Therapy-related myeloid neoplasms - what have we learned so far?

Abstract

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase Ⅱ inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapyrelated myeloid neoplasms would help developing riskadapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

Clonal selection in therapy‐related myelodysplastic syndromes and acute myeloid leukemia under azacitidine treatment

“…Patients #9 and #11 were AZA responders (respectively, mCR and SD with HI), whereas patients #14, #15, and #19 were in progression. Median number of AZA cycles was 5 (range, [3][4][5][6][7][8], and median OS was 14 months (range, [3][4][5][6][7][8][9][10][11][12][13][14][15]. In patients #9, #14, and #15, we failed to detect any change of mutated clone VAF under AZA treatment.…”

“…2,5 T-MN are frequently associated with recurrent chromosomal aberrations based on specific therapy with alkylating agents commonly leading to abnormalities of chromosome 5/7 (often in the setting of complex cytogenetics), while topoisomerase II inhibitors being associated with balanced rearrangements including 11q23 2,7,8 risk to develop t-MN is correlated with type, dose, and duration of treatment but also environment, age, and comorbidities of patient. 2,5 Additionally, recent studies strongly support that the presence of clonal hematopoiesis of indeterminate potential (CHIP) is significantly associated with the risk of developing a subsequent t-MN. 9,10 These studies suggest that pre-existing clones may be selected following cytotoxic chemotherapy.…”

“…Outcomes of t-MN are poor, with lower response rate and overall survival estimated around 10% at 5 years. 5 Azacitidine (AZA), a hypomethylating agent, is the standard treatment for AML, and MDS patients were not eligible for intensive chemotherapy. 11,12 Response rates for AZA treatment of t-MN are similar to de novo MDS but were associated with shorter survival.…”

Anti-cancer Activity of Vitamin-C Against Leukemia: A Review

“…The presence of blast cells on a complete blood count (CBC) is therefore very suspicious for leukemia. Blast cells are not typically found in the circulating blood of healthy individuals [17].…”

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“…Частота ризику виникнення t MDS/t AML суттєво менша після алогенної ТКМ, ніж після проведення традиційної ХТ. Вважається, що післятрансплантаційні ВН зумовлені режимом інтенсивного хіміотерапев тичного кондиціонування [4,28,29,45,75]. Індивідуальна варіабельність ризику розвитку t MDS/t AML зумовлена генетичною схильні стю до генотоксичних впливів ПТ та хіміопре паратів [1,2,21,24,35,54,67,60,77].…”