Leukemia research最新文献

{"title":"Association between myeloid disorders and adult onset-inflammatory syndromes, successful treatment with JAK-inhibitors: Case series and literature review","authors":"Rahul Mishra ,&nbsp;Cassandra Calabrese ,&nbsp;Akriti G. Jain ,&nbsp;Abhay Singh","doi":"10.1016/j.leukres.2024.107584","DOIUrl":"10.1016/j.leukres.2024.107584","url":null,"abstract":"<div><p>Approximately one-third of patients with myeloid disorders like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) exhibit inflammatory and autoimmune disorders (IADs). These IADs often include atypical and incomplete forms of common autoimmune conditions, and exhibit resistance to conventional immunosuppressive therapies. There is growing interest in molecular relationships between IADs and MDS/CMML to find potential targeted therapies. Recently, patients with somatic mutations in the <em>UBA1</em> gene were identified as having VEXAS syndrome. Herein, we present a concise case-series illustrating concurrent elderly-onset inflammatory manifestations and myeloid disorders (MDS, CMML, and idiopathic cytopenia of undetermined significance). These patients manifested inflammatory or autoimmune symptoms, including erythema nodosum, Raynaud's phenomenon, Sjogren syndrome, and refractory pruritus, having onset after 60-years of age. The inflammatory manifestations were largely refractory to traditional immunosuppressive regimens. Remarkably, treatment with a JAK-1 inhibitor, upadacitinib, in two cases yielded marked resolution of inflammatory symptoms, facilitating the gradual tapering of corticosteroids, improvement of hemoglobin levels, and reduction in serum C-reactive protein levels. Upon loss of response to upadacitinib, JAK-2 inhibitor ruxolitinib provided clinical benefit in one of the cases, facilitating further tapering of glucocorticoids. This arena warrants further exploration through prospective studies of larger cohorts to delineate optimal management strategies.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107584"},"PeriodicalIF":2.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624001504/pdfft?md5=274bd766483a1347ea587531359afb0f&pid=1-s2.0-S0145212624001504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes","authors":"Jonathan Lim ,&nbsp;David M. Ross ,&nbsp;Anna L. Brown ,&nbsp;Hamish S. Scott ,&nbsp;Christopher N. Hahn","doi":"10.1016/j.leukres.2024.107566","DOIUrl":"10.1016/j.leukres.2024.107566","url":null,"abstract":"<div><div>Epidemiological evidence of familial predispositions to myeloid malignancies and myeloproliferative neoplasms (MPN) has long been recognised, but recent studies have added to knowledge of specific germline variants in multiple genes that contribute to the familial risk. These variants may be common risk alleles in the general population but have low penetrance and cause sporadic MPN, such as the <em>JAK2</em> 46/1 haplotype, the variant most strongly associated with MPN. Association studies are increasingly identifying other MPN susceptibility genes such as <em>TERT</em>, <em>MECOM</em>, and <em>SH2B3</em>, while some common variants in <em>DDX41</em> and <em>RUNX1</em> appear to lead to a spectrum of myeloid malignancies. <em>RBBP6</em> and <em>ATM</em> variants have been identified in familial MPN clusters and very rare germline variants such as chromosome 14q duplication cause hereditary MPN with high penetrance. Rarely, there are hereditary non-malignant diseases with an MPN-like phenotype. Knowledge of those genes and germline genetic changes which lead to MPN or diseases that mimic MPN helps to improve accuracy of diagnosis, aids with counselling regarding familial risk, and may contribute to clinical decision-making. Large scale population exome and genome sequencing studies will improve our knowledge of both common and rare germline genetic contributions to MPN.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107566"},"PeriodicalIF":2.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation","authors":"Amrita Desai ,&nbsp;Yazeed Samara ,&nbsp;Dongyun Yang ,&nbsp;Brian Ball ,&nbsp;Adam Braun ,&nbsp;Paul Koller ,&nbsp;Amanda Blackmon ,&nbsp;Vaibhav Agrawal ,&nbsp;Hoda Pourhassan ,&nbsp;Idoroenyi Amanam ,&nbsp;Shukaib Arslan ,&nbsp;Salman Otoukesh ,&nbsp;Karamjeet Sandhu ,&nbsp;Ibrahim Aldoss ,&nbsp;Haris Ali ,&nbsp;Amandeep Salhotra ,&nbsp;Monzr M. Al Malki ,&nbsp;Andrew Artz ,&nbsp;Pamela Becker ,&nbsp;Eileen Smith ,&nbsp;Vinod Pullarkat","doi":"10.1016/j.leukres.2024.107565","DOIUrl":"10.1016/j.leukres.2024.107565","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;To compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12–77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55–0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27–0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37–0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Among patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the in","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107565"},"PeriodicalIF":2.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of transcriptomic profiles in relapsed inv(16) acute myeloid leukemia","authors":"Serena Travaglini ,&nbsp;Giorgia Silvestrini ,&nbsp;Enrico Attardi ,&nbsp;Maurizio Fanciulli ,&nbsp;Stefano Scalera ,&nbsp;Silvia Antonelli ,&nbsp;Luca Maurillo ,&nbsp;Raffaele Palmieri ,&nbsp;Mariadomenica Divona ,&nbsp;Ludovica Ciuffreda ,&nbsp;Arianna Savi ,&nbsp;Giovangiacinto Paterno ,&nbsp;Tiziana Ottone ,&nbsp;Caterina Barbieri ,&nbsp;Jaroslaw P. Maciejewski ,&nbsp;Carmelo Gurnari ,&nbsp;Gennaro Ciliberto ,&nbsp;Maria Teresa Voso","doi":"10.1016/j.leukres.2024.107568","DOIUrl":"10.1016/j.leukres.2024.107568","url":null,"abstract":"<div><p>Acute myeloid leukemia (AML) with inv(16) is typically associated with a favourable prognosis. However, up to 40 % of patients will eventually experience disease relapse. Herein, we dissected the genomic and transcriptomic profile of inv(16) AML to identify potential prognostic markers and therapeutic vulnerabilities. Sequencing data from 222 diagnostic samples, including 44 relapse/refractory patients, revealed a median of 1 concomitant additional mutation, cooperating with inv(16) in leukemogenesis. Notably, the mutational landscape at diagnosis did not differ significantly between patients experiencing primary induction failure or relapse when compared to the rest of the cohort, except for an increase in the mutational burden in the relapse/refractory group. RNA-Seq of unpaired diagnostic(n=7) and relapse(n=6) samples allowed the identification of oxidative phosphorylation (OXPHOS) as one of the most significantly downregulated pathways at relapse. Considering that OXPHOS could be targeted by Venetoclax/Azacitidine combination, we explored its biological effects on an inv(16) cell-line ME-1, but there was no additional advantage in terms of cell death over Azacitidine alone. To enhance Venetoclax efficacy, we tested <em>in vitro</em> effects of Metformin as a potential drug able to enhance chemosensitivity of AML cells by inhibiting the mitochondrial transfer. By challenging ME-1 with this combination, we observed a significant synergistic interaction at least similar to that of Venetoclax/Azacitidine. In conclusions, we identified a downregulated expression of oxidative phosphorylation (OXPHOS) at relapse in AML with inv(16), and explored the in vitro effects of metformin as a potential drug to enhance chemosensitivity in this setting.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107568"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of blinatumomab for the treatment of B‑precursor acute lymphoblastic leukemia pediatric patients with high‑risk first‑relapse in Mexico","authors":"Juan Pablo Diaz Martinez ,&nbsp;Therese Aubry de Maraumont ,&nbsp;Luis Miguel Camacho ,&nbsp;Laura Garcia","doi":"10.1016/j.leukres.2024.107560","DOIUrl":"10.1016/j.leukres.2024.107560","url":null,"abstract":"<div><h3>Background</h3><p>Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule that engages T cells to lyse CD19-expressing B cells. Based on a multicenter, open-label, phase 3, randomized clinical trial (Clinical Trials ID: NCT02393859), we aimed to evaluate the cost-effectiveness (CE) of blinatumomab compared to standard consolidation chemotherapy (SC) for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) from a Mexico healthcare payer perspective.</p></div><div><h3>Methods</h3><p>A decision-analytic model, a partitioned survival model, was used to estimate the life-years (LYs) and costs over a lifetime horizon. We assumed that patients who remained alive beyond a 5-year period were cured. To account for the lingering impacts of cancer treatment, an excess mortality rate was incorporated into the model. Event-free survival (EFS) and overall survival (OS) were estimated by fitting mixture-cure and standard parametric survival distributions to the time-to-event data from the phase 3 trial. The model accounted for treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT) costs, and subsequent treatment costs.</p></div><div><h3>Results</h3><p>Blinatumomab was associated with a lifetime gained of 5.11 years at an incremental cost of $621,111 MXN, relative to SC. The ICER for blinatumomab vs Standard of care was estimated to be $121,526 MXN/LY gained in the base case. Cost-effectiveness was sensitive to varying the time horizon. Blinatumomab had a probability of 99 % of being cost-effective, relative to SC, at the willingness to pay threshold defined in Mexico.</p></div><div><h3>Limitations</h3><p>Health-related quality of life values were not included in the analysis and therefore we did not estimate the quality-adjusted life-years gained.</p></div><div><h3>Conclusions</h3><p>Blinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107560"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624001267/pdfft?md5=04f550091c780aeebd987c84b18fa905&pid=1-s2.0-S0145212624001267-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinctive features associated with differentiation syndrome in acute promyelocytic leukemia in patients treated by all-trans retinoic acid and arsenic trioxide","authors":"Silvia Cingelova ,&nbsp;Eva Mikuskova ,&nbsp;Ludmila Demitrovicova ,&nbsp;Vanda Mikudova ,&nbsp;Alica Slobodova ,&nbsp;Jana Spanikova ,&nbsp;Radka Vasickova ,&nbsp;Denis Urban ,&nbsp;Lubos Drgona ,&nbsp;Iveta Oravcova","doi":"10.1016/j.leukres.2024.107567","DOIUrl":"10.1016/j.leukres.2024.107567","url":null,"abstract":"<div><p>In acute promyelocytic leukemia (APL), the combination treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) appears to have a synergistic effect. Due to this synergism, differentiation syndrome (DS) in APL assumes a distinct identity separate from the formerly known ATRA syndrome, with distinct temporal patterns, diagnostic parameters, and clinical behavior. We retrospectively evaluated single-center data of years 2013–2022. Patients with newly diagnosed APL were categorized into three groups (16 patients in ATRA/ATO standard-risk group, 3 patients in ATRA/chemotherapy standard-risk group, and 5 patients in ATRA/chemotherapy high-risk group). Our aim was to analyze leukocytosis, signs of DS, and hepatic impairment within the first 25 days of treatment. The incidence of DS in the ATRA/ATO SR group was 43.8 %, with a median of 4 days and 2 days from ATRA and ATO initiation, respectively. This group also exhibited higher peak levels of leukocytosis 34.5 (6.0–113.4) x10⁹/L (p = 0.0809). ALT elevation was more prevalent in the ATRA/ATO SR group (93.75 %), with 68.75 % grade 3–4 elevations (p = 0.0094). Importantly, all patients in this group had ALT levels that returned to normal during the subsequent consolidations. These findings suggest hepatopathy as a potential manifestation of ATRA/ATO induced leukocyte differentiation and/or DS. Diverse differentiation patterns were identified within the ATRA/ATO group, classifying patients into three distinct subgroups based on the concurrent dynamics of leukocytes and ALT levels, illustrating <strong>simultaneous, sequential, and divergent elevation patterns.</strong> These emphasize the different distribution of differentiation (organs vs. peripheral blood). We introduced real-world data and advocated for reevaluation of the current DS definition and associated diagnostic thresholds. Our study, conducted in a small country with a limited number of APL patients, acknowledges the inherent constraints in sample size. Further investigations with larger patient cohorts are warranted to validate and reinforce the outcomes observed in our study.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107567"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triplet therapy with gilteritinib, venetoclax, and azacitidine for relapsed/refractory FLT3mut acute myeloid leukemia","authors":"Qiang Fu ,&nbsp;Yunqi Wang ,&nbsp;Hongtao Liu ,&nbsp;Haitao Gao ,&nbsp;Wei Sun ,&nbsp;Qian Jiang ,&nbsp;Hao Jiang ,&nbsp;Kaiyan Liu ,&nbsp;Xiaojun Huang ,&nbsp;Feifei Tang","doi":"10.1016/j.leukres.2024.107564","DOIUrl":"10.1016/j.leukres.2024.107564","url":null,"abstract":"<div><p>The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory (R/R) <em>FLT3</em>-mutated (<em>FLT3</em>^<em>mut</em>) acute myeloid leukemia (AML) but the overall survival (OS) is only approximately 20 % and few patients achieve deep and/ or durable response. We retrospectively analyzed 29 R/R <em>FLT3</em>^<em>mut</em> AML patients treated on triplet regimens (gilteritinib+ venetoclax［VEN] +azacitidine［AZA]). Nineteen patients (65.5 %) had received prior FLT3 inhibitor therapy. The modified composite complete remission (mCRc) rate was 62.1 % (n = 18; CR, 4/29,13.8 %; CRi, 6/29, 20.7 %; MLFS, 8/29, 27.6 %). Among 18 patients achieved mCRc, FLT3-PCR negativity was 94.4 % (n=17), and flow-cytometry negativity was 77.7 % (n=14). The mCRc rate was 70 % (n=7) in 10 patients without prior FLT3 TKI exposure and 57.8 % (n=11) in 19 patients with prior FLT3 TKI exposure (P=0.52). At the end of the first cycle, the median time to ANC &gt; 0.5× 10⁹/L was 38 days and platelet &gt; 50× 10⁹/L was 31 days among responders, but 60-day mortality was 0 %. The estimated 2-year OS was 60.9 % for all R/R <em>FLT3</em>^<em>mut</em> patients. The 1-year OS was 80 % and 58.8 % in patients without and with prior FLT3 TKI exposure, respectively (P=0.79). The estimated 2-year OS was 62 % in 19 (65.5 %) patients who received allo-HSCT after triplet therapy and 37 % in 10 patients who did not receive allo-HSCT (P=0.03). In conclusion, triplet therapy with gilteritinib, VEN, and AZA is effective and safe and an excellent frontline option for R/R <em>FLT3</em>^<em>mut</em> AML.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107564"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance treatment significantly improves survival outcomes in relapsed/refractory B-ALL patients","authors":"Tingting Li ,&nbsp;Qingya Cui ,&nbsp;Sining Liu ,&nbsp;Zheng Li ,&nbsp;Wei Cui ,&nbsp;Mengyun Li ,&nbsp;Yunju Ma ,&nbsp;Xuanqi Cao ,&nbsp;Xiaming Zhu ,&nbsp;Liqing Kang ,&nbsp;Lei Yu ,&nbsp;Depei Wu ,&nbsp;Xiaowen Tang","doi":"10.1016/j.leukres.2024.107569","DOIUrl":"10.1016/j.leukres.2024.107569","url":null,"abstract":"<div><h3>Objective</h3><p>We aimed to evaluate the efficacy of decitabine consolidation after treatment with CD19/CD22 chimeric antigen receptor T-cell (CAR-T) for patients with relapsed/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL).</p></div><div><h3>Methods</h3><p>We retrospectively analysed 48 patients with r/r B-ALL who received CD19/CD22 CAR-T therapy between September 2017 and May 2021. Sixteen patients received decitabine consolidation (20 mg/m²/day for 5 days at 3-month intervals) after CAR-T therapy (DAC group), while 32 patients did not receive decitabine consolidation (CON group). Overall survival (OS), leukaemia-free survival (LFS), and cumulative incidence of relapse (CIR) were evaluated in both groups. Time-to-event analysis was performed using the Kaplan-Meier method.</p></div><div><h3>Results</h3><p>The median follow-up periods in the DAC and CON groups were 41.2 months and 28.6 months, respectively. The 4-year OS and 4-year LFS rates in both groups were 93.3 % and 64.3 % (P=0.029) and 87.5 % and 55.9 % (P=0.059), respectively. The 1-year CIR was 6.25 % and 28.6 %, respectively. Univariate and multivariate Cox regression analyses showed that decitabine consolidation after CAR-T therapy was significantly associated with superior OS (hazard ratio [HR]: 0.121, 95 % confidence interval [CI]: 0.015–0.947, P=0.044), and bridging to haematopoietic stem cell transplantation after CAR-T therapy was significantly associated with superior LFS (HR: 0.279, 95 %CI: 0.093–0.840, P=0.023).</p></div><div><h3>Conclusions</h3><p>Our study recommends decitabine consolidation after CD19/CD22 CAR-T therapy as a novel maintenance strategy to improve the survival outcomes of patients with r/r B-ALL.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107569"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics and outcomes of children, adolescent, and young adult patients with myelodysplastic neoplasms: A single-center retrospective analysis","authors":"David McCall ,&nbsp;Tareq Abuasab ,&nbsp;Juan Jose Rodriguez-Sevilla ,&nbsp;Shehab Fareed Mohamed ,&nbsp;Anish Patnaik ,&nbsp;Kirthi Devireddy ,&nbsp;Naszrin Arani ,&nbsp;Irtiza Sheikh ,&nbsp;Raehannah Jamshidi ,&nbsp;Amber Gibson ,&nbsp;Michael Roth ,&nbsp;Cesar Nuñez ,&nbsp;Miriam Garcia ,&nbsp;Kelly S. Chien ,&nbsp;Sanam Loghavi ,&nbsp;Sherry A. Pierce ,&nbsp;Koji Sasaki ,&nbsp;Ghayas Issa ,&nbsp;Branko Cuglievan ,&nbsp;Hagop Kantarjian ,&nbsp;Guillermo Garcia-Manero","doi":"10.1016/j.leukres.2024.107563","DOIUrl":"10.1016/j.leukres.2024.107563","url":null,"abstract":"<div><p>Myelodysplastic syndrome, or myelodysplastic neoplasms, are a rare finding in pediatric, adolescent, and young adult (AYA) patients. More literature is needed to highlight trends of survival or treatment resistance in subpopulations to improve treatment. Here we report a single center retrospective analysis of pediatric and AYA patients from 2000 to 2022 including molecular and cytogenetic data. Using the IPSS-R and IPSS-M, which have been reported exclusively in adults, and excluding patients with bone marrow failure syndromes, we analyzed 119 pediatric and AYA patients with myelodysplastic neoplasms. Therapy-related myelodysplastic neoplasms were present in 36 % of patients, and 31 % of patients developed acute myeloid leukemia. The 5-year overall survival (OS) rate for the entire cohort was 45 %. Contrary to young adults and older adults, mutations were not common in pediatrics. Those who underwent stem cell transplant (SCT)(at any time) had significantly longer median OS. Although SCT at any time improved OS in the de novo myelodysplastic neoplasm group, the choice of the initial treatment with intensive chemotherapy, hypomethylating agents, or SCT did not significantly alter OS. Median OS was shorter in the pediatric group (&lt;18 years old) and longer for those with isolated deletion of 5q or TET2 mutation, but these were not significant findings. Median OS was significantly shorter in those with monosomy 7 or 7q deletion and those with therapy-related myelodysplastic neoplasms. These findings build on previously reported findings and encourage the use of SCT along with molecular and cytogenetic analysis.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"144 ","pages":"Article 107563"},"PeriodicalIF":2.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic stem cell transplant with TBI-based myeloablative conditioning in adolescents and young adults with Philadelphia chromosome-negative ALL treated with pediatric protocols","authors":"Hiroaki Shimizu ,&nbsp;Jun Kato ,&nbsp;Susumu Tanoue ,&nbsp;Shun-ichi Kimura ,&nbsp;Takayoshi Tachibana ,&nbsp;Kaoru Hatano ,&nbsp;Kensuke Usuki ,&nbsp;Jun Taguchi ,&nbsp;Maki Hagihara ,&nbsp;Nobuhiro Tsukada ,&nbsp;Kaito Harada ,&nbsp;Satoshi Takahashi ,&nbsp;Satoru Takada ,&nbsp;Emiko Sakaida ,&nbsp;Shin Fujisawa ,&nbsp;Masahiro Onoda ,&nbsp;Nobuyuki Aotsuka ,&nbsp;Hiroshi Handa ,&nbsp;Yoshihiro Hatta ,&nbsp;Reiko Nakaseko ,&nbsp;Yoshinobu Kanda","doi":"10.1016/j.leukres.2024.107562","DOIUrl":"10.1016/j.leukres.2024.107562","url":null,"abstract":"<div><p>To investigate the safety of total body irradiation-based myeloablative conditioning (TBI-MAC) in adolescent and young adult (AYA) Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) patients treated with pediatric protocols, treatment outcomes of 106 AYA patients aged 16–39 years old undergoing allogeneic stem cell transplant (allo-SCT) with TBI-MAC in the first remission were compared according to chemotherapy types before transplant. Pediatric and adult protocols were used in 56 and 50 of the patients, respectively. The cumulative incidence (CI) of non-relapse mortality (NRM) and the overall survival (OS) rates were not significantly different between the pediatric-protocol and adult-protocol group (NRM: 4 % vs. 14 % at five years post-transplant, respectively, p = 0.26; OS: 81 % vs. 66 %, respectively, p = 0.14). Multivariate analysis for NRM revealed that a performance status &gt;0 (hazard ratio [HR] = 4.8) and transplant due to chemotherapy toxicities (HR = 3.5) were independent risk factors, but a pediatric protocol was not (HR = 0.48). The CI of NRM and the OS rates were also similar among patients aged over 24 years old. These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric protocols.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"144 ","pages":"Article 107562"},"PeriodicalIF":2.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}