Case 125 – Summary

Thanks for all your input in managing this case or iron deficiency anaemia in pregnancy.   Case 45 previously discussed anaemia in pregnancy and this case highlights changes in recommendations for oral iron replacement as well as indications and complications associated with intravenous iron.

Blood parameters and pregnancy

In pregnancy there is a physiological reduction in haemoglobin due to the dilutional effect from expansion of plasma volume as well as increased use of iron for foetal growth and maternal erythropoiesis. As such there are different thresholds used to define anaemia in pregnancy which are:

  • Hb <110 g/l in the first trimester
  • Hb <105 g/l in the second and third trimester 
  • Hb< 100g/L immediately postpartum

Other factors which may contribute towards anaemia are many and include iron, vitamin B12 and folate deficiency, haemoglobinopathies,  inflammatory disorders, haemolysis and bleeding.

Other changes to blood parameters which occur in pregnancy include a 20% increase in red cell mass with increase in MCV of up to 6fL, which may mask the reduced MCV which may be seen in iron deficiency. There may be a neutrophilia and monocytosis. The blood film may be left shifted. 

Risks of iron deficiency in pregnancy

Risks to the mother which may be associated with iron deficiency include fatigue, increased infection, reduced cognition, postpartum haemorrhage and possible need for blood transfusion.

Risks to the baby may include increased perinatal and neonatal mortality, pre‐term birth and low birth weight and less clear cut – possible neurodevelopmental issues. Haemoglobinopathy screening

Haemoglobinopathy screening

All pregnant women are offered a FBC and group and save as well as screening for haemoglobinopathy via the family origin questionnaire at their booking appointment (usually 8-12 weeks). All women in high risk areas (foetal prevalence of sickle cell disease >1.5/10 000) will have a haemoglobinopathy screen as well as those with risk identified from their family origin questionnaire and blood count. The screening programme looks for sickle cell disease, thalassaemia and some unusual haemoglobin variants.  It is not designed to pick up HbH disease in the foetus, although it may do.  

Oral iron replacement

If the routine blood count shows microcytic anaemia it is reasonable to assume this is due to iron deficiency and give a trial of iron whilst awaiting a haemoglobinopathy screen. If there is evidence of haemoglobinopathy, check a ferritin level before starting a trial of iron to avoid exacerbating iron overload.

Recent BSH guidelines for iron deficiency in pregnant women now recommend 40-80mg of elemental iron daily as once daily dosing or alternate day dosing has been found to lower hepcidin levels and maximise fractional absorption of iron whilst reducing adverse effects.  Daily dosing is suggested as a practical compromise aiming for optimum compliance and more rapid response. Alternate day dosing is suggested if nausea and epigastric discomfort is experienced. 

To optimise use of oral iron:  

  • Take with vitamin C to increase absorption
  • Take early in the morning on an empty stomach
  • Warn about potential adverse effects and how to manage them
  • Avoid taking with tannins (tea, red wine etc.)
  • Don’t take with PPIs or H2 receptor blockers

After starting oral iron treatment, the full blood count should be checked at 2-3 weeks and should demonstrate a rise in Haemoglobin if the anaemia is due to iron deficiency.

Once the Hb is in the normal range, replacement should continue for 3 months and until at least 6 weeks postpartum to replenish iron stores.

IV iron replacement

Consider IV iron replacement if:

  • Unable to tolerate different preparations of oral iron
  • Need quick increase in haemoglobin e.g. nearing delivery. BSH guidelines suggest it should be considered in women presenting after 34 weeks gestation with confirmed iron deficiency anaemia and an Hb of <100 g/L
  • No response to oral iron/malabsorption issues

IV iron is contraindicated in the first trimester and can rarely cause transient fetal bradycardia so the manufacturers recommend monitoring of the foetus during administration. It is also contraindicated in bacteraemia or decompensated liver disease or if there is a history of anaphylaxis or serious hypersensitivity following any IV iron preparation and suggested use with caution. The manufacturers recommend monitoring for 30 minutes after the infusion for any reactions, although the risk is low (<1/200,000). Extravasation can cause haemosiderin skin staining which may be permanent and any discomfort at the infusion site should be reviewed, the infusion stopped, and plastics advice sought if concern.

When to refer to specialist care

BSH guidelines recommend referral to specialist care if Hb <70 g/L and/or associated with significant symptoms or gestation >34 weeks, or if the Hb is failing to respond after 2–3 weeks of oral iron correctly taken. They state that iron deficiency anaemia should not affect decisions on the mode of delivery, but anaemia is associated with increased risk of PPH, hence women with Hb <100 g/l approaching birth should have an individualised plan. This should include consideration of IV access, birth in an obstetrician‐led unit and active management of third stage of labour.

Women with uncorrected anaemia antenatally should have a Hb check within 48 h of birth, as should those who have had blood loss >500 ml, or symptoms suggestive of postpartum anaemia.

References:

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Update 5

After 2 weeks the patient stopped taking the iron tablets as she was struggling with abdominal discomfort and constipation.  She is prescribed an IV iron infusion for later that week and attends for this but unfortunately she notices some discomfort and some brown discolouration spreading in her anticubital fossa a few minutes into the infusion.  The infusion is stopped. 

Questions:

  • What has happened here?
  • Are there any contraindications for iron infusions?
  • Are there any further steps which need to be taken to prepare for her labour?
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Update 4

The patient did not attend any further appointment for follow up FBC or her 28 week appt.  At 36 weeks she finally attended her midwife appointment and her FBC was as follows:

  • Hb 80g/L
  • MCV 76fL
  • MCH 22.7pg
  • MCHC 31.2%
  • PLT 154×10*9/L
  • WCC 9.2×10*9/L

Given your comments on the previous film, the following were added:

  • Ferritin 8μg/l
  • Vitamin B12 168pmol/L
  • Folate 5.2μg/L
  • LDH 118U/L (normal)
  • Reticulocytes 74 × 10*9/L
  • Bilirubin 9μmol/L

Questions:

  • What are your thoughts on the results?
  • What management might be appropriate?
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Update 3

As most of you told us the film shows microcytic red cells with occasional pencil cells and target cells. Some of you mentioned variable haemoglobinisation, some macrocytic cells, occasional spherocytes and suggested we check folate and vitamin B12 levels and investigate for hamolysis. 

As you told us the HPLC is normal. It shows no variant haemoglobin and the HbA2 is within normal limits suggesting no evidence of beta thalassaemia. 

The patient was given dietary advice as you suggested and we opted for a trial of daily dosing of 200mg ferrous sulphate. Recent BSH guidelines for iron deficiency in pregnant women now recommend 40-80mg of elemental iron daily as once daily dosing or alternate day dosing has been found to lower hepcidin levels and maximise fractional absorption of iron whilst reducing adverse effects.  Daily dosing is suggested as a practical compromise aiming for optimum compliance and more rapid response. 

We invited her to attend for a repeat full blood count 2 weeks later which was as follows:

  • Hb 91g/L
  • MCV 74fL
  • PLT 151×10*9/L
  • WCC 9.9×10*9/L

Questions:

  • What are your thoughts on the FBC now/?
  • Would you continue iron replacement? If so for how long?
  • What are the risks associated with iron deficiency in pregnancy?
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Case 125 – update 1

Our lady who is 8 weeks pregnant and feeling a little tired and sickly has a microcytic anaemia. You suggested that the most likely cause of the anaemia is iron deficiency but that we couldn’t rule out a haemoglobinopathy with the information currently available.

You suggested a trial of oral iron replacement  – we have had a few different dosages suggested.  You also advised her to start taking folic acid supplements to reduce the likelihood of neural tube defects in the baby.

Some of you mentioned the importance of checking ethnicity of the lady and her partner as well as any personal or family history of haemoglobinopathy. Her family origin questionnaire completed at her booking appointment shows that she and her partner are white and from the UK, as were her and the baby’s father’s parents.

Her blood film and HPLC are shown here:imageimage-2

Questions:

  • Any comments on the film?
  • Any comments on the HPLC?
  • What dosing regime would you use for her iron replacement and why?
  • When would you next check her blood count?

Don’t forget to add #Teamhaem to your replies so they can be easily seen by other followers!

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Case 125 – the beginning

A 19 yr old lady attends the GP surgery for her booking appointment.  She thinks she is about 8 weeks pregnant. She feels a little nauseous and weary but has no significant past medical history and has not been taking any medication. Her full blood count is 

  • Hb 80g/L
  • MCV 71fL
  • PLT 168×10*9/L
  • WCC 8.9×10*9/L

What do you think of her FBC?

Are there any further blood tests you might request?

Do you have any further advice for her?

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Case 124 – Summary

Many thanks for all of your input this week. We covered the case of a 68 year old lady presenting with macrocytic anaemia and thrombocytosis. Key points in initial investigation:

Exclude common causes – iron deficiency, B12/folate deficiency, myeloma screen, reactive causes, medications, myeloproliferative disorder (JAK2, CAL-R, MPL, BCR-ABL)

 

Her film showed evidence of dysplasia and so we organised a BM aspirate which confirmed dysplasia in two cell lineages. Cytogenetics confirmed our diagnosis of MDS with isolated del(5q)

Key recommendations regarding MDS del(5q)

Supportive care as per all patients with MDS:

Blood product support – although need to note that prognosis tends to be better (median survival at least 6 years) and so consider alternative strategies or iron chelation if indicated

Judicious treatment of infection

Psychological support

 

First-line to consider a trial of erythrocyte stimulating agent (ESA) e.g. EPO. Trial for 8 weeks, and then increase dose if no response for a further 8 weeks. Trial should last no longer than 16 weeks.

 

Patients who are transfusion-dependent or unsuitable/non-responders to ESA can be considered for lenalidomide – usually 10mg OD for 21 days in a 28 day cycle. Consider thromboprophylaxis on an individual basis

 

Further information is accessible on the BSH guideline:

 

https://b-s-h.org.uk/guidelines/guidelines/diagnosis-and-management-of-adult-myelodysplastic-syndromes/

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

 

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

 

TeamHaem are not a position of authority. It is an educational platform to allow discussion and learning.

 

 

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Case 124 – Update 2

Thank you for all of your input and suggestions. To summarise the case thus far:

  • 68 year old lady referred with a macrocytic anaemia and thrombocytosis:
    • Haemoglobin              87 g/L (115 – 165)
    • White cell count          5.2 x 109/L (4 – 11)
    • Platelets                      538 x 109/L (150 – 450)
    • Mean Cell Volume      108 fl (80 – 100)
  • No reversible cause identified on further investigation, and her blood film demonstrated some dysplastic features:

IMG_2154

We therefore organised a bone marrow aspirate which confirmed trilineage dysplasia, no excess blasts and no excess ring sideroblasts:

 

Cytogenetics has subsequently confirmed a diagnosis of MDS with isolated del(5q) (like many of you suggested – good work!)

 

The patient comes back to clinic for results. How would you communicate her prognosis? What treatment options, if any, would you discuss?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information. 

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 124 – Update 1

We are investigating a 68 year old lady referred with a macrocytic anaemia and thrombocytosis. Thanks for all of your helpful input thus far. Tests you have requested to date:

Haemoglobin              87 g/L (115 – 165)

White cell count          5.2 x 109/L (4 – 11)

Platelets                      538 x 109/L (150 – 450)

Mean Cell Volume      108 fl (80 – 100)

 

Folate/B12 – normal

LFTs – normal

Ferritin – normal (with a normal CRP)

Retics – borderline low

Haemolysis screen (LDH, DAT) – negative

Coag screen – negative

 

CT chest, abdomen, pelvis – no evidence of malignancy. No size significant lymphadenopathy and normal liver/spleen. Confirms previous right total hip replacement.

Blood film is prepared and shown below (the BMS comments that there is a lot of platelet clumping and platelet islands, and confirms a thrombocytosis):

IMG_2154

What does the blood film demonstrate? What would be the next step in your investigation of this lady?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 124 – The beginning

You are helping out in new patient haematology clinic. You have just had your post-lunch coffee and are raring to go! The next patient has been referred via the 2ww pathway by their GP for investigation of an abnormal FBC, with concern about an underlying malignancy. They are a 68 year old lady with a PMH of:

  • Hypertension
  • CKD stage 2
  • Mild asthma (PRN salbutamol only)
  • Total hip replacement 2012
  • Provoked DVT secondary to this in 2012 (completed 3 months of anticoagulation with warfarin)

Her FBC from the GP is as follows (normal range in brackets):

Haemoglobin               87 g/L (115 – 165)

White cell count          5.2 x 109/L (4 – 11)

Platelets                        538 x 109/L (150 – 450)

Mean Cell Volume      108 fl (80 – 100)

Haematocrit                0.45 (0.37 – 0.47)

Neutrophils                 3.6 x 109/L (2 – 7.5)

Lymphocytes               1.9 x 109/L (1.5 – 4.5)

How would you approach the clinical assessment of this patient? What further investigations would you organise?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

 Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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case 123 summary

Our case this week looked at a 44 year old gentleman with a new diagnosis of AML.

He presented with pancytopenia and blasts with auer rods on peripheral blood.

Investigations confirmed a diagnosis of AML.  PML – RARA was negative, and cell markers inkeeping with AML (CD33+, CD34+, CD13+, CD19+, CD56+, HLA-DR, CD17+, CD64+).  Cytogenetic and molecular studies showed t(8:21), C-KIT positive, FLT3 negative and NPM1 negative.  We decided to treat this patient initially with DA+myelotarg.

Initial investigations should include:

  • FBC
  • Clotting screen including fibrinogen and D-dimers
  •  Urea and electrolytes
  •  Liver function tests
  •  Urate
  •  CMV serology (in those patients who may be transplant candidates)
  •  HLA class 1 and 2 tissue typing for potential allogeneic stem cell
    transplant candidates
  • Marrow aspirate and trephine where possible for morphological
    assessment
  • Marrow EDTA sample for immunophenotyping
  • Marrow sample for cytogenetic and molecular analysis

 

Risk Stratification

A number of factors are known to affect prognosis of patients with AML including:

  1.  age
  2. peripheral white cell count
  3. marrow cytogenetics
  4. response to induction chemotherapy
  5. molecular studies

 

Cytogenetic abnormalities

  • Good risk:  t(8;21), inv(16), t(16;16), t(15;17)
  • Standard: Any patient not in either good or poor risk groups.
  • Poor risk: -5, -7, del(5q), abnormal (3q) or complex (5 or more abnormalities)..

 

Molecular markers

  • FLT3-ITD +, NPM1 – Poor Risk
  • FLT3-ITD +, NPM1+ Intermediate Risk
  • FLT3-ITD -, NPM1 – Intermediate Risk
  • FLT3-ITD -, NPM1 + Good Risk

 

Core binding factor

CBF in acute myeloid leukaemia represents 5-8% of all AMLs and has a relatively favourable prognosis.  In general CBF patients have a higher CR rate and an extended CR time. Therefore many centres may opt to treat with chemotherapy, rather than chemo + transplantation.

However the presence of C-KIT mutation ALONE is associated with a higher risk of relapse and shorter survival.  Studies have reported contradictory results with regards to prognostic significance of KIT mutation in combination with CBF.  Some studies suggest a decreased remission rate and survival whilst others suggest no effect of KIT mutation in CBF-AML.   It has also been proposed that C-KIT in AML patients with T(8:21) confers a poorer prognosis however no definite conclusions can be made in AML inv(16).

Treatment options may include

  • Trial
  • DA
  • DA+ myelotarg (as per NICE guidance in the UK)
  • DA+ midostaurin (if FLT3 positive)
  • CPX – (AML with previous MDS, AML with previous CMML, therapy associated-AML, AML with genetics consistent with MDS)
  • IHD inhibitors – (IHD1 ivosidenib, ID2 enasidenib)
  • Venetoclax (not currently available in UK)
  • Allogeneic stem cell transplant
  • TKI ???

 

There are no definitive answer to how all AML patients should be treated.  Individualised treatment plans are essential to improving outcomes in this population.  Below is a brief synopsis of treatments currently available/in trials with lots of references if anyone wants to do some further reading!

Myelotarg

NICE guidance for myelotarg

  • untreated de novo CD33+ AML
      • start with induction therapy when either the cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (that is, because the test was unsuccessful) or when their cytogenetic test results are not yet available and
      • start with consolidation therapy when their cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (because the test was unsuccessful)

 

Myelotarg has shown significant survival benefit for favourable and intermediate cytogenetic risk groups when assessed separately or together.  A consistent observation of myelotarg is a lack of benefit in patients with adverse risk. Therefore optimal use of myelotarg requires rapid identification of risk groups in order to allow avoidance of myelotarg in the adverse risk groups

Midostaurin

The addition of FLT3 inhibitor Midostaurin to treatment in patients who are FLT3 positive has been founds to improve 4 year overall survivial to 51% versus 44% in the group that recieved placebo.  Disease free survival has been reported at 26.7 months versus 15.5 months.

 

However either myelotarg or midostaurin can be chosen.  They cannot be used in combination and this once again highlights to need to clarify cytogenetic/molecular status before instigating treatment.

 

CPX

CPX is a dual drug liposomal encapsulation of cytarabine and daunorubicin.  Clinical studies have shown prolonged drug exposure and prolonged survival compared to DA 3+7, in older patients with newly diagnosed secondary AML.

This study included patients with the following diagnosis

  • therapy-related AML,
  • AML with a history of myelodysplastic syndrome [MDS] with and without prior hypomethylating agents,
  • AML with a history of chronic myelomonocytic leukemia [CMML],
  • de novo AML with MDS-related cytogenetic abnormalities

 

IDH inhibitors

IDH1 and IDH2 mutations are seen in approximately 15-20% of patients diagnosed with AML and these mutations are targeted by ivosidenib and enasidenib.  The mutations more frequently occur in patients of older age, with a normal karyotype and NPM1 mutation.  These treatment have been used so far in relapsed/refractory AML.  Enasidenib has been found to be effective salvage treatment inducing responses of approximately 40% of patients with IDH2 mutations.  There are ongoing phase 1/2 trials in newly diagnosed AML, which include these treatment upfront.

 

Venetoclax

Venetoclax has been approved in the United states by the FDA for use in combination with hypomethylating agents or low dose cytarabine as front line therapy for older patients with AML or those unfit for intensive treatment.  Venetoclax is a promising treatment for AML and to date has produced some deep and durable responses, with promising overall survival.  The challenges come with tumour lysis syndrome, continuation of treatment (i.e. do both treatments need to be continued lifelong), and predicting who will have a poor response to treatment

Dasatinib

Ongoing phase III trial currently.  Inital studies found acceptable toxicity and favourable outcomes with OS of 74.7%,

 

References

Prognostic Importance of C-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia: A Systematic Review.
Ayatollahi H1, Shajiei A2, Sadeghian MH2, Sheikhi M3, Yazdandoust E2, Ghazanfarpour M4, Shams SF2, Shakeri S2.  Hematol Oncol Stem Cell Ther. 2017 Mar;10(1):1-7. doi: 10.1016/j.hemonc.2016.08.005. Epub 2016 Sep 3.
The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia.
Allen C1, Hills RK, Lamb K, Evans C, Tinsley S, Sellar R, O’Brien M, Yin JL, Burnett AK, Linch DC, Gale RE.  Leukemia. 2013 Sep;27(9):1891-901. doi: 10.1038/leu.2013.186. Epub 2013 Jun 20.
The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy in Acute Myeloid Leukaemia : An Individual Patient Data Meta-analysis of Randomised Trials in .  Lancet Oncol. 2014 August ; 15(9): 986–996. doi:10.1016/S1470-2045(14)70281-5.

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation
Richard M. Stone, M.D.,  et al. August 3, 2017
N Engl J Med 2017; 377:454-464

CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia  Jeffrey E. Lancet et al.  Journal of Clinical Oncology 36, no. 26 (September 10, 2018) 2684-2692.
Stein EM, DiNardo CD, Fathi AT, et al: Ivosidenib or enasidenib combined with induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe, effective, and leads to MRD-negative complete remissions. 2018 ASH Annual Meeting & Exposition. Abstract 560. Presented December 3, 2018.
How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia.  Brian A. Jonas & Daniel A. Pollyea
Leukemia volume 33, pages2795–2804(2019)
Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial.  Paschka P et al.  Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.
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Case 123 update 2

The plan is to commence treatment with DA+myelotarg

Cytogenetic and molecular studies show

t(8:21)

C-KIT positive

FLT3 negative

NPM1 negative

Would this change your management?

How are you going to monitor response in this patient?

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Case 123 update 1

 Our 44 year old male presented with the following full blood count

Hb 62

WCC 35

plt 22

Blood film identified blasts, with auer rods.

Blood film shows blasts cells, auer rods noted, thrombocytopenia and anaemia.

Differential has included AML and APML

 

Flow cytometry on peripheral blood:

CD33+, CD34+, CD13, CD19, CD56, HLA-DR+, CD117+, CD64+

What is your immediate management for this patient?

 

Longer term management?

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Case 123

44 year old man present to GP with fatigue, SOB and petechial rash.

What investigations would you perform?  Level of urgency??

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Team Haem saves Christmas: The Summary

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The haemolysis is self-limiting

No more parasites are seen

The pitted red cells that have lost malaria

Are being chomped up in the spleen

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The DAT is clearly negative

Steroids were not given today

Jingle can go back to work

All elves shout hooray!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

SUMMARY

With a parasite count of >5%, poor Jingle had severe malaria

As per NICE and WHO recommendations, IV artesunate was started.  This cleared the parasites quickly.

Delayed haemolysis is a recognised complication of IV artesunate therapy.  There is no clear evidence to guide management and all data comes from case reports/series.  Some clinicians have given steroids, and a proportion do seem to be autoimmune, although it is likely to be self-limiting.

It appears that most of the haemolysis is due to the destruction of red cells that become pitted following death of the parasites.

Further reading:

Lalloo, D.G., Shingadia, D., Bell, D.J., Beeching, N.J., Whitty, C.J. and Chiodini, P.L., 2016. UK malaria treatment guidelines 2016. Journal of Infection72(6), pp.635-649.

https://cks.nice.org.uk/malaria#!topicSummary

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TeamHaem Saves Christmas Part 3

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Whilst sorting through the letters

Poor Jingle remembers a bite

A sneaky mosquito from an envelope

Then that naughty insect took flight

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The parasites numbered 7%

Treatment was started straight away

Intravenous artesunate

Should keep the malaria at bay

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Father Christmas is feeling better

Because Jingle has improved

No fevers and no more aches

He’s started singing Christmas tunes

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

But alas that’s not the end

Of this very sorry tale

For poor Jingle’s wee is dark

And he’s looking very pale!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Please review the blood film….

What is going on and what could be the mechanism?

What shall we do!

 

image005

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TeamHaem Saves Christmas Part 2

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Father Christmas is so worried

Jingle sorts out both his lists

He checks on who’s behaving

And makes sure no-one’s missed.

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Blood cultures have grown nothing

The blood film’s ready for review

There is no clear infectious cause

Please we all need help from you!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Please review the blood film and suggest next steps

What tests should be performed?

What treatment would you recommend?

 

Falciparumimage003

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TeamHaem help us save Christmas 2019! 🎄❄️ Part 1

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

A day or two ago 

Father Christmas needed help

Jingle, his top packing elf,

Just wasn’t feeling himself

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

His temperature was high

He was shaking head to toe

Mumbling, stumbling and confused

To the hospital he did go, Oh!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

‘Oh my muscles are so achy’

‘My head is pounding bad!”

They took some blood tests from his arm

And his platelets were down a tad.

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

What are our first steps?

 

Elf blood count: Hb 110, WBC 13, Neut 11, PLT 99

(Please note, elf physiology is extremely similar to humans)

 

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Case 121 – Summary!

This week we followed our patient with relapsed/refractory DLBCL through CAR T-cell therapy. We managed her cytokine release syndrome (CRS) and she is in remission thus far.

CAR T-cell therapy

Chimeric Antigen Receptor (CAR) T-cells are modified T cells in which the receptors are targeted against a specific tumour antigen. There a several ‘brands’ of CAR T-cells directed against CD19 which hold great promise in the treatment of relapsed/refractory B cell malignancies, including diffuse large B cell lymphoma (DLBCL), which has previously represented an area of unmet need.

Within the UK, eligibility and appropriateness for CAR T-cell therapy is discussed in MDT meetings at designated CAR T centres. Current products are licensed in DLBCL after two or more prior lines of treatment. Patients often require bridging therapy due to the timeframe of organising CAR T cell therapy (including MDT discussion, cell harvest, manufacture and production) and the therapy used is often down to clinician choice.

Patients receive lymphodepleting conditioning prior to infusion of CAR T-cell therapy. There is increasing recognition of specific toxicities related to CAR T-cell therapy:

 

Cytokine-release syndrome (CRS) is an escalated immune response triggered by CAR T-cell release of inflammatory mediators (cytokines) which often presents with fever, hypotension, hypoxia with or without evidence of end-organ dysfunction.

The severity of CRS can be graded according to the ASBMT Consensus Grading System

Table 1Table from Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595

Centres which administer CAR T-cell therapy should have an algorithm for assessment and management of patients receiving CAR T-cell therapy to ensure early recognition and intervention of acute toxicities.

Management will often be guided by the grade of CRS. Supportive measures should be used including anti-pyretics, IV fluids and oxygen. It is vitally important to consider infection and treat accordingly.

Hypotension or hypoxia refractory to adequate fluid challenges or oxygen therapy, or those with Grade 2 CRS, can be considered for management with tocilizumab, an anti-IL-6 therapy. Depending on response patients may require intensive care admission with cardiovascular support. Corticosteroids can be considered for patients with Grade 3 or 4 CRS or those refractory to treatment above.

Patients receiving CAR T-cell therapy should be monitored closely with assessment of fluid balance, organ systems and CRS grade at least twice daily, or more frequently if there is a change in clinical status

 

Immune effector cell-associated neurotoxicity syndrome (ICANS) represents a toxic encephalopathic state and often presents with CNS signs including confusion, impaired higher cognitive function and delirium.

The severity of CRS is often graded using the ASBMT consensus grading system which incorporates the ICE score (Immune effector Cell‐associated Encephalopathy).

Table 2Table from Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595

Management of ICANS is based on toxicity grade and options include supportive care, anti-IL-6 therapy (tocilizumab) when associated with CRS, or corticosteroids if not.

Patients receiving CAR T-cell therapy should be monitored closely with assessment of fluid balance, organ systems and ICANS grade at least 8 hourly, or more frequently if there is a change in clinical status. Both CRS and ICANS are reversible in most patients with the correct treatment, and so close monitoring and awareness of local policy is key.

There is also increasing recognition of medium term toxicities related to CAR T-cell therapy including prolonged cytopenias, risk for opportunistic infections, and B‐cell aplasia and hypogammaglobulinaemia.

 

References/further reading:

  • Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595
  • Yakoub-Agha, I et al. Management of adults and children undergoing CAR t-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica Nov 2019, haematol.2019.229781; DOI: 10.3324/haematol.2019.229781

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 121 – update 3!

We manage our patient with CAR T-cell therapy related CRS/ICANS with supportive care, including organ support from our critical care colleagues, and tocilizumab (anti-IL-6) therapy. She responds well to therapy and is stepped down to the haematology ward for ongoing care.

She is now 2 weeks following infusion of CAR T-cell therapy and observations are stable and she feels well.

How would you monitor this patient on discharge from hospital? What long term toxicities may you encounter?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality. 

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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