Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100474
Jeffrey Baron , Manu R. Pandey , Elizabeth A. Griffiths , Eunice S. Wang
{"title":"Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in Jehovah's witness patients","authors":"Jeffrey Baron , Manu R. Pandey , Elizabeth A. Griffiths , Eunice S. Wang","doi":"10.1016/j.lrr.2024.100474","DOIUrl":"10.1016/j.lrr.2024.100474","url":null,"abstract":"","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"22 ","pages":"Article 100474"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000645/pdfft?md5=3040d4d2694de947d12371d548eb36f2&pid=1-s2.0-S2213048924000645-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100471
Mobachir El Kettani , Kashish Shah , Hareem Farooq , Ke Li , Talha Badar
This case report explains an extraordinary presentation of chronic myeloid leukemia (CML) in a 39-year-old male with a T315I mutation, presenting with acute bilateral hearing loss and imbalance secondary to myeloid blast crisis. Neurological involvement was confirmed through MRI brain and cerebrospinal fluid analysis. Initial treatment with ponatinib and FLAG (fludarabine, cytarabine, G-CSF) regimen showed promise, but complications necessitated discontinuation. The patient's complex clinical trajectory, marked by complications and intolerance to tyrosine kinase inhibitors, highlights the intricate nature of CML blast crisis with T315I mutation management. Recognizing atypical presentations and early mutation analysis are pivotal for tailored treatment strategies.
{"title":"Chronic myeloid leukemia with involvement of membranous labyrinth","authors":"Mobachir El Kettani , Kashish Shah , Hareem Farooq , Ke Li , Talha Badar","doi":"10.1016/j.lrr.2024.100471","DOIUrl":"10.1016/j.lrr.2024.100471","url":null,"abstract":"<div><p>This case report explains an extraordinary presentation of chronic myeloid leukemia (CML) in a 39-year-old male with a T315I mutation, presenting with acute bilateral hearing loss and imbalance secondary to myeloid blast crisis. Neurological involvement was confirmed through MRI brain and cerebrospinal fluid analysis. Initial treatment with ponatinib and FLAG (fludarabine, cytarabine, G-CSF) regimen showed promise, but complications necessitated discontinuation. The patient's complex clinical trajectory, marked by complications and intolerance to tyrosine kinase inhibitors, highlights the intricate nature of CML blast crisis with T315I mutation management. Recognizing atypical presentations and early mutation analysis are pivotal for tailored treatment strategies.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"22 ","pages":"Article 100471"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221304892400061X/pdfft?md5=72e11a1ea336e7231d57c0f3856bed99&pid=1-s2.0-S221304892400061X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A 63-year-old male received a third allogeneic hematopoietic stem cell transplantation with voriconazole prophylaxis for relapsed acute myeloid leukemia. He developed septic arthritis without any typical skin lesions due to fungal infection on day 42. Treatment with liposomal amphotericin B was initiated following surgical debridement; however, he died of progressive fungal infection. Ribosomal DNA sequencing identified Fusarium solani species complex (FSSC) harboring voriconazole resistance. This clinical course indicates that breakthrough invasive fusariosis (azole-resistant FSSC infection) needs to be considered as a pathogen when patients with hematological malignancies develop septic arthritis without typical skin lesions during voriconazole prophylaxis.
一名 63 岁的男性因急性髓性白血病复发接受了第三次异基因造血干细胞移植,并使用了伏立康唑预防疗法。第 42 天,他因真菌感染出现了化脓性关节炎,但没有任何典型的皮肤损害。手术清创后,他开始接受脂质体两性霉素 B 治疗,但最终死于进行性真菌感染。核糖体 DNA 测序发现茄属镰刀菌种复合体(FSSC)对伏立康唑产生抗药性。这一临床病程表明,当血液恶性肿瘤患者在服用伏立康唑预防期间出现化脓性关节炎而无典型皮损时,突破性侵袭性镰刀菌病(耐唑类药物的 FSSC 感染)需要作为病原体加以考虑。
{"title":"Septic arthritis as breakthrough invasive fusariosis after cord blood transplantation","authors":"Shinichi Katsuoka , Hidehiro Itonaga , Yasushi Sawayama , Masahiko Chiwata , Haruka Watanabe , Yuichi Yamada , Machiko Fujioka , Takeharu Kato , Shinya Sato , Koji Ando , Masato Tashiro , Takahiro Takazono , Yoshitaka Imaizumi , Koichi Izumikawa , Katsunori Yanagihara , Hiroshi Mukae , Yasushi Miyazaki","doi":"10.1016/j.lrr.2024.100483","DOIUrl":"10.1016/j.lrr.2024.100483","url":null,"abstract":"<div><div>A 63-year-old male received a third allogeneic hematopoietic stem cell transplantation with voriconazole prophylaxis for relapsed acute myeloid leukemia. He developed septic arthritis without any typical skin lesions due to fungal infection on day 42. Treatment with liposomal amphotericin B was initiated following surgical debridement; however, he died of progressive fungal infection. Ribosomal DNA sequencing identified <em>Fusarium solani</em> species complex (FSSC) harboring voriconazole resistance. This clinical course indicates that breakthrough invasive fusariosis (azole-resistant FSSC infection) needs to be considered as a pathogen when patients with hematological malignancies develop septic arthritis without typical skin lesions during voriconazole prophylaxis.</div></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"22 ","pages":"Article 100483"},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2023.100408
Poorva Vaidya , Huan-You Wang , Michelle D. Don , Brian R. Hinds , James K. Mangan
Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine. The regimen induced a rapid bone marrow response and resolution of the leukemia cutis.
近早期 T 细胞前体急性淋巴细胞白血病(ETP-ALL)是一种罕见的血液系统恶性肿瘤,二线治疗方案有限。T细胞白血病也很少伴发切缘白血病,而切缘白血病多见于髓源性白血病。我们介绍了一例被诊断为近似 ETP-ALL 的成年男性患者,其 IDH2 和 DNMT3A 基因突变提示其为髓细胞源性白血病,并伴有切端白血病。患者在接受高CVAD和奈拉滨治疗后病情恶化,我们用BCL-2抑制剂venetoclax和低甲基化药物地西他滨对其进行治疗。该治疗方案迅速诱导了骨髓反应,并缓解了切缘白血病。
{"title":"IDH2-mutated near ETP-ALL with aggressive leukemia cutis and brisk response to venetoclax and decitabine","authors":"Poorva Vaidya , Huan-You Wang , Michelle D. Don , Brian R. Hinds , James K. Mangan","doi":"10.1016/j.lrr.2023.100408","DOIUrl":"https://doi.org/10.1016/j.lrr.2023.100408","url":null,"abstract":"<div><p>Near early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare hematologic malignancy, for which second line therapeutic options are limited. T-cell leukemias are also rarely associated with leukemia cutis, which is more often seen in leukemias of myeloid origin. We present the case of an adult male diagnosed with near ETP-ALL, with IDH2 and DNMT3A mutations, suggestive of a myeloid origin, and leukemia cutis. After the patient progressed on hyper-CVAD and nelarabine, we treated him with the BCL-2 inhibitor venetoclax and the hypomethylating agent decitabine. The regimen induced a rapid bone marrow response and resolution of the leukemia cutis.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"21 ","pages":"Article 100408"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048923000481/pdfft?md5=8515d6d9e67084a08d446cba27bdea9d&pid=1-s2.0-S2213048923000481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139100132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Real-world data on treatment patterns and outcomes of patients with acute myeloid leukemia unfit for intensive chemotherapy are lacking before the advent of precision medicine in this setting.
Herein, we present the Italian sub-analysis of the CURRENT study in AML patients unfit for first line intensive chemotherapy, evaluating patients’ outcomes between 2015 and 2018.
Among 74 evaluable patients, 62 received systemic treatments (most used therapy was hypomethylating agents), while 12 best supportive care.
Key results include both efficacy and safety data, as well as HCRU and treatment patterns. In first-line therapy cohort median OS was 13.4 months vs. 2.7 months for BSC.
{"title":"Real-world treatments and clinical outcomes in unfit AML patients receiving first-line treatment or best supportive care in Italy (CURRENT study)","authors":"Maria Paola Martelli , Nicola Di Renzo , Antonio Curti , Nicola Stefano Fracchiolla , Luca Maurillo , Morena Caira , Paola Finsinger , Giuliana Gualberti , Felicetto Ferrara , Attilio Olivieri","doi":"10.1016/j.lrr.2024.100453","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100453","url":null,"abstract":"<div><p>Real-world data on treatment patterns and outcomes of patients with acute myeloid leukemia unfit for intensive chemotherapy are lacking before the advent of precision medicine in this setting.</p><p>Herein, we present the Italian sub-analysis of the CURRENT study in AML patients unfit for first line intensive chemotherapy, evaluating patients’ outcomes between 2015 and 2018.</p><p>Among 74 evaluable patients, 62 received systemic treatments (most used therapy was hypomethylating agents), while 12 best supportive care.</p><p>Key results include both efficacy and safety data, as well as HCRU and treatment patterns. In first-line therapy cohort median OS was 13.4 months vs. 2.7 months for BSC.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"21 ","pages":"Article 100453"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000438/pdfft?md5=f5c1ed3740748c30eca95f71c3a15eda&pid=1-s2.0-S2213048924000438-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140063297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100421
T. Yagi , H. Kumagai , A. Shimada
Introduction
Inflammatory bowel disease (IBD) is characterized by chronic inflammation within the digestive tract. In myelodysplastic syndrome (MDS) and aplastic anemia (AA), inflammation in the bone marrow is thought to be one of the causes. There are case reports of MDS or AA combined with IBD. Among these patients, there were several cases who improved hematopoietic function and IBD symptoms after treatment for MDS or AA. However, there are no summarized reports of cases of IBD combined with MDS or AA in Japan. We retrospectively reviewed the reports of IBD combined with MDS or AA in Japan.
Methods
We collected reports on cases of IBD combined with MDS or AA in Japan using Igaku Chuo Zasshi [Ichushi] and PubMed, and reviewed those cases.
Results
We collected 45 cases of IBD combined with MDS or AA. There were 28 and 19 cases of IBD combined with MDS and AA, respectively. Two cases progressed from AA to MDS. Seven cases occurred in the same period. In 21 cases, MDS or AA occurred prior to IBD. In 5 cases, hematopoietic stem cell transplantation restored both IBD and hematopoietic function.
Conclusions
We performed the first literature review of combined cases of IBD and MDS or AA in Japan. Considering the timing of onset and treatment response, there may be common pathologies in IBD and MDS or AA. However, we could not collect treatment details. We plan to construct a nationwide database of complicated cases and elucidate the pathophysiology of these cases.
导言炎症性肠病(IBD)的特征是消化道内的慢性炎症。在骨髓增生异常综合征(MDS)和再生障碍性贫血(AA)中,骨髓炎症被认为是病因之一。有 MDS 或 AA 合并 IBD 的病例报告。在这些患者中,有几例患者在接受 MDS 或 AA 治疗后,造血功能和 IBD 症状得到改善。然而,在日本还没有 IBD 合并 MDS 或 AA 病例的总结报告。我们回顾性地回顾了日本关于 IBD 合并 MDS 或 AA 的报告。方法我们通过 Igaku Chuo Zasshi [Ichushi] 和 PubMed 收集了日本关于 IBD 合并 MDS 或 AA 的病例报告,并对这些病例进行了回顾。IBD 合并 MDS 和 AA 的病例分别为 28 例和 19 例。2例从AA发展为MDS。7例发生在同一时期。21例患者的MDS或AA发生在IBD之前。结论我们首次对日本的 IBD 和 MDS 或 AA 合并病例进行了文献综述。考虑到发病时间和治疗反应,IBD 和 MDS 或 AA 可能存在共同病理。但是,我们无法收集治疗细节。我们计划建立一个全国性的复杂病例数据库,并阐明这些病例的病理生理学。
{"title":"A META-ANALYSIS OF COMPLICATED CASES OF INFLAMMATORY BOWEL DISEASE AND BONE MARROW FAILURE SYNDROME IN JAPAN","authors":"T. Yagi , H. Kumagai , A. Shimada","doi":"10.1016/j.lrr.2024.100421","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100421","url":null,"abstract":"<div><h3>Introduction</h3><p>Inflammatory bowel disease (IBD) is characterized by chronic inflammation within the digestive tract. In myelodysplastic syndrome (MDS) and aplastic anemia (AA), inflammation in the bone marrow is thought to be one of the causes. There are case reports of MDS or AA combined with IBD. Among these patients, there were several cases who improved hematopoietic function and IBD symptoms after treatment for MDS or AA. However, there are no summarized reports of cases of IBD combined with MDS or AA in Japan. We retrospectively reviewed the reports of IBD combined with MDS or AA in Japan.</p></div><div><h3>Methods</h3><p>We collected reports on cases of IBD combined with MDS or AA in Japan using Igaku Chuo Zasshi [Ichushi] and PubMed, and reviewed those cases.</p></div><div><h3>Results</h3><p>We collected 45 cases of IBD combined with MDS or AA. There were 28 and 19 cases of IBD combined with MDS and AA, respectively. Two cases progressed from AA to MDS. Seven cases occurred in the same period. In 21 cases, MDS or AA occurred prior to IBD. In 5 cases, hematopoietic stem cell transplantation restored both IBD and hematopoietic function.</p></div><div><h3>Conclusions</h3><p>We performed the first literature review of combined cases of IBD and MDS or AA in Japan. Considering the timing of onset and treatment response, there may be common pathologies in IBD and MDS or AA. However, we could not collect treatment details. We plan to construct a nationwide database of complicated cases and elucidate the pathophysiology of these cases.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"21 ","pages":"Article 100421"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000116/pdfft?md5=eed8f5705846a42368e187499e377e4d&pid=1-s2.0-S2213048924000116-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100418
M. Wakamatsu , H. Muramatsu , H. Sato , M. Ishikawa , D. Nakajima , R. Konno , Y. Kawashima , M. Hamada , Y. Okuno , O. Ohara , Y. Takahashi
Introduction
Inherited bone marrow failure syndrome (IBMFS) is characterized by a heterogeneous group of disorders with marked cytopenia in one hematopoietic cell lineage. Aldehyde Degradation Deficiency Syndrome (ADDS) is one of the newly discovered IBMFS, caused by a combined deficiency of ADH5 and ALDH2, which are important for the degradation of endogenously produced formaldehyde. Here, we utilized recent technological advances in data-independent proteomic analysis to establish a diagnostic testing for IBMFS, including ADDS.
Methods
We performed a multi-omics analysis of in-depth proteomic analysis, targeted capture DNA sequencing, and RNA sequencing among patients with IBMFS.
Results
In-depth non-targeted proteomic analysis was performed on 74 samples obtained from 60 patients with IBMFS and 14 healthy controls. We identified eight independent proteomic clusters (C1-C8), with ribosome pathway-related proteins specifically downregulated in C1 and C2, enriched for Diamond-Blackfan anemia and Schwachman-Diamond syndrome, respectively. In the 74 samples, four patients with ADDS showed significantly reduced ADH5 protein expression, whereas the remaining samples showed normal expression. To provide a large-scale rapid screening system in a practical clinical setting, targeted proteomic analysis was performed using a small panel, including ADH5 proteins, in a developmental cohort of 417 samples with hematological malignancies and healthy controls. ADH5 protein expression levels were significantly reduced in ADDS, and its sensitivity and specificity values were 100.0% and 97.5%, respectively.
Conclusions
We have performed the first integrated multi-omics analysis for IBMFS, and demonstrated that clinical applications of targeted proteomic assays would be useful in diagnosing for IBMFS, including ADDS.
{"title":"DIAGNOSTIC UTILITY OF ALDEHYDE DEGRADATION DEFICIENCY SYNDROME USING PROTEOMIC ANALYSIS","authors":"M. Wakamatsu , H. Muramatsu , H. Sato , M. Ishikawa , D. Nakajima , R. Konno , Y. Kawashima , M. Hamada , Y. Okuno , O. Ohara , Y. Takahashi","doi":"10.1016/j.lrr.2024.100418","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100418","url":null,"abstract":"<div><h3>Introduction</h3><p>Inherited bone marrow failure syndrome (IBMFS) is characterized by a heterogeneous group of disorders with marked cytopenia in one hematopoietic cell lineage. Aldehyde Degradation Deficiency Syndrome (ADDS) is one of the newly discovered IBMFS, caused by a combined deficiency of ADH5 and ALDH2, which are important for the degradation of endogenously produced formaldehyde. Here, we utilized recent technological advances in data-independent proteomic analysis to establish a diagnostic testing for IBMFS, including ADDS.</p></div><div><h3>Methods</h3><p>We performed a multi-omics analysis of in-depth proteomic analysis, targeted capture DNA sequencing, and RNA sequencing among patients with IBMFS.</p></div><div><h3>Results</h3><p>In-depth non-targeted proteomic analysis was performed on 74 samples obtained from 60 patients with IBMFS and 14 healthy controls. We identified eight independent proteomic clusters (C1-C8), with ribosome pathway-related proteins specifically downregulated in C1 and C2, enriched for Diamond-Blackfan anemia and Schwachman-Diamond syndrome, respectively. In the 74 samples, four patients with ADDS showed significantly reduced ADH5 protein expression, whereas the remaining samples showed normal expression. To provide a large-scale rapid screening system in a practical clinical setting, targeted proteomic analysis was performed using a small panel, including ADH5 proteins, in a developmental cohort of 417 samples with hematological malignancies and healthy controls. ADH5 protein expression levels were significantly reduced in ADDS, and its sensitivity and specificity values were 100.0% and 97.5%, respectively.</p></div><div><h3>Conclusions</h3><p>We have performed the first integrated multi-omics analysis for IBMFS, and demonstrated that clinical applications of targeted proteomic assays would be useful in diagnosing for IBMFS, including ADDS.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"21 ","pages":"Article 100418"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000086/pdfft?md5=210b5b55130fba593fda02ab4629f2e9&pid=1-s2.0-S2213048924000086-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100431
E. Diral, G. Bergonzi, S. Mastaglio, C. Tresoldi, P. Ronchi, M. Ponzoni, M. Cristante, D. Clerici, L. Vago, M. Bernardi, F. Ciceri
Introduction
Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center.
Methods
We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol.
Results
27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR.
Conclusions
aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS.
{"title":"MOLECULAR INTERNATIONAL PROGNOSTIC SCORING SYSTEM FOR MYELODYSPLASTIC SYNDROMES: A MONOCENTRIC EXPERIENCE","authors":"E. Diral, G. Bergonzi, S. Mastaglio, C. Tresoldi, P. Ronchi, M. Ponzoni, M. Cristante, D. Clerici, L. Vago, M. Bernardi, F. Ciceri","doi":"10.1016/j.lrr.2024.100431","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100431","url":null,"abstract":"<div><h3>Introduction</h3><p>Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center.</p></div><div><h3>Methods</h3><p>We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol.</p></div><div><h3>Results</h3><p>27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR.</p></div><div><h3>Conclusions</h3><p>aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":"21 ","pages":"Article 100431"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000219/pdfft?md5=1c5b2853f0f0334709793e7375ff3b13&pid=1-s2.0-S2213048924000219-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100445
A. Shastri, S. Chakraborty, C. Morganti, H. Zhang, B. Rivera-Pena, K. Ito, M. Konopleva
Introduction
High-risk MDS & AML are the result of malignant transformation of an immature hematopoietic precursor. Venetoclax (Ven) is a selective inhibitor of the anti-apoptotic BCL2 protein that is FDA approved for the treatment of AML, despite which, the overall cure rates in HR-MDS and AML are dismal. Signal transducer and activator of transcription 3 (STAT3) is de-methylation and overexpression in MDS & AML stem cells. It is associated with an adverse prognosis in a large cohort of patients. We have also demonstrated that STAT3 controls several important leukemic drivers such as the anti-apoptotic protein MCL1, which is the central mechanism of venetoclax resistance.
Methods
Ven resistant AML cell lines (MOLM-13, MV-4-11) demonstrated an increased expression of STAT3/ Phospho-STAT3 and the down-stream effector MCL1 when compared to parental cell lines. Data from > 90 AML patients treated with prior venetoclax show that high expression of STAT3 correlated with worse overall survival and remission duration.
Results
A clinical degrader of STAT3 resulted in degradation of STAT3 in both parental and ven resistant cancer cell lines. STAT3 degradation also resulted in increased apoptosis in parental & Ven resistant MOLM-13 cell line. In primary patient colony assays, there was increased erythroid and myeloid differentiation on treatment with a STAT3 degrader. Furthermore, murine model of venetoclax resistance showed significant reduction in STAT3 & MCL1 on treatment with the STAT3 degrader.
Conclusions
Targeting STAT3 and downstream MCL1 is novel strategy in MDS/AML that can spur clinical development of the STAT3 degraders especially given the significant side profile of direct MCL1 inhibitors.
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Pub Date : 2024-01-01DOI: 10.1016/j.lrr.2024.100454
Kazunori Nakase , Kenkichi Kita
Although the expression of interleukin-2 receptor α-chain (IL-2Rα, CD25) has been provided prognostic significance independent of known biomarkers in acute myeloid leukemia (AML), the functional role of CD25 molecule remains unknown. Since IL-2 can be trans-presented via CD25 to another cell, CD25+AML cells may deliver environmental IL-2 to surrounding immune cells to produce myeloid growth factors for their proliferation. We hypothesize that cellular interactions via IL-2/CD25 axis in the bone marrow microenvironment contributes to the growth advantage of these AML cells and affects the clinical outcome of those AML patients.
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