Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia

Kumar, Varun; Ailawadhi, Sikander; Bojanini, Leyla; Mehta, Aditya; Biswas, Sunil Kumar; Sher, Taimur; Roy, Vivek; Vishnu, Prakash; Marin-Acevedo, Julian A.; Alegria, Victoria R.; Paulus, Aneel; Aulakh, Sonikpreet; Iqbal, Madiha; Manochakian, Rami; Tan, Winston; Chanan‐Khan, Asher; Ailawadhi, Meghna

doi:10.1038/s41408-019-0237-1

Cited by 56 publications

(68 citation statements)

References 32 publications

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“…Other studies have found AML/MDS in 3–5% of fludarabine treated patients which is in line with our findings 16,18 . Higher risk of treatment associated AML/MDS was also seen in another study of fludarabine‐based combination therapy (fludarabine and cyclophosphamide (FC), RFC and RFC with mitoxantrone) in treated versus untreated patients 19 .…”

Section: Discussionsupporting

confidence: 91%

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population‐based study

Cunha‐Bang

Rostgaard²,

Andersen

et al. 2021

Br J Haematol

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Patients with chronic lymphocytic leukaemia (CLL) have an increased risk of new malignancies. However, limited data have been published about the impact of CLL treatment on this risk. Here we followed a Danish population-based cohort of CLL patients for risks of new malignancies. Patients in the Danish CLL registry (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) were included. Up to 50 CLL-free matched comparators were identified. First-line treatment was categorized into four groups; bendamustine, chlorambucil, fludarabine or other. Patients were followed from CLL diagnosis for individual types of malignancy. Adjusted hazard ratios (HR) for new malignancies and 95% confidence intervals (95% CI) were calculated. Overall, 4286 CLL patients and 214 150 controls developed 594 and 20 565 new malignancies respectively. Risk of new malignancies was increased for CLL patients. Chemotherapy treatment was registered for 1064 (25%) patients with CLL. Chemotherapy was associated with increased HR (1Á51, 95% CI: 1Á3-1Á8) of any new malignancy. Specifically, fludarabine was associated with an increased risk of myelodysplastic syndrome (MDS) (HR 4Á93, 95% CI: 1Á2-19Á8). Patients with CLL are at increased risk of other haematological and solid malignancies compared to the general population. Chemotherapy exposure is associated with increased risk of second malignancies and fludarabine is associated with increased risk of MDS.

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Section: Discussionsupporting

confidence: 91%

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population‐based study

Cunha‐Bang

Rostgaard²,

Andersen

et al. 2021

Br J Haematol

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“…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 . 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) …”

Section: Introductionmentioning

confidence: 99%

“…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). 5 Treatment of CLL is about to change dramatically; from therapy based on cytotoxic drugs, to therapy based on drugs targeting signaling pathways, and importantly, free for cytotoxic drugs.…”

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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“… 3 Moreover, the risk of SPM in patients with chronic lymphocytic leukemia (CLL) as well as the epidemiologic correlation of melanoma with CLL has been studied by several teams. 1 – 9 …”

Section: Introductionmentioning

confidence: 99%

Clinical considerations about the coexistence of melanoma and chronic lymphocytic leukemia in the era of targeted therapies, triggered by rare clinical scenarios. A case series and review of the literature

et al. 2020

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The epidemiologic correlation of melanoma and chronic lymphocytic leukemia (CLL) has been the subject of several population studies. In the present article, through the presentation of five illustrative cases of patients with melanoma and CLL, several aspects of this complex relationship are highlighted, with a focus on the increased incidence of melanoma in patients with CLL, its speculated etiology, and the impact of CLL stage and disease duration on the incidence and prognosis of melanoma. Furthermore, the rare entity of the synchronous diagnosis of melanoma and CLL in biopsied lymph nodes is discussed, along with its implications on the diagnostic and therapeutic procedures. In addition, the available data on the treatment choices in patients with melanoma and CLL are presented and the efficacy and safety of fludarabine, anti-CD20 monoclonal antibodies, new targeted therapies for CLL, and checkpoint inhibitors are further discussed. Finally, since no formal guidelines are available for the management of this group of patients, guidelines are proposed for skin-cancer screening in patients with CLL, for the correct interpretation of BRAF mutation analysis in lymph-node specimens with ‘collision of tumors,’ and for the optimal use of imaging studies in the diagnosis of metastatic disease in patients with CLL and melanoma, while a treatment approach for such patients is also suggested. The information and proposed guidelines provided in the present article comprise a useful guide for physicians managing such patients, focusing on diagnostic challenges and therapeutic dilemmas posed by the coexistence of the two disease entities.

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Trends in the risk of second primary malignancies among survivors of chronic lymphocytic leukemia

Cited by 56 publications

References 32 publications

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population‐based study

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population‐based study

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

Clinical considerations about the coexistence of melanoma and chronic lymphocytic leukemia in the era of targeted therapies, triggered by rare clinical scenarios. A case series and review of the literature

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