Case 108 – Update 3!

Thank you for the ongoing contributions to our case!

Our patient achieved a complete response following radiotherapy treatment alone (30Gy) and remained under haematology follow-up.

Unfortunately 5 years later he attends the haematology clinic earlier than scheduled as he has unintentionally lost 2kg over the past 4 months and more recently has noted an inguinal mass.

A repeat PET scan which shows non-bulky, stage 3 disease including 5cm splenomegaly.

Questions:

  1. How would you manage our patient now? Any further investigations?

 

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 108 – Update 2!

Thank you for everyone’s contributions in obtaining the diagnosis of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)!

The lymph node morphology demonstrates large atypical cells with multiple nucleoli (lymphocyte-predominant cells) embedded within follicles.

The IHC is as follows:

  • Lymphocyte-predominant cells:CD20+, CD45+, CD75+, PAX5+, CD5-, CD15-, CD30-, EBV-
  • Follicles (T cell rosettes around the LP cells): CD4+, CD57+, PD1+

This histopathological form is consistent with the typical pattern of NLPHL (pattern A or B).

A PETCT has revealed stage 1A disease with several non-bulky unilateral cervical lymph nodes.

Questions:

  1. How would you treat our patient?
  2. Any additional information you’d like to help aid your decision?

 

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 108 – Update 1!

Thank you to all the contributions so far!

We have now established that our 32 year old mans neck mass has been gradually increasing in size since he noted it 6 months ago. He has otherwise been well in himself except for feeling more tired. He has no other associated symptoms, no travel history, other medical conditions. he is not on any medications.

His examination reveals unilateral cervical lymphadenopathy (approx 3cm).

An ultrasound demonstrated the mass was indeed a lymph node with disrupted architecture with an uniformly hypo‐echoic enlarged node with the loss of the fatty hilum.

Subsequently histology was obtained by an excision biopsy:

Questions:

  1. Any suggestions on the diagnosis? What immunohistochemistry would you request to help?
  2. What further investigations would you perform?

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 108 – Update 1

Thank you to all the contributions so far!

We have now established that our 32 year old mans neck mass has been gradually increasing in size since he noted it 6 months ago. He has otherwise been well in himself except for feeling more tired. He has no other associated symptoms, no other medical conditions and no significant travel history. He is not on any medications.

His examination reveals unilateral cervical lymphadenopathy (approx 3cm).

An ultrasound demonstrated the mass was indeed a lymph node with disrupted architecture with an uniformly hypo‐echoic enlarged node with the loss of the fatty hilum.

Subsequently histology was obtained by an excision biopsy:

 

Questions:

  1. Any suggestions on the diagnosis? What immunohistochemistry would you request to help?
  2. What further investigations would you perform?

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 108 – The Beginning

You review a 32 year old man in outpatients who has been referred for a neck lump. On examination he has a 2cm cervical lymph node which he originally noticed approximately 6 months ago. He has had no night sweats but feels tired although states he has been working nights.

Questions:

  1. What is your differential diagnosis for a neck lump?
  2. What investigations would you perform?

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 107 – summary

Thank you for your contribution in this week’s #teamhaem case.

This week we have been looking at Transient Leukaemia of Down Syndrome (TL-DS).

Background

Between 5%- 30% children with Down syndrome (DS) are born with Transient Leukaemia of Down syndrome (TL-DS), aka transient abnormal myelopoiesis (TAM) or transient myeloproliferative disorder (TMD).

  • A clonal disorder, with circulating megakaryoblasts and dysplastic changes in peripheral blood

  • TL-DS is driven by mutations in the haematopoiesis transcription factor gene GATA1, and is only seen in conjunction with trisomy 21, either constitutional or acquired

  • May present with overt clinical features but some are only identified through blood film and/or by GATA1 mutation analysis

  • Many cases resolve without treatment

  • 15-23% cases result in early death

  • 20-23% survivors will develop acute myeloid leukaemia of Down syndrome (ML-DS) in the first 4 years of life

  • Overall event-free survival 63-68%

  • Those with previous TL-DS has a Risk of ML-DS 150 times greater than non-DS children (AML risk in all DS is about 1-2%)
  • Risk of ALL in previous TL-DS 30 times greater than those without DS (and with poorer outcome)

Definitions, clinical features and diagnosis:

  • A congenital leukaemia unique to neonates with DS or mosaic trisomy 21

  • Clonal disorder

  • TL-DS cells spread throughout the body, infiltrating the liver, pleural and pericardial spaces, skin and to a LESSER extent, the bone marrow

  • Presence of an acquired N-terminal mutation in exon 2 or exon 3 of the key haematopoietic transcription factor gene GATA1, resulting in a truncated GATA1 protein

  • Paired TL-DS and ML-DS samples show the same GATA1 mutations, indicating that they are clonally linked conditions

  • GATA1 mutations are not detected in remission samples after treatment of ML-DS nor are they present in other DS and non DS leukaemias

  • GATA1 mutation(s) are not leukaemogenic in cells that are not trisomic for chromosome 21

  • Studies using next generation sequencing (NGS) indicate that cases classified clinically as TL-DS or by blast >10%, all have detectable GATA1 mutations

  • Of note, in studies, 98% of neonates with DS had circulating blasts, the great majority had no clinical features of TL-DS and no detectable GATA1 mutation

  • Hence TL-DS = the presence of a GATA1 mutation in a neonate with DS or mosaic DS, combined with an increased blast count, or features suggestive of TL-DS

Blast count threshold

  • > 10% peripheral blasts in the first week of life identifies all neonates with clinical features of TL-DS

  • Blast count requires careful examination of a peripheral blood film in the first week of life, ideally in the first 3 days of life, by a haematologist experienced in reviewing neonatal blood films
  • automated blast counts are not accurate
  • Blast count assessment after the first week of life may underestimate the prevalence of disease, as blast% falls rapidly after birth
  • Neonates with intra-uterine growth restriction (IUGR) or other history of placental insufficiency (e.g. maternal hypertension, pre-eclampsia or diabetes mellitus) may have lower blast counts despite large GATA1 clones

Clinical features

  • Clinical features can be variable and may be absent (or present in the absence of TL-DS)
  • they can spread locally, spill into the peripheral blood and infiltrate through the liver as well as distant tissues
  • Hepatomegaly, hepatic fibrosis
  • splenomegaly (30% cases, often due to portal vein obstruction, splenic infiltration is rare)
  • Malignant effusions in pleural and pericardial spaces
  • And/or as papular or vesicopustular rash due to skin deposits of blast cells (skin nodules are rare)
  • Hepatopathy – Jaundice, Abnormal LFTs (raised transaminases with conjugated hyperbilirubinaemia)
  • Hyperleucocytosis
  • Coagulopathy
  • Multi-organ failure
  • Thrombocytopenia (which is common in DS even without TL-DS)
  • Neutrophilia
  • Anaemia

Morphology

  • Leukaemic cells are megakaryoblastic, originate from abnormal megakaryocyte-erythroid precursors in the fetal liver
  • Blasts are pleomorphic, with prominent nucleoli and basophilic, blebbed cytoplasm, in keeping with erythroid-megakaryocytic origin
  • Megakarycotye fragments often a prominent feature

Immunophenotying

  • Distinct from other leukaemias
  • Variable co-expression of:
  • stem cell markers CD34 & CD117
  • Myeloid markers CD33/CD13
  • Platelet glycoproteins CD36, CD41, CD42, CD61
  • Aberrant expression of CD56, CD7, low expression of CD11a
  • HLA-DR in 30%
  • Negative for MPO, CD15, CD14, glycophorin A
  • Bone marrow examination is NOT useful, since blasts originate in the liver and marrow blasts are variable and lower than in peripheral blood. Bone marrow involvement does NOT correlate with disease severity

Investigations:

  • All neonates with known or a high suspicion of DS should be examined for features suggestive of TL-DS
  • FBC & blood film within first 3 days of life with formal assessment of blast %
  • Those with features of TL-DS should have additional tests:
    • LFTs including conjugated bilirubin
    • CXR
    • ECHO
    • AUSS
  • Those with features of TL-DS and blasts>10% should have peripheral blood tested for GATA1 mutation
  • Those who did not have a peripheral blasts performed in the first 3 days of life or where there was significant IUGR (where blast count may be suppressed) should be considered at risk in first 4-8 weeks of life and be monitored accordingly. Consider GATA1 mutation analysis

Silent TL-DS

  • Recent studies found that at least half of DS neonates with GATA1 mutations have blasts < 10% and have no clinical features of TL-DS.
  • The prevalence of GATA1 mutation in DS neonates with blast % 1-10% is around 20%
  • Where this is a GATA1 mutation and a peripheral blast =< 10% in the first week of life in a neonate with DS or mosaic trisomy 21 is termed Silent TL-DS or Silent TAM
  • These children have a much lower rate of transformation to ML-DS (<3%) compared to those with clinical TL-DS which has a transformation rate of 10-30%
  • Therefore routine screening for GATA1 is not recommended when blast % =<10%, unless blast % was not assessed or unreliable

Risk factors for poor outcome & life threatening symptoms

  • Most TL-DS resolve spontaneously without sequelae
  • Clinical TL-DS has an early mortality of 15-23%. This is in excess of any other childhood cancers in the UK
  • Risk factors/life threatening symptoms leading to early death:
    • Progressive hepatopathy with cholestasis (conjugated bilirubin > 83umol/L, ascites or massive hepatomegaly
    • Hepatosplenomegaly (beyond umbilicus or causing respiratory or feeding compromise)
    • WBC > 100 x 10^9/L or leucostasis
    • Multi-organ failure
    • Hydrops fetalis
    • Pleural or pericardial effusions
    • Renal failure
    • Disseminated intravascular coagulation/coagulopathy with bleeding

Treatment

  • Those with life threatening symptoms should be considered for treatment with cytarabine
  • TL-DS and ML-DS blasts are extremely sensitive to cytarabine
  • Very low doses of cytarabine can be successfully used
  • Cytarabine should be given urgently at a dose of 1-1.5mg/kg/day for 5-7 days either intravenously or subcutaneously
  • Monitor closely due to risk of neutropenia and sepsis
  • Repeated courses of cytarabine can be considered to achieve control if severe liver dysfunction persists
  • Exchange transfusion and leukapheresis may be used in acute count reduction but is not definitive treatment
  • Cytarabine should NOT be used to prevent later development of ML-DS

Monitoring & Follow up

  • Those without life threatening symptoms can be monitored without treatment, and most will resolve spontaneously
  • Peripheral blasts will disappear in days to months (most by 2 months)
  • Progression to ML-DS 20-23% in those with clinical TL-DS (numbers vary slightly in different studies)
  • FBC & blood film usually return to normal in most
  • TL-DS cases should be monitored with FBC, LFTs until spontaneous resolution
  • If persistent abnormal FBC, GATA1 mutation analysis should be considered
  • All children with previous TL-DS or silent TL-DS should be monitored for progression to ML-DS every 3 months till 2 years of age.
  • If FBC & film are normal, then monitor 6 monthly till 4 years of age, as most ML-DS will develop by the age of 2
  • Any abnormal blood counts should promt early bone marrow aspirate and trephine (as aspirate is frequently difficult due to marrow fibrosis and trephine biopsy is essential in diagnosing ML-DS)

References:

1. WHO Classification of Tumours of Haematopoetic and Lymphoid Tissues

2. Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome – BSH Guidelines. 2018. BJH.

3. GATA factor mutations in Hematologic Disease. Blood Journal 2017

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 107 – update 3

CXR and ECHO show no significant abnormalities. Abdo USS confirms hepatosplenomegaly but no ascites. There are no skin rashes and his blood tests are stable.

Blood film report:

Polycythaemic film. Pleomorphic blasts with evidence of cytoplasmic blebbing. Manual blast count 15%. Megakaryocyte fragments seen.

Immunophenotyping:

CD45 weak population = 12% of total nucleated cells.
CD34 variable (+/neg), CD13 weak, CD33+, CD7+, CD117+,

CD41a+
HLA DR variable (+/neg).                                                                

Flow cytometry has demonstrated a population of myeloid precursor cells with aberrant CD7 expression. There is megakaryocyte marker expression consistent with a picture of Transient Leukaemia in the context of Down syndrome (TL-DS).
Trisomy 21 and GATA1 mutation have been confirmed. Coagulation was checked and there is no evidence of DIC.

Questions:

1. What factors would determine whether treatment is required?

2. If treatment is indicated, what would you do?

3. How do you plan to follow up this baby and why?

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 107 – update 2

You think the baby has some dysmorphic features. You look at his blood film.

You also check his conjugated bilirubin and request CXR, abdominal USS and ECHO.

Questions:

1. What are the main features and why?

2. What factors might affect the % of certain cells seen on the film?

3. What immunophenotyping would you be expecting? Why do conjugated bilirubin?

4. What do we look for in CXR and ECHO?

5. Would you do any genetic/mutation studies?

6. What is the role for bone marrow biopsy?

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 107 – update 1

You meet the baby with his mother. He was a little floppy at birth and not feeding well with a low grade fever. He is on 2L oxygen but with no respiratory distress. He is visibly jaundiced.

The mother is a 25 year old, this is her second child, delivered normally at 38 weeks. The baby weighed 2.8kg. She did not attend regular antenatal appointments and had no prenatal screening.

You examine the baby and he is indeed a bit floppy. The liver and spleen are palpable at 1 and 2cm below costal margins, respectively. His ears and mouth seem rather small and he has upward slanting eyes. You also notice a deep crease in both palms.

These are the initial blood results:

Hb 236g/l (130-180)

MCV 100fl (82-98)

WCC 25×109/l (4-11)

Neutrophils 11.45×109/l (1.7-7.5)

Lymphocytes 2.1×109/l  (1.5-4.5)

Platelets 65×109/l (150-450)

Retics 200×109 (50-150)

U&E – normal

LDH – normal

Bilirubin 289umol/l (5-21)

Total protein 49

Albumin 30

Alkaline phosphatase 286iu/l (83-248)

Alanine aminotransferase 15iu/l (0-35)

Questions:

1. What is your interpretation of these results?

2. Any other additional clinical examinations / features should you look for which might be significant?

3. Based on your physical examination of the baby, what other additional investigations would be useful and why?

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 107 – the beginning

Welcome to our new #TeamHaem case.

You are the haematology registrar. You get a phone call from a junior doctor on the neonatal ward. They have a 2 day old baby boy with jaundice. The baby seems stable, though he is needing some oxygen and not feeding as well as expected. They plan to do some blood tests and start phototherapy. She has been asked by her senior to discuss with haematology whether there are specific blood tests they should perform.

You decide to go and see the baby for yourself to make an assessment of the situation.

Questions:

1. What would you like to know about the baby in terms of history?

2. What would you look for in clinical examination?

3. What Initial investigations would you like?

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 106 – Summary

Thank you all for your contributions this week.

 

We focused on a patient with a new diagnosis of primary immune thrombocytopenia (ITP), please refer to TeamHaem case 11 for a full summary of this condition.

 

In the wake of a new BSH good practice guideline, our goal this week was to evaluate our patient’s risk of developing glucocorticoid-induced osteoporosis following initiation of first line ITP management with steroids. How many of us have started steroid therapy for a patient without considering the impact their treatment may have on their bone health?

 

Background

Fragility fractures occur in up to half of all patients receiving long-term steroids, vertebral fractures are the most common. This is a major source of preventable morbidity and disability.

Steroids directly inhibit bone formation by triggering osteoblast apoptosis and blocking normal osteoblast activity. Indirectly, steroids also reduce bone mineral density by inhibiting calcium absorption from the gut.

Changes in bone mineral density and the increased risk of fragility fractures occur quickly after the onset of steroid use (within first 3-6 months). Therefore, osteoporosis risk assessment must occur at the time of treatment initiation.

For all adult patients commencing glucocorticoids:

  • Give lifestyle advice to reduce risk factors associated with fragility fractures
    • Weight-bearing exercise, smoking cessation, decrease alcohol intake
  • Check serum calcium and vitamin D levels
  • Adequate daily vitamin D (800 iu) and calcium (7001200 mg) intake in adults is recommended, consider oral supplementation 

Initial fracture risk assessment

  • Patients at high risk of fracture should be considered for oral alendronate or risedronate
  • Everyone aged ≥70 years, can be considered high risk and treatment should be considered without the requirement for further assessment 
  • Men aged ≥50 years and post‐menopausal women with a previous fragility fracture can also be considered high risk and treatment should be considered without the requirement for further assessment
  • Everyone else >40 years old should be assessed by FRAX score without bone mineral density (BMD) assessment at treatment onset ( www.sheffield.ac.uk/FRAX/tool.jsp) to define risk 
  • Intermediate risk should have a dual energy x‐ray absorptiometry (DXA) scan and femoral neck BMD entered into FRAX® to define high and low risk. However, a decision can be made clinically in patients where a DXA results is unlikely to be available in a timely manner).
  • Adults aged <40 years and children do not routinely require assessment.

Patients receiving similar glucocorticoid regimens for relapse 

  • Is there a steroid sparing alternative?
  • If the patient has previously had bone protection, restart it
  • If re-treated within a year consider men aged ≥50 years and post‐menopausal women high risk and treat with bone protection
  • Other adults aged ≥40 years should undergo fracture risk assessment 

Bisphosphonates

Contraindicated

·        Hypocalcaemia

·        Hypersensitivity

·        Severe renal impairment

·        Pregnancy

·        Lactation

Avoid

·        In patients who are unable to sit/stand for 30 – 60 minutes

·        Oesophageal stricture

·        Achalasia

Considerations

·        Risk of osteonecrosis

·        Dental health

Main learning points when commencing steroids for in a patient with new ITP:

  1. Adults should receive lifestyle advice (regular weight‐bearing exercise, stop smoking, reduce alcohol intake to ≤2 units/day).
  1. Adults should receive adequate daily intake of calcium (700–1200 mg) and vitamin D (800 IU) through diet if possible or supplements if needed
  1. Bone loss and increased fracture risk occur early after initiation of glucocorticoids, bone‐protective treatment should therefore be started at the onset of therapy in patients at increased risk of fracture.

References:

Hill, Q. A., Grainger, J. D., Thachil, J. , Provan, D. , Evans, G. , Garg, M. , Bradbury, C. , Bagot, C. , Kanis, J. A., Compston, J. E. and , (2019), The prevention of glucocorticoid‐induced osteoporosis in patients with immune thrombocytopenia receiving steroids: a British Society for Haematology Good Practice Paper. Br J Haematol. doi:10.1111/bjh.15735

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Case 106 – update 2

Our patient is in haematology outpatient clinic.

We have excluded any secondary causes for an isolated thrombocytopenia and are considering first line therapy with prednisolone 1mg/kg/day with gastric protection (our local #TeamHaem preference).

We have considered the potential risks of starting glucocorticoid therapy in our patient. We have recognised that osteoporosis needs to be assessed and have found a new good practice guideline from BSH to help!

 

So #TeamHaem… using the flowchart below, what should we do?

Questions:

  1. What general advice would you give to any patient commencing steroid therapy?
  1. If indicated, please calculate the FRAX score (https://www.sheffield.ac.uk/FRAX/tool.aspx) for our patient and make recommendations about her risk of glucocorticoid-induced osteoporosis
  1. What action would you take given our patient’s calculated risk?

References:

Hill, Q. A., Grainger, J. D., Thachil, J. , Provan, D. , Evans, G. , Garg, M. , Bradbury, C. , Bagot, C. , Kanis, J. A., Compston, J. E. and , (2019), The prevention of glucocorticoid‐induced osteoporosis in patients with immune thrombocytopenia receiving steroids: a British Society for Haematology Good Practice Paper. Br J Haematol. doi:10.1111/bjh.15735

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Case 106 – update 1

You are checking the results from yesterday’s surgery and review our patients consultation notes:

61 year old female, previously fit and well

·        Easy bruising over both lower limbs for 2-3 weeks. No constitutional symptoms

·        No significant past medical history

·        No previous bleeding history

·        No family history of bleeding disorders

·        Moderate alcohol intake. Non-smoker

·        Recently separated from a long-term partner. No concerns about trauma or physical abuse

·        Physical examination unremarkable other than several 2-3cm bruises over both legs and faint petechiae

The lab have called through her results:

Hb 120, MCV 82, Plt 8, WCC 6, Neutrophil 4

Coagulation screen shows PT, APTT, Fibrinogen results within the normal range

Autoimmune and viral screens are unremarkable

There is an added film comment:

Genuine thrombocytopenia. No aggregates on film or clot in sample. Occasional large platelet present. No primitive cells. Morphology otherwise unremarkable. 

 

Questions:

  1. How do you interpret these results?

  1. What action do you take?

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. 

Remember to use #Teamhaem on all your posts to help us follow the case! 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 106 – the beginning

Welcome to our new #TeamHaem case!

You are working in a GP surgery.

You see from your urgent surgery list that the next patient has registered with the practice within the last 24 hours and has told the receptionist she has ‘easy bruising’.

You have a quick look through your records, but unfortunately her old GP notes are not yet available. You note that she is 61 years old, and call her in…

  1. What information would you focus on in the history and examination?
  2. What initial investigations would you perform?

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week.

Remember to use #teamhaem on all your posts to help us follow the case! 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 105 update 2

Our patient was discussed at MDT and as many have suggested, he is treated with intensive chemotherapy.

MATRIX – HD MTX, cytarabine, thiotepa and rituximab is the current regime recommended in the UK.  Intrathecal chemotherapy is not advocated in the BSH guidelines.  MTX should be delivered at doses of at least 3g/m2 with an infusion time of 2-4 hours.

He had a repeat MRI after two cycles showing complete remission.  His stem cells were harvested after the second cycle. He goes onto to have a further 2 cycles of MATRIX followed by autologous stem cell transplant.

Repeat MRI at 6 weeks following treatment shows no evidence of disease.  However 5 months following ASCT he presents with slurred speech and further MRI shows two new cerebral lesions.

 

What is your differential? Management plan?

 

 

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Case 105 update 1

MRI performed at the tertiary centre showed no evidence of a cerebral lesion.  You therefore plan with the neurosurgical team to stop the steroids and repeat the MRI after a short interval (2-4 weeks) whilst monitoring the patient closely.

 

Alongside this plan you have requested the following investigations

  • FBC, – within normal parameters
  • U&ES, – no abnormality
  • LFTS, – no abnormality
  • blood film – morphologically normal
  • LDH, – elevated
  • testicular ultrasound – no evidence of testicular lesion
  • CSF examination – flow cytometry or PCR for IGHV gene rearrangements – no clonal B cell population identified
  • PET-CT – no evidence of systemic involvement
  • HIV/hepatitis screen – negative
  • Paraprotein – no evidence of a paraprotein
  • opthalomology review – slit lamp exam – no abnormality

 

Repeat MRI exam at 2 weeks shows evidence of a cerebral lesion.  A biopsy is carried out which confirms DLBCL.  Steroids are recommenced. The MRI and histology findings are discussed at MDT.

 

How would you manage this patient?  How do you decide upon treatment plan?

What type of regime would you use?

How would you assess response to treatment?

What are the risks to the patient? how would these be managed?

Would you offer any other treatment alongside intensive chemotherapy?

 

 

 

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Case 105

Welcome back!

During your on call as the haematology registrar on the 2nd January you are contacted by the neurosurgical team.  A 54 year gentleman had been referred into the tertiary centre from a local hospital over the Christmas holidays.  He had presented to his local hospital with weakness of the right arm and some “altered behaviour” over the previous week.  CT head on admission had shown an isolated cerebral mass with surrounding oedema.  Steroids had been administered prior to transfer.  Symptoms had shown some signs of improvement on arrival to the tertiary centre.

The neurosurgical team would like some input from haematology as the suspicion is that of CNS lymphoma.

What would you advise?

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CASE 105 – summary

Primary CNS lymphoma

 

1% of all non Hodgkin lymphomas, 3 % of all brain tumours.  It may [resent with a range of symptoms including focal motor deficits and behavioural change as seen in the patient in this case.

 

Investigations should include:

  • Bloods – FBC/U&ES/LFTS/LDH/PARAPROTEIN/BLOOD FILM/HEPATITIS/HIV
  • Contrast enhanced MRI – brain and spine
  • Slit lamp exam and ophthalmology review – if necessary vitreous biopsy
  • Stereotactic brain biopsy is recommended for histological diagnosis
  • PET – CT – to determine systemic involvement.
  • Bone marrow not essential if PET excludes systemic disease, normal FBC and no evidence of monoclonal paraprotein
  • Testicular ultrasound (testicular involvement cannot be excluded on PET)
  • Performance status
  • CSF examination – cytology and flow.  IGH rearrangments by PCR may improve diagnostic yield
  • neuropsychological assessment
  • LVEF assessment
  • Baseline MMSE

 

 

Steroids

Steroids had already been administered to the patient in our case.  Steroids can have a substantial negative impact on yielding diagnosis and therefore should be avoided if possible prior to biopsy.  Non‐diagnostic rates range from 33% after a short course (<1 week) to 57% after a longer course of steroid.  If steroids have already been given, repeating the MRI to determine if the lesion is still visible is essential following discontinuation of steroids.  If no lesion is visible, close monitoring/imaging is essential in these patients until biopsy is possible.

Intraocular involvement

Up to 20% of primary CNS lymphomas have intraocular involvement, which can be difficult to establish.  Slit lamp exam and opthalmoscopy are essential followed by vitreous biopsy if necessary.  Intravitreal chemotherapy is not routinely recommended in patients who are fit for HD-MTX based regime, but could be consider for patients who are not fit for this treatment and who have isolated intraocular disease.

 

Treatment approach

The gentleman’s performance status was 2 at presentation, however his family inform you he was working full time prior to the Christmas holidays, suggesting a performance status of 0 prior to the onset of symptoms of lymphoma.  He was also reasonably fit, undertaking moderate exercise once or twice a week.  Performance status is frequently impaired due to the nature of disease, therefore decision for treatment should be based on physiological fitness.  Our patient was discussed at MDT and as many have suggested, he is treated with intensive chemotherapy.

Treatment approach should be considered in two stages

  1. Remission induction
  2. Consolidation (radiotherapy or autologous stem cell transplant)

 

Remission induction

For the patient the approach of choice would be intensive methotrexate based induction immunochemotherapy.  MATRIX was a regime suggested by most of our followers and most commonly used in the UK.  MATRIX has a clear overall survival benefit over HD-MTX/cytarabine regime

MATRIX  – HD MTX, cytarabine, thiotepa and rituximab.  MTX should be delivered at doses of at least 3g/m2 with an infusion time of 2-4 hours.  This is due penetration of the CNS being influenced by the total dose and the rate of infusion – this rapid infusion maximises the therapeutic CSF concentrations. The additional benefit of intrathecal chemotherapy is unknown, given risks of the procedure and low level of evidence, guidelines suggest intrathecal chemotherapy should not be undertaken.

Treatment related mortality associated with MATRIX is 4-7%.  Treatment related deaths more commonly occur in the first cycle.  Supportive treatment for this regime should include GCSF, PCP and herpes simplex prophylaxis.  As our patient suffered with a serious infection following cycle 1, it is important to reassess the chemotherapy plan prior to the second cycle.   Guidelines suggest reducing the dose of cytarabine and thiotepa by 25%

Consolidation

Clinicians should aim for this to be undertaken within 6-8 weeks from the first day of the final induction chemotherapy.

Patients who had recieved tiotepa based chemotherapy regime and have achieved at least stable disease should be considered for autologous stem cell transplant.  BEAM should not be used as conditioning for transplant, due to previous trials showing poor outcomes.  Stem cell collection can be undertaken following cycle 1 or 2

Our patient completed 4 cycles of chemotherapy and ASCT.  Follow should include a response assessment at 1-2 months, then MRI every 3-4 months for up to 2 years.

 

Unfortunately we discovered he had relapsed shortly after treatment.  Perhaps we will cover this in a future case!

 

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Christmas quiz

Thankyou for taking part in our Christmas quiz!

Here are the questions and answers!

1. Which animals have:

• Blue blood

• Green blood

• Yellow blood

2. The Japanese traditionally associate blood groups with personality. Can you match them up correctly?

• Unpredictable, distant, careful, considerate, efficient and sensitive

• Serious, calm, composed, level headed and trustworthy

• Outgoing, expressive, clumsy, flexible, idealistic, natural leader, carefree and generous

• Curious, excitable, cheerful, bright, enthusiastic  and independent

3. Where were the first allogeneic stem cell transplants done?

4. Who was Anthony Nolan?

5. When was the American register started and who campaigned for it?

6. When did the 1 millionth BMT (worldwide) take place?

7.What is Christmas disease?

8.What incident in WW2 resulted in information that helped develop a chemotherapy agent?

9.What was the original source of vincristine?

10. Where does palitaxel come from?

11. How were platinum chemos discovered?

Answers!

Answers:

1.

Blue – spiders, crustacions, squids, octopuses and some types of molluscs. Green – many types of worms, slugs and leeches

Yellow – starfish/beetles/sea cucumber/sea squirts

2.

a)AB

b)A

c)O

d)B

3. Yugoslavia – after a radiation leak at a nuclear research facility. 5 workers, none engrafted.

4. Anthony Nolan was a child with Wiscott Aldrich syndrome. Born 1971. Never received transplant and died age 8. His mum started the register in 1974

5. American register started 1986, family of Laura Graves who was a child with leukaemia. Her donor was found in lab of her hospital.

6. 2012

7. Haemophilia B

8.An air raid in Bari, Italy led to hundreds of soldiers and civilians having mustard gas exposure. Survivors were found to have low lymphocytes. Results were combined with the Yale study group which lead to the search for similar compounds resulting in mustine chemotherapy.

9. Madagascan periwinkle

10. Pacific yew tree bark

11. Bacteria on agar plates stopped dividing when electricity applied to them – turned out platinum on electrodes was the cause, leading to development of chemo.

Let us know if we have missed anything!

Thankyou for all your participation with teamhaem this year, we couldn’t do it without you!

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TeamHaem saves Christmas 🎄- the summary

“A DOAC, dear sir, and some stockings to boot!”

“Thank you dear doctor, now off I must shoot!”
“Take it easy!” I called as he jumped up tall,

“We’ll review you in clinic, here’s a helpline to call.

 

Please take care not to fall from your sleigh!”

He gave me a wink and then bounded away.

 

So TeamHaem saves Christmas and all the elves cheer

Merry Christmas to all and a Happy New Year!

 

For guidelines relating to VTE management see:

https://journal.chestnet.org/article/S0012-3692(15)00335-9/fulltext

http://www.hematology.org/VTE/

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. Remember to use #teamhaem on all your posts to help us follow the case! 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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