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Leukemia risk models in primary myelofibrosis: an International Working Group study

Leukemia volume 26, pages 1439–1441 (2012)Cite this article

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Overall survival in primary myelofibrosis (PMF) is assessed by the International Prognostic Scoring System (IPSS),1 at time of diagnosis, or the dynamic IPSS (DIPSS)2 or DIPSS-plus,3 at any time during the disease course, in the absence and presence of cytogenetic information, respectively. DIPSS-plus is based on eight risk factors: age>65 years, constitutional symptoms, hemoglobin <10 g/dl, transfusion need, leukocyte count >25 × 109/l, platelet count <100 × 109/l, circulating blasts ⩾1% and unfavorable karyotype. The latter includes complex karyotype or any one or two abnormalities that include +8, −7/7q-, i(17q), −5/5q-, 12p-, inv(3) or 11q23 rearrangement.4 In regards to leukemia-free survival (LFS), recent studies have highlighted the prognostic significance of monosomal karyotype (MK),5 unfavorable karyotype,3, 4, 6 circulating blasts ⩾3%,7 platelet count <100 × 109/l,3, 7 transfusion need8, 9 and DIPSS.10 Similarly, patients with PMF or post-polycythemia vera/essential thrombocythemia myelofibrosis face a higher risk of death and leukemic transformation (LT) in the presence of chromosome 17 abnormalities, circulating blasts ⩾10% or platelets <50 × 109/l.11 In the current study, multivariable and receiver operating characteristic (ROC) analyses were applied to an institutional database of 884 karyotypically annotated patients with PMF, in order to define karyotype-dependent and karyotype-independent risk models for LFS. A separate cohort of 525 patients from an international database2 was used to validate the karyotype-independent model.

The diagnoses of PMF and LT were according to the World Health Organization criteria.12 All statistical analyses considered clinical and laboratory parameters obtained at the time of referral to the Mayo Clinic. Variables considered in patients from the international database were those obtained at the time of initial diagnosis. ROC plots were prepared to determine the best discriminant levels for continuous variables in predicting LT. The end point used in this regard (that is, the binary outcome) was the occurrence or non-occurrence of LT at 5 years after diagnosis.13 In other words, patients were classified as alive and leukemia-free/censored when follow-up time was >5 years and as leukemia/uncensored for patients known to have transformed into acute leukemia before this time point. The performance of the selected cut-off values was quantified by the area under the ROC curve (AUC). LFS was calculated from the date of first referral to date of LT (uncensored) or death/last contact (censored). LFS survival curves were prepared by the Kaplan-Meier method and compared by the log-rank test. Cox proportional hazard regression model was used for multivariable analysis. P-values <0.05 were considered significant. The Stat View (SAS Institute, Cary, NC, USA) and JMP (SAS Institute) statistical packages were used for all computations.

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References

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Acknowledgements

Studies performed at the University of Florence and University of Pavia, related to creation of the international database, were funded by a special Grant from ‘AIRC 5 per mille’ to the AGIMM group (AIRC-Gruppo Italiano Malattie Mileoproliferative); for a complete list of AGIMM investigators see at http://www.progettoagimm.it.

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Authors and Affiliations

  1. Division of Hematology, Rochester, MN, USA

    A Tefferi, A Pardanani, N Gangat & K H Begna

  2. Division of Hematopathology, Rochester, MN, USA

    C A Hanson

  3. Division of Cytogenetics, Mayo Clinic, Rochester, MN, USA

    D L Van Dyke

  4. Department of Internal Medicine, Division of Hematology, Ospedale di Circolo e Fondazione Macchi, Varese, Italy

    D Caramazza & F Passamonti

  5. Department of Critical Care, Section of Hematology, University of Florence, Florence, Italy

    A M Vannucchi

  6. Division of Hematology, Ospedale Niguarda Ca’ Granda, Milan, Italy

    E Morra

  7. Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico S Matteo, University of Pavia, Pavia, Italy

    M Cazzola

  8. Department of Hematology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain

    A Pereira & F Cervantes

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  1. A Tefferi
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Correspondence to A Tefferi.

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Tefferi, A., Pardanani, A., Gangat, N. et al. Leukemia risk models in primary myelofibrosis: an International Working Group study. Leukemia 26, 1439–1441 (2012). https://doi.org/10.1038/leu.2011.374

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