Clinicopathologic correlates and natural history of atypical chronic myeloid leukemia

Abstract Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age (P = .022) and dyslipidemia (P = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued (P = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.

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Natural History of Southeast Asian Chronic Myeloid Leukemia Patients with Different BCR-ABL Gene Variants

Acta Haematologica ◽

10.1159/000093641 ◽

2006 ◽

Vol 116 (2) ◽

pp. 114-119 ◽

Cited By ~ 4

Author(s):

C.U. Auewarakul ◽

S. Huang ◽

M. Yimyam ◽

S. Boonmoh

Keyword(s):

Chronic Myeloid Leukemia ◽

Natural History ◽

Myeloid Leukemia ◽

Southeast Asian ◽

Gene Variants ◽

History Of

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The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia

Blood Advances ◽

10.1182/bloodadvances.2016003889 ◽

2017 ◽

Vol 1 (13) ◽

pp. 802-811 ◽

Cited By ~ 9

Author(s):

Lucy C. Fox ◽

Katherine D. Cummins ◽

Ben Costello ◽

David Yeung ◽

Rebecca Cleary ◽

...

Keyword(s):

Cardiovascular Risk ◽

Pleural Effusion ◽

Chronic Myeloid Leukemia ◽

Natural History ◽

Myeloid Leukemia ◽

Key Points ◽

History Of

Key PointsPrescribing appropriately for age and cardiovascular risk is likely to result in minimal permanent toxicity-related dasatinib cessation. CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion.

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Bone Marrow Features and Natural History of BCR/ABL-Positive Thrombocythemia and Chronic Myeloid Leukemia Compared to BCR/ABLNegative Thrombocythemia in Essential Thrombocythemia and Polycythemia Vera

Journal of Hematology & Thromboembolic Diseases ◽

10.4172/2329-8790.1000192 ◽

2015 ◽

Vol 03 (02) ◽

Author(s):

Jan Jacques Michiels

Keyword(s):

Bone Marrow ◽

Chronic Myeloid Leukemia ◽

Natural History ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloid Leukemia ◽

History Of

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Clinicopathologic Correlates and Natural History of Atypical Chronic Myeloid Leukemia

10.1101/2020.09.10.291641 ◽

2020 ◽

Author(s):

Guillermo Montalban-Bravo ◽

Rashmi Kanagal-Shamanna ◽

Koji Sasaki ◽

Lucia Masarova ◽

Kiran Naqvi ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Median Overall Survival ◽

Treatment Modalities ◽

Limited Data ◽

Multivariable Model ◽

Ras Pathway ◽

Improved Outcomes ◽

History Of ◽

Atypical Chronic Myeloid Leukemia

ABSTRACTThere is limited data on the clonal mechanisms underlying leukemogenesis, prognostic factors, and optimal therapy for atypical chronic myeloid leukemia (aCML). We evaluated the clinicopathological features, outcomes, and responses to therapy of 65 patients with aCML. Median age was 67 years (range 46-89). The most frequently mutated genes included ASXL1 (83%), SRSF2 (68%), and SETBP1 (58%). Mutations in SETBP1, SRSF2, TET2, and GATA2 tended to appear within dominant clones, with frequent SRSF2 and SETBP1 codominance, while other RAS pathway mutations were more likely to appear as minor clones. Acquisition of new, previously undetectable mutations at transformation was observed in 63% of evaluable patients, the most common involving signaling pathway mutations. Hypomethylating agents were associated with the highest response rates and duration. With a median overall survival of 25 months (95% CI 20-30), intensive chemotherapy was associated with worse OS than other treatment modalities, and allogeneic stem cell transplantation was the only therapy associated with improved outcomes (HR 0.044, 95% CI 0.035-0.593, p=0.007). Age, platelet count, BM blast percentage, and serum LDH levels were independent predictors of survival and were integrated in a multivariable model which allowed to predict 1-year and 3-year survival.

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