Intermittent low dose dasatinib therapy brought about a beneficial effect in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) without inducing severe adverse events (AEs). An 85-year-old male patient, who received twice-weekly, thrice-weekly, or four-times-weekly administration of 20 mg/day dasatinib after once-weekly administration, achieved a major molecular response two years after the start of dasatinib treatment and later sometimes achieved a deep molecular response, maintaining the efficacy for 11 years. The mean daily dose ranged from 5.7 mg to 11.4 mg. Furthermore, a 79-year-old male patient, who received thrice-weekly or every other day administration of 20 mg/day dasatinib after once-weekly administration, achieved a deep molecular response at four and half years after the start of dasatinib treatment. The mean daily dose is 8.6 mg. Intermittent low dose dasatinib therapy appears to be feasible in elderly patients with CML-CP. The goal of treatment in elderly patients with CML-CP appears to be different from that in younger patients, since they often suffer from serious AEs in the case of standard dose tyrosine kinase inhibitor therapy, followed by the dose reduction or cessation of treatment.
{"title":"Long-term follow-up of efficacy and safety in elderly patients with chronic myeloid leukemia treated with intermittent low dose dasatinib therapy","authors":"Masahiro Imamura , Yusuke Nakamura , Daisuke Hidaka , Reiki Ogasawara , Kohei Okada , Junichi Sugita , Shuichi Ota","doi":"10.1016/j.lrr.2024.100452","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100452","url":null,"abstract":"<div><p>Intermittent low dose dasatinib therapy brought about a beneficial effect in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) without inducing severe adverse events (AEs). An 85-year-old male patient, who received twice-weekly, thrice-weekly, or four-times-weekly administration of 20 mg/day dasatinib after once-weekly administration, achieved a major molecular response two years after the start of dasatinib treatment and later sometimes achieved a deep molecular response, maintaining the efficacy for 11 years. The mean daily dose ranged from 5.7 mg to 11.4 mg. Furthermore, a 79-year-old male patient, who received thrice-weekly or every other day administration of 20 mg/day dasatinib after once-weekly administration, achieved a deep molecular response at four and half years after the start of dasatinib treatment. The mean daily dose is 8.6 mg. Intermittent low dose dasatinib therapy appears to be feasible in elderly patients with CML-CP. The goal of treatment in elderly patients with CML-CP appears to be different from that in younger patients, since they often suffer from serious AEs in the case of standard dose tyrosine kinase inhibitor therapy, followed by the dose reduction or cessation of treatment.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000426/pdfft?md5=462f4213710ba69f39849c2a008dab4a&pid=1-s2.0-S2213048924000426-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139992805","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.2024.100480
{"title":"Diagnostic challenges in classification of plasmacytoid dendritic cell proliferation associated with acute myeloid leukemia in the context of secondary-type mutations","authors":"","doi":"10.1016/j.lrr.2024.100480","DOIUrl":"10.1016/j.lrr.2024.100480","url":null,"abstract":"","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000700/pdfft?md5=3172dfc2a3e647cdf8499ed2843b484b&pid=1-s2.0-S2213048924000700-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271782","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.2024.100478
The t(10;17)(p15;q21) translocation is a very rare recurrent cytogenetic aberration, and produced ZMYND11::MBTD1 fusion gene. To date, nine cases of acute leukemia with the t(10;17)(p15;q21) translocation have been reported, but the case of AML with ZMYND11::MBTD1 after chemotherapy and radiotherapy have not been reported. Epirubicin-based chemotherapy or radiotherapy for breast cancer increases the risk of developing secondary leukemia. We report a case of AML with the ZMYND11::MBTD1 fusion gene that developed after epirubicin-based chemotherapy and radiotherapy for breast cancer. previous chemotherapy and radiotherapy may be associated with poor prognosis of AML with ZMYND11/MBTD1.
{"title":"Acute myeloid leukemia with a ZMYND11::MBTD1 fusion gene following chemotherapy and radiotherapy for breast cancer: A case report","authors":"","doi":"10.1016/j.lrr.2024.100478","DOIUrl":"10.1016/j.lrr.2024.100478","url":null,"abstract":"<div><p>The t(10;17)(p15;q21) translocation is a very rare recurrent cytogenetic aberration, and produced <em>ZMYND11::MBTD1</em> fusion gene. To date, nine cases of acute leukemia with the t(10;17)(p15;q21) translocation have been reported, but the case of AML with <em>ZMYND11::MBTD1</em> after chemotherapy and radiotherapy have not been reported. Epirubicin-based chemotherapy or radiotherapy for breast cancer increases the risk of developing secondary leukemia. We report a case of AML with the <em>ZMYND11::MBTD1</em> fusion gene that developed after epirubicin-based chemotherapy and radiotherapy for breast cancer. previous chemotherapy and radiotherapy may be associated with poor prognosis of AML with <em>ZMYND11/MBTD1</em>.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000682/pdfft?md5=ce7223922598a44c6fcf072460505d41&pid=1-s2.0-S2213048924000682-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049343","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.2024.100415
T. Maeda , A. Matsuda , J. Kanda , H. Kawabata , T. Ishikawa , K. Tohyama , A. Kitanaka , K. Araseki , K. Shimbo , T. Hata , T. Suzuki , H. Kayano , K. Usuki , M. Shindo-Ueda , N. Arima , M. Nohgawa , A. Ohta , S. Chiba , Y. Miyazaki , S. Nakao , K. Mitani
Introduction
While genetic aberrations are becoming increasingly critical in disease classification, morphological abnormalities defined by a 10% threshold in each lineage continue to play a significant role as a diagnostic tool for myelodysplastic neoplasms (MDS). However, erythroid lineage dysplasia has been reported in some cases of aplastic anemia (AA), a phenomenon noted as common in the UK guidelines.
Methods
We assessed the impact of erythroid dysplasia on the survival in AA patients enrolled in an ongoing prospective registry, central morphological review (blinded), and follow-up study of AA and MDS conducted by the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes. Furthermore, we compared the prognosis of AA patients with erythroid dysplasia with that of patients diagnosed in the same study with MDS presenting with single-lineage erythroid dysplasia (“MDS-SLED”). According to this study's definition, the criteria for excluding MDS are stringent, considering both bone marrow cellularity and megakaryocyte counts. Therefore, AA is not diagnosed when a decrease is not observed in the megakaryocyte count.
Results
The study included a total of 32 cases of AA with erythroid dysplasia, 56 cases of AA without dysplasia, and 47 cases of MDS-SLED. The overall survival or leukemia-free survival showed no significant difference between AA patients with and without erythroid dysplasia (both p=0.14). Nevertheless, distinct differences were seen between AA with erythroid dysplasia and those diagnosed with MDS-SLED (both p<0.0001).
Conclusions
Erythroid dysplasia should not exclude an AA diagnosis. In particular, megakaryocyte count plays an important role in differentiating between MDS from AA.
导言虽然基因畸变在疾病分类中变得越来越重要,但作为骨髓增生异常性肿瘤(MDS)的诊断工具,各系10%阈值定义的形态学异常仍发挥着重要作用。我们评估了红系发育不良对参加日本全国特发性骨髓衰竭综合征研究小组正在进行的前瞻性登记、中央形态学审查(盲法)以及 AA 和 MDS 随访研究的 AA 患者生存率的影响。此外,我们还将患有红细胞发育不良的 AA 患者的预后与同一研究中确诊的患有单系红细胞发育不良的 MDS("MDS-SLED")患者的预后进行了比较。根据该研究的定义,排除 MDS 的标准非常严格,既要考虑骨髓细胞性,又要考虑巨核细胞计数。因此,如果未观察到巨核细胞计数减少,则不能诊断为 AA。结果该研究共纳入 32 例伴红细胞发育不良的 AA 患者、56 例无发育不良的 AA 患者和 47 例 MDS-SLED 患者。有红细胞发育不良和无红细胞发育不良的AA患者的总生存率和无白血病生存率无明显差异(P均=0.14)。结论红细胞发育不良不应排除 AA 的诊断。结论红细胞发育不良不应排除 AA 的诊断,尤其是巨核细胞计数在区分 MDS 和 AA 方面起着重要作用。
{"title":"THE PROGNOSTIC IMPACT OF ERYTHROID DYSPLASIA IN APLASTIC ANEMIA AND MYELODYSPLASTIC NEOPLASMS WITH SINGLE-LINEAGE DYSPLASIA","authors":"T. Maeda , A. Matsuda , J. Kanda , H. Kawabata , T. Ishikawa , K. Tohyama , A. Kitanaka , K. Araseki , K. Shimbo , T. Hata , T. Suzuki , H. Kayano , K. Usuki , M. Shindo-Ueda , N. Arima , M. Nohgawa , A. Ohta , S. Chiba , Y. Miyazaki , S. Nakao , K. Mitani","doi":"10.1016/j.lrr.2024.100415","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100415","url":null,"abstract":"<div><h3>Introduction</h3><p>While genetic aberrations are becoming increasingly critical in disease classification, morphological abnormalities defined by a 10% threshold in each lineage continue to play a significant role as a diagnostic tool for myelodysplastic neoplasms (MDS). However, erythroid lineage dysplasia has been reported in some cases of aplastic anemia (AA), a phenomenon noted as common in the UK guidelines.</p></div><div><h3>Methods</h3><p>We assessed the impact of erythroid dysplasia on the survival in AA patients enrolled in an ongoing prospective registry, central morphological review (blinded), and follow-up study of AA and MDS conducted by the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes. Furthermore, we compared the prognosis of AA patients with erythroid dysplasia with that of patients diagnosed in the same study with MDS presenting with single-lineage erythroid dysplasia (“MDS-SLED”). According to this study's definition, the criteria for excluding MDS are stringent, considering both bone marrow cellularity and megakaryocyte counts. Therefore, AA is not diagnosed when a decrease is not observed in the megakaryocyte count.</p></div><div><h3>Results</h3><p>The study included a total of 32 cases of AA with erythroid dysplasia, 56 cases of AA without dysplasia, and 47 cases of MDS-SLED. The overall survival or leukemia-free survival showed no significant difference between AA patients with and without erythroid dysplasia (both p=0.14). Nevertheless, distinct differences were seen between AA with erythroid dysplasia and those diagnosed with MDS-SLED (both p<0.0001).</p></div><div><h3>Conclusions</h3><p>Erythroid dysplasia should not exclude an AA diagnosis. In particular, megakaryocyte count plays an important role in differentiating between MDS from AA.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000050/pdfft?md5=7573e4ade75876432a3b6af05c0b0267&pid=1-s2.0-S2213048924000050-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103396","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.2024.100419
J. Seo , C. Lee , Y. Koh , C.H. Sun , J.-M. Lee , H. An , M. Kim
Introduction
Accurate risk assessment of bone marrow failure syndrome (BMFS) is crucial for early diagnosis and intervention.
Methods
We used complete blood count (CBC) data to develop a predictive model for BMFS. Retrospective CBC data were collected from Seoul National University Hospital and Seoul St. Mary's Hospital of the Catholic Medical Center in South Korea. We developed binary classifiers for aplastic anaemia (AA) and myelodysplastic syndrome (MDS) and generated a BMFS classifier to determine the maximum probability. Classifiers were developed using multiple feature sets consisting of 13, 17, 25, or 28 CBC features to ensure applicability to various CBC testing settings. Performance was evaluated using the area under the receiver operating characteristic curve (AUROC).
Results
XGBoost achieved the best AUROCs, 0·953–0·961 for the AA classifier and 0·910–0·935 for the MDS classifier, across multiple CBC feature sets. The BMFS classifier, combining the AA and MDS classifiers, demonstrated an AUROC of 0·915–0·936. When using cut-off probabilities to achieve a 95% sensitivity, the specificities ranged from 68% to 79%. External validation on an independent dataset yielded an AUROC of 0·932–0·942, a sensitivity of 93–96%, and a specificity of 65–82% at the aforementioned cut-offs.
Conclusions
Our predictive model provides a practical guide for diagnosing BMFS based on basic demographics and CBC data available during the first clinical encounter. It provides a reliable risk assessment tool for primary physicians, facilitating a more effective triage, timely referrals, and improved patient care.
{"title":"MACHINE-LEARNING-BASED PREDICTIVE CLASSIFIER FOR BONE MARROW FAILURE SYNDROME USING COMPLETE BLOOD COUNT AND CELL POPULATION DATA","authors":"J. Seo , C. Lee , Y. Koh , C.H. Sun , J.-M. Lee , H. An , M. Kim","doi":"10.1016/j.lrr.2024.100419","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100419","url":null,"abstract":"<div><h3>Introduction</h3><p>Accurate risk assessment of bone marrow failure syndrome (BMFS) is crucial for early diagnosis and intervention.</p></div><div><h3>Methods</h3><p>We used complete blood count (CBC) data to develop a predictive model for BMFS. Retrospective CBC data were collected from Seoul National University Hospital and Seoul St. Mary's Hospital of the Catholic Medical Center in South Korea. We developed binary classifiers for aplastic anaemia (AA) and myelodysplastic syndrome (MDS) and generated a BMFS classifier to determine the maximum probability. Classifiers were developed using multiple feature sets consisting of 13, 17, 25, or 28 CBC features to ensure applicability to various CBC testing settings. Performance was evaluated using the area under the receiver operating characteristic curve (AUROC).</p></div><div><h3>Results</h3><p>XGBoost achieved the best AUROCs, 0·953–0·961 for the AA classifier and 0·910–0·935 for the MDS classifier, across multiple CBC feature sets. The BMFS classifier, combining the AA and MDS classifiers, demonstrated an AUROC of 0·915–0·936. When using cut-off probabilities to achieve a 95% sensitivity, the specificities ranged from 68% to 79%. External validation on an independent dataset yielded an AUROC of 0·932–0·942, a sensitivity of 93–96%, and a specificity of 65–82% at the aforementioned cut-offs.</p></div><div><h3>Conclusions</h3><p>Our predictive model provides a practical guide for diagnosing BMFS based on basic demographics and CBC data available during the first clinical encounter. It provides a reliable risk assessment tool for primary physicians, facilitating a more effective triage, timely referrals, and improved patient care.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000098/pdfft?md5=19ebce038be1abecd2d1fc4fb7c72b94&pid=1-s2.0-S2213048924000098-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103420","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.2024.100446
T. Yabushita , T. Chinen , D. Kitagawa , T. Kitamura , S. Goyama
Introduction
Decitabine (DAC) is an epigenetic drug clinically used for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, its exact mechanism of action is unclear.
Methods
To uncover the mechanisms underlying resistance to HMA, we performed genome-scale CRISPR activation screen using murine MDS/AML cells expressing ASXL1 and SETBP1 mutants (cSAM).
Results
Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. In addition, transcriptome and metabolome analyses combined with our screen revealed the involvement of cholesterol metabolism in DAC resistance. Inhibition of cholesterol synthesis using statins delayed mitotic progression, suggesting that cholesterol is also important for proper mitosis. Moreover, co-treatment with DAC and statin caused mitotic catastrophe and showed synergistic growth-inhibitory effects in leukemia cells.
Conclusions
These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.
{"title":"MITOTIC PERTURBATION IS A KEY MECHANISM OF ACTION OF DECITABINE IN MYELOID TUMOR TREATMENT","authors":"T. Yabushita , T. Chinen , D. Kitagawa , T. Kitamura , S. Goyama","doi":"10.1016/j.lrr.2024.100446","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100446","url":null,"abstract":"<div><h3>Introduction</h3><p>Decitabine (DAC) is an epigenetic drug clinically used for the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, its exact mechanism of action is unclear.</p></div><div><h3>Methods</h3><p>To uncover the mechanisms underlying resistance to HMA, we performed genome-scale CRISPR activation screen using murine MDS/AML cells expressing ASXL1 and SETBP1 mutants (cSAM).</p></div><div><h3>Results</h3><p>Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. In addition, transcriptome and metabolome analyses combined with our screen revealed the involvement of cholesterol metabolism in DAC resistance. Inhibition of cholesterol synthesis using statins delayed mitotic progression, suggesting that cholesterol is also important for proper mitosis. Moreover, co-treatment with DAC and statin caused mitotic catastrophe and showed synergistic growth-inhibitory effects in leukemia cells.</p></div><div><h3>Conclusions</h3><p>These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000360/pdfft?md5=2b1491f56cdd45cbc1b15efc15f2ef43&pid=1-s2.0-S2213048924000360-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103895","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}
An 82-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) complicated by hepatocarcinoma was presented. Remission induction therapy of hyper-CVAD with half dose reduction achieved hematological complete remission (CR), but accompanied with elevated alanine aminotransferase and hyperbilirubinemia. The patient was thought intolerable for hyper-CVAD with half dose reduction due to liver toxicity, and treatment was switched to blinatumomab. Hematological CR was sustained after nine cycles of blinatumomab without exacerbation of liver dysfunction. After five courses of blinatumomab, hepatocarcinoma was treated successfully by trans-arterial chemoembolization. Two years after the diagnosis of ALL, the patient was alive in CR status of ALL.
患者是一名 82 岁的男性,患有费城染色体阴性急性淋巴细胞白血病(ALL)并发肝癌。减半剂量的高CVAD缓解诱导治疗取得了血液学完全缓解(CR),但伴有丙氨酸氨基转移酶升高和高胆红素血症。由于肝脏毒性,该患者被认为不能耐受减半剂量的超CVAD治疗,因此改用blinatumomab治疗。经过9个周期的blinatumomab治疗后,血液学CR得以维持,肝功能异常没有加重。5个疗程的blinatumomab治疗后,经动脉化疗栓塞术成功治疗了肝癌。确诊为 ALL 两年后,患者仍以 ALL CR 状态存活。
{"title":"Successful treatment with blinatumomab for acute lymphoblastic leukemia in an older adult patient complicated with hepatocarcinoma","authors":"Masuho Saburi , Masanori Sakata , Rika Maruyama , Yousuke Kodama , Keiichi Uraisami , Hiroyuki Takata , Yasuhiko Miyazaki , Katsuya Kawano , Yasuhiro Kodama , Eiichi Ohtsuka","doi":"10.1016/j.lrr.2024.100413","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100413","url":null,"abstract":"<div><p>An 82-year-old man with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) complicated by hepatocarcinoma was presented. Remission induction therapy of hyper-CVAD with half dose reduction achieved hematological complete remission (CR), but accompanied with elevated alanine aminotransferase and hyperbilirubinemia. The patient was thought intolerable for hyper-CVAD with half dose reduction due to liver toxicity, and treatment was switched to blinatumomab. Hematological CR was sustained after nine cycles of blinatumomab without exacerbation of liver dysfunction. After five courses of blinatumomab, hepatocarcinoma was treated successfully by trans-arterial chemoembolization. Two years after the diagnosis of ALL, the patient was alive in CR status of ALL.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000037/pdfft?md5=37801a150130aa202f96391dc9459b77&pid=1-s2.0-S2213048924000037-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139694412","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.2024.100423
A. Shakirova, M. Latypova, T. Gindina, N. Mamaev
Introduction
The 5q- deletion is macrocytic anemia syndrome with special clinical characteristics and relatively longer median survival with low probability of AML progression. The classification of this disease as MDS is still under debates. Molecular studies, such as tracking the leukemia-associated marker BAALC, may clarify this issue. Here we evaluated BAALC-expressing stem cells (BAALC-e SCs) in patient's with isolated 5q- syndrome and with different chromosomal abnormalities.
Methods
The study includes analysis of bone marrow (BM) from 16 patients with isolated 5q deletion and 15 samples of 5q- combined with additional non-identical chromosomal abnormalities. BMs from 10 MDS patients without 5q- but carrying other cytogenetic aberrations were studied as control group. Serial measurements of BAALC-e SCs were performed by qPCR using BAALC RQ Kit (Inogene, Russia). Cytogenetic study included standard karyotyping and FISH.
Results
The data analysis revealed that only 10% (2/16) of patients with isolated 5q- had BAALC gene overexpression. Further on, low BAALC-expressing stem cells were characteristic also in the group of 5q- combined with additional non-identical chromosomal aberrations (56%). Meanwhile, in control group this rate was higher (100%).
Conclusions
The presented data of BAALC-e SCs burdens in patients with isolated 5q- syndrome indicate that this pathology differs from typical MDS and can be considered as ribosomopathy with low risk of transformation to MDS or AML. From this position, the biological advantages of 5q deletion syndrome are obvious as an optimal clinical model for further study of MDS and AML formation at the level of leukemia-initiating cells.
{"title":"NEW SHOWINGS OF 5Q- SYNDROME BASED ON SERIAL MEASUREMENTS OF BAALC-EXPRESSING STEM CELLS BURDEN IN BONE MARROW.","authors":"A. Shakirova, M. Latypova, T. Gindina, N. Mamaev","doi":"10.1016/j.lrr.2024.100423","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100423","url":null,"abstract":"<div><h3>Introduction</h3><p>The 5q- deletion is macrocytic anemia syndrome with special clinical characteristics and relatively longer median survival with low probability of AML progression. The classification of this disease as MDS is still under debates. Molecular studies, such as tracking the leukemia-associated marker <em>BAALC</em>, may clarify this issue. Here we evaluated <em>BAALC</em>-expressing stem cells (<em>BAALC</em>-e SCs) in patient's with isolated 5q- syndrome and with different chromosomal abnormalities.</p></div><div><h3>Methods</h3><p>The study includes analysis of bone marrow (BM) from 16 patients with isolated 5q deletion and 15 samples of 5q- combined with additional non-identical chromosomal abnormalities. BMs from 10 MDS patients without 5q- but carrying other cytogenetic aberrations were studied as control group. Serial measurements of <em>BAALC</em>-e SCs were performed by qPCR using BAALC RQ Kit (Inogene, Russia). Cytogenetic study included standard karyotyping and FISH.</p></div><div><h3>Results</h3><p>The data analysis revealed that only 10% (2/16) of patients with isolated 5q- had <em>BAALC</em> gene overexpression. Further on, low <em>BAALC</em>-expressing stem cells were characteristic also in the group of 5q- combined with additional non-identical chromosomal aberrations (56%). Meanwhile, in control group this rate was higher (100%).</p></div><div><h3>Conclusions</h3><p>The presented data of <em>BAALC</em>-e SCs burdens in patients with isolated 5q- syndrome indicate that this pathology differs from typical MDS and can be considered as ribosomopathy with low risk of transformation to MDS or AML. From this position, the biological advantages of 5q deletion syndrome are obvious as an optimal clinical model for further study of MDS and AML formation at the level of leukemia-initiating cells.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221304892400013X/pdfft?md5=418d9db7b324d20272e66defd848c656&pid=1-s2.0-S221304892400013X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103267","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.2024.100417
K. Albiroty, A. Al Mughairy
Introduction
SAMD9L mutation has been associated with hematological malignancies. The mutation has diverse hematological phenotypes ranging from Myelodysplastic syndrome (MDS) to Acute myeloid leukemia (AML)involving chromosome 7 aberration and recently described the emerging phenotype of aplastic anemia. We report two siblings with SAMD9L germline mutation born to asymptomatic consanguineous parents. each with different hematological phenotype.
Methods
Case #1: A 7- year old girl presented with thrombocytopenia & 4% peripheral blasts. She has no dysmorphic features . Family history is negative for hematological malignancies or BMF. She was diagnosed with MDS- Monomsomy7 . She transformed to AML over few weeks During this period her sibling presented with aplastic anemia, his (WES) revealed germline SAMD9L mutation which was detected in his sister . During chemotherapy of AED; there was interrupted due to septic shock so She was bridged with (Azacitadine + Venetoclax) prior to haploidentical BMT Case#2: A10- week old male presented with respiratory symptoms. He was diagnosed with Aplastic anemia and CMV pneumonitis .He was not dysmorphic WES revealed germline SAMD9L Mutation. although normal immunology workup, Natural Killer cell dysfunction was suspected based on SAMD9L mutation detection, early age of presentation, & resistant CMV-Viremia. He was treated for CMV infection and decided for haploidentical BMT
Results
We suggest to include SAMD9/SAMD9L in the standard AMLMDS genetic panel if additional system involved like immunodeficiency, neurological or genitourinary anomaly.
Conclusions
the heterogeneity of SAMD9L mutation even in family. High index of suspicious of this germline mutation is warranted in children with MDS.
{"title":"FAMILIAL SAMD9L MUTATION WWTH VARIABLE CLINICAL PHENOTYPE OF MDS/AML MONOSOMY 7 AND APLASTIC ANEMIA: A CASE OF TWO AFFECTED SIBLINGS..","authors":"K. Albiroty, A. Al Mughairy","doi":"10.1016/j.lrr.2024.100417","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100417","url":null,"abstract":"<div><h3>Introduction</h3><p>SAMD9L mutation has been associated with hematological malignancies. The mutation has diverse hematological phenotypes ranging from Myelodysplastic syndrome (MDS) to Acute myeloid leukemia (AML)involving chromosome 7 aberration and recently described the emerging phenotype of aplastic anemia. We report two siblings with SAMD9L germline mutation born to asymptomatic consanguineous parents. each with different hematological phenotype.</p></div><div><h3>Methods</h3><p>Case #1: A 7- year old girl presented with thrombocytopenia & 4% peripheral blasts. She has no dysmorphic features . Family history is negative for hematological malignancies or BMF. She was diagnosed with MDS- Monomsomy7 . She transformed to AML over few weeks During this period her sibling presented with aplastic anemia, his (WES) revealed germline SAMD9L mutation which was detected in his sister . During chemotherapy of AED; there was interrupted due to septic shock so She was bridged with (Azacitadine + Venetoclax) prior to haploidentical BMT Case#2: A10- week old male presented with respiratory symptoms. He was diagnosed with Aplastic anemia and CMV pneumonitis .He was not dysmorphic WES revealed germline SAMD9L Mutation. although normal immunology workup, Natural Killer cell dysfunction was suspected based on SAMD9L mutation detection, early age of presentation, & resistant CMV-Viremia. He was treated for CMV infection and decided for haploidentical BMT</p></div><div><h3>Results</h3><p>We suggest to include SAMD9/SAMD9L in the standard AMLMDS genetic panel if additional system involved like immunodeficiency, neurological or genitourinary anomaly.</p></div><div><h3>Conclusions</h3><p>the heterogeneity of SAMD9L mutation even in family. High index of suspicious of this germline mutation is warranted in children with MDS.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000074/pdfft?md5=9fe5ef3a9e359bef1eab407e716570b4&pid=1-s2.0-S2213048924000074-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103418","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.2024.100436
N. Takasugi , A. Sato , K. Koh , A. Nakazawa , M. Kato
Introduction
Somatic or germline mutations in genes regulating Ras-MAPK pathway have been identified in majority of Juvenile myelomonocytic leukemia (JMML) cases. Mosaicism of KRAS and NRAS mutations in JMML were reported, with variation in the proportion of cells carrying these mutations across different organs. However, how this proportion is distributed across different organs had not been clarified whereas prevalence of somatic oncogenic KRAS mutations are known.
Methods
Our study focused on one JMML patient with mosaic KRAS G12D mutation and uniparental disomy at the 12p locus, who developed aggressive transformation, invasion into multiple organs and subsequently died. DNA from FFPE biopsy samples of eighteen organs were analyzed using mutation-specific digital PCR (dPCR). The variant allele frequency (VAF) of KRAS G12D and hetero SNP at the 12p locus were analyzed in each samples to remove the impact of mutation by infiltrating tumor cells and to estimate the percentage of KRAS mutant cells.
Results
KRAS G12D mutations were identified in samples from sixteen of eighteen analyzed tissues. The frequency of KRAS G12D mutated alleles varied among different tissue type and the median VAF was 5.9% (2.0% -29.3%). The VAF were relatively high in gastrointestinal tract (stomach, colon, ileum), liver and spleen, whereas the VAF were low or undetected in testis, heart and spinal cord.
Conclusions
Our findings suggest that KRAS mosaic mutations can exhibit tissue specificity like somatic oncogenic mutations. These tissue distribution might be associated with pathogenesis of JMML and other types of cancer with mosaicism.
{"title":"KRAS MOSAIC MUTATION AND ITS TISSUE SPECIFICITY IN JUVENILE MYELOMONOCYTIC LEUKEMIA","authors":"N. Takasugi , A. Sato , K. Koh , A. Nakazawa , M. Kato","doi":"10.1016/j.lrr.2024.100436","DOIUrl":"https://doi.org/10.1016/j.lrr.2024.100436","url":null,"abstract":"<div><h3>Introduction</h3><p>Somatic or germline mutations in genes regulating Ras-MAPK pathway have been identified in majority of Juvenile myelomonocytic leukemia (JMML) cases. Mosaicism of <em>KRAS</em> and <em>NRAS</em> mutations in JMML were reported, with variation in the proportion of cells carrying these mutations across different organs. However, how this proportion is distributed across different organs had not been clarified whereas prevalence of somatic oncogenic <em>KRAS</em> mutations are known.</p></div><div><h3>Methods</h3><p>Our study focused on one JMML patient with mosaic <em>KRAS</em> G12D mutation and uniparental disomy at the 12p locus, who developed aggressive transformation, invasion into multiple organs and subsequently died. DNA from FFPE biopsy samples of eighteen organs were analyzed using mutation-specific digital PCR (dPCR). The variant allele frequency (VAF) of <em>KRAS</em> G12D and hetero SNP at the 12p locus were analyzed in each samples to remove the impact of mutation by infiltrating tumor cells and to estimate the percentage of <em>KRAS</em> mutant cells.</p></div><div><h3>Results</h3><p><em>KRAS</em> G12D mutations were identified in samples from sixteen of eighteen analyzed tissues. The frequency of <em>KRAS</em> G12D mutated alleles varied among different tissue type and the median VAF was 5.9% (2.0% -29.3%). The VAF were relatively high in gastrointestinal tract (stomach, colon, ileum), liver and spleen, whereas the VAF were low or undetected in testis, heart and spinal cord.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that <em>KRAS</em> mosaic mutations can exhibit tissue specificity like somatic oncogenic mutations. These tissue distribution might be associated with pathogenesis of JMML and other types of cancer with mosaicism.</p></div>","PeriodicalId":38435,"journal":{"name":"Leukemia Research Reports","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213048924000268/pdfft?md5=75171d6574de57b01fac22c459f88044&pid=1-s2.0-S2213048924000268-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140103878","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}