Myeloproliferative Disorders in the - PDF document

Myeloproliferative Disorders in the Myeloproliferative Disorders in the Elderly: Clinical Presentation and Elderly: Clinical Presentation and Role of Bone Marrow ExaminationRole of Bone Marrow ExaminationArati V. Rao, M.D.Arati V. Rao, M.D.Division of Medical Oncology and GeriatricsDivision of Medical Oncology and GeriatricsDuke University Medical CenterDuke University Medical CenterDurham VA Medical CenterDurham VA Medical CenterDurham, NC. USADurham, NC. USASIOG, Madrid. November 10, 2007SIOG, Madrid. November 10, 2007 Chronic Myeloproliferative Chronic Mye

loproliferative Disorders (MPD)Disorders (MPD)BcrBcr--Abl NegativeAbl Negative----Polycythemia Vera (PV)Polycythemia Vera (PV)----Essential Thrombocytosis (ET)Essential Thrombocytosis (ET)----Agnogenic Myeloid Metaplasia/ Agnogenic Myeloid Metaplasia/ Idiopathic MyelofibrosisIdiopathic MyelofibrosisBcrBcr--Abl PositiveAbl Positive----Chronic Myeloid LeukemiaChronic Myeloid Leukemia Introduction IntroductionOlder patients with high blood cell counts Older patients with high blood cell counts more likely to be referred for further more likely to be referred for fur

ther evaluation, including Bone Marrow (BM) evaluation, including Bone Marrow (BM) biopsybiopsyMedian age of diagnosis of MPD is 60 years Median age of diagnosis of MPD is 60 years with 25with 25--50% patients over 60 years of age50% patients over 60 years of ageHistopathological data not mandatory for Histopathological data not mandatory for diagnosis of MPD diagnosis of MPD BM Biopsy is not without complications, BM Biopsy is not without complications, especially in elderlyespecially in elderly Complications from BM Biopsy Complications from BM BiopsyBain et al

: 26 adverse events among Bain et al: 26 adverse events among 54,890 BM biopsies54,890 BM biopsiesHemorrhage in 14 patients: six needing Hemorrhage in 14 patients: six needing blood transfusion and one deathblood transfusion and one deathRisk factors for hemorrhage were:Risk factors for hemorrhage were:----diagnosis of MPDdiagnosis of MPD----aspirin therapy or bothaspirin therapy or both----warfarin therapywarfarin therapy----disseminated intravascular coagulation disseminated intravascular coagulation ----obesity obesity BM Biopsy in the Elderly BM Biopsy in th

e ElderlyHigher coHigher co--morbiditiesmorbiditiesAging hematopoeitic systemAging hematopoeitic systemIncreased qualitative platelet Increased qualitative platelet defects and/or coagulopathydefects and/or coagulopathyincreased bleedingincreased bleeding Objectives ObjectivesPrimary objective:Primary objective:Determine by retrospective review, what percentage Determine by retrospective review, what percentage of elderly patients referred to the Hematologyof elderly patients referred to the Hematology--Oncology clinic at the Durham Veterans Affairs Oncology clin

ic at the Durham Veterans Affairs Medical Center with a suspicion of MPD, who Medical Center with a suspicion of MPD, who subsequently undergo BM biopsy actually have an subsequently undergo BM biopsy actually have an underlying disorder like CML, PV, ET, or MF underlying disorder like CML, PV, ET, or MF Secondary objectives:Secondary objectives:1. Determine clinical characteristics of these elderly 1. Determine clinical characteristics of these elderly patients and compare them to their younger patients and compare them to their younger counterpartscounterpart

s2. Determine if complications occurred as a result of 2. Determine if complications occurred as a result of BM biopsy i.e. infection, bleeding, or hematomaBM biopsy i.e. infection, bleeding, or hematoma Eligibility Criteria Eligibility CriteriaAll patients referred to the HematologyAll patients referred to the Hematology--Oncology clinic at the Durham Veterans Affairs Oncology clinic at the Durham Veterans Affairs Medical Center between July 1, 2000 to June 9, Medical Center between July 1, 2000 to June 9, 2005 specifically to rule out a MPD. These 2005 specifi

cally to rule out a MPD. These included:included:Leukocytosis particularly neutrophilia i.e. White Leukocytosis particularly neutrophilia i.e. White �Blood Cell Count 12 x 10�Blood Cell Count 12 x 1099�/L and neutrophils �/L and neutrophils 7.5 x 107.5 x 1099/L /L �Polycythemia i.e. Hematocrit 42% in females �Polycythemia i.e. Hematocrit 42% in females �and 47% in males�and 47% in males�Thrombocytosis i.e. platelet count 500 x 10�Thrombocytosis i.e. platelet count 500 x 1099/L /L Re

sults ResultsN=141 patients referred for leukocytosis, N=141 patients referred for leukocytosis, polycythemia, and/or thrombocytosispolycythemia, and/or thrombocytosisN=76 (54%) ()N=76 (54%) ()were 60 yearswere 60 yearsOlder patients with more coOlder patients with more co--morbidities: morbidities: 39/65 (60%) older patients with 2 co39/65 (60%) older patients with 2 co--morbid conditions vs. 24/76 (31.5%) in morbid conditions vs. 24/76 (31.5%) in younger patients (younger patients (p=0.0068p=0.0068))Most common coMost common co--morbid conditions: morbid co

nditions: Hypertension and Type 2 DMHypertension and Type 2 DM Clinical and Demographic Features Clinical and Demographic Features60607474Smoking/ Tobacco Smoking/ Tobacco useuse26262020Aspirin useAspirin use4488ThromboThrombo--embolic embolic complicationscomplications39/6539/6524/7624/762 co2 co--morbid morbid conditionsconditions8888SplenomegalySplenomegaly16161212FatigueFatigue65 65 76 76 Total Total n=141n=141Age Age 60 years60 yearsAge Age ParameterParameter BM Biopsy BM BiopsyIn all 66/141 (47%) patients underwent a In all 66/141 (47%) patients underwent a

BM aspiration and biopsyBM aspiration and biopsy53% had no BM examination: 53% had no BM examination: combination of patient and physician combination of patient and physician factors for refusalfactors for refusalOf the 66 who underwent BM biopsy 25 Of the 66 who underwent BM biopsy 25 (38%) patients ()(38%) patients ()patients 60 years; patients 60 years; p=0.0003 p=0.0003 Results of BM Biopsy Results of BM Biopsy0000Any Any complication complication after BM after BM biopsybiopsy991111PV n=20PV n=20191966ET n=25ET n=259 9 6 6 CML n=15CML n=150.00670.006730

(65%)30 (65%)16 (35%)16 (35%)Chromosomal Chromosomal analysis n=46analysis n=460.00030.000341 (62%)41 (62%)25 (38%)25 (38%)BM biopsy BM biopsy n=66n=66PP--valuevalue60 years60 yearsn=65 (46 %)n=65 (46 %)n=76 (54%)n=76 (54%)Total patientsTotal patientsnn--=141=141 Yield from BM Biopsy Yield from BM BiopsyPatients Patients 60 years 60 years n=41, 37 (90%) n=41, 37 (90%) patients in all diagnosed with CML patients in all diagnosed with CML (majority bcr(majority bcr--abl +), PV or ETabl +), PV or ETPatients Patients (92%) in all diagnosed with CML ( all (92%) in al

l diagnosed with CML ( all bcrbcr--abl +), PV or ETabl +), PV or ETNo increased risk of infection, bleeding No increased risk of infection, bleeding or hemorrhage in either groupor hemorrhage in either group Other Diagnosis Other DiagnosisIncludes patients without BM biopsy (n=75) Includes patients without BM biopsy (n=75) and 6 patients who underwent a BM biopsyand 6 patients who underwent a BM biopsyLeukocytosis of unknown origin n=25Leukocytosis of unknown origin n=25Reactive Leukocytosis ( drugs, smoking, Reactive Leukocytosis ( drugs, smoking, inflammations)

n=13inflammations) n=13Secondary Erythrocytosis (based on Secondary Erythrocytosis (based on smoking history, oxygen saturation, sleep smoking history, oxygen saturation, sleep apnea) n=20apnea) n=20Secondary Thrombocytosis (infection, Secondary Thrombocytosis (infection, inflammation, iron deficiency anemia) n=8inflammation, iron deficiency anemia) n=8Unknown causes n=15Unknown causes n=15 Limitations Limitations53% patients did not have BM biopsy: 53% patients did not have BM biopsy: may have been able to diagnose may have been able to diagnose higher number o

f MPDshigher number of MPDsNo complications from BM biopsy ? No complications from BM biopsy ? due to selection of specific patientsdue to selection of specific patientsNo data on JAK2 V617F mutationNo data on JAK2 V617F mutationRetrospective review of predominantly Retrospective review of predominantly male patientsmale patients Conclusions Conclusions--11Older patients referred for MPD workOlder patients referred for MPD work--up have up have more comore co--morbid conditionsmorbid conditionsNo differences in clinical features and No differences in clinical fea

tures and thrombothrombo--embolic diseaseembolic diseaseOlder patients with suspected MPD undergo Older patients with suspected MPD undergo more BM examinationsmore BM examinationsIn patients with presumed MPD, a BM biopsy In patients with presumed MPD, a BM biopsy is of high yield in diagnosis of MPDis of high yield in diagnosis of MPDNo increase in risk of complications from BM No increase in risk of complications from BM examinationexamination BM Biopsy for Diagnosis of PV BM Biopsy for Diagnosis of PVMarrow histology is not part of PVSG diagnostic criteriaBM

histology is part of minor criterion in the WHO classification Inter-observer variation in quantifying erythroid and megakaryocytic proliferationTHUS: Role of BM biopsy in the evaluation of PV remains controversial! BM Biopsy for Diagnosis of ET BM Biopsy for Diagnosis of ETBM histology is part of PVSG diagnostic BM histology is part of PVSG diagnostic criteria and WHO criteriacriteria and WHO criteriaNeed to rule out CML, MF, MDS, and show Need to rule out CML, MF, MDS, and show stainable iron i.e. no Fe deficiencystainable iron i.e. no Fe deficiencyET can be di

vided into histologically distinct subgroups (true ET, prefibrotic MF, and early overt MF) with different prognosisInterobserver variation in assessing megakaryocyte morphology THUS: Role of BM biopsy in the evaluation of ET remains controversial! Conclusions Conclusions--22Notably in our retrospective study :Notably in our retrospective study :No diagnosis of MPD was made without No diagnosis of MPD was made without BM biopsy BM biopsy In patients ( young and old) with In patients ( young and old) with presumed MPD, a BM biopsy was of high presumed MPD, a BM bio

psy was of high yield in making a diagnosis of MPDyield in making a diagnosis of MPDIn JAK2 era: algorithms for diagnosis In JAK2 era: algorithms for diagnosis suggest confirming diagnosis of MPD suggest confirming diagnosis of MPD with a BM biopsy even if peripheral blood with a BM biopsy even if peripheral blood PCR for JAK2 V617F mutation is positivePCR for JAK2 V617F mutation is positive Acknowledgements AcknowledgementsNeela Dasgupta Goswami, M.D.Neela Dasgupta Goswami, M.D.Harvey Jay Cohen, M.D.Harvey Jay Cohen, M.D.Rebecca L. Yost, PARebecca L. Yost, PA--C