partial remission while treated with lenalidomide-based regimens, using the dominant inheritance model. Moreover, one of these SNPs, namely rs1705814T > C, was correlated with shorter progression-free survival (HR = 2.49; 95%CI = 1.31–4.74, p = .0054, Bonferroni corrected p = .033). It is suggested that selected germline CRBN allelic variants (rs1714327G > C and rs1705814T > C) affect lenalidomide efficacy in patients with relapsed/refractory MM.
International journal of cardiology, Jan 15, 2017
Algorithm of anthracycline-based chemotherapy with favourable cardio-oncological outcome should b... more Algorithm of anthracycline-based chemotherapy with favourable cardio-oncological outcome should be clearly re-defined for lymphoma patients with significant pre-existing cardiovascular diseases. A clinical benefit of liposomal forms of anthracycline is still debatable. Polish registry included observations of 138 lymphoma patients with concomitant cardiovascular disorders who received liposomal doxorubicin as cardioprotective alternative of conventional form. It was created to analyse the importance of a strategy of administration of conventional/liposomal doxorubicin and a lifetime doxorubicin dose for development of acute decompensated heart failure (ADHF) as a reason of premature chemotherapy discontinuation. ADHF was the cause of premature termination of chemotherapy only in 11 patients (7.97%). The five new episodes of ADHF related to liposomal doxorubicin were recorded in subgroup of 70 patients with pre-existing heart failure (7.14%). There was the similar incidence of ADHF w...
British Journal of Haematology, 2004
The genetic basis of Diamond-Blackfan anaemia (DBA), a congenital erythroid hypoplasia that shows... more The genetic basis of Diamond-Blackfan anaemia (DBA), a congenital erythroid hypoplasia that shows marked clinical heterogeneity, remains obscure. However, the fact that nearly one-quarter of patients harbour a variety of mutations in RPS19, a ribosomal protein gene, provides an opportunity to examine whether haplo-insufficiency of RPS19 protein can be demonstrated in certain cases. To that end, we identified 19 of 81 DBA index cases, both familial and sporadic, with RPS19 mutations. We found 14 distinct insertions, deletions, missense, nonsense and splice site mutations in the 19 probands, and studied mutations in 10 patients at the RNA level and in three patients at the protein level. Characterization of the mutations in 10 probands, including six with novel insertions, nonsense and splice site mutations, showed that the abnormal transcript was detectable in nine cases. The RPS19 mRNA and protein in CD34+ bone marrow cells identified haplo-insufficiency in three cases predicted to have one functional allele. Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency.
Blood, 2020
Background: AML is the most common acute leukemia in adults. While most adults < 60 years achi... more Background: AML is the most common acute leukemia in adults. While most adults < 60 years achieve complete remission (CR) with intensive induction chemotherapy, approximately one third have primary refractory disease and, overall, the majority of AML patients still relapse despite having attained initial remission (Dohner et al, Blood 2017). The combination of an anthracycline and cytarabine has been the mainstay of intensive AML induction for more than 50 years. Combined with cytarabine (AraC), high-dose daunorubicin (90 mg/m2) in induction (DA-90) resulted in a higher rate of CR (70.6% vs. 57.3%, P<0.001) and improved overall survival (OS) (median 23.7 vs. 15.7 months; P = 0.003), without increased serious adverse events compared with DA-45 (Fernandez et al, NEJM, 2009). In two PALG randomized trials, the combination of cladribine with DA (DAC regimen) also resulted in significantly increased CR after a single induction course, compared with the standard two-drug induction (...
Hematology in Clinical Practice
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Veneto... more Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. Venetoclax, a BCL-2 inhibitor, in combination with rituximab is an effective therapeutic option approved for the treatment of refractory and relapsed CLL. Neutropenia diagnosed before or during the above-mentioned therapy is a significant clinical problem, which often involves the need to reduce the dose or temporarily discontinue venetoclax in the initial period of therapy. In Experts' opinion, the use of granulocyte colony-stimulating factor (G-CSF) during venetoclax-rituximab combined therapy is reasonable in patients with baseline neutrocyte count < 1000-500/mm 3 and with high-risk neutropenia. The second important group for the use of G-CSF are patients developing grade 3 asymptomatic neutropenia during venetoclax dose escalation. Using G-CSF can prevent episodes that affect the maintenance of the venetoclax dose intensity and treatment continuity.
International Journal of Hematology
Development of secondary CML has only been casually described, with few reports attempting to ana... more Development of secondary CML has only been casually described, with few reports attempting to analyze and explain the mechanisms behind this phenomenon. Reported cases vary with regard to presumed pathogenesis and clinical characteristics, but similarities can be observed. This report presents the case of a patient diagnosed with CALR and ASXL1-mutated primary myelofibrosis who developed CML 13 years after the initial diagnosis. In contrast with previously reported cases, this patient did not have JAK2 or ABL1 gene mutations, and also exhibited primary resistance to tyrosine kinase inhibitor (TKI) treatment. Here, we analyze the molecular evolution of CML and describe successful treatment with concomitant therapy including a TKI and JAK inhibitor. This report aims to deepen clinical experience and further broaden knowledge about chronic myeloproliferative neoplasms.
International Journal of Cancer, 2020
We evaluated the association between germline genetic variants located within the 3′‐untranlsated... more We evaluated the association between germline genetic variants located within the 3′‐untranlsated region (polymorphic 3′UTR, ie, p3UTR) of candidate genes involved in multiple myeloma (MM). We performed a case‐control study within the International Multiple Myeloma rESEarch (IMMEnSE) consortium, consisting of 3056 MM patients and 1960 controls recruited from eight countries. We selected p3UTR of six genes known to act in different pathways relevant in MM pathogenesis, namely KRAS (rs12587 and rs7973623), VEGFA (rs10434), SPP1 (rs1126772), IRF4 (rs12211228) and IL10 (rs3024496). We found that IL10‐rs3024496 was associated with increased risk of developing MM and with a worse overall survival of MM patients. The variant allele was assayed in a vector expressing eGFP chimerized with the IL10 3′‐UTR and it was found functionally active following transfection in human myeloma cells. In this experiment, the A‐allele caused a lower expression of the reporter gene and this was also in agreement with the in vivo expression of mRNA measured in whole blood as reported in the GTEx portal. Overall, these data are suggestive of an effect of the IL10‐rs3024496 SNP on the regulation of IL10 mRNA expression and it could have clinical implications for better characterization of MM patients in terms of prognosis.
British Journal of Haematology, 2022
The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse o... more The efficacy of salvage treatment of diffuse large B-cell lymphoma (DLBCL) patients who relapse or progress (rrDLBCL) after initial therapy is limited. Efficacy and safety of ofatumumab with iphosphamide, etoposide and cytarabine (O-IVAC) was evaluated in a single-arm study. Dosing was modified for elderly patients. Patients received up to six cycles of treatment. The primary end-point was the overall response rate (ORR). Patients were evaluated every two cycles and then six and 12 months after treatment. Other end-points included progression-free survival (PFS), event-free survival (EFS), overall survival (OS) and safety. Seventy-seven patients received salvage treatment with O-IVAC. The average age was 56.8 years; 39% had an Eastern Cooperative Oncology Group (ECOG) performance status of at least 3; 78% had disease of Ann Arbor stage 3 or 4; 58% received one or more prior salvage therapies. The ORR for O-IVAC was 54.5%. The median duration of study follow-up was 70 months. The median PFS and EFS were 16.3 months each. The median OS was 22.7 months. Age, ECOG performance status and the number of prior therapy lines were independent predictors of survival. Treatment-related mortality was 15.5%. O-IVAC showed a high response rate in a difficult-to-treat population and is an attractive treatment to bridge to potentially curative therapies.
Hematology in Clinical Practice, 2011
Podział chłoniaka Hodgkina (HL) na 2 typy: guzkowy i klasyczny oraz wyróżnienie w tym drugim 4 po... more Podział chłoniaka Hodgkina (HL) na 2 typy: guzkowy i klasyczny oraz wyróżnienie w tym drugim 4 podtypów nie oddaje w pełni zróżnicowania tej choroby pod względem biologii. Przekłada się to również na niedoskonały podział kliniczny na 3 grupy o odmiennym rokowaniu oraz brak satysfakcjonujących możliwości indywidualizacji leczenia. Konsekwencją są odmienne standardy leczenia, szczególnie postaci obciążonych czynnikami ryzyka. Leczenie według schematu BEACOPP w wersji eskalowanej (BEACOPPesk) pozwala na uzyskanie trwałej remisji u niemal 90% chorych, ale jest obciążone znaczną toksycznością wczesną i późną. Tolerancja leczenia zgodnie ze schematem doksorubicyna, bleomycyna winblastyna i dakarbazyna (ABVD) jest lepsza, ale trwałą odpowiedź uzyskuje się tylko u 70% chorych. Jest wiele danych sugerujących, że u chorych z HL wczesna ocena za pomocą pozytonowej tomografii emisyjnej (PET) w połączeniu z tomografią komputerową (CT) w trakcie standardowego leczenia według schematu ABVD pozwala przewidywać odpowiedź na to leczenie. Dodatni wynik badania wskazuje na niepowodzenie i konieczność intensyfikacji terapii. W badaniach retrospektywnych dowiedziono skuteczności tego sposobu postępowania i stanowią one podstawę do prowadzenia prospektywnych badań klinicznych weryfikujących skuteczność wykorzystania wczesnego badania PET do optymalizacji leczenia chorych z wczesną i zaawansowaną postacią HL.
Chora lat 79 dotychczas nie chorująca, obciązona napadowymmigotaniem przedsionkow, zostala przyje... more Chora lat 79 dotychczas nie chorująca, obciązona napadowymmigotaniem przedsionkow, zostala przyjeta na oddzial onko-logii klinicznej z rozpoznanym chloniakiem Hodgkina (HL)celem rozpoczecia leczenia. Przy przyjeciu chora w stanieogolnym średnim, gorączkująca, z objawami postepującegowyniszczenia. Gorsze samopoczucie u chorej pojawilo siew polowie lipca 2012 roku pod postacią ogolnego oslabienia,dolegliwości bolowych w okolicy lewej lopatki, chudnieciai potow nocnych. Dolegliwości chorej stopniowo narastaly,w szczegolności utrata masy ciala (15 kg), do ktorej dolączylysie poty nocne, a nastepnie stany gorączkowe. Chora zostalaprzyjeta do szpitala rejonowego w Gdyni, gdzie stwierdzonow tomografii komputerowej (TK) powiekszenie licznychgrup wezlowych: nadobojczykowe obustronnie najwieksze28 26 20 mm, w klatce piersiowej przytchawicze i środ-piersiowe najwieksze do 17 10 mm oraz podostrogowokonglomerat wezlow chlonnych o wymiarach 43 17 mm,a takze w prawej wnece i za odnogami przepony. S...
We present the Proteome Quality Index (PQI; http:// pqi-list.org), a much-needed resource for use... more We present the Proteome Quality Index (PQI; http:// pqi-list.org), a much-needed resource for users of bacterial and eukaryotic proteomes. Completely sequenced genomes for which there is an available set of protein sequences (the proteome) are given a oneto five-star rating supported by 11 different metrics of quality. The database indexes over 3000 proteomes at the time of writing and is provided via a website for browsing, filtering and downloading. Previous to this work, there was no systematic way to account for the large variability in quality of the thousands of proteomes, and this is likely to have profoundly influenced the outcome of many published studies, in particular large-scale comparative analyses. The lack of a measure of proteome quality is likely due to the difficulty in producing one, a problem that we have approached by integrating multiple metrics. The continued development and improvement of the index will require the contribution of additional metrics by us and...
Haematologia, 2020
In Poland, 800–900 new cases of classical Hodgkin’s lymphoma (cHL) are diagnosed annually. Despit... more In Poland, 800–900 new cases of classical Hodgkin’s lymphoma (cHL) are diagnosed annually. Despite relatively good results of first-line treatment, 20–25% of patients relapse and the chances of their cure become much smaller. The paper presents the consensus of the Polish experts on the management of patients with relapsed and refractory cHL in 2020, taking into account generally accepted international recommendations, approved indications and the Polish reimbursement conditions. The proposed recommendations were voted by all authors. The recommendations that were agreed by the majority are presented in the paper. For each recommendation, the most important information supporting its legitimacy and information justifying the dissenting opinions of the authors of the consensus were quoted.
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Papers by Jan Maciej Zaucha