igazi kirstenbosch october 2014 childhood leukaemia and lymphoma alan davidson haematology /...

iGazi KirstenboschOctober 2014

CHILDHOOD LEUKAEMIA AND LYMPHOMA

Alan Davidson

Haematology / Oncology Service

Red Cross Children’s Hospital

Gauteng and the WC: 85 new cases / yr among children 0-15

years

Bottom line1 new case per paediatrician per yearA handful of cases per GP per career

CHILDHOOD CANCER IS RARE!

Childhood Cancer vs Adult Cancer

Adult tumours Mainly carcinomas (epithelial in origin):

breast, colon, lung, cervix or uterus. These are often slow growing, and response to chemotherapy is relatively poor.

Prevention and screening are critical. Classic warning signs are useful. Screening tests pick up early or pre-malignant lesions.

Childhood tumours Leukaemias and lymphomas, and deep

seated Embryonal tumours and sarcomas. They have a high mitotic rate, are fast growing and usually respond well to chemotherapy.

Screening tests are generally unhelpful. Our focus is on Early detection via Warning

Signs

Pallor plus Bleeding Bone Pain Adenopathy Unexplained Neurological Signs Unexplained Mass Eye Changes Fever / Apathy / Weight Loss

WHAT ARE THE WARNING SIGNS?

iGazi at Kirstenbosch October 2014

INCIDENCE BY DIAGNOSIS ...


HUGE ADVANCE IN SURVIVAL SINCE 1960s

2005-2009 @ RCCH431/590 are alive …Overall Survival = 73.1%


BUT RESULTS VARY BY TUMOUR


WHAT’S THE IMPACT OF EARLY DIAGNOSIS?

Prognosis is generally better than for adults … for example … Leukaemia 75% 5 year survival Wilms Tumour 50-95% 5 year survival

EARLIER diagnosis = BETTER outcome

At RCCH we see 130-140 new cases / year … Many present with advanced disease AND have presented to the health service several times over the preceding weeks or months

These delays make treatment more difficult AND decrease the chances of success ...


IMPROVED PROGNOSIS“What a Difference a Day (or two) Makes”

0 50 100 150 200 250 300 350

T ime - months

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ulative Proportion S

urviving

S tage I 94.4% S tage II 96.2% S tage III 84.9% S tage IV 54.2%

Comple te CensoredCh i-squa re = 22 .898 d f = 3 p = 0 .00004


BURKITT LYMPHOMA

O ver all 5 -year S ur vi valLM B Chemother apy

1988-2004[Log Rank p value 0 .0 6 ]

Complete Cens ored

Stage II and III [88.2% ]

Stage IV [66.0% ]

0 20 40 60 80 100 120 140 160 180 200 220

Time - months

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ulative Proportion S

urviving iGazi at Kirstenbosch October 2014

WILMS TUMOUR TREATMENT…

Surgery (primary or delayed) for all

Chemotherapy Stage I or II: Vincristine + Dactinomycin Stage III or IV: Add DOXORUBICIN

RENAL BED RADIOTHERAPY for local Stage III PULMONARY RADIOTHERAPY for lung metastases

LESS TOXICITY“Smaller Omelette ... Less Eggs”


CLASSIFICATION OF HAEMATOLOGICAL MALIGNANCIES

IN CHILDHOOD

LEUKAEMIAS (Bone Marrow infiltration by blasts exceeds 25%)

Acute Lymphoblastic Leukaemia (75%)(B- or T-cell) Acute Myeloid Leukaemia (20%) Chronic Myeloid Leukaemia (3%)

LYMPHOMAS (Nodal / Extranodal ... BM < 25%)

Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma

Lymphoblastic Lymphoma (usually T-cell)

Burkitt Lymphoma and leukaemia Anaplastic Large Cell Lymphoma


HAEMATOLOGICAL MALIGNANCIES

WHAT DO THEY HAVE IN COMMON? Malignant proliferation of white cells (lymphoid or myeloid)

WHAT ARE THE IMPORTANT DIFFERENCES? Different ages: ALL peaks between 2 and 5 years

Others all more common in older kids (6-14)

Different acuity: Slow growing or rapidly growing Different sites: Nodes, Hepatosplenomegaly, Thymus,

BM, CSF +/- Elevated markers of tumour turnover (LDH, uric acid)

… combination is relatively specific BUT not sensitive

WHAT’S CRITICAL? Some can be “pre-treated” by steroids, and may mimic

conditions usually treated with steroids (JRA, ITP). Think before you write!

SIVIWE Aged 2 ½ years History: bleeding gums, pallor, fever x 2 weeks

macroscopic haematuria and painful left elbow x 3 days

Exam: T 38oC, wet and dry petechiaegeneralised adenopathy, 8cm hepar, 4cm

spleen Labs: Hb 3.2 Plts 15 WCC 280 (95% blasts)

LDH 2457 ALT 20 Urate 0.5

PANCYTOPAENIA


PANCYTOPAENIA

SIVIWE Aged 2 ½ years History: bleeding gums, pallor, fever x 2 weeks

macroscopic haematuria and painful left elbow x 3 days

Exam: T 38oC, wet and dry petechiaegeneralised adenopathy, 8cm hepar, 4cm

spleen Labs: Hb 3.2 Plts 15 WCC 280 (95% blasts)

LDH 2457 ALT 20 Urate 0.5

Diagnosis? Acute Lymphoblastic Leukaemia Differential Diagnosis? Acute Myeloid Leukaemia Treatment? Phone call / IV fluid / Allopurinol / Products


BONE PAIN

GODFREY Aged 8 years History: pain in the right leg with a limp x 2 weeks Exam: febrile, few tender cervical nodes, no liver or spleen

bilateral knee and hip tenderness, no effusions

Labs: Hb 13 Plts 346 WCC 8.6 ESR 131 LDH 3048 ALT 25 Urate 0.3(Orthopaedics) Bone Scan suggestive of

leukaemia Bone Marrow packed (few blasts on scanning the smear)


BONE PAIN

GODFREY Aged 8 years History: pain in the right leg with a limp x 2 weeks Exam: febrile, few tender cervical nodes, no liver or spleen

bilateral knee and hip tenderness, no effusions Labs: Hb 13 Plts 346 WCC 8.6 ESR 131

LDH 3048 ALT 25 Urate 0.3(Orthopaedics) Bone Scan suggestive of

leukaemia Bone Marrow packed (few blasts on scanning the smear)

Diagnosis? Acute Lymphoblastic Leukaemia Teaching Point: This presentation frequently delays in

diagnosisPrognosis not affected unless given

steroids / MTX

GUM HYPERTROPHY

AXOLILE Aged 13 years History: lethargy, gum swelling x 2 months Exam: generalised adenopathy

gum hypertrophyno hepatosplenomegaly

Labs: Hb 5.1 Plts 11 WCC 96LDH 514


GUM HYPERTROPHY

AXOLILE Aged 13 years History: lethargy, gum swelling x 2 months Exam: generalised adenopathy

gum hypertrophyno hepatosplenomegaly

Labs: Hb 5.1 Plts 11 WCC 96LDH 514

Clinical Diagnosis?Acute Myeloid Leukaemia


MICHAEL Aged 7 years

History: several URTIssnoring x 6 weeks

Exam: massive proptosis with audible sturtorno nodes or hepatosplenomegaly

Labs: Hb 11.3 Plts 207 WCC 6.4 (3/88/7/1 … 1 suspicious cell)

LDH 776 ALT 11

CHLOROMAS


MICHAEL Aged 7 years

History: several URTIssnoring x 6 weeks

Exam: massive proptosis with audible sturtorno nodes or hepatosplenomegaly

Labs: Hb 11.3 Plts 207 WCC 6.4 (3/88/7/1 … 1 suspicious cell)

LDH 776 ALT 11

Differential Diagnosis?Acute Myeloid LeukaemiaRhabdomyosarcomaNeuroblastoma

CHLOROMAS

THE MASSIVE SPLEEN

CINDY Aged 7 years History: long history of non-specific symptoms

(LOA, LOW) Exam: massive splenomegaly (into left iliac fossa) Labs: Hb 6.1 Plts 344 WCC 508

Differential Neuts 35% Lymphs 20% Monos 20% Eos 4% Baso 6% Metas 5% Myelos 3% Blasts 7%

LDH 1303 Urate 0.29


THE MASSIVE SPLEEN




LDH 1303 Urate 0.29

Diagnosis? Chronic Myeloid Leukaemia Differential Diagnosis? LCH / Gaucher Disease

The “less” massive spleen could be infection (malaria) / portal hypertension / haemolytic anaemia


THE MASSIVE SPLEEN




LDH 1303 Urate 0.29

NOTE: This is a typical chronic leukaemia differentialFor acute leukaemias one would expect: Differential Neuts 3% Lymphs 10%

Monos 7% Eos 4% Blasts 76% iGazi at Kirstenbosch October 2014

LYMPH NODES

ROBERT Aged 10 years History: right-sided cervical nodes for six months

NO TB contact Exam: two groups of nodes in posterior triangle (largest 4 x

6cm)no other nodes or hepatosplenomegaly

Labs: Hb 10.5 Plts 283 WCC 4 ESR 67 Mantoux negative LDH 204CXR – subtle widening of mediastinumCT scans – paratracheal & mesenteric nodes,

splenic lesionsBone Marrow clear


LYMPH NODES

ROBERT Aged 10 years History: right-sided cervical nodes for six months

NO TB contact Exam: two groups of nodes in posterior triangle (largest 4

x 6cm)no other nodes or hepatosplenomegaly

Labs: Hb 10.5 Plts 283 WCC 4 ESR 67 Mantoux negative LDH 204CXR – subtle widening of mediastinumCT scans – paratracheal & mesenteric nodes,

splenic lesionsBone Marrow clear

Diagnosis? Hodgkin’s Disease Differential Diagnosis? TB, TB and TB! (ALCL)

THE MEDIASTINAL MASS

SIMON Aged 11 years History: anterior chest pain,

cough and wheeze x 2 weeks Exam: facial swelling / prominent neck veins

no nodes or hepatosplenomegaly Labs: Hb 12.6 WCC 10.1 Plts 375

LDH 809 Urate 0.35CXR – anterior mediastinal mass Mantoux – negative


THE MEDIASTINAL MASS

SIMON Aged 11 years History: anterior chest pain,

cough and wheeze x 2 weeks Exam: facial swelling / prominent neck veins

no nodes or hepatosplenomegaly Labs: Hb 12.6 WCC 10.1 Plts 375

LDH 809 Urate 0.35CXR – anterior mediastinal mass Mantoux – negative

Diagnosis? T-cell Lymphoma Needs URGENT REFERRAL

ABDOMINAL NODES …

XOLA Aged 9 years History: painless abdominal distension Exam: no nodes

doughy abdomen with ascites Labs: Hb 10.9 Plts 689 WCC 16.9 ESR 90

Mantoux negative and CXR clearUSS abdomen – mesenteric nodes /

thickened bowel wall Treated for TB … no response … At our request: LDH 1423 / Urate 0.64


XOLA Aged 9 years History: painless abdominal distension Exam: no nodes

doughy abdomen with ascites Labs: Hb 10.9 Plts 689 WCC 16.9 ESR 90

Mantoux negative and CXR clearUSS abdomen – mesenteric nodes /

thickened bowel wall Treated for TB … no response … At our request: LDH 1423 / Urate 0.64

Diagnosis? Burkitt Lymphoma Again needs URGENT REFERRAL

ABDOMINAL NODES …

… AND A JAW MASS?

XOLA Aged 9 years

Burkitt Lymphoma …

Endemic version with jaw mass is uncommon at RCCH (10%)

Watch for involvement of the bone marrow and/or CNS

THE PELVIC MASS

SARAH Aged 10 years History: abdominal pain and vomiting x 6 days Exam: apyrexial without nodes or hepatosplenomegaly

RIF mass - tender Labs: Hb 9.7 Plts 662 WCC 9 LDH 487 Urate 0.89

CXR clearUSS abdomen – lobulated pelvic mass with

iliac nodes


SARAH Aged 10 years History: abdominal pain and vomiting x 6 days Exam: apyrexial without nodes or hepatosplenomegaly

RIF mass - tender Labs: Hb 9.7 Plts 662 WCC 9 LDH 487 Urate 0.89

CXR clearUSS abdomen – lobulated pelvic mass with

iliac nodes

Diagnosis? Burkitt Lymphoma Biopsy ONLY! Leave in the important bits!

THE PELVIC MASS


THE CURVEBALLS

SHAUN Aged 3 years

History: abdominal pain and meningism Exam: signs of cord compression following LP Labs: Normal FBC LDH 921 Urate 0.5

MRI – brain, spine and kidney lesionsBone Marrow: Burkitt leukaemia

EUGENIA Aged 15 years

History: chronic lung disease Exam: chronic RML and RLL collapse …

no response to antibiotics Labs: Normal FBC LDH 921 Urate 0.5

Biopsy: DLBCL

SHAUN Aged 3 years EUGENIA Aged 15 years

HIV positive leukaemias and lymphomas Occur at a younger age Unusual sites Unusual histologies Often aggressive

THE CURVEBALLS


MAKING A PROMPT DIAGNOSIS

WATCH FOR THE WARNING SIGNS and SYMPTOMS

Pancytopaenia and Bone Pain Suspicious Adenopathy Atypical Thoracic or Abdominal Masses or Testicular Swelling Chloromas, Gum Hypertrophy CNS Involvement … ICP, cranial palsies, chloromas, ICHaem

KNOW AND RECOGNISE THE TYPICAL PRESENTATIONS

Do only the tests you need to confirm your suspicions FBC and Diff / LDH (ALT) and Uric acid / CXR / (HIV) Then use the TELEPHONE

THANKS FOR YOUR ATTENTION

Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa. 18 October 2014

igazi kirstenbosch october 2014 childhood leukaemia and lymphoma alan davidson haematology /...

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