scholarly journals A Paraneoplastic Syndrome Characterized by Extremity Swelling with Associated Inflammatory Infiltrate Heralds Aggressive Transformation of Myelodysplastic Syndromes/Myeloproliferative Neoplasms to Acute Myeloid Leukemia: A Case Series

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
James K. Mangan ◽  
Selina M. Luger
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Intensive Therapy ◽  
Myeloproliferative Neoplasm ◽  
Case Series ◽  
Disease Status ◽  
Inflammatory Syndrome ◽  
Acute Myeloid

There has been a long history of reports describing a variety of paraneoplastic phenomena associated with myelodysplastic syndromes, particularly those with autoimmune manifestations. We report here a series of patients with an antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) that underwent aggressive transformation to acute myeloid leukemia (AML). In each case, the transformation to AML was preceded by an inflammatory syndrome characterized by unilateral extremity swelling and an associated inflammatory skin infiltrate, as well as other signs of inflammation, including profound hyperferritinemia without evidence of a hemophagocytic syndrome. We suggest that such an inflammatory syndrome may herald aggressive transformation of MDS/MPN to AML. Patients with known MDS/MPN who present with these features may benefit from early bone marrow examination to assess disease status. Early intervention with corticosteroids in select patients may result in improvement or resolution of the symptoms and permit intensive therapy for AML to be delivered.

scholarly journals Protracted Clonal Trajectory of a JAK2 V617F-Positive Myeloproliferative Neoplasm Developing during Long-Term Remission from Acute Myeloid Leukemia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Stephen E. Langabeer ◽  
Karl Haslam ◽  
Maria Anne Smyth ◽  
John Quinn ◽  
Philip T. Murphy
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Time Frame ◽  
Divergent Evolution ◽  
Common Precursor ◽  
Previously Treated ◽  
Acute Myeloid

Although transformation of the myeloproliferative neoplasms (MPNs) to acute myeloid leukemia (AML) is well documented, development of an MPN in patients previously treated for, and in remission from, AML is exceedingly rare. A case is described in which a patient was successfully treated for AML and in whom a JAK2 V617F-positive MPN was diagnosed after seven years in remission. Retrospective evaluation of the JAK2 V617F detected a low allele burden at AML diagnosis and following one course of induction chemotherapy. This putative chemoresistant clone subsequently expanded over the intervening seven years, resulting in a hematologically overt MPN. As AML relapse has not occurred, the MPN may have arose in a separate initiating cell from that of the AML. Alternatively, both malignancies possibly evolved from a common precursor defined by a predisposition mutation with divergent evolution into MPN through acquisition of the JAK2 V617F and AML through acquisition of different mutations. This case emphasizes the protracted time frame from acquisition of a disease-driving mutation to overt MPN and further underscores the clonal complexity in MPN evolution.

scholarly journals Low Incidence of V617FJAK2 Mutation in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4957-4957
Author(s):  
Gueorgui Balatzenko ◽  
Branimir Spassov ◽  
Yanica Georgieva ◽  
Vasil Hrischev ◽  
Margarita Guenova
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Myeloproliferative Neoplasms ◽  
Polymorphism Analysis ◽  
Jak2 Mutation ◽  
Mutation Status ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Background: V617F JAK2 mutation is a typical molecular finding in BCR-ABL-negative myeloproliferative neoplasms (MPN). The same abnormality has also been reported in other myeloid malignancies. However, the data regarding the incidence and clinical relevance of V617F JAK2 in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are conflicting. Aim: To establish the incidence and clinical significance of V617F JAK2 mutation in AML and MDS patients in our institution. Materials and Methods : AML and MDS patients with isolated bone marrow mononuclear cells were included in this study, as follows: (i) 139 AML patients (71 females; 68 males; mean age of 57.5±15.3 years), including: 122 - de novo AML, 7 - therapy related AML (t-AML) and 10 - secondary AML (sAML) after primary MPN [3 V617F JAK2(+), 2 V617F JAK2(-) and 5 with unknown initial V617F JAK2 status]; (ii) 35 MDS patients. V617F JAK2 mutation status was determined using allele-specific polymerase chain reaction (PCR) and PCR RFLP (Restriction Fragment Lenght Polymorphism) analysis. Results: V617F JAK2 mutation was detected in 3 AML patients: (i) in 1/122 (0.8%) de novo AML patients - male patient with minimally differentiated AML, with no antecedent MPN and the leukemic population showed aberrant myeloid phenotype with co-expression of CD7 and overexpression of EVI1 gene, (ii) in 2/10 (20.0%) patients with sAML after MPN and both patients had V617F JAK2(+) sAML after V617F JAK2(+) primary myelofibrosis. Interestingly; in the same group, a female patient with V617F JAK2(+) essential thrombocythemia developed 5 years later V617F JAK2(-) sAML with an aberrant myelomonocytic phenotype and co-expression of CD56. None of the patients with t-AML or MDS tested positive for V617F JAK2. Conclusion: V617F JAK2 mutation is a rare finding in AML and MDS patients. Higher incidence was observed in sAML after MPN. However, the mutation status at the AML stage may not be identical as that detected during the primary MPN. Disclosures No relevant conflicts of interest to declare.

scholarly journals Familial Aggregation of Acute Myeloid Leukemia and Myelodysplastic Syndromes

2012 ◽  
Vol 30 (2) ◽  
pp. 179-183 ◽  
Author(s):  
Lynn R. Goldin ◽  
Sigurdur Y. Kristinsson ◽  
Xueying Sharon Liang ◽  
Åsa R. Derolf ◽  
Ola Landgren ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Familial Aggregation ◽  
Young Patients ◽  
Myeloid Malignancies ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Acute Myeloid

Purpose Apart from rare pedigrees with multiple cases of acute myeloid leukemia (AML), there is limited data on familial aggregation of AML and myelodysplastic syndromes (MDSs) in the population. Patients and Methods Swedish population-based registry data were used to evaluate risk of AML, MDS, and other malignancies among 24,573 first-degree relatives of 6,962 patients with AML and 1,388 patients with MDS compared with 106,224 first-degree relatives of matched controls. We used a marginal survival model to calculate familial aggregation. Results AML and/or MDS did not aggregate significantly in relatives of patients with AML. There was a modest risk ratio (RR, 1.3; 95% CI, 0.9 to 1.8) in myeloproliferative/myeloid malignancies combined. The risks for any hematologic or any solid tumor were modestly but significantly increased. Relatives of patients with MDS did not show an increased risk for any hematologic tumors. In contrast, we found a significantly increased risk (RR, 6.5; 95% CI, 1.1 to 38.0) of AML/MDS and of all myeloid malignancies combined (RR, 3.1; 95% CI, 1.0 to 9.8) among relatives of patients diagnosed at younger than age 21 years. Conclusion We did not find evidence for familial aggregation of the severe end of the spectrum of myeloid malignancies (AML and MDS). The risks of myeloproliferative neoplasms were modestly increased with trends toward significance, suggesting a possible role of inheritance. In contrast, although limited in sample size, relatives of young patients with AML were at increased risk of AML/MDS, suggesting that germline genes may play a stronger role in these patients. The increased risk of all hematologic malignancies and of solid tumors among relatives of patients with AML suggests that genes for malignancy in general and/or other environmental factors may be shared.

scholarly journals Development of a myelodysplastic/myeloproliferative neoplasm-unclassifiable in a patient with acute myeloid leukemia: a case report and literature review

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110184
Author(s):  
Meifang Zhao ◽  
Jingnan Sun ◽  
Shanshan Liu ◽  
Hongqiong Fan ◽  
Yu Fu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Hematologic Malignancies ◽  
Prior History ◽  
History Of ◽  
Factor Therapy ◽  
Growth Factor Therapy ◽  
Acute Myeloid

Myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) are a heterogeneous group of hematologic malignancies characterized by dysplastic and myeloproliferative overlapping features in the bone marrow and blood. The occurrence of the disease is related to age, prior history of MPN or MDS, and recent cytotoxic or growth factor therapy, but it rarely develops after acute myeloid leukemia (AML). We report a rare case of a patient diagnosed with AML with t(8; 21)(q22; q22) who received systematic chemotherapy. After 4 years of follow-up, MDS/MPN-unclassifiable occurred without signs of primary AML recurrence.

scholarly journals Number of Mutations and Type of Prior Myeloproliferative Neoplasm Are Prognostic Factors in Acute Myeloid Leukemia Post Myeloproliferative Neoplasms

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2806-2806 ◽  
Author(s):  
Edmond Chiche ◽  
Sarah Bonnet ◽  
Sarah Bertoli ◽  
Andrew T Kuykendall ◽  
Lauris Gastaud ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Induction Treatment ◽  
Calr Mutations ◽  
Acute Myeloid

Abstract BACKGROUND Post myeloproliferative neoplasms (MPN) acute myeloid leukemia (AML) occurs respectively in 1.5%, 7.0% and 11% of patients with essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). This subgroup of AML has very poor prognosis and are often excluded from clinical trials. Therefore, only few cohorts including molecular data are available. MATERIAL AND METHODS We retrospectively collected data from 111 patients treated in four centers in France for post MPN-AML. Clinical, molecular and treatment information was available for all patients at AML and MPN stages. DNA was extracted from samples at diagnosis of MPN chronic phase, at diagnosis of AML phase and after induction treatment. JAK2-V617F mutations were identified by qPCR (Ipsogen® MutaQuant kit, Qiagen, Germany), MPL-W515L/K mutations were identified by PCR (Ipsogen® MutaScreen kit, Qiagen, Germany) and CALR mutations were identified by conventional sequencing (Applied Biosystems, 3500Genetic Analyzer). NGS on 36 genes using Ampliseq librairy and Ion Proton sequencing (Thermofisher, Waltham, MA, USA) were performed in 96/111 patients. Overall response rate (ORR) was defined by complete remission (CR), CR with incomplete hematologic recovery (CRi), partial remission (PR) and stable disease (SD). Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). RESULTS 111 patients treated for post MPN-AML were retrospectively included in this study. Sex ratio M/F was 54%/46%. Median age at AML diagnosis was 66 years (28-89, range). Cytogenetic categories were favorable, intermediate and adverse in 2 (2%), 51 (46%) and 47 (42%) patients, respectively. 25/111 (23%) patients had a monosomal karyotype (MK). Median number of additional mutations excluding from JAK2/MPL/CALR mutations was 2 (0-6, range). The most frequent additional mutations were TP53 (23%), ASXL1 (17%), TET2 (13%), SRSF2 (10%), DNMT3A (8%), SF3B1 (8%) and RUNX1 (8%). Only 2 patients were mutated for NPM1 and 2 and 4 patients were FLT3-ITD and FLT3-TKD, respectively. Prior MPN were PV, ET and PMF in 20%, 34% and 46% of patients, respectively. First line treatment was intensive chemotherapy (IC) for 61 (55%) patients, hypomethylating agents (HMA) for 10 (9%) or other treatments including best supportive care, cytoreduction for the other ones. 24/111 (22%) underwent to ASCT. ORR was 54% (with 30/71 (42%) in CR/CRi) in patients treated by IC or HMA. We did not identify factors predicting a higher rate of CR/CRi. OS was 12 months [6-18] and was not influenced by transplant, cytogenetic categories or by the type and allele frequencies of JAK2/CALR/MPL mutations. OS was significantly longer in the group treated with HMA as compared to IC (10 versus 46 months, respectively, p=0.006); in patients with prior PV as compared to ET or MF (26 months [0-57] versus 10 months [7-13] versus 10 months [4-16] respectively, p=0.07) and in patients with presence of additional mutations other than JAK2/CALR/MPL (5 months [0-12] versus 46 months [32-60] in 38 patients without mutation versus 58 patients with presence of at least one mutation, respectively, p=0.04). By multivariate analysis, only presence of additional mutations was predictive for OS with a hazard ratio (HR) = 0.42 [0.18-0.97] (p=0.04). Finally, we followed the VAFs of JAK2 in seven patients before and after IC. We observed in 2 patients an increase of JAK2 clone correlated with CR whereas no variation of VAFs was associated with absence of CR. CONCLUSIONS In conclusion, we confirmed the poor prognosis of post MPN AML. Classical AML prognostic factors were not validated in our cohort. We identified the presence of mutations other than JAK2/MPL/CALR as the main prognostic factor whereas post-PV AML appeared to do better than post-ET and post-PMF AML. The very poor result of IC with or without ASCT highlights the need to develop specific clinical trials in this subgroup of AML. Disclosures Kuykendall: Celgene: Honoraria; Janssen: Consultancy. Sallman:Celgene: Research Funding, Speakers Bureau. Cluzeau:CELGENE: Consultancy; MENARINI: Consultancy; JAZZ PHARMA: Consultancy.

scholarly journals Familial risks of acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms

Blood ◽  
2018 ◽  
Vol 132 (9) ◽  
pp. 973-976 ◽  
Author(s):  
Amit Sud ◽  
Subhayan Chattopadhyay ◽  
Hauke Thomsen ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Acute Myeloid

scholarly journals Treatment-Related Risk Factors for Transformation to Acute Myeloid Leukemia and Myelodysplastic Syndromes in Myeloproliferative Neoplasms

2011 ◽  
Vol 29 (17) ◽  
pp. 2410-2415 ◽  
Author(s):  
Magnus Björkholm ◽  
Åsa R. Derolf ◽  
Malin Hultcrantz ◽  
Sigurdur Y. Kristinsson ◽  
Charlotta Ekstrand ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndromes ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasms ◽  
Alkylating Agents ◽  
Primary Myelofibrosis ◽  
Special Focus ◽  
Related Factors ◽  
Increased Risk ◽  
Acute Myeloid

Purpose Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU). Methods On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk. Results Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P32), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P32 greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation. Conclusion The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P32 and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors.

scholarly journals Secondary Acute Myeloid Leukemia in a One-Year-Old Girl Diagnosed with JAK2-V617F Mutation Positive Myeloproliferative Neoplasm

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Gary M. Woods ◽  
Rajinder P. S. Bajwa ◽  
Samir B. Kahwash ◽  
Terri Guinipero
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Myeloproliferative Neoplasms ◽  
Pediatric Population ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Secondary Acute Myeloid Leukemia ◽  
One Year ◽  
Acute Myeloid

Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by hyperproliferation of hematologic cell lines and have been associated with tyrosine kinase JAK2-V617F mutations. Secondary acute myeloid leukemia (sAML) is a known complication of JAK2-V617F+ MPNs and bears a poor prognosis. Although the evolution of a JAK2-V617F+ MPN to a mixed-lineage leukemia has been reported in the pediatric population, no evolutions into sAML have been described. We present a case of a one-year-old girl diagnosed with JAK2-V617F+ MPN with evolution into sAML. Despite initial morphologic remission, she eventually relapsed and succumbed to her disease.

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