Malignant Haematology - Do’s and Don’ts

Michael Harvey Haematology Department

Liverpool Hospital

Don’t….

Overdiagnose…

What do do about paraproteins?

• Occur in ~6 percent of population over 70

• Check UEC, CMP, FBC, urine protein

• If asymptomatic, small paraprotein < 10 g/L, age > 70, would not investigate further

• 20 percent chance of myeloma over 2010-15 years

• Only treat myeloma if “related organ or tissue injury” ROTI) e.g. “CRAB” (Calcium elevation, Renal insufficiency, Anaemia < 100g/L or 2 g/L drop from baseline, Bones, lytic lesions)

• Selectivity in patients in whom do BM biopsy/skeletal survey

Approach to paraproteins

Which patients with paraproteins should be referred to a haematologist?

LOVV RISK GROUP • • • • • •

lgG M protein < 15 g/I lgA M protein < I 0 g/I Asymptomatic No other abnormal results BJ P positive or negative Uninvolved immunoglobulins low or normal

Follow up by non-haematologist:

HIGH RISK GROUP •

•

•

• • •

Symptomatic of suspected myeloma or lymphoprol iferative disorder Abnormal physical signs suggestive of underlying plasma cell or lymphoprol iferative disorder Unexplained abnormal investigation results (blood or X-ray) lgG M-protein > 15 g/1 lgA M-protein > I 0 g/1 Any lgD or lgE M-protein irrespective of concentration

• Repeat serum or urine electrophoresis every 3-4 months and extend interval to 6-12 months if stable and no symptoms

Clinical concern during follow up • Refer to

Haematologist for investigation and

management • Supply patient with

information leaflet

Abnormalities with a low probability of underlying haematolgical malignancy

Abnormality Comment

Isolated neutropenia Isolated >1.0 rarely significant

Isolated mild neutrophilia Total WCC < 15 usually chronic infection, inflammation, steroids

Isolated mild thrombocytopeniaIf isolated, investigate if < 100. Think of chronic liver disease,

exclude HIV

Hb 100-120 g/L Check haemotinics, TFTs, renal function

Don’t over treat…

• Chronic lymphocytic leukaemia

• Follicular B cell lymphomas

• Multiple myeloma (indolent or “smouldering”)

• Essential thrombocythaemia

Don’t do fine needle biopsies of lymph nodes

• Insufficient material for biopsy of lymphomas

• Will miss Hodgkin lymphoma

• Excision biopsy or core minimum

Don’t do routine followup CT scans in patients with lymphoma who achieve CR• most patients have obvious relapse based on

signs, symptoms and blood tests

• relapse commonly occurs between visits and/or scans

• “background noise” of CT and PET scans expose patients to the risks of “overdiagnosis”

• no evidence of improved outcome with “surveillance scans”

Do…

Refer urgently patients with a high probability of acute leukaemia/high grade

lymphoma• Obvious significant lymphadenopathy e.g. > 2 cm,

mediastinal mass

• Blasts on blood film

• Significant pancytopenia e.g. platelets < 50 X10^9/L, Hb < 100 g/L , neutrophils < 1.0 X 10^9/L unless other explanation e.g. chronic liver disease/portal HT

• Other triggers for urgent referral: hypercalcaemia, high LDH

Suspect cord compression

Suspect thoracic inlet obstruction

Fever and rash…

Treat fever in neutropenic or immunosuppressed patients urgently

• Neutrophils < 1.0 = neutropenia

• In practical terms, treat any patient who is significantly immunosuppressed (recent chemotherapy, previous transplant, hyposplenic) the same way

• Urgent IVI antibiotics with cover for Pseudomonas (and pneumococcus in the hyposplenic patients)

…be aware of nonbacterial infectious complications

…give prophylaxis for patients with HBsAg and/or HBcore antibodies who are

immunosuppressed

Exotic infections

Rash post allogeneic stem cell transplant

Post transplant• Revaccination at 6-12 months if off all immunosuppression and no GVHD

• Tetanus-diphtheria toxoid

• Haemophilus influenzae b conjugate (Hib)

• Pneumococcal vaccine (PPV23) (note second dose at 24 months)

• Inactivated polio vaccine (IPV)

• Hepatitis B vaccine

• 14 months post transplant

• Tetanus-diphtheria toxoid

• Haemophilus influenzae b conjugate (Hib)

• Inactivated polio vaccine (IPV)

• Hepatitis B vaccine

• 24 months post transplant

• Tetanus-diphtheria toxoid Haemophilus influenzae b conjugate (Hib)

• Pneumococcal vaccine (PPV23)

• Inactivated polio vaccine (IPV)

• Hepatitis B vaccine

• Influenza vaccine is given annually starting > 6 months after stem cell transplantation

Do - vaccinate (care with live vaccines)

• Pneumococcal and influenzal vaccines for patients with CLL, myeloma and related disorders

• Identify and vaccinate surgically and functionally asplenic patients

• Revaccinate patients after autologous or allogeneic stem cell transplant (6-12 mo after and off immunosuppression) -avoid live vaccines

Hyposplenic patients• Initial vaccinations:

• Prevenar-13 IMI (= Pneumococcal Conjugate vaccine 13-valent) 0.5 ml IMI (not repeated)

• Menactra (= 4-valent Meningococcal Conjugate vaccine) (first dose) 0.5 ml IMI

• Hibirix 0.5 ml IMI (not required if had previous HiB vaccination)

• 8 weeks later:

• Pneumovax-23 (= Pneumococcal polysaccharide vaccine 23-valent) 0.5 ml IMI (repeat every 5 years)

• Menactra (= 4-valent Meningococcal Conjugate vaccine)(second dose) 0.5 ml IMI

• +/- Bexsero (group B meningococcal vaccine)

• Annual Fluvax 0.5 ml IMI

…be vigilant for long term complications of therapies in haematology

• Second malignancies (esp breast, skin, lung, thyroid) in irradiated fields esp Hodgkin lymphoma and primary mediastinal lymphomas

• Hypothyroidism (neck radiation)

• Cardiovascular effects of anthracyclines and cardiac radiation

• Nilotinib (CML): increase in metabolic syndrome & need for tight control of risk factors