Bloody Minded

Join us in our third straight week of incredibly nice and incredibly talented haematology gurus as Professor John Moore joins us as an expert guest to discuss stem cell transplant in the myeloid disease setting. 
TIMESTAMPS
 1:00 – HYTTIOAOA
 1:47 – Introducing Professor John Moore
 8:06 – Advice to RMOs on the Allo Term
 11:02 – The history of allogeneic transplantation
 18:26 – Modern morbidity/mortality from alloSCT for AML
 23:05 – Use of transplant scoring systems
 27:29 – The role of MRD in transplant decisions
 30:04 – MAC vs. RIC – Choice of Conditioning
 38:15 – The role of PTCy
 40:17 – Second allogeneic transplants
 42:02 – DLI
 43:08 – Biallelic TP53 – no good options
 45:29 – Free rein in the trials space
 49:11 – AlloSCT/CAR-T for autoimmune disease
 55:05 – Take Home Messages 
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This week we continue the pattern of guests who are really really ridiculously good at haematology and also really really ridiculously nice people as well. We are very excited to be joined by Dr Michael Krigstein who many of you would know as the a molecular haematology guru who has gotten countless patients through their diagnoses and countless haematology trainees through their exams.
Timestamps:
01:30 - Introducing Dr Michael Krigstein
04:23 - Getting into Lab Haem
08:30 - The Mechanics of NGS
16:57 - Learning to report - RCPA Modules
19:58 - After the NGS - Curation
24:14 - NGS - Not a panacea
28:45 - Why NGS is bad at ITDs
32:42 - Panel Design
36:37 - RNA vs DNA Panels
39:16 - The future of NGS in haematology
46:56 - A standout case
53:36 - Wrapup

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Check out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

What happens when you take someone who is really really ridiculously good at haematology and also a really really ridiculously nice person as well? You get Dr Jad Othman, consultant Haematologist and Haematopathologist at Royal North Shore Hospital in Sydney who will be joining us today to discuss the use of measurable residual disease in acute myeloid leukaemia.
Dr Othman is well suited to this topic, having written his doctoral thesis on molecular disease assessment in AML, sitting on the European LeukaemiaNet (ELN)-DAVID MRD Working Group as well as numerous ALLG AML and MDS working groups. We're delighted to have him field the Bloody Minded Crew's questions today. 
Timestamps
01:00 - The boys making outdated millenial references
02:50 - Getting to know Dr Jad Othman
09:50 - The concept of MRD
11:55 - Lab techniques for MRD
17:59 - Why doesn't everyone have an MRD marker?
20:51 - What makes a good MRD assay?
24:14 - Patients without a molecular MRD marker
26:21 - Clinical case
30:30 - What we do with MRD results
31:47 - The NPM1/FLT3 PB/BM situation
35:31 - Why MRD is actually helpful
39:40 - Why single agent treatment in AML is challenging
44:33 - The 2025 ELN DAVID update
48:44 - Does doing MRD improve OS?
52:21 - The INTERCEPT study
55:41 - Wrap up and summary

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Check out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au

Here’s a question, what do CD123, CD4 and CD56 have in common? Other than pleasing The Count on Sesame Street. Sorry, another question perhaps - what happens if you cross a plasma cell and a dendritic cell? The answers to these questions can be found on a most enigmatic myeloid cell - the plasmacytoid dendritic cell. And what happens when these rare beasts become neoplastic - why BPDCN of course. Embark on a journey into this weird and not so wonderful (but highly examinable) neoplasm with the Bloody Minded Crew 
TIMESTAMPS
 0:57 – A glimpse into Cale's psyche
 2:39 – Intro to BPDCN
 6:56 – What IS a plasmacytoid dendritic cell?
 10:24 – Pathological PDCs in BPDCN
 11:42 – Clinical presentation – lots of rash talk
 15:23 – Morphology in BPDCN
 17:48 – Immunophenotype
 21:16 – Karyotypic and molecular features
 22:44 – Treatment of BPDCN
 24:00 – A bit on prognostic markers
 25:03 – Transplant
 25:28 – Tagraxofusp
 29:15 – Other treatment options
 31:33 – Take home messages 
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“It’s pronounced nuc-ul-ophosmin” “Nucleophosmin”. “Noo-clee-o-phosmin”. FLT3-ITD got you In The Dumps? Have a Total Knowledge Deficit about TKD mutations? Struggling with the A-B-Cs of NPM1 mutations? Want to know how a cat sarcoma is somehow related to AML? Join the Bloody Minded Crew as they flit about the laboratory looking at the structure of FLT3 and NPM1, what these proteins usually do and how we test for mutations in the advanced myeloid episode.
== Edit 6/5/26 = We've been made aware that strictly speaking the current MANE approved transcript for NPM1.1 has only 11 exons and therefore the mutations are best to be considered in Exon 11 as opposed to exon 12 - in contrast to what we said. ==
Timestamps
0:52 - Bloody Minded issues a formal apology
2:40 - Introducing molecular chaperones
5:05 - What even NPM1?
9:30 - Functions of NPM1
10:55 - Molecular biology of NPM1 in disease
15:42 - Why the subtypes are important
19:53 - NPM1 prognosis
21:35 - MRD testing in NPM1
25:52 - NPM1 summary
27:13 - Intro to FLT3
28:30 - Mandatory FLT3 history
36:28 - FLT3 pathogenesis
37:37 - FLT3 structure, ITD vs TKD
41:16 - The juxtamembrane domain
42:53 - Prognostic features in FLT3
44:17 - TKD mutations
46:26 - FLT3 in the lab
50:30 - Take home messages
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Check out show notes, additional references and (sometimes) extra content at www.bloodyminded.com.au