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Clin Lab 2022 May;68(5)

Background: Based on the 2017 revision of the World Health Organization Classification, therapy-related myeloid neoplasms consist of therapy-related acute myeloid leukemia, therapy-related myelodysplastic syndromes, and therapy-related myelodysplastic/myeloproliferative neoplasms, which exist as a late-occurring complication of radiation and/or chemotherapy treatment due to previous application of iatrogenic mutagenic agents.

Methods: Here we present the first described case of therapy-related acute monocytic leukemia mimicking lym-phoma after chemotherapy and radiotherapy for breast cancer.

Results: Based on immunophenotypic analysis and biopsy of the BM, the patient was diagnosed with acute monocytic leukemia (AML FAB M5b) according to WHO classification. Read More

Ann Lab Med 2022 09;42(5):590-596

Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.

The translocation (3;21)(q26.2;q22.1) is a unique cytogenetic aberration that characterizes acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) in patients with AML and myelodysplastic syndrome (MDS) or a therapy-related myeloid neoplasm. Read More

Clin Lab 2022 Feb;68(2)

Background: According to the 2017 WHO classification, therapy related myeloid neoplasms refer to therapy-related acute myeloid leukemia, therapy-related myelodysplastic syndromes, and therapy-related myelodysplastic/ myeloproliferative neoplasms, which happen as a belated occurring complication of chemotherapy and/or radiation therapy due to prior iatrogenic exposure of mutagenic agents.

Results: Herein, we present a very rare case of bone marrow metastasis from testicular seminoma coexisting with treatment-associated acute myeloid leukemia.

Conclusions: This paper highlights the rare and easily misdiagnosed morphological feature of bone marrow. Read More

Pediatr Blood Cancer 2022 05 22;69(5):e29499. Epub 2021 Dec 22.

Department of Pediatrics, UCSF Benioff Children's Hospital San Francisco, University of California San Francisco, San Francisco, California, USA.

Therapy-related myeloid neoplasms (t-MN) are a distinct subgroup of myeloid malignancies with a poor prognosis that include cases of therapy-related myelodysplastic syndrome (t-MDS), therapy-related myeloproliferative neoplasms (t-MPN) and therapy-related acute myeloid leukemia (t-AML). Here, we report a series of patients with clinical features consistent with juvenile myelomonocytic leukemia (JMML), an overlap syndrome of MDS and myeloproliferative neoplasms that developed after treatment for another malignancy. Read More

Best Pract Res Clin Haematol 2021 12 23;34(4):101327. Epub 2021 Oct 23.

Novartis Institutes for BioMedical Science, Cambridge, MA, USA. Electronic address:

Clonal hematopoiesis (CH) - a biological state in which one or a small number of hematopoietic stem or progenitor cells contribute disproportionately to blood cell production, usually as a result of somatic gene mutations in the stem cells - is often considered to be a precursor to myeloid neoplasia, especially myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, the majority of people with CH never develop an overt myeloid neoplasm, and CH can be a precursor to lymphoid cancers as well as myeloid neoplasms. In addition, CH increases all-cause mortality and augments the risk of several non-neoplastic medical conditions, including atherosclerotic cardiovascular disease. Read More

Blood Adv 2022 02;6(4):1278-1295

Hospital Virgen de la Salud, Toledo, Spain.

Secondary acute myeloid leukemia (sAML) comprises a heterogeneous group of patients and is associated with poor overall survival (OS). We analyze the characteristics, treatment patterns, and outcomes of adult patients with sAML in the Programa Español de Tratamientos en Hematología (PETHEMA) registry. Overall, 6211 (72. Read More

Acta Clin Belg 2022 Jun 1;77(3):658-663. Epub 2021 Jul 1.

Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

Introduction: Therapy-related myeloid neoplasms (t-MN) are frequently categorized according to previous therapy or pattern of cytogenetic abnormalities. Our objective was to evaluate and compare the mutational profile of and t-MN by next generation sequencing.

Methods: Sixty-four samples from patients with t-MN, previously treated for a solid tumor (mainly breast), or AML, MDS, MDS/MPN were selected for our study. Read More

Cancer 2021 04 18;127(8):1186-1207. Epub 2021 Mar 18.

Department of Leukemia, MD Anderson Cancer Center, Houston, Texas.

The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. Read More

Am J Clin Pathol 2021 02;155(2):179-210

Division of Hematopathology, Mayo Clinic, Rochester, MN.

Objectives: To report the findings of the 2019 Society for Hematopathology/European Association for Haematopathology Workshop within the categories of reactive eosinophilia, hypereosinophilic syndrome (HES), germline disorders with eosinophilia (GDE), and myeloid and lymphoid neoplasms associated with eosinophilia (excluding entities covered by other studies in this series).

Methods: The workshop panel reviewed 109 cases, assigned consensus diagnosis, and created diagnosis-specific sessions.

Results: The most frequent diagnosis was reactive eosinophilia (35), followed by acute leukemia (24). Read More

Mod Pathol 2021 02 27;34(2):300-313. Epub 2020 Oct 27.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Sporadic reports of t(3;12)(q26.2;p13) indicate that this abnormality is associated with myeloid neoplasms, myelodysplasia, and a poor prognosis. To better characterize neoplasms with this abnormality, we assessed 20 patients utilizing clinicopathological data, cytogenetic, and targeted next-generation sequencing analysis. Read More

Genes (Basel) 2020 07 6;11(7). Epub 2020 Jul 6.

Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.

A subset of acute myeloid leukemia (AML) arises either from an antecedent myeloid malignancy (secondary AML, sAML) or as a complication of DNA-damaging therapy for other cancers (therapy-related myeloid neoplasm, t-MN). These secondary leukemias have unique biological and clinical features that distinguish them from de novo AML. Over the last decade, molecular techniques have unraveled the complex subclonal architecture of sAML and t-MN. Read More

Leukemia 2021 03 29;35(3):835-849. Epub 2020 Jun 29.

Clinical Hematology Department, Hospital General Universitari de València, Valencia, Spain.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). Read More

Biol Blood Marrow Transplant 2020 08 19;26(8):1543-1551. Epub 2020 Apr 19.

Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.

This study aimed to investigate allogeneic hematopoietic cell transplantation (HCT) outcomes and risk factors in adult patients with therapy-related myeloid neoplasm (t-MN) using Japanese registry data. Between 2002 and 2012, a total 12,169 adult patients underwent HCT for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). Of these, 565 with t-MN were identified. Read More

Mod Pathol 2019 12 1;32(12):1712-1726. Epub 2019 Aug 1.

Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.

Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35. Read More

Biol Blood Marrow Transplant 2019 09 6;25(9):1770-1778. Epub 2019 Jun 6.

Division of Hematology, Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. Read More

Am J Clin Pathol 2016 Apr 25;145(4):459-66. Epub 2016 Mar 25.

From the Departments of Laboratory Medicine and Pathology

Objectives: Isolated deletion (20q) is relatively common in myeloid neoplasms and has been rarely reported in cases of therapy-related myelodysplastic syndrome (MDS). Our aim was to characterize cases of isolated del(20q) in bone marrow biopsy specimens from patients with a history of chemotherapy with morphologic findings insufficient for a diagnosis of MDS.

Methods: In this retrospective study from one institution, we identified 22 patients with isolated del(20q) and no or minimal dysplasia and evaluated clinical and pathologic characteristics. Read More

Am J Hematol 2016 Feb;91(2):227-32

Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, Texas.

Acute myeloid leukemia (AML) is defined as ≥20% myeloblasts, representing a change from original guidelines where ≤30% blasts were considered as myelodysplastic syndromes (MDS), and 20-29% blasts classified as refractory anemia with excess blasts in transformation (RAEB-T). Whether the diagnostic bone marrow blast percentage has current value with regards to patient prognostication or identification of optimal treatment strategies is unclear. We retrospectively studied 1652 treatment-naïve adults with MDS or AML and ≥10% blasts from January 2000 to April 2014. Read More

J Clin Oncol 2015 Nov 24;33(31):3641-9. Epub 2015 Aug 24.

Lene Sofie Granfeldt Østgård, Mette Nørgaard, Eigil Kjeldsen, and Jan Maxwell Nørgaard, Aarhus University Hospital, Aarhus; Henrik Sengeløv, Mette Klarskov Andersen, and Lone Smidstrup Friis, The University Hospital Rigshospitalet, Copenhagen; Inge Høgh Dufva, Herlev University Hospital, Herlev; Claus Werenberg Marcher and Birgitte Preiss, Odense University Hospital, Odense; Marianne Severinsen, Aalborg University Hospital, Aalborg, Denmark; and Bruno C. Medeiros, Stanford University School of Medicine, Stanford, CA.

Purpose: Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age.

Patients And Methods: In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Read More

Leukemia 2016 Jan 15;30(1):242-7. Epub 2015 May 15.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Dec;22(6):1757-60

Department of Hematology, Tianjin Medical University Cancer Institue and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. E-mail:

Therapy-related myelodysplasia syndromes/acute myeloid leukemia (t-MDS/AML) is a clinical syndrome occurring as a late complication after chemotherapy and (or) radiotherapy, attracting much more attention owing to the improved treatment agents and longer survival of many treated patients. According to the WHO classification of 2008, t-MDS/AML is a serious complication of chemotherapy or radiotherapy given to a malignant or nonmalignant condition consisting of t-AML, t-MDS and t-MDS/myeloproliferative diseases (t-MDS/MPD). This review mainly focuses on the pathogenesis, relationship with primary tumour, treatment and prognosis of t-MDS/AML. Read More

Best Pract Res Clin Haematol 2014 Jun 19;27(2):141-53. Epub 2014 Jul 19.

Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address:

Polycythemia vera, essential thrombocythemia, and primary myleofibrosis are chronic myeloproliferative neoplasms (MPNs) associated with an increased morbidity and mortality. MPNs are also associated with progression to acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The "true" rate of transformation is not known mainly due to selection bias in clinical trials and underreporting in population-based studies. Read More

Leuk Res 2014 Oct 11;38(10):1162-4. Epub 2014 Aug 11.

Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, United States.

Int J Clin Exp Pathol 2014 15;7(7):3512-23. Epub 2014 Jun 15.

Department of Hematopathology, The University of Texas MD Anderson Cancer Center Houston, Texas.

Hematological neoplasms developed in patients with a history of cytotoxic therapies comprise a group of diseases with a poor clinical outcome, and collectively categorized as "therapy-related myeloid neoplasms" (t-MN) in the 2008 World Health Organization (WHO) Classification. In recent years, numerous publications have emerged, and these studies have greatly expanded the scope of our understanding in this field. We here focused our review on several selected areas including secondary malignancies occurring in patients with autoimmune diseases; radiation therapy alone as a causative agent; the similarity and differences between therapy-related myelodysplastic syndromes (t-MDS) and acute myeloid leukemia (t-AML); clinical behavior and treatment outcome of t-AML patients with favorable cytogenetics; the incidence and clinical features of myelodysplastic/myeloproliferative neoplasms, as well as acute lymphoblastic leukemia and myeloproliferative neoplasms in patients with prior cytotoxic exposure. Read More

Biol Blood Marrow Transplant 2014 Jun 7;20(6):837-43. Epub 2014 Mar 7.

Division of Blood and Marrow Transplantation, Stanford University, Stanford, California. Electronic address:

Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative therapy for the myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but treatment toxicity has been a barrier to its more widespread use. The nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) permits the establishment of donor hematopoiesis necessary for the graft-versus-malignancy effect and is protective against acute graft-versus-host disease (aGVHD), but it has minimal direct cytotoxicity against myeloid diseases. We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS (n = 32), therapy-related myeloid neoplasms (n = 15), MPN (n = 9), and chronic myelomonocytic leukemia (n = 5). Read More

Ann Hematol 2013 Oct 10;92(10):1335-43. Epub 2013 May 10.

Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 72, Houston, TX 77030, USA.

The presence of moderate to severe bone marrow (BM) fibrosis has been shown to be an adverse feature in patients with primary myelodysplastic syndromes (MDS). However, the clinical importance of BM fibrosis is not clear in therapy-related MDS. We retrieved all therapy-related MDS (t-MDS) cases (n = 266) diagnosed at our hospital over a 10-year period (2003-2012). Read More

Am J Clin Pathol 2012 Dec;138(6):855-66

Dept of Pathology, Department of Medicine, Duke University Medical Center,Durham, NC 27710, USA.

We describe 41 cases of myeloid neoplasms (MNs) secondary to plasma cell myeloma (PCM). The types of MN included myelodysplastic syndrome (MDS) in 34 (82.9%), acute myeloid leukemia (AML) in 4 (9. Read More

Semin Hematol 2012 Oct;49(4):323-9

Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Service d'hématologie clinique, Paris 13 university, Bobigny, France.

Azacitidine (AZA) improves long-term outcomes of higher-risk myelodysplastic syndrome (MDS) and is now the reference frontline therapy of higher-risk MDS not eligible for allogeneic stem cell transplant. Notably, in a phase III randomized trial, AZA significantly prolonged overall survival (OS) compared to conventional care regimens, in all cytogenetic subgroups. Nevertheless, further improvement of outcome for those patients is warranted, partly by researching for better prognostic factors of response to AZA, and also by developing new therapeutic strategies, in particular by combining AZA and other drugs known to have an effect in MDS. Read More

Leuk Lymphoma 2013 Mar 21;54(3):639-42. Epub 2012 Aug 21.

Am J Hematol 2012 Jul 6;87(7):684-6. Epub 2012 May 6.

Mayo Medical School, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Among 6,565 consecutive abnormal cytogenetic reports at our institution, 3,192 (49%) constituted sole abnormalities, of which 230 (7%) involved chromosome 7: monosomy 7 (n = 98), 7q- (n = 51), der(1;7)(q10;p10) (n = 44), balanced translocations (n = 15), ring 7 (n = 13), and 7p- (n = 9). The most frequent histopathologic correlates were myelodysplastic syndromes (MDS; 28%), acute myeloid leukemia (AML; 17%), secondary or therapy-related MDS/AML (13%), primary myelofibrosis (PMF; 7%), and chronic myelomonocytic leukemia (6%). Monosomy 7 was the most frequent in each one of these disease categories except PMF where 7q- was more frequent. Read More

Am J Hematol 2013 Mar 6;88(3):240-1. Epub 2012 May 6.

Department of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.