IGazi Kirstenbosch October 2014 CHILDHOOD LEUKAEMIA AND LYMPHOMA Alan Davidson Haematology /...
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Transcript of 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 ...
iGazi at Kirstenbosch October 2014
HUGE ADVANCE IN SURVIVAL SINCE 1960s
2005-2009 @ RCCH431/590 are alive …Overall Survival = 73.1%
iGazi at Kirstenbosch October 2014
BUT RESULTS VARY BY TUMOUR
iGazi at Kirstenbosch October 2014
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 ...
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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”
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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)
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
Diagnosis? Chronic Myeloid Leukaemia Differential Diagnosis? LCH / Gaucher Disease
The “less” massive spleen could be infection (malaria) / portal hypertension / haemolytic anaemia
iGazi at Kirstenbosch October 2014
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
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
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
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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
iGazi at Kirstenbosch October 2014
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