The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

Vardiman, James W.; Thiele, Jüergen; Arber, Daniel A.; Brunning, Richard D.; Borowitz, Michael J.; Porwit, Anna; Harris, Nancy L.; Beau, Michelle M. Le; Hellström‐Lindberg, Eva; Tefferi, Ayalew; Bloomfield, Clara D.

doi:10.1182/blood-2009-03-209262

Cited by 3,881 publications

(3,353 citation statements)

References 112 publications

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“…Patients ages 18 years and older with a diagnosis of MDS, CMML, or AML according to the World Health Organization (WHO) classification system,28 based on bone marrow aspirate and biopsy performed within 30 days before starting CC‐486, could participate. Patients must have had an Eastern Cooperative Oncology Group performance status score of 0‐2 and life expectancy of at least 3 months.…”

Section: Methodsmentioning

confidence: 99%

Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies

Savona

Kolibaba²,

Conkling

et al. 2018

American J Hematol

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CC‐486 (oral azacitidine) is an epigenetic modifier in clinical development for treatment of hematological cancers. This study of extended CC‐486 dosing included patients with myelodysplastic syndromes (MDSs), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). After a pharmacokinetic assessment period, 31 patients (MDS n = 18, CMML n = 4, and AML n = 9) entered a clinical phase in which they received CC‐486 300 mg once‐daily for 21 days of repeated 28‐day cycles. Median age was 71 years (range: 53‐93); 42% of patients were aged ≥75 years. A total of 5 patients with AML (63%) had prior MDS. Median number of CC‐486 treatment cycles was 4 (range: 1‐32). The most common treatment‐emergent adverse events (TEAEs) were gastrointestinal (84% of patients) and hematologic (81%). Most common grade 3‐4 TEAEs were neutropenia (n = 13, 42%) and anemia (n = 9, 29%). Ten patients experienced grade 4 neutropenia. Infrequently, CC‐486 dose was interrupted or reduced due to gastrointestinal (n = 5, 16%) or hematologic (n = 6, 19%) TEAEs. Overall response rate (complete remission [CR], CR with incomplete hematological recovery [CRi], partial remission [PR], marrow CR) in the MDS/CMML subgroups was 32% and in the AML subgroup (CR/CRi/PR) was 22%. Red blood cell transfusion independence rates in the MDS/CMML and AML subgroups were 33% and 25%, respectively, and 2 MDS/CMML patients attained hematologic improvement as a best response on‐study. No baseline gene mutation was predictive of response/nonresponse. CC‐486 allows flexible dosing and schedules to improve tolerability or response. Neutropenia in early treatment cycles deserves scrutiny and may warrant initiation of prophylactic antibiotics.KEY POINTSThe safety profile of oral CC‐486 was comparable to that of injectable azacitidine; most adverse events were hematological and gastrointestinal.Extended (21‐day/cycle) CC‐486 dosing induced responses in patients with hematological malignancies, many of whom had prior DNMTi failure.

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Section: Methodsmentioning

confidence: 99%

Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies

Savona

Kolibaba²,

Conkling

et al. 2018

American J Hematol

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“…The diagnoses of PMF and leukemic transformation were made according to WHO criteria. 1 Patients with blast-phase disease at the time of their referral to Mayo Clinic were excluded from the study. MPL and JAK2 mutation analyses were performed according to previously published methods.…”

Section: Methodsmentioning

confidence: 99%

“…1 Myelofibrosis is further subcategorized as primary myelofibrosis (PMF) and post-PV or post-ET MF. 2 Luminaries in PMF include Gustav Heuck (1854Heuck ( -1940, who described the disease in 1879 3 ; William Dameshek (1900Dameshek ( -1969, who coined the term myeloproliferative disorders in 1951 4 ; Philip Fialkow , who led the effort in deciphering the stem cell-derived clonal nature of MPN between 1967 and 1981 5,6 ; Vainchenker (b.…”

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confidence: 99%

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Tefferi

Lasho

Jimma

et al. 2012

Mayo Clinic Proceedings

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199

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Objective: To share our decades of experience with primary myelofibrosis and underscore the importance of outcomes research studies in designing clinical trials and interpreting their results. Patients and Methods: One thousand consecutive patients with primary myelofibrosis seen at Mayo Clinic between November 4, 1977, and September 1, 2011, were considered. The International Prognostic Scoring System (IPSS), dynamic IPSS (DIPSS), and DIPSS-plus were applied for risk stratification. Separate analyses were included for patients seen at time of referral (Nϭ1000), at initial diagnosis (Nϭ340), and within or after 1 year of diagnosis (Nϭ660). Results: To date, 592 deaths and 68 leukemic transformations have been documented. Parameters at initial diagnosis vs time of referral included median age (66 vs 65 years), male sex (61% vs 62%), red cell transfusion need (24% vs 38%), hemoglobin level less than 10 g/dL (38% vs 54%), platelet count less than 100 ϫ 10 9 /L (18% vs 26%), leukocyte count more than 25 ϫ 10 9 /L (13% vs 16%), marked splenomegaly (21% vs 31%), constitutional symptoms (29% vs 34%), and abnormal karyotype (31% vs 41%). Mutational frequencies were 61% for JAK2V617F, 8% for MPLW515, and 4% for IDH1/2. DIPSS-plus risk distributions at time of referral were 10% low, 15% intermediate-1, 37% intermediate-2, and 37% high. The corresponding median survivals were 17.5, 7.8, 3.6, and 1.8 years vs 20.0, 14.3, 5.3, and 1.7 years for patients younger than 60 years of age. Compared with both DIPSS and IPSS, DIPSS-plus showed better discrimination among risk groups. Five-year leukemic transformation rates were 6% and 21% in low-and high-risk patients, respectively. Conclusion: The current document should serve as a valuable resource for patients and physicians and provides context for the design and interpretation of clinical trials.

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“…The World Health Organization (WHO) classificationbased prognostic scoring system (WPSS) adds some important criteria such as transfusion dependency and cytogenetic risk group in order to classify MDS patients into 5 risk classes: very low risk, low risk, intermediate risk, high risk, and very high risk (6,7).…”

Section: Methodsmentioning

confidence: 99%

Systemic and immune manifestations in myelodysplasia: A multicenter retrospective study

Hollanda¹,

Beucher²,

Henrion³

et al. 2011

Arthritis Care & Research

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Objective. The presence of systemic and/or immune manifestations in myelodysplasia has been currently reported. The influence of these manifestations on the natural outcome of myelodysplastic syndrome has to be considered. We present a multicenter retrospective study (2002-2009) of patients with myelodysplastic syndrome disclosing systemic and/or immune manifestations. Methods. Forty-six patients with myelodysplasia presenting with systemic and/or immune manifestations were compared in terms of survival with 189 patients with myelodysplasia lacking these features. Results. The clinical picture in these cases consisted of fever (13%), arthralgia or arthritis (13%), and cutaneous manifestations (67%). Four cases of systemic vasculitis have been reported in our series, and they have a worse prognosis. Immune anomalies were recorded in 29% of the cases, and the presence of cryoglobulins was also associated with a worse prognosis. Conclusion. A difference in survival between patients with myelodysplastic syndrome with systemic manifestations and patients lacking these manifestations has been observed in the presence of systemic vasculitis and/or cryoglobulins.

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The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

Cited by 3,881 publications

References 112 publications

Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies

Extended dosing with CC‐486 (oral azacitidine) in patients with myeloid malignancies

One Thousand Patients With Primary Myelofibrosis: The Mayo Clinic Experience

Systemic and immune manifestations in myelodysplasia: A multicenter retrospective study

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