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Salmanton‐García, Jon; Marchesi, Francesco; Navrátil, Milan; Piukovics, Klára; Principe, Maria Ilaria; Criscuolo, Marianna; Bilgin, Yavuz M.; Fracchiolla, Nicola S.; Vena, Antonio; Romano, Alessandra; Falces‐Romero, Iker; Sgherza, Nicola; Heras‐Fernando, Inmaculada; Biernat, Monika M.; Petzer, Verena; Žák, Pavel; Weinbergerová, Barbora; Samarkos, Michail; Erben, Nurettin; Praet, Jens; López‐García, Alberto; Labrador, Jorge; Lahmer, Tobias; Drgoňa, Ľuboš; Merelli, Maria; Cuccaro, Annarosa; Martín‐Pérez, Sonia; Dávila‐Valls, Julio; Farina, Francesca; Cattaneo, Chiara; Pinczés, László Imre; Magyari, Ferenc; Espigado, Ildefonso; Buquicchio, Caterina; Vinh, Donald C.; Stoma, Igor; Čerňan, Martin; Prezioso, Lucia; Papa, Mario Virgilio; Plantefeve, Gaëtan; Khedr, Reham Abdelaziz; Batinić, Josip; Magliano, Gabriele; Erdem, Simge; Khostelidi, Sofya; Čolović, Natasha; Nappi, Davide; García‐Ramírez, Patricia; Góra, Jakub; Callejas‐Charavia, Marta; Tłusty, Jędrzej; Bakker, Martijn; Wojtyniak, Elwira; Antić, Darko; Magdziak, Agnieszka; Dargenio, Michelina; Idrizović, Larisa; Pantić, Nikola; Stojanoski, Zlate; Eisa, Noha; Otašević, Vladimir; Marchetti, Monia; Mackenzie, Erica; Garcia‐Vidal, Carolina; Aujayeb, Avinash; Almasari, Ahlam; Miranda‐Castillo, Carolina; Gavriilaki, Eleni; Coppola, Nicola; Busca, Alessandro; Adžić‐Vukičević, Tatjana; Schönlein, Martin; Hersby, Ditte Stampe; Gräfe, Stefanie K.; Glenthøj, Andreas; Aiello, Tommaso Francesco; Cvetanoski, Milche; Mitrović, Mirjana; Cerchione, Claudio; Prin, Romane; Varricchio, Gina; Arellano, Elena; Córdoba, Raúl; Mayer, Jiří; Víšek, Benjamín; Wolf, Dominik; Anastasopoulou, Amalia N.; Delia, Mario; Musto, Pellegrino; Leotta, Dario; Bavastro, Martina; Limongelli, Alessandro; Sciumè, Mariarita; Ven, Lukas; Fianchi, Luana; Brunetti, Sara Caterina; Drozd‐Sokołowska, Joanna; Dąbrowska‐Iwanicka, Anna; Cornely, Oliver A.; Pagano, Livio
doi: 10.1002/ajh.27565pmid: 39715069
Community‐acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large‐scale, real‐world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA‐EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. The study assessed epidemiology, clinical characteristics, risk factors, and outcomes. The study examined 1312 patients with HM diagnosed with CARV during the 2023–2024 autumn–winter season. Of these, 59.5% required hospitalization, with 13.5% needing ICU admission. The overall mortality rate was 10.6%, varying by virus: parainfluenza (21.3%), influenza (8.8%), metapneumovirus (7.1%), RSV (5.9%), or SARS‐CoV‐2 (5.0%). Poor outcomes were significantly associated with smoking history, severe lymphopenia, secondary bacterial infections, and ICU admission. This study highlights the severe risk CARV poses to patients with HM, especially those undergoing active treatment. The high rates of hospitalization and mortality stress the need for better prevention, early diagnosis, and targeted therapies. Given the severe outcomes with certain viruses like parainfluenza, tailored strategies are crucial to improving patient outcomes in future CARV seasons.
Lecumberri, Ramón; Ruiz‐Artacho, Pedro; Trujillo‐Santos, Javier; Marcos‐Jubilar, María; Pérez‐Pinar, Montserrat; Quéré, Isabelle; Claver, Gisela; Gorostidi, Juan; Bikdeli, Behnood; Monreal, Manuel; ,
doi: 10.1002/ajh.27579pmid: 39791523
Managing acute venous thromboembolism (VTE) in patients with thrombocytopenia is challenging. We used data from the RIETE registry to investigate the impact of baseline thrombocytopenia on early VTE‐related outcomes, depending on the initial presentation as pulmonary embolism (PE) or isolated lower‐limb deep vein thrombosis (DVT). From March 2003 to November 2022, 90 418 patients with VTE were included. Thrombocytopenia was categorized as severe (< 50 000/μL, n = 303) or moderate (50 000–99 999/μL, n = 1882). The primary outcome, fatal PE within 15 days after diagnosis, and secondary outcomes, including major bleeding and recurrent VTE, were analyzed using multivariable‐adjusted models. Among 52 703 patients with PE, the 15‐day case‐fatality rates from PE were 5.8% for severe thrombocytopenia, 4.5% for moderate thrombocytopenia, and 1.1% for normal platelet counts. In 37 715 patients with isolated DVT, the cumulative incidence of fatal PE were 0, 0.2%, and 0.05%, respectively. Multivariable analysis revealed a five‐fold increase in the risk for fatal PE in severe thrombocytopenia (adjusted HR: 4.89; 95%CI: 2.55–9.39) without significant differences between severe and moderate thrombocytopenia. Thrombocytopenia, either moderate or severe, was also associated with increased risk for both, major bleeding and recurrent VTE at 15 days. Initial presentation with PE substantially worsened prognosis compared to isolated DVT. In conclusion, in patients with acute VTE, thrombocytopenia at baseline was associated with increased risk of early death from PE, a finding that was driven by the subgroup whose initial presentation was PE.
Kongtim, Piyanuch; Chumnumsiriwath, Piyatida; Vittayawacharin, Pongthep; Jeyakumar, Deepa; Lee, Benjamin J.; Doh, Jean; Griffin, Shawn P.; Van Etten, Richard A.; Ciurea, Stefan
doi: 10.1002/ajh.27581pmid: 39777927
Lurain, Kathryn; Ramaswami, Ramya; Oksenhendler, Eric; Boutboul, David; Dalla Pria, Alessia; Ulrich, Lara; Shanmugasundaram, Krithika; Uldrick, Thomas S.; Bower, Mark; Yarchoan, Robert; Gérard, Laurence; Steinberg, Seth M.
doi: 10.1002/ajh.27580pmid: 39812325
Primary effusion lymphoma (PEL) is an HIV‐associated B‐cell non‐Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV‐associated NHL. We derived the PEL‐Prognostic score (PEL‐PS) from an international real‐world training set of 59 patients with HIV‐associated PEL who received first‐line anthracycline‐containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022. We identified prognostic factors associated with overall survival (OS). In a multivariable Cox model, ECOG ≥ 3 (p = 0.007; hazard ratio [HR] = 4.0 [95% CI: 1.5–11.1]) and hemoglobin < 8 g/dL (p = 0.006; HR = 3.8 [95% CI: 1.5–9.7]) were jointly associated with lower survival probability. The resulting PEL‐PS separated patients with no negative prognostic factors (score 0: hemoglobin ≥ 8 g/dL and ECOG ≤ 2, 48.1% of patients) with median OS of 10.6 years versus patients with 1–2 negative prognostic factors (score 1–2: hemoglobin < 8 g/dL and/or ECOG ≥ 3, 51.9% of patients) with median OS of 0.8 years (p < 0.0001). The PEL‐PS was then validated in 58 patients with HIV‐associated PEL treated with first‐line anthracycline‐containing chemotherapy at Hôpital Saint‐Louis in France over the same period: median OS in patients with PEL‐PS 0 was 16.9 years versus 0.6 years in patients with PEL‐PS score of 1–2 (p < 0.0001). The PEL‐PS identifies patients with good and poor prognosis. Patients with poor prognosis may benefit from novel therapies.
Kantarjian, Hagop; Short, Nicholas J.; Jain, Nitin; Haddad, Fadi G.; Kadia, Tapan; Yilmaz, Musa; Ferrajoli, Alessandra; Sasaki, Koji; Alvarado, Yesid; Pemmaraju, Naveen; Senapati, Jayastu; Garris, Rebecca; Ravandi, Farhad; Jabbour, Elias
Lassen, Therese; Nielsen, Torsten H.; Heymann, Annika; Nielsen, Lene K.; Larsen, Morten K.; Gang, Anne O.; Johansen, Christoffer; Pedersen, Lars M.
doi: 10.1002/ajh.27577pmid: 39757700
Despite advances in treatment, approximately 15% of patients with diffuse large B‐cell lymphoma (DLBCL) who achieve complete remission (CR) after first‐line therapy will experience a relapse. However, there is no consensus on the optimal follow‐up strategies for detecting relapse after achieving CR. This population‐based study, based on the Danish Lymphoma Registry (LYFO), identified a total of 1634 patients diagnosed with DLBCL between 2010 and 2017, including 105 patients who achieved CR following first‐line R‐CHOP‐like therapy and subsequently relapsed. The median follow‐up time was 6 years (range 3–8 years). Most cases of relapse were symptomatic (83%), with B symptoms and peripheral lymphadenopathy being the most common. Asymptomatic relapses were identified through physical examination (1%), blood tests (3%), or imaging findings (13%). The proportion of relapses identified outside routine visits was 70%. Only 5% of scheduled routine visits led to a relapse diagnosis, whereas 74% of unscheduled visits initiated by the patient outside routine follow‐up resulted in relapse detection. Our findings highlight that systematic, scheduled monitoring of patients in remission after first‐line treatment contributes only modestly to the early detection of disease recurrence. Future studies should explore alternative methods of relapse surveillance rather than relying solely on pre‐scheduled clinical follow‐up.
Wei, Qing; Hu, Shimin; Loghavi, Sanam; Toruner, Gokce A.; Ravandi‐Kashani, Farhad; Tang, Zhenya; Li, Shaoying; Xu, Jie; Daver, Naval; Medeiros, L. Jeffrey; Tang, Guilin
doi: 10.1002/ajh.27575
Ntanasis‐Stathopoulos, Ioannis; Filippatos, Charalampos; Ntanasis‐Stathopoulos, Anastasios; Malandrakis, Panagiotis; Kastritis, Efstathios; Tsitsilonis, Ourania E.; Dimopoulos, Meletios A.; Terpos, Evangelos; Gavriatopoulou, Maria
doi: 10.1002/ajh.27582pmid: 39784302
This meta‐analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival hazard ratios (β_PFS = ‐0.20, p < 0.001, β_OS = ‐0.12, p = 0.023). These associations remained significant for newly diagnosed patients (β_PFS = ‐0.35, p < 0.001), and they were consistent but not significant for relapsed/refractory patients (β_PFS = ‐0.06, p = 0.635). Sustained MRD negativity at 1 year was strongly correlated with prolonged PFS (β_PFS = ‐0.30, p < 0.001). In conclusion, this comprehensive meta‐analysis supports MRD as a surrogate for survival in MM.
Cooper, Nichola; Jansen, A. J. Gerard; Bird, Robert; Mayer, Jiří; Sholzberg, Michelle; Tarantino, Michael D.; Garg, Mamta; Ypma, Paula F.; McDonald, Vickie; Percy, Charles; Košťál, Milan; Goncalves, Isaac; Bogdanov, Lachezar H.; Gernsheimer, Terry B.; Diab, Remco; Yao, Mengjie; Daak, Ahmed; Kuter, David J.
Showing 1 to 10 of 29 Articles
Oral budesonide exerts local effects with negligible systemic glucocorticoid activity, due to rapid first‐pass metabolism, therefore, could potentially be efficacious in preventing gastrointestinal (GI) acute GVHD (aGVHD). We explored the use of budesonide, added to posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil, for prevention of GI aGVHD after allogeneic hematopoietic stem cell transplantation (AHSCT) in a prospective observational study and treated 80 patients with a median age of 53 years (range 19–74). Results were compared with a publicly available CIBMTR dataset of 646 patients who received PTCy‐based GVHD prophylaxis (CIBMTR Study # GV17‐02) (control). Cumulative incidence (CI) of 3‐month grade 2–4 and grade 3–4 aGVHD in the budesonide and control groups were 3.8% vs. 34.4% (p < 0.001) and 1.3% vs. 9.8% (p = 0.029), respectively. One‐year GRFS (70.5% vs. 31.5%, p < 0.001), PFS (73.4% vs. 52.8%, p = 0.003), and OS (80.1% vs. 64.2%, p = 0.038) were significantly higher in the budesonide group compared with control group. Propensity score‐adjusted analyses showed that the addition of budesonide significantly decreased risk of aGVHD grade 2–4 (HR 0.29, p < 0.001), grade 3–4 (HR 0.12, p = 0.045), and cGVHD (HR 0.22, p < 0.001), which resulted in better GRFS (HR 0.38, p < 0.001), PFS (HR 0.58, p = 0.012), and OS (HR 0.72, p = 0.044). Similar results were found when using propensity score‐matched analysis restricted to recipients of haploidentical transplantation. In conclusion, addition of budesonide to PTCy‐based GVHD prophylaxis is safe and effective in preventing severe acute GI GVHD with significantly improved GRFS. These results could facilitate transition to peripheral blood grafts for all allogeneic transplant recipients.
doi: 10.1002/ajh.27576pmid: 39757533
Adding inotuzumab ozogamicin (InO) to hyper‐CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)‐negative B‐cell acute lymphoblastic leukemia (B‐ALL). Patients with newly diagnosed B‐ALL received up to four cycles of hyper‐CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m2 was added on Days 1 and 8 to two cycles of high‐dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse‐free survival (RFS) rate. Seventy‐five patients were treated (median age of 33 years; range, 18–59), of whom 37 (49%) received hyper‐CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next‐generation sequencing (sensitivity: 1 × 10−6) was achieved in 79% of patients in cohort 2. The median follow‐up was 44 months (range, 13–90) overall, and 26 months (range, 8–39) in cohort 2. For the entire cohort, the estimated 3‐year RFS rate was 82% and the 3‐year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper‐CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B‐ALL.
Chromoanagenesis (CAG) encompasses a spectrum of catastrophic genomic events, including chromothripsis, chromoanasynthesis, and chromoplexy. We studied CAG in 410 patients with a diagnosis of acute myeloid leukemia (AML), 292 newly diagnosed (ND), and 118 refractory/relapsed, using optical genome mapping. CAG was identified by the presence of clusters (with 10 or more breakpoints) of structural abnormalities and/or segmental copy number alterations within one or more chromosomal regions. CAG was detected in 65 (16%) patients. Compared with patients without CAG, those with CAG showed significantly (p < 0.0001) higher frequencies of highly complex karyotype (92% vs. 11%), monosomal karyotype (88% vs. 12%), extensive clonal heterogeneity (75% vs. 7%), gene amplification (49% vs. 1%), and TP53 deletion/mutation (92% vs. 9%). Overall, CAG was detected in about two‐thirds of AML patients who exhibited the abovementioned high‐risk cytogenetic abnormalities/karyotype. Among the 42 patients with ND AML and CAG, 36 received treatments and follow‐ups, and 28 (78%) had no or only partial response to therapy. Among patients with ND AML, those with CAG had a shorter overall survival than those without CAG (median survival: 5 vs. 14 months, p < 0.0001). However, in multivariate analysis, CAG did not appear to be an independent risk factor for survival. These results indicate that CAG is frequently associated with high‐risk chromosomal alterations and genomic instability in AML and may contribute to treatment refractoriness and inferior survival in this subset of AML patients.
doi: 10.1002/ajh.27539pmid: 39844469
Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017–004012‐19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long‐term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE‐eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment‐related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment‐related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients.