Back
Essential Thrombocythemia (ET) and Polycythemia Vera (PV) Symptom Burden: Phenotypic Cluster Analysis Among an International Sample of 1,141 ET and PV Patients
Journal article

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) Symptom Burden: Phenotypic Cluster Analysis Among an International Sample of 1,141 ET and PV Patients

  • Emanuel, Robyn M. Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA,
  • Dueck, Amylou C. Mayo Clinic, Scottsdale, AZ, USA,
  • Geyer, Holly Lynn Hematology, Mayo Clinic, Scottsdale, AZ, USA,
  • Kiladjian, Jean-Jacques Hôpital Saint-Louis et Université Paris Diderot, Paris, France,
  • Slot, Stefanie Department of Hematology, VU University Medical Center, Amsterdam, Netherlands,
  • Zweegman, Sonja VU University Medical Center, Amsterdam, Netherlands,
  • te Boekhorst, Peter Erasmus Medical Center, Rotterdam, Netherlands,
  • Commandeur, Suzan Department of Dermatology, LUMC, Leiden, Netherlands,
  • Schouten, Harry C Department of Hematology, University Medical Center Maastricht, Maastricht, Netherlands,
  • Sackmann, Federico GATLA, Grupo Argentino de Tratamiento de Leucemia Aguda, Buenos Aires, Argentina,
  • Fuentes, Ana Kerguelen Department of Haematology, University Hospital La Paz, Madrid, Spain,
  • Hernandez, Dolores Hematology, Hospital Universitario La Paz, Madrid, Spain,
  • Pahl, Heike L. Clinical Research Center Experimental Anaesthesiology, University Hospital Freiburg, Freiburg, Germany,
  • Griesshammer, Martin Hematology and Oncology, Johannes Wesling Clinic Minden, Minden, Germany,
  • Stegelmann, Frank Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany,
  • Doehner, Konstanze Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany,
  • Lehmann, Thomas Hematology, University Hospital Basel, Basel, Switzerland,
  • Bonatz, Karin Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany,
  • Reiter, Andreas III. Medizinische Klinik, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany,
  • Boyer, Françoise Service d'Hématologie Clinique, Centre Hospitalier Universitaire, Angers, France,
  • Etienne, Gabriel Institut Bergonie, Bordeaux, France,
  • Ianotto, Jean-Christophe Centre Hospitalier Universitaire, Brest, France,
  • Ranta, Dana Department of Hematology, Nancy University Hospital, Vandoeuvre-Les-Nancy, France,
  • Roy, Lydia CHU de Poitiers et INSERM CIC 802, Poitiers University Hospital, Poitiers, France,
  • Cahn, Jean-Yves Onco-Hematologie, CHU-Grenoble, Grenoble, France,
  • Harrison, Claire N Guy's and St Thomas' NHS FoundationTrust, London, United Kingdom,
  • Radia, Deepti H Dept. of Haematology, Guys and St Thomas NHS Foundation Trust, London, United Kingdom,
  • Muxi, Pablo J. Unidadde Hematología, Hospital Británico, Montevideo, Uruguay,
  • Maldonado, Norman I School of Medicine, University of Puerto Rico, San Juan, PR, PR,
  • Besses, Carlos Hematology, Hospital del Mar, Barcelona, Spain,
  • Cervantes, Francisco Hematology Department, Hospital Clinic, University of Barcelona, Barcelona, Spain,
  • Johansson, Peter Department of Medicine, Hematology and Coagulation Section, Gothenburg, Sweden,
  • Barbui, Tiziano A.O. Ospedali Riuniti di Bergamo, Bergamo, Italy,
  • Barosi, Giovanni IRCCS Policlinico S.Matteo Foundation, Pavia, Italy,
  • Vannucchi, Alessandro M. University of Florence, Florence, Italy,
  • Passamonti, Francesco Ospedale di Circolo e Fondazione Macchi, Varese, Italy,
  • Andreasson, Bjorn Internal Medicine, NU Hospital Organization, Uddevalla, Sweden,
  • Ferarri, Maria L Biol. Sci., Ospedali Riuniti di Bergamo, Bergamo, Italy,
  • Rambaldi, Alessandro Hematology, Ospedali Riuniti, Bergamo, Italy,
  • Birgegard, Gunnar Dept. of Hematology, University Hospital, Uppsala, Sweden,
  • Xiao, Zhijian Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China,
  • Xu, Zefeng MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China,
  • Zhang, Yue State Key Laboratory of Experiment Hematology, Institute of Hematology & Blood Diseases Hospital, Center for Stem Cell Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China,
  • Sun, Xiujuan MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China,
  • Xu, Junqing MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China,
  • Zhang, Peihong Department of Pathology, Institute of Hematology, Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin, China,
  • Gale, Robert Peter Imperial College, London, United Kingdom,
  • Tefferi, Ayalew Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA,
  • Mesa, Ruben A. Mayo Clinic Arizona, Scottsdale, AZ, USA
Show more…
Published in:
  • Blood. - American Society of Hematology. - 2012, vol. 120, no. 21, p. 1726-1726
Immunology
Cell Biology
Biochemistry
Hematology
English Abstract
Abstract 1726

Background:
We previously reported that symptom burden among persons with ET and PV can be severe and adversely affect QOL. The presence of severe symptoms is linked to poor prognosis. There is considerable inter-subject heterogeneity regarding which symptoms are present in which subjects. No studies have empirically evaluated whether disease characteristics can be grouped in related symptom clusters. Using our previously validated 18 item Myeloproliferative Neoplasm Assessment Form (MPN-SAF) (Blood 2011;118:401–408) given in conjunction with the 9 item Brief Fatigue Inventory (BFI) (Cancer 1999;85:1186–1196), we sought to evaluate symptom burden by means of cluster analysis.


Methods:
Data was collected from an international cohort of subjects with MPNs including demographics, disease features and the completed BFI and MPN-SAF instruments. Surveyed symptoms included fatigue, early satiety, abdominal pain and discomfort, inactivity, headaches, concentration, dizziness, extremity tingling, insomnia, sexual difficulties, mood changes, cough, night sweats, pruritus, bone pain and fever on a 0 (absent) to 10 (worst-imaginable) scale. Development of symptom clusters was based on consideration of r-squared in hierarchical clustering using Ward linkage. Final cluster assignment was based on the nonhierarchical k-means method. Comparisons between symptom clusters were based on ANOVA and chi-squared tests.


Results:

Subject Demographic and Disease Characteristics:
Data from 1,141 subjects with PV (N=519) and ET (N=622) was prospectively collected (Chinese 236, French 305, German 45, Italian 114, Dutch 191, English 56, Spanish 109, Swedish 85. Age (mean 59, range, 26–87) and gender (54% F) were typical. Five clusters were selected (Figure 1). Frequencies of prior bleeding, spleen size, anemia, presence of any lab abnormality, language, gender, and MPN type varied significantly between clusters (P<0.05).


Cluster 1:
The “Reduced Symptom” Profile (n=421 (37%; 60% ET, 40% PV) The largest cluster, subjects had increased complaints of sexual difficulties and fatigue. There was a slightly higher proportion of subjects with ET (60%) versus PV. There were fewer lab abnormalities (28% prevalence) and less prior bleeding (3%) compared to other clusters. Spleen size was smallest of the cluster (1 cm below costal margin).


Cluster 2:
The “Fatigue-dominant” Group (n=286 (25%; 56% ET, 44% PV)). Subjects in this cluster were predominantly female and had relatively few laboratory abnormalities (19%) than other cohorts. They are characterized by high severity of fatigue compared to end-organ symptoms. Symptom profiles emphasize fatigue, QOL and insomnia with some end-organ complaints. The cohor 63% of the cohort.


Cluster 3:
The “End-Organ Complaints” Group (n=210 (18%; 49% ET, 51% PV)). Male predominant (56%), subjects had mainly macro-vascular symptom complaints including sexual difficulties, insomnia, and overall QOL, with few microvascular related symptoms (low itching/night sweats).


Cluster 4:
“Cognitive Complaints” Cluster (n=110 (10%; 53% ET, 47% PV)). The smallest cluster and female predominant (64%), main complaints include fatigue, insomnia, loss of concentration, numbness, and sad mood.


Cluster 5:
The “Highly Symptomatic” Cluster (n=114 (10%; 44% ET, 56% PV)). Subjects had many cognitive complaints and symptoms correlated with severe micro-vascular abnormalities (pruritus) and or splenomegaly. This cluster had the largest spleen sizes (mean 3 cm), the highest prevalence of prior thrombosis (29%), and highest frequency of lab abnormalities (43%). Cognitive and end-organ complaints were rated as most severe.



Conclusion:
This analysis offers new means of evaluating persons with PV and ET utilizing symptom clusters. Laboratory and physical abnormalities differed significantly between symptom clusters indicating that our groupings likely result from biological alterations present in specific disease phenotypes. Future studies should investigate correlations between clusters and prognosis and genotype.


Disclosures:
Kiladjian: Celgene: Research Funding; Novartis: Honoraria, Research Funding; Shire: Honoraria. Roy:Novartis, BMS: Speakers Bureau. Harrison:Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees. Passamonti:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Mesa:Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/92765
Statistics
Document views: 25 File downloads: