Therapy-related acute myeloid leukemia following treatment of lymphoid malignancies

Therapy-related myeloid neoplasms (t-MNs) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. t-MNs result from a complex interaction between individual predisposition and exposition to toxic agents. Some different biological and clinical characteristics can be recognized according to the type of anticancer drug. Compared to de novo myeloid neoplasms, prognosis of t-MN is dismal. Age and karyotype are the most important prognostic factors for t-MN, which should be treated with frontline chemotherapy treatments that are appropriate for patients with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) with similar disease characteristics. Allogeneic stem cell transplantation should be considered particularly for unfavorable karyotypes and younger patients with aggressive disease.

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“…Time to t-MN diagnosis was influenced by patient age, type of lymphoproliferative diseases, and treatment. 33 …”

Section: Epidemiology and Prognosismentioning

confidence: 99%

Therapy-related myeloid neoplasms: clinical perspectives

Fianchi

Criscuolo

Fabiani

et al. 2018

OTT

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“…Little is known about the epidemiology of second hematological malignancies (SHM) in patients with chronic lymphocytic leukemia (CLL) not participating in clinical trials . Prevalence of t‐MDS and t‐AML in chemotherapy/chemoimmunotherapy‐treated patients with CLL is about 1%‐8% in CLL populations reported from tertiary referral institutions or clinical trials with median age between 60 and 65 years, for example, about 10 years younger than the “real‐world” CLL population . Reports on a general unselected CLL population are based on cancer registries .…”

Section: Introductionmentioning

confidence: 99%

“…clinical trials with median age between 60 and 65 years, for example, about 10 years younger than the "real-world" CLL population. 10 Reports on a general unselected CLL population are based on cancer registries. 11,12 Among 15 915 patients with CLL surviving at least 1 year after diagnosis of CLL registered in 11 SEER registries in USA between 1992 and 2006, only 13 cases of acute non-lymphoblastic leukemia were registered (mean person-years at risk 4.3).…”

mentioning

confidence: 99%

Chronic lymphocytic leukemia and secondary hematological malignancies: A nation‐wide cancer registry study

Lenartova

Johannesen

Tjønnfjord

2020

European J of Haematology

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More than 20 000 patients are diagnosed with chronic lymphocytic leukemia (CLL) in USA each year. 1 The annual incidence of CLL is approximately 320 cases in Norway, in a population of 5.3 million. 2 The overall 5-year survival reached 85% in USA (2009USA ( -2015 and 79% in Norway (2003-2012), and in USA, estimated 178.206 patients lived with CLL in 2016 Patients with CLL face substantial morbidity due to other causes than CLL: for example, infections, autoimmune diseases, and second solid and hematological malignancies. 4 Little is known about the epidemiology of second hematological malignancies (SHM) in patients with chronic lymphocytic leukemia (CLL) not participating in clinical trials. 5-9 Prevalence of t-MDS and t-AML in chemotherapy/ chemoimmunotherapy-treated patients with CLL is about 1%-8% in CLL populations reported from tertiary referral institutions or Abstract Objective: Chronic lymphocytic leukemia (CLL) treatment has changed dramatically, and landscape of second hematologic malignancies (SHM) evolves in the new era of targeted therapy. No data were available about the real-world burden of SHM. Methods: All 2631 patients with CLL in the Cancer registry of Norway registered 2003-2012 were included. Results: After median follow-up of 6.6 years, 103 patients (4%) developed SHM. Diffuse large B-cell lymphoma (DLBCL) was most common (n = 65; 63%). Median survival was 9.3 years (95% CI; 8.9-9.8) in non-SHM patients and 1.7 years in DLBCL, 0.8 years in Hodgkin lymphoma (n = 12), and 2.8 years in myeloid neoplasia (n = 15;95% CI: 0.3-2.6, 0.6-2.9, and 0.4-5.3, respectively; P < .001). Outcomes were poorest for SHM patients treated for CLL (HR 2.76, 95% CI 1.4-5.5, P = 0.003). A higher proportion of men and younger age were found in SHM patients (median age 66 vs 72 years in non-SHM; P < .001; men 68% vs 57%, P = .03). Myeloid neoplasia was rare (incidence rate 1/1000 person-years; 95% CI: 0.6-1.5) and tended to occur later than DLBCL in patients treated for CLL (median time from CLL to SHM 62 vs 45 months; P = .09).Conclusions: SHM and especially myeloid malignancies were rare in chemoimmunotherapy era. K E Y W O R D Schemoimmunotherapy, chronic lymphocytic leukemia, epidemiology, Nation-wide cancer registry, real-world, second hematologic malignancy, therapy-related myeloid neoplasiaThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…AML following previous chemotherapy or radiation treatment (t-AML) can be regularly observed in patients with history of lymphoma (e.g., Hodgkin’s disease) or breast cancer (Bertoli et al 2016 ; Linassier et al 2000 ). Cytogenetic analyses of t-AML reveal aberrations–e.g., t(8;21) or inv(16)—that are associated with a good prognosis in de novo AML according to the ELN classification (Gustafson et al 2009 ; Döhner et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of induction chemotherapy with intermediate-dosed cytarabine and subsequent allogeneic stem cell transplantation on the outcome of high-risk acute myeloid leukemia

Fleischmann

Schnetzke

Frietsch

et al. 2021

J Cancer Res Clin Oncol

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Background Acute myeloid leukemia (AML) with antecedent hematological disease (s-AML) and treatment-related AML (t-AML) predicts poor prognosis. Intensive treatment protocols of those high-risk patients should consider allogeneic stem cell transplantation (allo-HSCT) in first complete remission (CR). Despite allo-HSCT, relapse rate remains high. Induction chemotherapy with liposomal cytarabine and daunorubicin (CPX-351) has been approved for patients with AML with myeloid-related changes (AML-MRC) or t-AML based on improved survival and remission rates compared to standard 7 + 3 induction. Patients and methods 110 patients with newly diagnosed s-AML or t-AML at a university hospital were analyzed retrospectively. Median age was 62 years (24–77 years). A total of 65 patients with s-AML after MDS (59%) and 23 patients (20.9%) with t-AML were included. Induction chemotherapy consisted of intermediate-dosed cytarabine (ID-AraC) in combination with idarubicin (patients up to 60 years) or mitoxantrone (patients over 60 years). In patients subsequently undergoing allo-HSCT, reduced conditioning regimens (RIC) were applied prior to transplantation in 47 of 62 patients (76%). Results Induction chemotherapy with ID-AraC resulted in an overall response rate of 83% including complete remission (CR/CRi) in 69 patients (63%) with a low rate of early death (2.7%). Most relevant non-hematologic toxicity consisted of infectious complications including sepsis with need of intensive care treatment in five patients (4.5%) and proven or probable invasive fungal disease in eight patients (7.2%). Relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) of the whole cohort were 19 months (0–167), 10 months (0–234) and 15 months (0–234), respectively (p < 0.0001). A significant improvement of OS was observed in patients who underwent allo-HSCT compared to those without subsequent allo-HSCT: 9 vs. 46 months, p < 0.0001. Rate of transplantation-related mortality (TRM) in the early phase post allo-HSCT was low (0.9% at day 30 and 1.8% at day 90, respectively). RIC conditioning results in OS rate of 60% after 60 months post allo-HSCT (median OS not reached). Conclusion S-AML and t-AML patients receiving induction chemotherapy with intermediate-dosed cytarabine showed satisfactory response rate and consolidation therapy with allo-HSCT after full or reduced-intensity conditioning further improved survival in these patients with similar outcome as reported for CPX-351.

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Therapy-related acute myeloid leukemia following treatment of lymphoid malignancies

Cited by 11 publications

References 38 publications

Therapy-related myeloid neoplasms: clinical perspectives

Therapy-related myeloid neoplasms: clinical perspectives

Chronic lymphocytic leukemia and secondary hematological malignancies: A nation‐wide cancer registry study

Impact of induction chemotherapy with intermediate-dosed cytarabine and subsequent allogeneic stem cell transplantation on the outcome of high-risk acute myeloid leukemia

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