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1
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Li XL, Li M, Yang H, Tian J, Shi ZW, Wang LZ, Song K. Chronic myelogenous leukemia secondary to colon cancer: A case report. World J Gastrointest Oncol 2025; 17:102021. [DOI: 10.4251/wjgo.v17.i4.102021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 01/26/2025] [Accepted: 02/18/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Colon cancer is a common malignancy of the digestive tract. An estimated 1148515 new cases of colon cancer were reported in 2020 worldwide. Chronic myeloid leukemia (CML) is a malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells, with an annual incidence rate of 1-2 cases per 100000 people worldwide. Leukemia can be secondary to solid tumors, and vice versa. Reports on CML secondary malignant tumors account for 8.7% but CML secondary to malignancy is extremely rare. Therapy-related CML is a rare but potentially fatal adverse event of chemotherapy or radiotherapy. Herein, we report a case of CML with colon cancer and discuss this unique patient population. Our findings can provide effective raw data and guidance for the diagnosis of this clinical disease.
CASE SUMMARY A 61-year-old male patient attended our hospital due to leukocytosis for 5 days. In February 2020, the patient was diagnosed with colon cancer and underwent radical surgery and conventional chemotherapy with a stable condition. He was diagnosis was CML-chronic phase (Sokal score of 0.72) after examination. He was treated with imatinib (400 mg daily). When his conditions improved, the patient was discharged from our hospital and visited the outpatient department for follow-up twice a month.
CONCLUSION CML in patients with colon cancer is extremely rare. Secondary hematological tumors may be multifactorial, and the exact mechanism is currently unknown. Owing to the slow progression of the disease, patients with CML show no symptoms in the early stage. However, with disease progression, obvious but non-specific symptoms may appear, including fever, anemia, bleeding tendency, and hypertrophy. Therefore, complete blood count monitoring for routine examination is recommended after cancer treatment for early detection of occult hematological tumors.
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Affiliation(s)
- Xiao-Lan Li
- Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Min Li
- Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Hua Yang
- Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Juan Tian
- Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Zi-Wei Shi
- Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Ling-Zhi Wang
- Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
| | - Kui Song
- Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou 416000, Hunan Province, China
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Guilhot F, Hehlmann R. Long-term outcomes of tyrosine kinase inhibitors in chronic myeloid leukemia. Blood 2025; 145:910-920. [PMID: 39486043 DOI: 10.1182/blood.2024026311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/22/2024] [Accepted: 10/22/2024] [Indexed: 11/03/2024] Open
Abstract
ABSTRACT Long-term outcomes with tyrosine kinase inhibitors (TKIs) show that their impact on chronic myeloid leukemia (CML) is sustained as shown by 13 studies with 5- to 14-year-follow-up, and numerous shorter-term studies of newly diagnosed chronic-phase CML. Twenty-five years of imatinib (IM) treatment confirm its beneficial effect on survival and possible cure of CML. Large, randomized, academic, treatment-optimization studies have confirmed and extended the pivotal International Randomized Study on Interferon and STI571. The 3 academic trials in Germany, France, and the United Kingdom did not show benefit of the IM-interferon (IFN) combination, despite the immunomodulatory properties of IFN. Second-generation (2G) TKIs induce responses faster than IM and recognize IM-resistance mutations but do not prolong survival compared with IM. Adverse drug-related reactions (ADRs) limit the general use of 2GTKIs despite frequent but mostly mild IM-ADRs. Molecular monitoring of treatment efficacy has been established serving as an example for other neoplasms. Comorbidities, transcript type, and the negative impact of high-risk additional chromosomal abnormalities were addressed. A new prognostic score (European Treatment and Outcome Study long-term survival score) accounts for the fact that the majority of patients with CML die of other causes. Non-CML determinants of survival have been identified. Large and long-term observational studies demonstrate that progress with CML management has also reached routine care in most but not all instances. Despite merits of 2GTKIs, IM remains the preferred treatment option for CML because of its efficacy and superior safety.
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Affiliation(s)
| | - Rüdiger Hehlmann
- Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany
- European LeukemiaNet Foundation, Weinheim, Germany
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3
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McGrath R, Fay M, McAnena L. Chronic myelomonocytic leukaemia causing orbital inflammation. BMJ Case Rep 2024; 17:e258203. [PMID: 39477459 DOI: 10.1136/bcr-2023-258203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2025] Open
Abstract
We present a case of acute-onset orbital inflammation with rapidly progressive proptosis, episcleral venous stasis with raised intraocular pressure and loss of vision in a patient with a recent diagnosis of chronic myelomonocytic leukaemia (CMML). The patient's orbital inflammation and ocular hypertension showed no response to topical and systemic pressure-lowering agents and non-steroidal anti-inflammatory agents but resolved rapidly after the commencement of intravenous steroids. The patient was subsequently treated with the hypomethylating agent azacitidine with good systemic control of CMML with no further orbital inflammation. CMML is strongly associated with systemic inflammatory disease, possibly due to the upregulation of inflammatory pathways in the abnormal monocytes. CMML is a rare cause of orbital or ocular inflammation but should be considered in patients with persistent monocytosis.
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Affiliation(s)
- Robert McGrath
- Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Michael Fay
- Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Lisa McAnena
- Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland
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Álvarez-Reguera C, Prieto-Peña D, Herrero-Morant A, Sánchez-Bilbao L, Batlle-López A, Fernández-Luis S, Paz-Gandiaga N, Blanco R. Features of immune mediated diseases in JAK2 (V617F)-positive myeloproliferative neoplasms and the potential therapeutic role of JAK inhibitors. Eur J Intern Med 2024; 123:102-106. [PMID: 38044168 DOI: 10.1016/j.ejim.2023.11.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 11/20/2023] [Indexed: 12/05/2023]
Abstract
OBJECTIVE The Janus Kinase (JAK) 2 (V617F) mutation is the most frequently detected in myeloproliferative neoplasms (MPN). JAK2(V617F) mutation displays a pro-inflammatory phenotype that may be associated to a higher risk of immune mediated diseases (IMIDs), thromboembolic complications or other cancers. We aimed to evaluate the prevalence and main features of both rheumatic and non-rheumatic IMIDs in a cohort of MPNs patients with JAK2 (V617F) mutation. METHODS Study of all patients diagnosed with MPNs and JAK2 (V617F) mutation at a tertiary hospital in Northern Spain from 2004 to 2022. We focused on patients with rheumatic IMIDs to assess the time from IMIDs diagnosis to the detection of JAK2V617F mutation, the clinical course and severity of the disease, potential thrombotic complications, malignancies and therapeutic response. RESULTS 130 patients (73 men/57 women; mean age, 70.1 ± 14.5 years) were identified. Fifty-four (41.5 %) patients were diagnosed with at least one IMID. The prevalence of rheumatic IMIDs was 7.7 % (n = 10), including rheumatoid arthritis (n = 4), polymyalgia rheumatica (n = 3), Sjögren syndrome (n = 1), antiphospholipid syndrome (n = 1) and autoinflammatory syndrome with WDR1 mutation (n = 1). Thrombotic complications were observed in 4 of these 10 patients. The clinical course of the rheumatic IMID was mild in most cases and responded to conventional immunosuppressive therapy. One patient was successfully treated with Baricitinib, a JAK1/JAK2 inhibitor. CONCLUSIONS A high prevalence of rheumatic IMIDs is observed in patients with MPNs and JAK2 (V617F) mutation. JAK inhibitors might be a targeted therapy option in these patients.
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Affiliation(s)
- Carmen Álvarez-Reguera
- Immunopathology Research Group, IDIVAL, Rheumatology, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, ES-39008, Santander, Spain
| | - Diana Prieto-Peña
- Immunopathology Research Group, IDIVAL, Rheumatology, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, ES-39008, Santander, Spain
| | - Alba Herrero-Morant
- Immunopathology Research Group, IDIVAL, Rheumatology, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, ES-39008, Santander, Spain
| | - Lara Sánchez-Bilbao
- Immunopathology Research Group, IDIVAL, Rheumatology, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, ES-39008, Santander, Spain
| | - Ana Batlle-López
- IDIVAL, Hematology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Sara Fernández-Luis
- IDIVAL, Hematology, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Nerea Paz-Gandiaga
- IDIVAL, Department of genetics, Hospital Universitario Marqués de Valdecilla, Santander, Spain
| | - Ricardo Blanco
- Immunopathology Research Group, IDIVAL, Rheumatology, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n, ES-39008, Santander, Spain.
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BalajiSubramanian S, Al-Hajri T, Satyapal N, Al-Bulushi M, Al Sheibani SM, Al Kalbani FKM, Al-Saadi M, Al Musalhi MN, Al Wahshi HA. A Rare Case of Dual Metachronous Primary Malignancies, Chronic Myeloid Leukemia, and Tongue Carcinoma in a Patient With Long-Standing Systemic Lupus Erythematosus: A Case Report and Review of Literature. Cureus 2024; 16:e56648. [PMID: 38646281 PMCID: PMC11032168 DOI: 10.7759/cureus.56648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/21/2024] [Indexed: 04/23/2024] Open
Abstract
Patients with long-standing autoimmune diseases like systemic lupus erythematosus (SLE) are at a higher risk of developing hematological malignancies. However, chronic myeloid leukemia (CML) has rarely been reported in patients with SLE. Advancements in medical diagnostics and treatment have led to the life expectancy of SLE and CML patients moving closer to that of the general population, and it is not uncommon to encounter more than one malignancy in a cancer survivor. Although squamous cell carcinoma (SCC) of the skin has been reported in CML patients, mucosal SCC of the head and neck has rarely only been reported in CML survivors. The objective of this case report is to share our experience in treating a patient with dual metachronous primary malignancies, CML, and tongue carcinoma, along with long-standing SLE, managed by a multidisciplinary team.
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Affiliation(s)
| | - Thuraya Al-Hajri
- Department of Radiation Oncology, The Royal Hospital, Muscat, OMN
| | - Namrata Satyapal
- Department of Radiation Oncology, The Royal Hospital, Muscat, OMN
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Nakamura Y, Itoh Y, Wakimoto N. Improvement of immune thrombocytopenia with imatinib therapy following chronic myeloid leukemia. Int J Hematol 2022; 117:613-617. [PMID: 36374396 PMCID: PMC9661458 DOI: 10.1007/s12185-022-03492-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 11/07/2022] [Accepted: 11/07/2022] [Indexed: 11/16/2022]
Abstract
Immune thrombocytopenia (ITP) and chronic myeloid leukemia (CML) are rarely observed concurrently. Here we report the case of a patient with ITP who developed CML that has been well controlled with tyrosine kinase inhibitor (TKI) therapy. A 55-year-old man was diagnosed with ITP. No cytogenetic abnormalities were found at the time of initial diagnosis. Four years later, he began corticosteroid therapy for progression of thrombocytopenia. At that time, the Philadelphia (Ph) chromosome was observed in 7 of 20 bone marrow (BM) cells, suggesting concurrent CML in the subclinical stage. Prednisolone resulted in a partial response. Seven months after starting prednisolone, he exhibited hematological features of CML with an increase in Ph-positive cells. TKI therapy with imatinib mesylate was started to treat CML and maintained at a daily dose of 400 mg. The patient achieved and sustained a major molecular response. His platelet count also increased, enabling discontinuation of corticosteroid therapy. TKIs have been reported to show various immunological off-target effects. In this case, off-target effects of TKI might have improved ITP by suppressing the autoimmune response. Alternatively, reconstitution of immune systems by Ph-negative cells or cancellation of immunoreaction against CML could have exerted favorable effects on ITP.
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Affiliation(s)
- Yuichi Nakamura
- Department of Hematology, Saitama Medical University Hospital, 38 Morohongo, Moroyama-Machi, Iruma-Gun, Saitama, 350-0495 Japan
| | - Yoshihiro Itoh
- Department of Hematology, Saitama Medical University Hospital, 38 Morohongo, Moroyama-Machi, Iruma-Gun, Saitama, 350-0495 Japan
| | - Naoki Wakimoto
- Department of Hematology, Saitama Medical University Hospital, 38 Morohongo, Moroyama-Machi, Iruma-Gun, Saitama, 350-0495 Japan
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Mehra N, Varmeziar A, Chen X, Kronick O, Fisher R, Kota V, Mitchell CS. Cross-Domain Text Mining to Predict Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia. Cancers (Basel) 2022; 14:4686. [PMID: 36230609 PMCID: PMC9563938 DOI: 10.3390/cancers14194686] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/04/2022] [Accepted: 09/23/2022] [Indexed: 12/02/2022] Open
Abstract
Tyrosine kinase inhibitors (TKIs) are prescribed for chronic myeloid leukemia (CML) and some other cancers. The objective was to predict and rank TKI-related adverse events (AEs), including under-reported or preclinical AEs, using novel text mining. First, k-means clustering of 2575 clinical CML TKI abstracts separated TKIs by significant (p < 0.05) AE type: gastrointestinal (bosutinib); edema (imatinib); pulmonary (dasatinib); diabetes (nilotinib); cardiovascular (ponatinib). Next, we propose a novel cross-domain text mining method utilizing a knowledge graph, link prediction, and hub node network analysis to predict new relationships. Cross-domain text mining of 30+ million articles via SemNet predicted and ranked known and novel TKI AEs. Three physiology-based tiers were formed using unsupervised rank aggregation feature importance. Tier 1 ranked in the top 1%: hematology (anemia, neutropenia, thrombocytopenia, hypocellular marrow); glucose (diabetes, insulin resistance, metabolic syndrome); iron (deficiency, overload, metabolism), cardiovascular (hypertension, heart failure, vascular dilation); thyroid (hypothyroidism, hyperthyroidism, parathyroid). Tier 2 ranked in the top 5%: inflammation (chronic inflammatory disorder, autoimmune, periodontitis); kidney (glomerulonephritis, glomerulopathy, toxic nephropathy). Tier 3 ranked in the top 10%: gastrointestinal (bowel regulation, hepatitis, pancreatitis); neuromuscular (autonomia, neuropathy, muscle pain); others (secondary cancers, vitamin deficiency, edema). Results suggest proactive TKI patient AE surveillance levels: regular surveillance for tier 1, infrequent surveillance for tier 2, and symptom-based surveillance for tier 3.
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Affiliation(s)
- Nidhi Mehra
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Armon Varmeziar
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Xinyu Chen
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Olivia Kronick
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Rachel Fisher
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
| | - Vamsi Kota
- Division of Hematology and Oncology, Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA
| | - Cassie S. Mitchell
- Laboratory for Pathology Dynamics, Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA 30332, USA
- Center for Machine Learning, Georgia Institute of Technology, Atlanta, GA 30332, USA
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8
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Yu Y, Liu JL, Tian DS. Anti-N-methyl-D-aspartate receptor encephalitis associated with chronic myelogenous leukemia, causality or coincidence? A case report. BMC Neurol 2022; 22:153. [PMID: 35461209 PMCID: PMC9034597 DOI: 10.1186/s12883-022-02675-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 04/12/2022] [Indexed: 11/10/2022] Open
Abstract
Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune paraneoplastic encephalitis, and is primarily associated with ovarian teratomas. Here, we report the first case of a patient diagnosed with chronic myelogenous leukemia (CML) during the recovery phase of anti-NMDAR encephalitis. Case presentation The patient was admitted with fever, headache, and seizures. Brain MRI revealed a cerebrospinal fluid (CSF)-containing arachnoid cyst in the left temporal lobe with no other abnormal signals. EEG showed diffuse background slowing in the delta-theta range. The patient tested positive for anti-NMDAR antibodies in both the serum and CSF. One year after the onset of encephalitis, the patient was referred to the Department of Hematology for extreme leukocytosis. Karyotype analysis showed the presence of Philadelphia chromosome t(9;22)(q34;q11). Quantitative reverse transcriptase PCR analysis further identified BCR/ABL1 fusion transcripts; thus, CML was diagnosed. Conclusions To the best of our knowledge, this is the first case of anti-NMDAR encephalitis associated with CML. This report should alert clinicians to consider CML as a malignancy that is possibly associated with limbic encephalitis.
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9
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Second Cancer Onset in Myeloproliferative Neoplasms: What, When, Why? Int J Mol Sci 2022; 23:ijms23063177. [PMID: 35328597 PMCID: PMC8954627 DOI: 10.3390/ijms23063177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/12/2022] [Accepted: 03/14/2022] [Indexed: 11/18/2022] Open
Abstract
The risk of developing a solid cancer is a major issue arising in the disease course of a myeloproliferative neoplasm (MPN). Although the connection between the two diseases has been widely described, the backstage of this complex scenario has still to be explored. Several cellular and molecular mechanisms have been suggested to link the two tumors. Sometimes the MPN is considered to trigger a second cancer but at other times both diseases seem to depend on the same source. Increasing knowledge in recent years has revealed emerging pathways, supporting older, more consolidated theories, but there are still many unresolved issues. Our work aims to present the biological face of the complex clinical scenario in MPN patients developing a second cancer, focusing on the main cellular and molecular pathways linking the two diseases.
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10
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Barcellini W, Giannotta JA, Fattizzo B. Autoimmune Complications in Hematologic Neoplasms. Cancers (Basel) 2021; 13:cancers13071532. [PMID: 33810369 PMCID: PMC8037071 DOI: 10.3390/cancers13071532] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/22/2021] [Accepted: 03/24/2021] [Indexed: 12/14/2022] Open
Abstract
Autoimmune cytopenias (AICy) and autoimmune diseases (AID) can complicate both lymphoid and myeloid neoplasms, and often represent a diagnostic and therapeutic challenge. While autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) are well known, other rarer AICy (autoimmune neutropenia, aplastic anemia, and pure red cell aplasia) and AID (systemic lupus erythematosus, rheumatoid arthritis, vasculitis, thyroiditis, and others) are poorly recognized. This review analyses the available literature of the last 30 years regarding the occurrence of AICy/AID in different onco-hematologic conditions. The latter include chronic lymphocytic leukemia (CLL), lymphomas, multiple myeloma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and acute leukemias. On the whole, AICy are observed in up to 10% of CLL and with higher frequencies in certain subtypes of non-Hodgkin lymphoma, whilst they occur in less than 1% of low-risk MDS and CMML. AID are described in up to 30% of myeloid and lymphoid patients, including immune-mediated hemostatic disorders (acquired hemophilia, thrombotic thrombocytopenic purpura, and anti-phospholipid syndrome) that may be severe and fatal. Additionally, AICy/AID are found in about 10% of patients receiving hematopoietic stem cell transplant or treatment with new checkpoint inhibitors. Besides the diagnostic difficulties, these AICy/AID may complicate the clinical management of already immunocompromised patients.
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Affiliation(s)
- Wilma Barcellini
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (J.A.G.); (B.F.)
- Correspondence: ; Tel.: +39-025-503-3256
| | - Juri Alessandro Giannotta
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (J.A.G.); (B.F.)
| | - Bruno Fattizzo
- Hematology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (J.A.G.); (B.F.)
- Department of Oncology and Oncohematology, University of Milan, 20122 Milan, Italy
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11
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Aitken MJL, Benton CB, Issa GC, Sasaki K, Yilmaz M, Short NJ. Two Cases of Possible Familial Chronic Myeloid Leukemia in a Family with Extensive History of Cancer. Acta Haematol 2021; 144:585-590. [PMID: 33735874 DOI: 10.1159/000513925] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Accepted: 12/18/2020] [Indexed: 11/19/2022]
Abstract
CML is defined by the presence of an oncogenic fusion protein caused by a reciprocal translocation between chromosomes 9q and 22q. While our molecular understanding of CML pathogenesis has revolutionized drug development for this disease, we have yet to identify many predisposing factors for CML. Familial occurrence of CML has been rarely reported. Here, we describe 2 cases of CML in a 24-year-old woman and in her 73-year-old maternal great aunt. We describe genetic variants in these patients and report on their environmental exposures that may have contributed to CML pathogenesis. The possible familial association of these 2 cases of CML warrants further investigation into more definitive etiologies of this disease.
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Affiliation(s)
- Marisa J L Aitken
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- McGovern Medical School, Houston, Texas, USA
| | - Christopher B Benton
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Rocky Mountain Cancer Center, Denver, Colorado, USA
| | - Ghayas C Issa
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Koji Sasaki
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Musa Yilmaz
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nicholas J Short
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA,
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12
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Larfors G, Richter J, Själander A, Stenke L, Höglund M. Increased Risk of Chronic Myeloid Leukemia Following Gastric Conditions Indicating Helicobacter pylori Infection: A Case-Control Study. Cancer Epidemiol Biomarkers Prev 2019; 29:151-156. [PMID: 31619405 DOI: 10.1158/1055-9965.epi-19-0758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 09/04/2019] [Accepted: 10/09/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND On the basis of a previous report of increased chronic myeloid leukemia (CML) risk following peptic ulcer, we hypothesized that chronic Helicobacter pylori infection could serve as a risk factor for CML. METHODS In a population-based, retrospective case-control study, we used Swedish registry data on 980 patients with CML and 4,960 age- and sex-matched controls to investigate associations between markers of previous infection with Helicobacter pylori and CML incidence. RESULTS Previous diagnoses of dyspepsia, gastritis or peptic ulcers, as well as previous proton pump inhibitor (PPI) medication, were all associated with a significantly increased risk of CML (RRs, 1.5-2.0; P = 0.0005-0.05). Meanwhile, neither inflammatory bowel disease nor intake of NSAIDs were associated with CML, indicating that it is not gastrointestinal ulcer or inflammation per se that influences risk. CONCLUSIONS The consistent associations suggest a shared background between gastric conditions and CML, and strengthen the case that Helicobacter pylori could constitute this common risk factor. IMPACT As the etiology of CML is practically unknown, and Helicobacter pylori could potentially be a therapeutic target, even this indirect evidence encourages further studies on the potential involvement of Helicobacter pylori in CML etiology.
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Affiliation(s)
- Gunnar Larfors
- Department of Medical Sciences, Unit of Hematology, Uppsala University, Uppsala, Sweden.
| | - Johan Richter
- Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden
| | - Anders Själander
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Leif Stenke
- Division of Hematology, Department of Medicine, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden
| | - Martin Höglund
- Department of Medical Sciences, Unit of Hematology, Uppsala University, Uppsala, Sweden
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13
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Autore F, Sorà F, Chiusolo P, Annunziata M, Iurlo A, Cattaneo D, Galimberti S, Bajer JA, Sica S. 'Secondary chronic myeloid leukemia': comparison between patients previously exposed or not to chemo- and/or radiotherapy. Leuk Lymphoma 2019; 60:3584-3586. [PMID: 31294653 DOI: 10.1080/10428194.2019.1639162] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Francesco Autore
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Federica Sorà
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | | | | | - Alessandra Iurlo
- Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Daniele Cattaneo
- Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | | | - Simona Sica
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Jamy O, Sarmad R, Costa L. Risk and outcomes of second malignant neoplasms in chronic myeloid leukemia survivors. Leuk Res 2019; 82:1-6. [PMID: 31108340 DOI: 10.1016/j.leukres.2019.05.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Revised: 05/01/2019] [Accepted: 05/11/2019] [Indexed: 10/26/2022]
Abstract
The risk of second malignant neoplasms (SMN) in chronic myeloid leukemia (CML) survivors remains unclear. We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate the risk and subsequent outcomes of SMN in CML survivors. There were 3407 patients included. Of these, 170 (4.99%) developed a SMN with SIR of 1.40 (95% C.I. 1.19-1.62). An increased risk was noted for cancers of the respiratory tract, genitourinary (GU) tract and skin excluding basal cell and squamous cell carcinoma. Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and gastrointestinal (GI) tract. Patients with GU malignancies developing after CML had worse overall survival than patients without prior CML diagnosis (P = 0.018). There was no difference in survival between post-CML and non-post-CML patients with respiratory or GI malignancies.
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Affiliation(s)
- Omer Jamy
- Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, United States.
| | - Rehan Sarmad
- Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, United States
| | - Luciano Costa
- Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, United States
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15
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Chattopadhyay S, Zheng G, Sud A, Yu H, Sundquist K, Sundquist J, Försti A, Hemminki A, Houlston R, Hemminki K. Risk of second primary cancer following myeloid neoplasia and risk of myeloid neoplasia as second primary cancer: a nationwide, observational follow up study in Sweden. LANCET HAEMATOLOGY 2018; 5:e368-e377. [PMID: 30075833 DOI: 10.1016/s2352-3026(18)30108-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 06/26/2018] [Accepted: 06/28/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers-ie, development of second primary cancer in patients who have previously had myeloid cancer, and risks of myeloid neoplasia in patients who have previously had another cancer-to provide insight into possible mechanisms beyond side-effects of treatment and shared risk factors. METHODS Using the Swedish Family-Cancer Database, we identified 35 928 individuals with primary myeloid cancer, including myeloproliferative neoplasms, acute myeloid leukaemia, chronic myeloid leukaemia, and myelodysplastic syndrome diagnosed between 1958 and 2015. The Swedish Family-Cancer Database includes every individual registered as a resident in Sweden starting in 1932, with full parental history. The primary endpoint was the assessment of relative risks (RRs) for second primary cancer, which we performed using means of incidence rate ratios, regressed over a generalised Poisson model. FINDINGS Between 1958 and 2015, overall relative risk of second primary cancers was significantly increased after acute myeloid leukaemia (RR 1·29, 95% CI 1·17-1·41), chronic myeloid leukaemia (1·52, 1·35-1·69), myelodysplastic syndrome (1·42, 1·26-1·59), and all myeloproliferative neoplasms (1·37, 1·30-1·43) relative to the incidence of these cancers as first primary cancer. With myeloid neoplasia as a second primary cancer, risks were significantly increased for acute myeloid leukaemia (1·57, 1·48-1·65), chronic myeloid leukaemia (1·26, 1·13-1·40), and myelodysplastic syndrome (1·54, 1·42-1·67) relative to the incidence of these myeloid neoplasms as first primary cancers. Relative risk of upper aerodigestive tract cancer, squamous cell skin cancer, and non-Hodgkin lymphoma as second primary cancers were increased after all four types of myeloid neoplasia relative to their incidence as first primary cancers. High risks of myelodysplastic syndrome and acute myeloid leukaemia as second primary cancers were found after haematological cancers (RRs between 5·08 and 10·04). INTERPRETATION The relative risks of second primary cancer are important for the long-term management of patients with myeloid cancers. The bi-directional associations of myeloid cancers with many other cancers suggest a number of candidate mechanisms that might contribute to the development and aetiology of a second primary cancer. These mechanisms might include immune dysfunction or the effects of treatment, and these should be assessed in future investigations. FUNDING Deutsche Krebshilfe, Jane and Aatos Erkko Foundation, Sigrid Juselius Foundation, Finnish Cancer Organizations, Swedish Research Council, ALF from Region Skåne, and Bloodwise.
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Affiliation(s)
- Subhayan Chattopadhyay
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine, University of Heidelberg, Heidelberg, Germany.
| | - Guoqiao Zheng
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine, University of Heidelberg, Heidelberg, Germany
| | - Amit Sud
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Hongyao Yu
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine, University of Heidelberg, Heidelberg, Germany
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA; Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan
| | - Jan Sundquist
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA; Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan
| | - Asta Försti
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Akseli Hemminki
- Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Finland; Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
| | - Richard Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK; Division of Molecular Pathology, The Institute of Cancer Research, London, UK
| | - Kari Hemminki
- Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden
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16
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Incidence and risk factors of secondary cancers after allogeneic stem cell transplantation: analysis of a single centre cohort with a long follow-up. Bone Marrow Transplant 2018; 54:334-337. [PMID: 30104720 DOI: 10.1038/s41409-018-0290-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 06/19/2018] [Accepted: 07/14/2018] [Indexed: 11/09/2022]
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17
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No increased prevalence of malignancies among first-degree relatives of 800 patients with chronic myeloid leukemia: a population-based study in Sweden. Leukemia 2017; 31:1825-1827. [DOI: 10.1038/leu.2017.131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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18
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Koller PB, Kantarjian HM, Nogueras-Gonzalez GM, Jabbour E, Verstovsek S, Borthakur G, Estrov Z, Wierda WG, Garcia-Manero G, Ferrajoli A, Ravandi F, O'Brien SM, Cortes JE. Chronic myeloid leukemia among patients with a history of prior malignancies: A tale of dual survivorship. Cancer 2016; 123:609-616. [PMID: 27763690 DOI: 10.1002/cncr.30362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Revised: 09/01/2016] [Accepted: 09/02/2016] [Indexed: 11/06/2022]
Abstract
BACKGROUND Some patients with chronic myeloid leukemia (CML) have a history of previous malignancies. To the authors' knowledge, outcomes for CML diagnosed in these patients have not been well described. The current study was conducted to determine the outcome of patients with CML and a history of prior malignancies. METHODS The current study included patients who were enrolled in clinical trials of tyrosine kinase inhibitors as initial therapy for CML in chronic phase from July 2000 to January 2014. RESULTS Of the 630 patients with CML who were treated with frontline tyrosine kinase inhibitors, 626 had a known prior malignancy status. Of these, 45 patients (7%) had a prior malignancy other than nonmelanoma skin cancer whereas 17 patients (3%) had a history of nonmelanoma skin cancers alone. Characteristics of CML were similar between the patients with no prior malignancy, those with a prior malignancy, and those with nonmelanoma skin cancer. Patients with a prior malignancy were found to have an older median age compared with the other 2 groups. The most common prior malignancies were nonmelanoma skin cancer in 20 patients, breast cancer in 11 patients, melanoma in 7 patients, prostate cancer in 6 patients, and colorectal cancer in 5 patients. With regard to CML, the event-free survival, transformation-free survival, and failure-free survival rates were found to be similar between the groups. There was a statistically significantly decreased survival in the group with a prior malignancy versus the group with no prior malignancy versus the group with nonmelanoma skin cancer. In a multivariate analysis, advanced age and an elevated creatinine level were found to be associated with worse survival after a diagnosis of CML. CONCLUSIONS Patients with CML with a history of prior malignancies appear to have the same excellent outcome as patients with no prior malignancies. In the few instances in which concomitant therapy for other malignancies was required during therapy with tyrosine kinase inhibitors, this was able to be accomplished without significant toxicity. Cancer 2017;123:609-616. © 2016 American Cancer Society.
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Affiliation(s)
- Paul B Koller
- Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Hagop M Kantarjian
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | - Elias Jabbour
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Srdan Verstovsek
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gautam Borthakur
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Zeev Estrov
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - William G Wierda
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | - Alessandra Ferrajoli
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Farhad Ravandi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Susan M O'Brien
- Chao Family Comprehensive Cancer Center, University of California at Irvine, Orange, California
| | - Jorge E Cortes
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas
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