{"title":"Nivolumab for CNS relapsed refractory primary mediastinal B-cell lymphoma: case report and review of the literature.","authors":"Adir Shaulov, Noa Gross Even-Zohar, Shlomzion Aumann, Arnon Haran, Eduard Linetsky","doi":"10.1080/10428194.2024.2396043","DOIUrl":"https://doi.org/10.1080/10428194.2024.2396043","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126120","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}
Pub Date : 2024-09-02DOI: 10.1080/10428194.2024.2398660
Marina Deodato, Anna Maria Frustaci, Arianna Zappaterra, Alberto Rapella, Carlo Gambacorti-Passerini, Roberto Cairoli, Marco Montillo, Alessandra Tedeschi
Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in ∼80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation-such as TP53, NOTCH1, MYC, CDKN2A-confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents.
里氏转化(RT)是指慢性淋巴细胞白血病(CLL)或小淋巴细胞淋巴瘤(SLL)演变为侵袭性淋巴瘤,最常见的是弥漫大 B 细胞淋巴瘤。这种并发症罕见且具有侵袭性,预后差,生存率低。80%的病例与潜在的 CLL/SLL 存在克隆关系,这是影响预后的主要因素之一。治疗方法历来以化学免疫疗法为主,但参与细胞存活和增殖的基因(如 TP53、NOTCH1、MYC、CDKN2A)经常发生突变,从而对标准疗法产生耐药性。在过去几年中,人们对 RT 的生物学机制有了进一步的了解,从而确定了新型选择性药物可能针对的基因和分子病变。通路和检查点抑制剂、双特异性抗体和 CAR T 细胞疗法目前正在研究中,是很有前景的治疗方案。本综述总结了目前有关新型治疗药物的生物学证据和现有数据。
{"title":"Advances in the understanding of molecular genetics and therapy of Richter transformation in chronic lymphocytic leukemia.","authors":"Marina Deodato, Anna Maria Frustaci, Arianna Zappaterra, Alberto Rapella, Carlo Gambacorti-Passerini, Roberto Cairoli, Marco Montillo, Alessandra Tedeschi","doi":"10.1080/10428194.2024.2398660","DOIUrl":"https://doi.org/10.1080/10428194.2024.2398660","url":null,"abstract":"<p><p>Richter's transformation (RT) is defined as the evolution of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This complication is rare and aggressive, with poor prognosis and dismal survival. Clonal relationship with the underlying CLL/SLL, observed in ∼80% of cases, represents one of the main factors affecting prognosis. Treatment has been historically based on chemoimmunotherapy, but frequent mutations in genes involved in cell survival and proliferation-such as TP53, NOTCH1, MYC, CDKN2A-confer resistance to standard treatments. During the last years, advances in the knowledge of the biological mechanisms underlying RT allowed to identify genetic and molecular lesions that can potentially be targeted by novel selective agents. Pathway and checkpoint inhibitors, bispecific antibodies and CAR T-cell therapy are currently under investigation and represent promising treatment options. This review summarizes current biological evidence and available data on novel therapeutic agents.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108897","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}
Pub Date : 2024-09-01Epub Date: 2024-05-13DOI: 10.1080/10428194.2024.2353434
Alexander Coltoff, Andrew Kuykendall
Dysregulated JAK/STAT hyperactivity is essential to the pathogenesis of myelofibrosis, and JAK inhibitors are the first-line treatment option for many patients. There are four FDA-approved JAK inhibitors for patients with myelofibrosis. Single-agent JAK inhibition can improve splenomegaly, symptom burden, cytopenias, and possibly survival in patients with myelofibrosis. Despite their efficacy, JAK inhibitors produce variable or short-lived responses, in part due to the large network of cooperating signaling pathways and downstream targets of JAK/STAT, which mediates upfront or acquired resistance to JAK inhibitors. Synergistic inhibition of JAK/STAT accessory pathways can increase the rates and duration of response for patients with myelofibrosis. Two recently reported, placebo-controlled phase III trials of novel agents added to JAK inhibition met their primary endpoint, and additional late-stage studies are ongoing. This paper will review role of dysregulated JAK/STAT signaling, biological plausible additional therapeutic targets and the recent advancements in combination strategies with JAK inhibitors for myelofibrosis.
JAK/STAT活性失调是骨髓纤维化发病机制的关键,JAK抑制剂是许多患者的一线治疗选择。目前有四种 JAK 抑制剂获 FDA 批准用于骨髓纤维化患者。单药 JAK 抑制剂可改善骨髓纤维化患者的脾脏肿大、症状负担、细胞减少症,并可能改善患者的存活率。尽管疗效显著,但JAK抑制剂产生的反应不一或持续时间较短,部分原因是JAK/STAT的信号通路和下游靶点之间存在庞大的合作网络,从而导致患者对JAK抑制剂产生前期或获得性耐药性。协同抑制 JAK/STAT 辅助通路可提高骨髓纤维化患者的应答率并延长应答时间。最近报道的两项在JAK抑制剂基础上添加新型药物的安慰剂对照III期试验达到了主要终点,其他后期研究正在进行中。本文将综述JAK/STAT信号传导失调的作用、生物学上可信的其他治疗靶点,以及近期骨髓纤维化与JAK抑制剂联合治疗策略的进展。
{"title":"Emerging drug profile: JAK inhibitors.","authors":"Alexander Coltoff, Andrew Kuykendall","doi":"10.1080/10428194.2024.2353434","DOIUrl":"10.1080/10428194.2024.2353434","url":null,"abstract":"<p><p>Dysregulated JAK/STAT hyperactivity is essential to the pathogenesis of myelofibrosis, and JAK inhibitors are the first-line treatment option for many patients. There are four FDA-approved JAK inhibitors for patients with myelofibrosis. Single-agent JAK inhibition can improve splenomegaly, symptom burden, cytopenias, and possibly survival in patients with myelofibrosis. Despite their efficacy, JAK inhibitors produce variable or short-lived responses, in part due to the large network of cooperating signaling pathways and downstream targets of JAK/STAT, which mediates upfront or acquired resistance to JAK inhibitors. Synergistic inhibition of JAK/STAT accessory pathways can increase the rates and duration of response for patients with myelofibrosis. Two recently reported, placebo-controlled phase III trials of novel agents added to JAK inhibition met their primary endpoint, and additional late-stage studies are ongoing. This paper will review role of dysregulated JAK/STAT signaling, biological plausible additional therapeutic targets and the recent advancements in combination strategies with JAK inhibitors for myelofibrosis.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916693","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}
Pub Date : 2024-09-01Epub Date: 2024-06-02DOI: 10.1080/10428194.2024.2350670
Charlotte B Wagner, Kelley Julian, Baylee Bryan, Mary N Steinbach, Samuel Shewan, Lindsay Maxwell, Meghan Vigil, Ghulam Rehman Mohyuddin, Amandeep Godara, Brian McClune, Glicelda Galarza Fortuna, Douglas Sborov
{"title":"Novel chemotherapy combination of carfilzomib with dexamethasone, cyclophosphamide, etoposide and cisplatin (K-DCEP) for the treatment of relapsed/refractory aggressive plasma cell dyscrasias.","authors":"Charlotte B Wagner, Kelley Julian, Baylee Bryan, Mary N Steinbach, Samuel Shewan, Lindsay Maxwell, Meghan Vigil, Ghulam Rehman Mohyuddin, Amandeep Godara, Brian McClune, Glicelda Galarza Fortuna, Douglas Sborov","doi":"10.1080/10428194.2024.2350670","DOIUrl":"10.1080/10428194.2024.2350670","url":null,"abstract":"","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200263","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}
Pub Date : 2024-09-01Epub Date: 2024-05-11DOI: 10.1080/10428194.2024.2347577
Cassandra P Wang, Juanita E Ferreira, Alexander Placek, Paibel Aguayo-Hiraldo, Gordana Raca, Brent L Wood, Karin P Miller, Thomas Coates, David R Freyer, Alexandra E Kovach
Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.
RUNX1 基因的种系变异与 RUNX1 家族性血小板紊乱伴骨髓恶性肿瘤(RUNX1-FPDMM)有关,其特点是罹患骨髓增生异常综合征(MDS)和/或急性髓系白血病的风险增加。据描述,FPDMM 患者还可能罹患 B 细胞或 T 细胞急性淋巴细胞白血病。我们介绍了一名患有RUNX1-FPDMM的儿科患者,经过十年的连续血细胞计数监测,该患者演变为并发MDS和T细胞急性淋巴细胞白血病。我们旨在强调这种独特疾病可能面临的治疗挑战和临床决策,以及异基因造血干细胞移植在首次完全缓解中的潜在治疗作用。
{"title":"A <i>de novo</i> germline <i>RUNX1</i> variant preceding development of concurrent T-lymphoblastic leukemia and myelodysplastic syndrome.","authors":"Cassandra P Wang, Juanita E Ferreira, Alexander Placek, Paibel Aguayo-Hiraldo, Gordana Raca, Brent L Wood, Karin P Miller, Thomas Coates, David R Freyer, Alexandra E Kovach","doi":"10.1080/10428194.2024.2347577","DOIUrl":"10.1080/10428194.2024.2347577","url":null,"abstract":"<p><p>Germline variants of the RUNX1 gene are associated with RUNX1 Familial Platelet Disorder with Associated Myeloid Malignancies (RUNX1-FPDMM), which is characterized by an increased risk of developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. Patients with FPDMM have also been described to develop B- or T-cell acute lymphoblastic leukemia. We present a pediatric patient with RUNX1-FPDMM that evolved into concurrent MDS and T-cell acute lymphoblastic leukemia after a decade of monitoring with serial blood counts. We aim to highlight the treatment challenges and clinical decision-making that may be anticipated in this unique disorder, as well as the potentially curative role for allogenic hematopoietic stem cell transplant in the first complete remission.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909187","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}
Pub Date : 2024-09-01Epub Date: 2024-05-15DOI: 10.1080/10428194.2024.2349700
Jennifer Marvin-Peek, Wei-Ying Jen, Hagop M Kantarjian, David McCue, Fadi G Haddad, William Wierda, Alessandra Ferrajoli, Jan Burger, Tareq Abusab, Jeffrey Jorgensen, Sa A Wang, Keyur Patel, Sanam Loghavi, Susan O'Brien, Farhad Ravandi
We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40-18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (p = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings.
{"title":"Long-term results of the sequential combination of cladribine and rituximab in Hairy cell leukemia.","authors":"Jennifer Marvin-Peek, Wei-Ying Jen, Hagop M Kantarjian, David McCue, Fadi G Haddad, William Wierda, Alessandra Ferrajoli, Jan Burger, Tareq Abusab, Jeffrey Jorgensen, Sa A Wang, Keyur Patel, Sanam Loghavi, Susan O'Brien, Farhad Ravandi","doi":"10.1080/10428194.2024.2349700","DOIUrl":"10.1080/10428194.2024.2349700","url":null,"abstract":"<p><p>We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event-free survival (EFS) or overall survival (OS). With a median follow-up of 7.8 years (range: 0.40-18.8), eight patients have experienced disease relapse (5.8%), 4/111 with newly diagnosed HCL (3·6%) and 4/10 with HCLv (40%) (<i>p</i> = 0.002). The 10-year EFS and OS rates were 86.7% and 91.1%, respectively. Grade 3 adverse events were observed in 28 participants (20·1%), mostly due to infections. Treatment of HCL with sequential cladribine followed by rituximab is associated with excellent efficacy and safety results both in the frontline and relapsed settings.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945123","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}
Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.
{"title":"RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma.","authors":"Yuji Kobayashi, Koji Ando, Yoshitaka Imaizumi, Hikaru Sakamoto, Hideaki Kitanosono, Masataka Taguchi, Hiroyuki Mishima, Akira Kinoshita, Shara Bekytbek, Maki Baba, Takeharu Kato, Makiko Horai, Hidehiro Itonaga, Shinya Sato, Koh-Ichiro Yoshiura, Yasushi Miyazaki","doi":"10.1080/10428194.2024.2393258","DOIUrl":"https://doi.org/10.1080/10428194.2024.2393258","url":null,"abstract":"<p><p>Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed <i>RUNX1</i>expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC<sub>50</sub>s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying <i>RUNX1</i> mutations. In the present study, we demonstrated that IC<sub>50</sub>s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes <i>c-MYC</i> expression. We showed that RUNX1 expression is regulated <i>via</i> SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108899","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}
The tumor microenvironment's cells can promote or inhibit tumor formation, and there are no reports on the CD4/CD8 ratio's association with outcomes post allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the pre-transplant peripheral blood CD4/CD8 ratio in 168 patients who underwent their first allo-HSCT for hematological malignancies at our institution. When patients were divided into two groups according to the median CD4/CD8 ratio 1.35 (range, 0.09-19.89), the high CD4/CD8 ratio group had a higher incidence of relapse, equivalent non-relapse mortality and worse overall survival (OS) than the low CD4/CD8 ratio group. In a multivariate analysis, the CD4/CD8 ratio was significantly associated with an increased risk of relapse, although there was a marginally significant difference in OS. The pre-transplant peripheral blood CD4/CD8 ratio could be a novel biomarker for predicting the prognosis of allo-HSCT.
{"title":"Association of the pre-transplant CD4/CD8 ratio with the prognosis following allogeneic hematopoietic stem cell transplantation.","authors":"Takashi Nagayama, Shin-Ichiro Fujiwara, Ryutaro Tominaga, Daizo Yokoyama, Atsuto Noguchi, Shuka Furuki, Takashi Oyama, Shunsuke Koyama, Rui Murahashi, Hirotomo Nakashima, Takashi Ikeda, Kazuki Hyodo, Shin-Ichiro Kawaguchi, Yumiko Toda, Kento Umino, Daisuke Minakata, Kaoru Morita, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Ken Ohmine, Yoshinobu Kanda","doi":"10.1080/10428194.2024.2352614","DOIUrl":"10.1080/10428194.2024.2352614","url":null,"abstract":"<p><p>The tumor microenvironment's cells can promote or inhibit tumor formation, and there are no reports on the CD4/CD8 ratio's association with outcomes post allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the pre-transplant peripheral blood CD4/CD8 ratio in 168 patients who underwent their first allo-HSCT for hematological malignancies at our institution. When patients were divided into two groups according to the median CD4/CD8 ratio 1.35 (range, 0.09-19.89), the high CD4/CD8 ratio group had a higher incidence of relapse, equivalent non-relapse mortality and worse overall survival (OS) than the low CD4/CD8 ratio group. In a multivariate analysis, the CD4/CD8 ratio was significantly associated with an increased risk of relapse, although there was a marginally significant difference in OS. The pre-transplant peripheral blood CD4/CD8 ratio could be a novel biomarker for predicting the prognosis of allo-HSCT.</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065850","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}
Pub Date : 2024-09-01Epub Date: 2024-05-06DOI: 10.1080/10428194.2024.2344060
Peter A von dem Borne, Berit M Kemps-Mols, Liesbeth C de Wreede, Adriaan A van Beek, Tjeerd J F Snijders, Daniëlle van Lammeren, Janneke Tijmensen, Aniko Sijs-Szabó, Mirjam A Oudshoorn, Constantijn J M Halkes, Peter van Balen, W A Erik Marijt, Jennifer M L Tjon, Joost S P Vermaat, Hendrik Veelken
Cytokine release syndrome (CRS) occurs frequently after haplo-identical allogeneic stem cell transplantation (alloSCT) with post-transplant cyclophosphamide (PTCy), increasing nonrelapse mortality (NRM) and decreasing survival. Data on CRS in HLA-matched alloSCT are limited and effects of specific HLA-mismatches on CRS development unknown. We hypothesized that in HLA-matched alloSCT increasing degrees of HLA-mismatching influence CRS incidence, NRM and survival. Retrospective analysis of 126 HLA-matched PTCy-alloSCT patients showed that higher degrees of HLA-mismatching significantly increased CRS incidence (26%, 75% and 90% CRS with 12/12, 10/10 and 9/10 matched donors, respectively). Maximum temperature during CRS increased with higher HLA-mismatch. Specific associations between HLA-mismatches and CRS could be determined. Grade 2 CRS and CRS-induced grade 3 fever were associated with significantly increased NRM (p < 0.001 and p = 0.003, respectively) and inferior survival (p < 0.001 and p = 0.005, respectively). NRM was mainly caused by disease conditions that may be considered CRS-induced inflammatory responses (encephalopathy, cryptogenic organizing pneumonia and multi-organ failure).
单倍体同种异体干细胞移植(alloSCT)后,移植后环磷酰胺(PTCy)会经常出现细胞因子释放综合征(CRS),增加非复发死亡率(NRM),降低存活率。有关HLA匹配异体干细胞移植中CRS的数据有限,特定HLA错配对CRS发展的影响尚不清楚。我们假设,在 HLA 匹配的异体干细胞移植中,HLA 错配程度的增加会影响 CRS 的发生率、NRM 和存活率。对126例HLA匹配的PTCy-alloSCT患者进行的回顾性分析表明,HLA不匹配程度越高,CRS发生率越高(12/12、10/10和9/10匹配供者的CRS发生率分别为26%、75%和90%)。CRS期间的最高体温随HLA错配程度的升高而升高。HLA错配与CRS之间的具体关系可以确定。2 级 CRS 和 CRS 引起的 3 级发热与 NRM 的显著增加(分别为 p p = 0.003)和存活率的降低(分别为 p p = 0.005)有关。NRM主要由可被视为CRS诱发炎症反应的疾病状况(脑病、隐源性有组织肺炎和多器官功能衰竭)引起。
{"title":"The degree of HLA matching determines the incidence of cytokine release syndrome and associated nonrelapse mortality in matched related and unrelated allogeneic stem cell transplantation with post-transplant cyclophosphamide.","authors":"Peter A von dem Borne, Berit M Kemps-Mols, Liesbeth C de Wreede, Adriaan A van Beek, Tjeerd J F Snijders, Daniëlle van Lammeren, Janneke Tijmensen, Aniko Sijs-Szabó, Mirjam A Oudshoorn, Constantijn J M Halkes, Peter van Balen, W A Erik Marijt, Jennifer M L Tjon, Joost S P Vermaat, Hendrik Veelken","doi":"10.1080/10428194.2024.2344060","DOIUrl":"10.1080/10428194.2024.2344060","url":null,"abstract":"<p><p>Cytokine release syndrome (CRS) occurs frequently after haplo-identical allogeneic stem cell transplantation (alloSCT) with post-transplant cyclophosphamide (PTCy), increasing nonrelapse mortality (NRM) and decreasing survival. Data on CRS in HLA-matched alloSCT are limited and effects of specific HLA-mismatches on CRS development unknown. We hypothesized that in HLA-matched alloSCT increasing degrees of HLA-mismatching influence CRS incidence, NRM and survival. Retrospective analysis of 126 HLA-matched PTCy-alloSCT patients showed that higher degrees of HLA-mismatching significantly increased CRS incidence (26%, 75% and 90% CRS with 12/12, 10/10 and 9/10 matched donors, respectively). Maximum temperature during CRS increased with higher HLA-mismatch. Specific associations between HLA-mismatches and CRS could be determined. Grade 2 CRS and CRS-induced grade 3 fever were associated with significantly increased NRM (<i>p</i> < 0.001 and <i>p</i> = 0.003, respectively) and inferior survival (<i>p</i> < 0.001 and <i>p</i> = 0.005, respectively). NRM was mainly caused by disease conditions that may be considered CRS-induced inflammatory responses (encephalopathy, cryptogenic organizing pneumonia and multi-organ failure).</p>","PeriodicalId":18047,"journal":{"name":"Leukemia & Lymphoma","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858883","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}