Viola Maria Popov

Spitalul Clinic Colentina

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Horia Bumbea

Carol Davila University of Medicine and Pharmacy

Mihaela Andreescu

Spitalul Clinic Colentina

Meilin Omer

Spitalul Clinic Colentina

Ana Maria Vlădăreanu

Clinical Emergency Hospital Bucharest

Camelia Dobrea

Carol Davila University of Medicine and Pharmacy

Oana Pătrinoiu

Spitalul Clinic Colentina

MŠ

Martin Šimkovič

University Hospital Hradec Králové

Lydia Scarfò

Vita-Salute San Raffaele University

Paolo Ghia

IRCCS Ospedale San Raffaele

Marta Coscia

University of Insubria

Cooperative Institutions

Carol Davila University of Medicine and Pharmacy

Centre for Research and Technology Hellas

National and Kapodistrian University of Athens

Clinical Emergency Hospital Bucharest

Spitalul Clinic Colentina

AstraZeneca (Brazil)

Regeneron (United States)

Triangle

Bristol-Myers Squibb (Switzerland)

Emergency University

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Evaluation of the impact of Covid-19 infection on the evolution and prognosis of patients with acute leukaemia

Revista română de medicină de laborator (2021)

Meilin Omer Ana Maria Vlădăreanu Viola Maria Popov Mihaela Andreescu Lelia Iliescu

Abstract Introduciton : COVID19 is one of the largest pandemics. Since December 2019 until now the coronavirus has infected over 131 million people. The mortality rate in the general population varies between 1 to 5%, with a potential of over 30% in patients with neoplasms. Methods : The main objective of the study was to identify some peculiarities of the evolution, complications and treatment of patients with acute leukaemia and COVID-19. The study was retrospective and included 50 patients with acute leukaemia and COVID-19. Results : Recent administration of chemotherapy was identified in 20 patients with acute myeloblastic leukaemia and 4 patients with acute lymphoblastic leukaemia. The newly diagnosed patients or those undergoing intensive chemotherapy, in particular elderly patients, had a severe form of COVID-19 and an unfavourable evolution, and these clinical situations were identified as predictive factors for adverse outcomes. Patients with acute lymphoblastic leukaemia had a shorter survival curve compared to patients with acute myeloblastic leukaemia. Pneumonia was present especially in patients with acute myeloblastic leukaemia, most patients having over 30% of lung fields affected (55.26%). Patients with an unfavourable outcome had significantly increased median values of C-reactive protein, procalcitonin and interleukin6. Conclusions : Patients with acute leukaemia, especially acute myeloblastic leukaemia who have been diagnosed with COVID-19 infection require special attention because they may associate complications and adverse outcomes of COVID-19. The results we obtained require evaluation in a larger group of patients and analysis in the follow-up period after COVID-19.

Procalcitonin

10.2478/rrlm-2021-0032

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Citations (1)

Diffuse large B-cell lymphoma and polycythemia vera discovered at the onset - a rare association and its possible importance in lymphoma prognosis.

PubMed (2016)

Viola Maria Popov Camelia Dobrea Mihai Popescu Iancu Emil Pleşea Valentin Titus Grigorean

Diffuse large B-cell lymphoma (DLBCL) represent the most frequently non-Hodgkin's lymphoma (NHL) (over 30%), especially in developing countries. Many associations of NHL with another neoplasia were described following chemotherapy or radiotherapy regimens. The coexistence of DLBCL with myeloproliferative neoplasms (MPNs) JAK2V617F positive at the onset was very rare reported in the literature. We describe a clinical case of a 52-year-old man who presented both diagnoses at the onset - DLBCL and MPN - polycythemia vera (PV) type. The patient was treated with two CHOP cycles (Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone) followed by six R-CHOP (Rituximab-CHOP) cycles, together with a platelet-reducing agent, achieving remission for 20 months, followed by a relapse which is under treatment. The clonally expansion of an abnormal pluripotent hematopoetic stem cell could be responsible for both, PV and DLBCL. However, recent reports suggested the possible involvement of two different clones. The clinical significance and the role of JAK2 mutation in the evolution of patients with NHLs, including DLBCL are still unknown. Further genetic and clinical studies have to point out common gene mutations for the two diseases and their connection with the diseases behavior under the treatment.The coexistence of NHLs and especially DLBCLs and MPNs JAK2 positive is very rare. Although DLBCL alone has good prognosis, other prognostic factors should be checked when it is associated with PV. The presence of JAK2V617F seems to be a candidate but whose role in DLBCL evolution, natural or under treatment has to be cleared up.

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Management of a case of Castleman’s disease coexisting with or occurring after transplanted Hodgkin’s lymphoma

Revista română de medicină de laborator (2023)

Mihaela Andreescu Sabina Zurac Andreea Lacatusu Andrei T. Tudor Nicoleta Ilie

Abstract Castleman’s disease is a benign lymphoproliferative disorder. The coexistence of Hodgkin’s lymphoma and multicentric Castle-man’s disease is a rare phenomenon. We discuss a case of a 48-year-old female patient who had been in the records of the Colentina Hematology Clinic since 2019, with the diagnosis of classic Hodgkin’s Lymphoma, nodular sclerosis type I BNLI, stage IIXB. For this, she underwent 3 courses of ABVD and 2 courses of BEACOPP, without showing complete remission on PET/CT evaluation at the end of treatment. After that, we initiated rescue therapy and performed 4 IGEV courses, followed by autologous stem cell transplantation. For maintenance treatment, we opted for Brentuximab, but it was discontinued after the first administration due to the appearance of adverse reactions. Subsequently, we decided to perform radiotherapy with 20 fractions cumulating a total dose of 36 Gy. Shortly after the radiotherapy, symptoms reappeared which were suspected to be in the context of a relapse of the disease. For confirmatory diagnosis, we performed a new PET-CT which highlighted metabolically active ganglion images. Further, were carried out lymph node biopsy for histopathological and immunohistochemical examinations were carried out. The underlying disease was diagnosed as plasmacytic subtype, HHV8 negative, multicentric Castleman’s disease. For treatment, we relied on administrations of Siltuximab treatment therapy that showed complete remission. Castleman’s disease presents a unique diagnostic challenge, but a confirmatory diagnosis can be based on a biopsy examination, advisable after each relapse.

ABVD

Nodular sclerosis

Castleman disease

Lymph node biopsy

Lymphoproliferative Disorders

10.2478/rrlm-2023-0007

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Frontline treatment with the combination obinutuzumab ± chlorambucil for chronic lymphocytic leukemia outside clinical trials: Results of a multinational, multicenter study by ERIC and the Israeli CLL study group

American Journal of Hematology (2020)

Yair Herishanu Adir Shaulov Riva Fineman Sandra Bašić‐Kinda Ariel Aviv

In recent years, considerable progress has been made in frontline therapy for elderly/physically unfit patients with CLL. The combination of obinutuzumab and chlorambucil (O-Clb) has been shown to prolong progression free survival (PFS, median PFS-31.5 months) and overall survival (OS) compared to chlorambucil alone. More recently, obinutuzumab given in combination with either ibrutinib or venetoclax improved PFS but not OS when compared to O-Clb. In this retrospective multinational, multicenter co-operative study, we evaluated the efficacy and safety of frontline treatment with O ± Clb in unfit patients with CLL, in a "real-world" setting. Patients with documented del (17p13.1)/TP53 mutation were excluded. A total of 437 patients (median age, 75.9 years; median CIRS score, 8; median creatinine clearance, 61.1 mL/min) were included. The clinical overall response rate was 80.3% (clinical complete and partial responses in 38.7% and 41.6% of patients, respectively). Median observation time was 14.1 months and estimated median PFS was 27.6 months (95% CI, 24.2-31.0). In a multivariate analysis, high-risk disease [del (11q22.3) and/or IGHV-unmutated], lymph nodes of diameter > 5 cm, obinutuzumab monotherapy and reduced cumulative dose of obinutuzumab, were all independently associated with shorter PFS. The median OS has not yet been reached and estimated 2-year OS is 88%. In conclusion, in a "real-world" setting, frontline treatment with O-Clb achieves PFS comparable to that reported in clinical trials. Inferior outcomes were noted in patients with del (11q22.3) and/or unmutated IGHV and those treated with obinutuzumab-monotherapy. Thus, O-Clb can be still considered as legitimate frontline therapy for unfit CLL patients with low-risk disease.

Obinutuzumab

Chlorambucil

IGHV@

10.1002/ajh.25766

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Hypolipemiant besides antileukemic effect of imatinib mesylate

Leukemia Research (2009)

R Gologan Gabriela Constantinescu D. Georgescu Daniela Ostroveanu Didona Vasilache

Imatinib Mesylate

Concomitant

Mesylate

10.1016/j.leukres.2009.02.024

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MECOM,HBS1L-MYB,THRB-RARB, JAK2, andTERTpolymorphisms defining the genetic predisposition to myeloproliferative neoplasms: A study on 939 patients

American Journal of Hematology (2017)

Adrian P. Trifa Claudia Bănescu Anca Bojan Cristian M. Voina Ștefana Popa

Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100 polymorphisms are known to significantly predispose to MPN. This study aimed to establish the additional contribution of the recently described MECOM rs2201862, HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483 controls. MECOM rs2201862 associated significantly with each MPN entity, except for ET, and with all major molecular sub-types, especially those CALR-mutated (OR = 1.4; 95% CI = 1.1-1.8; P-value = .005). HBS1L-MYB rs9376092 associated only with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1-1.7; P-value = .003). THRB-RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1-2.1; P-value = .04). Surprisingly, JAK2 46/1 haplotype was associated significantly not only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95% CI = 1.1-1.8; P-value = .01). TERT rs2736100 was associated equally strong with all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1, TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to MPN.

Genetic predisposition

MYB

10.1002/ajh.24946

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Citations (29)

LEUKEMIJA I TRUDNOĆA. NIJE DALJE ŠTETNA POVEZANOST

Gynaecologia et perinatologia (2008)

Ana‐Maria Vlădăreanu Viola Maria Popov Veronica Vasilache Cristina Marinescu Horia Bumbea

Purpose. Even though there are no solid data regarding chemotherapy treated leukemia during pregnancy, the results based on short series reports show that the management of such condition can be safely achieved during the second and third trimester. We present three personal cases of pregnant women treated with cytostatic agents, two of them accidentally receiving complete chemotherapy during the entire pregnancy without malformative consequences. First case. A 19 yrs old woman diagnosed with chronic myeloid leukemia who conceived spontaneously and mistook the pregnancy signs for a relapse of the disease. During the pregnancy she continued the treatment, receiving until the fifth month an association of Hydroxyurea and alfa-interferon and afterwards switched to Imatinib until term. She presented at 38–39 weeks and delivered by cesarean section a little girl of 3510 g in a perfect state of health. The blood count of both mother and child were normal. Second case. A similar situation in a young woman with lymphoblastic acute leukemia under treatment with Vincristin, Methotrexat, Purinethol. She presented in advanced spontaneous labour at 33–34 weeks and delivered a little girl of 1700 g without malformative signs and normal blood count. Third case. A 17 years old girl who was diagnosed with acute myeloid leukemia at 29 weeks pregnancy. She received induction chemotherapy with Ara-C, due to the significant bone marrow infiltrate and disease induced disseminated intravascular coagulopathy. She presented premature uterine contractions at 32 weeks and delivered by cesarean section a premature boy of 1750g with Apgar score 8. The infant did not present any malformation (by clinical and ultrasound examination) and the blood count was normal. The studies have shown so far that in the case of chronic myeloid leukemia, the treatment with Imatinib was associated with 50% apparently normal live infants and that chemotherapy for acute leukemia during the second or third trimester may not require termination of pregnancy, because both remission and delivery of a normal infant are likely to be obtained.

Girl

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Modest contribution of JAK2 V617F allele burden to the occurrence of major thrombosis in polycthemia vera and essential thrombocythemia

Blood Cells Molecules and Diseases (2018)

Adrian P. Trifa Claudia Bănescu Cristian M. Voina Ștefana Popa Tunde Torok

JAK2 V617F

10.1016/j.bcmd.2018.09.003

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Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia/Lymphoma—Romanian Experience

Journal of Clinical Medicine (2020)

Alina Tănase Andrei Coliță Oana Gabriela Craciun Lavinia Lipan Zsofia Várady

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3–5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26–57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3–44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL.

Adult T-cell leukemia/lymphoma

10.3390/jcm9082417

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Citations (15)

CML-084 COVID-19 – Trigger for Chronic Myeloid Leukemia Evolution?

Clinical Lymphoma Myeloma & Leukemia (2023)

Viola Maria Popov Mihaela Andreescu

2019-20 coronavirus outbreak

10.1016/s2152-2650(23)01124-2

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