IGazi Kirstenbosch October 2014 CHILDHOOD LEUKAEMIA AND LYMPHOMA Alan Davidson Haematology / Oncology Service Red Cross Children’s Hospital.

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Presentation transcript:

iGazi Kirstenbosch October 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 line 1 new case per paediatrician per year A 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 RCCH 431/590 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 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” iGazi at Kirstenbosch October 2014

BURKITT LYMPHOMA 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 38 o C, wet and dry petechiae generalised 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 38 o C, wet and dry petechiae generalised 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 diagnosis Prognosis not affected unless given steroids / MTX

GUM HYPERTROPHY AXOLILE Aged 13 years History: lethargy, gum swelling x 2 months Exam: generalised adenopathy gum hypertrophy no hepatosplenomegaly Labs: Hb 5.1 Plts 11 WCC 96 LDH 514 iGazi at Kirstenbosch October 2014

GUM HYPERTROPHY AXOLILE Aged 13 years History: lethargy, gum swelling x 2 months Exam: generalised adenopathy gum hypertrophy no hepatosplenomegaly Labs: Hb 5.1 Plts 11 WCC 96 LDH 514 Clinical Diagnosis? Acute Myeloid Leukaemia iGazi at Kirstenbosch October 2014

MICHAEL Aged 7 years History: several URTIs snoring x 6 weeks Exam: massive proptosis with audible sturtor no 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 URTIs snoring x 6 weeks Exam: massive proptosis with audible sturtor no 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 Leukaemia Rhabdomyosarcoma Neuroblastoma 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 DifferentialNeuts 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 DifferentialNeuts 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 DifferentialNeuts 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 differential For acute leukaemias one would expect: DifferentialNeuts 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 204 CXR – subtle widening of mediastinum CT scans – paratracheal & mesenteric nodes, splenic lesions Bone 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 204 CXR – subtle widening of mediastinum CT scans – paratracheal & mesenteric nodes, splenic lesions Bone 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 0.35 CXR – 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 0.35 CXR – 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 clear USS 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 clear USS 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 clear USS 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 clear USS 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 lesions Bone 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