Thread by @TransfusionWM

Day 2 of #BSH2017 and am going malignant for a change.... MPDs coming up

Dr Jyoti Nangalia on genetic influences on phenotype in MPD #BSH2017

How can 3 genes cause 1 phenotype and how can 1 gene cause 3 phenotypes? #BSH2017

JAK2, MPL and CALR most frequent but many many other gene mutations seen in MPDs #BSH2017

DNA methylation of TET2 and DNMT3a appears to impact on stem cell expansion #BSH2017

ASXL1 affects histone methylation and is mutated in 25% MF #BSH2017

Many of these mutations are found in the blood of "healthy" adults, w frequency increasing with aging #BSH2017

Diagnosis of MPDs remains a heirearchy with absence of PRV features required to diagnose ET #BSH2017

Lots of overlap w JAK2+ ET more likely incr neuts, thrombotic events & higher hct compared to MPL or CALR #BSH2017

Homo or heterozygosity of jak2 and type of mutation influences phenotype; exon12 mutns do not cause ET #BSH2017

Pts w homozygous jak2 much more likely to have PRV vs ET #BSH2017

TET2 mutns common in elderly. Order of TET2 and JAK2 mutns in those w both can influence phenotype #BSH2017

MPL is the thrombopoeitin receptor and in ET is a gain of function mutation. MPL mutatns present at older age #BSH2017

As mutation burden of MPL goes up, risk of fibrosis increases #BSH2017

CALR mutations are frame shifts and lead to a novel c terminus. This affects MPL binding in the ER #BSH2017

Biology explains why CALR and MPL mutations only affect platelet count #BSH2017

In MF additional mutations occur. No. mutations correlates w survival and risk of AML #BSH2017

"Triple negative" ET are phenotypically female w benign course in 66%. Is this really a malignant clone? #BSH2017

Other two thirds of triple neg ET are genetically heterogenous #BSH2017

Triple negative myelofibrosis on the other hand has a worse prognosis than those with jak2, MPL or CALR #BSH2017

Dr Martin Greisshammer on MPDs in pregnancy #BSH2017

Increasing problem as higher freq MPD in women, delaying pregnancy til later life and earlier diagnosis of MPDs #BSH2017

Male factors - spermogenesis is 10 weeks hence advise men to have 3/12 off HU prior to conception #BSH2017

Organogenesis between 3-8/40 most crucial time for women #BSH2017

Risk of thrombosis and bleeding both incr by MPDs in pregnancy but pregnancy doesn't appear to influence course of the disease #BSH2017

Outcome data for preg in MPNs is variable but recent UK data reassuring ncbi.nlm.nih.gov/pubmed/27612319 #BSH2017

JAK2 mutations associated w late preg loss, CALR tend to have better outcomes #BSH2017

Pre and post 2007 outcomes appear to be different - something has improved outcomes but ?what #BSH2017

Interferon is only cytoreduction that can be used in pregnancy #BSH2017

.@BritSocHaem guidelines for management of MPD in preg are internationally recognised onlinelibrary.wiley.com/doi/10.1111/j.… #BSH2017

Better outcomes seen with more strict monitoring of FBC &foetus, control of hct & use of LMWH in higher risk pts #BSH2017

Little definitive evidence for aspirin but use is probably beneficial &is regarded as std of care #BSH2017

Postpartum period is highest risk time for mother #BSH2017

All cytoreduction including IFN contraindicated in breastfeeding #BSH2017

Platelet count usually decreases in preg. Preg not considered an additional risk factor wrt consideration of cytoreductn #BSH2017

Now Wendy Osborne on CML in the elderly #BSH2017

Quicker and deeper response w Dasatinib and nilotinib vs imatinib but no overall survival benefit (?yet) seen #BSH2017

Imatinib now significantly less costly #BSH2017

Side effects like peripheral oedema may be negligible in young patients but can tip the balance (literally) in the elderly #BSH2017

One approach is to get control and then reduce dose in presence of any side effects #BSH2017

Arthralgia, myalgia and gi disturbance common imatinib side effects #BSH2017

>10% PCR at 6/12; >1% at 12/12 considered failures of therapy by ELN guidelines #BSH2017

Nilotinib, dasatinib and bosutinib all available now by NICE guidance #BSH2017

Cardiovascular toxicity and prolonged QTc w nilotinib of concern in elderly who may also have CV disease or risk factors #BSH2017

Q Risk2 score used by GPs to calculate cardiovascular risk #BSH2017

BP monitoring of all elderly CML patients is important #BSH2017

Pleural effusions in 33% pts on dasatinib. Stop drug = reolution of effn - no drains required. More have non specific SOB #BSH2017

Again, lower doses can be effective for disease control &can be reintroduced after effusions #BSH2017

Bosutinib causes GI symptoms which may be poorly tolerated by the elderly #BSH2017

Ponatinib in England only for those w T315I mutations #BSH2017

CV and thyroid side effects also occur #BSH2017

Nilotinib more difficult to administer - BD & some foods to avoid, timing of meals important. Elderly enjoy their marmalade! #BSH2017

Polypharmacy v important as most on other medications #BSH2017

Telephone clinics and text results service can improve quality of life. Technology in healthcare not just for the young! #BSH2017

Stopping therapy in STIM, TWISTER &DESTINY studies providing evidence that 40% pts can stop treatment BUT more monitoring needed #BSH2017

3 really excellent talks in the MPD session this morning! #BSH2017