Gupta Dikshat Gopal, Varma Neelam, Sharma Praveen, Truica Mihai I, Abdulkadir Sarki A, Singh Parmod, Singh Sachdeva Man Updesh, Naseem Shano, Siddiqui Mohammad Rizwan, Bose Parveen, Binota Jogeshwar, Malhotra Pankaj, Khadwal Alka, Trehan Amita, Varma Subhash
Department of Urology and Pathology, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Cancer. 2023 Nov 1;129(21):3390-3404. doi: 10.1002/cncr.34957. Epub 2023 Jul 27.
The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced.
The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n = 1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL.
Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p < .05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p < .05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p < .05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p < .05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p < .05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance.
The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India.
Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n = 1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p < .05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p < .05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.
低收入国家关于急性淋巴细胞白血病（ALL）预后重要基因亚型的血液学、临床、流式细胞术免疫表型及微小残留病结果的已发表文献稀缺。对于诸如BCR::ABL1样ALL等新分类，患者层面数据的稀缺更为明显。
作者对复发性基因融合和BCR::ABL1样ALL病例进行了全面检测，随后进行免疫表型分析，并获得了来自印度的一大队列（n = 1021）患者的临床结局参数。该队列包括大量BCR::ABL1样ALL亚型和ALL其他基因亚型的患者。
与BCR::ABL1阴性病例相比，BCR::ABL1阳性和BCR::ABL1样ALL患者年龄显著更大，男性占优势，白细胞计数更高（p <.05）。B系ALL（B-ALL）亚型的逻辑回归模型显示，分化簇（CD）36是BCR::ABL1样ALL的一个具有统计学显著意义的强预测标志物（p <.05）。此外，与BCR::ABL1阴性ALL相比，BCR::ABL1样ALL患者CD36表达频率显著更高（p <.05）。在临床症状方面，与BCR::ABL1阴性ALL病例相比，淋巴结病是BCR::ABL1样ALL中一个具有统计学显著意义的强预测标志物（p <.05）。在治疗结局方面，BCR::ABL1阳性ALL病例中的微小残留病（MRD）阳性具有统计学意义（p <.05），与BCR::ABL1阴性ALL病例相比，BCR::ABL1样ALL病例的MRD阳性率较高，但未显示出统计学意义。
研究结果表明应采用新疗法和个性化治疗方案来提高B-ALL中新纳入实体的总生存率。这是第一份描述印度患者中ALL预后重要亚型的血液学、临床、流式细胞术免疫表型及微小残留病结果的报告。
描述来自印度的急性淋巴细胞白血病（ALL，n = 1021）预后重要亚型的血液学、临床、流式细胞术免疫表型及微小残留病结果。我们建立了两个关于分化簇（CD）标志物和临床症状的独立逻辑回归模型，以区分ALL的预后重要亚型。CD标志物的逻辑回归分析显示，与BCR::ABL1阴性ALL病例相比，CD36是BCR::ABL1样ALL病例的一个强预测指标。临床症状的逻辑回归分析显示，淋巴结病显著预测BCR::ABL1样ALL（p <.05）。在治疗结局方面，BCR::ABL1阳性ALL的微小残留病（MRD）具有统计学意义（p <.05），与BCR::ABL1阴性ALL相比，BCR::ABL样ALL病例的MRD阳性率较高，但未显示出统计学意义。
