Cytogenetics-based risk prediction of blastic transformation of chronic myeloid leukemia in the era of TKI therapy.

Despite the success of BCR‐ABL‐specific tyrosine kinase inhibitors (TKIs) such as imatinib in chronic phase (CP) chronic myeloid leukaemia (CML), patients with blast phase (BP)‐CML continue to have a dismal outcome with median survival of less than one year from diagnosis. Thus BP‐CML remains a critical unmet clinical need in the management of CML. Our understanding of the biology of BP‐CML continues to grow; genomic instability leads to acquisition of mutations which drive leukaemic progenitor cells to develop self‐renewal properties, resulting in differentiation block and a poor‐prognosis acute leukaemia which may be myeloid, lymphoid or bi‐phenotypic. Similar advances in therapy are urgently needed to improve patient outcomes; however, this is challenging given the rarity and heterogeneity of BP‐CML, leading to difficulty in designing and recruiting to prospective clinical trials. This review will explore the treatment of BP‐CML, evaluating the data for TKI therapy alone, combinations with intensive chemotherapy, the role of allogeneic haemopoietic stem cell transplantation, the use of novel agents and clinical trials, as well as discussing the most appropriate methods for diagnosing BP and assessing response to therapy, and factors predicting outcome.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.18370

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

Chronic myeloid leukemia (CML) is a slow-growing type of cancer that originates in the blood-forming cells of the bone marrow and is caused by a chromosomal mutation that is thought to occur spontaneously. CML could potentially lead to the development of myeloid sarcoma (MS), which is a rare neoplasm composed of immature myeloid cells that could evolve into a tumor mass at any anatomical site other than the bone marrow. MS can develop spontaneously or as a result of another form of myeloid neoplasm. Most instances of CML precede blast phase (BP) within two to three years after the first diagnosis of CML chronic phase (CP) at the age of pre-tyrosine kinase inhibitor (TKI) treatment. MS developing in CML patients during the era of TKI treatment is infrequently mentioned in the literature, primarily in single-case studies. As a result, the prognostic influence of MS in CML patients has not been well investigated. In the age of TKI treatment, it is uncertain whether MS and medullary BP have comparable clinical and prognostic relevance. The precise diagnosis of MS is critical for effective treatment, which is frequently delayed due to a high risk of misdiagnosis. This review focuses on the relationship between the development of MS from CML, and it culminates with recommendations for future hematology practice. A literature search was conducted in multiple databases, and the studies were appraised based on the inclusion and exclusion criteria. Finally, studies to date have shown that the existence of CML and its possible progression to MS in individuals map out the numerous implications this disease has in hematology practice. Though occurrences are uncommon in general, the prognosis for patients is bleak, necessitating the exploration and implementation of diagnostic and therapy advancements. Because there is limited evidence in the literature on its existence in the medullary chronic phase and outcomes in the era of TKI, it must be carefully investigated because it might be the first symptom of progressive illness prior to hematological progression.

/pdf/the-progression-of-chronic-myeloid-leukemia-to-myeloid-8hmhcp6t.pdf

The Progression of Chronic Myeloid Leukemia to Myeloid Sarcoma: A Systematic Review

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.

Myeloid sarcoma: an uncommon presentation of myeloid neoplasms; a case series of 4 rare cases reported in a tertiary care institute.

Background Myeloid sarcoma (MS) is a rare hematological tumor that presents with extramedullary tumor masses comprising myeloid blasts. A controversial issue is whether MS involving normal hematopoietic sites (liver, spleen, and lymph nodes) should be excluded in future studies. We aimed to compare MS characteristics and outcomes involving hematopoietic and non-hematopoietic sites and construct a prognostic nomogram exclusively for the latter. Methods Data from patients diagnosed with MS between 2000 and 2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. According to the primary site, patients were classified as having MS involving hematopoietic sites (hMS) or non-hematopoietic sites (eMS). Clinical characteristics and survival outcomes were compared between the two groups using Wilcoxon, chi-square, and log-rank tests. Cox regression analysis was used to identify eMS prognostic factors to establish prognostic nomograms. The models’ efficiency and value were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results In total, 694 patients were enrolled, including 86 with hMS and 608 with eMS. There were no sex, race or marital status distribution differences between the two groups. Patients with eMS had better overall and cancer-specific survival rates than those with hMS. Additionally, prognostic factor effects differed between the two groups. Patients with eMS were randomly divided into the training (number of patiens, n=425) and validation cohorts (n=183). Age, first primary tumor, primary site, and chemotherapy were used to establish nomograms. The C-index values of overall survival (OS) and cancer-specific survival (CSS) nomograms were 0.733 (validation: 0.728) and 0.722 (validation: 0.717), respectively. Moreover, ROC, calibration curves, and DCA confirmed our models’ good discrimination and calibration ability and potential clinical utility value. Conclusion Our study described the differences between patients with eMS and those with hMS. Moreover, we developed novel nomograms based on clinical and therapeutic factors to predict patients with eMS’ 1-, 3- and 5-year survival rates.

https://www.frontiersin.org/articles/10.3389/fonc.2022.989366/pdf

Incidence, clinical characteristics, and prognostic nomograms for patients with myeloid sarcoma: A SEER-based study

Myeloid sarcoma (MS) is a rare neoplasm consisting of immature myeloid cells that forms a tumor mass at an anatomic site other than the bone marrow (BM).1 MS may develop de novo or secondary to other types of myeloid neoplasm. MS is most often associated with acute myeloid leukemia (AML), and develops in 2–5% of AML patients.2, 3 Less frequently, MS can arise in patients with chronic myelogenous leukemia (CML), mainly in the setting of blast phase (BP) or accelerated phase (AP).3, 4, 5 Traditionally, MS is considered the equivalent of AML, and is one of diagnostic criteria for CML-BP, regardless of the blast count in the BM or peripheral blood. According to the 2008 World Health Organization criteria, CML-BP can be diagnosed when: (1) blasts are ⩾20% in the BM or peripheral blood (medullary BP); or (2) there is an extramedullary blast proliferation, in other words, MS.

/pdf/differential-clinical-and-prognostic-impact-of-myeloid-2tp0c8r6m4.pdf

Differential clinical and prognostic impact of myeloid sarcoma vs medullary myeloid blast phase of chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy

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Differential clinical and prognostic impact of myeloid sarcoma vs medullary myeloid blast phase of chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy