treatment manual pediatric hematology and oncology

152 Pages·2016·6.17 MB·English

by  An Michiels

TREATMENT MANUAL
PEDIATRIC HEMATOLOGY AND
ONCOLOGY
TABLE OF CONTENTS

HEMATOLOGY AND ONCOLOGY
1. Leukemia .......................................................................................................................................................... 4
2. MDS syndromes and JMML: ............................................................................................................................ 6
3. Severe Aplastic Anemia ................................................................................................................................... 6
4. Lymphomas ...................................................................................................................................................... 7
5. Brain tumors .................................................................................................................................................... 8
6. Bone tumors .................................................................................................................................................. 12
7. Extracranial germ cell tumors………………………………..………………………………………………………………………………...13
8. Neuroblastoma .............................................................................................................................................. 13
9.Kidney tumors ................................................................................................................................................. 14
10. Liver tumors ................................................................................................................................................. 14
11. Soft tissue sarcomas .................................................................................................................................... 15
12. Retinoblastoma ............................................................................................................................................ 16
13. Other tumors ............................................................................................................................................... 17
14. Histiocytosis ................................................................................................................................................. 17

SUPPORTIVE CARE
1. Infection ......................................................................................................................................................... 24
2. Mucositis ........................................................................................................................................................ 25
3. Anti-emetics ................................................................................................................................................... 26
4. Transfusion..................................................................................................................................................... 27
5. Tumor lysis syndrome .................................................................................................................................... 32
6. Menses suppression in adolescent girls ........................................................................................................ 34
7. Supportive care in asplenic patients .............................................................................................................. 37

BENIGN HEMATOLOGY
1. Severe Anemia in childhood .......................................................................................................................... 38
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2. Lead intoxication ............................................................................................................................................ 43
3. Hemolytic anemia .......................................................................................................................................... 49
4. Major sickle cell syndromes ........................................................................................................................... 62
5. Thalassemia ................................................................................................................................................... 70
6.Neutropenia .................................................................................................................................................... 76
7.Trombopenia (including ITP) ........................................................................................................................... 81
8.Disorders of hemostasis.................................................................................................................................. 93
9. Thrombosis in childhood.............................................................................................................................. 105
10. Adenopathies ............................................................................................................................................. 119
11. Recurrent or severe infections in childhood .............................................................................................. 119
12. Aplastic Anemia ......................................................................................................................................... 119

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Hematology and Oncology
1. Leukemia
1.1.ALL
General information
• Incidence: most frequent childhood malignancy. Accounts for 23 % of pediatric malignant diagnoses.
Belgium: +/- 65 cases anually
• Risk factors: most patients have no identifiable risk factors. See document Superior Health Council
http://tinyurl.com/HGR-8548-kinderleukemie
 Prenatal exposure to X-rays
 Post-natal exposure to high doses of radiation
 Down syndrome and other genetic conditions
 Certain inherited genetic polymorphisms e.g. ARID5B
• Outcome: overall 85-90 % 5y OS. Importance of risk stratification and treatment adjustment.
1.1.1. Precursor B/T- ALL
A. ≥ 1 year
• CLG Treatment recommendations . (Yves Benoit-UZ Gent).
B. < 1 year
• INTERFANT-06: International collaborative treatment protocol for infants under one year with acute
lymphoblastic or biphenotypic leukemia. Study Open (Alice Ferster-HUDERF).
C. ALL Phi+
• Amended EsPhALL . Treat as per study protocol. Study closed.
D. ALL and Down syndrome
• Study in preparation (Veerle Mondelaers –UZ Gent).
E. Relapses ALL
• EORTC 58111 IntreALL SR 2010: International study for treatment of standard risk childhood
relapsed ALL 2010. Study open (Alice Ferster – HUDERF)
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• EORTC 58111 IntreALL HR 2010: International study for treatment of high risk childhood relapsed
ALL 2010. Study in preparation (Alice Ferster – HUDERF)
F. Stem cell Transplantation
• ALL SCT ped 2012 Forum NOR (no randomization): Allogeneic stem cell transplantation in children
and adolescents with acute lymphoblastic leukaemia. In preparation (Sophie Dupont – UCL)

1.1.2. Mature B-ALL
• High risk B-NHL and B-AL: Inter- B-NHL ritux 2010: Intergroup trial for children or adolescents with B-
NHL or B-AL: evaluation of rituximab efficacy and safety in high risk patients. For group B and
C. Study Open (Anne Uyttebroeck – UZ Leuven).

1.2.AML
1.2.1. AML
• NOPHO DBH AML 2012 Research study for treatment of children and adolescents with acute
myeloid leukaemia 0-18 years. Study Open (Barbara de Moerloose- UZ Gent).

1.2.2. AML Down Syndrome
• Down Syndrome: ML DS 2006: Myeloid Leukemia Down Syndrome 2006. Study not open in Belgium.
Registration possible. Contact Veerle Mondelaers - UZ Gent.

1.2.3. APML
• ICC APL Study 01. Treat as per study protocol: Treatment study for patients with acute promyelocytic
leukemia under 21 years of age. Study not open in Belgium. Registration is possible.

1.2.4. Relapsed AML
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• AML relapse: Pediatric relapsed AML 2010/01. International randomized phase III study on the
treatment of children and adolescents with refractory or relapsed acute myeloid leukemia. In
preparation (Barbara De Moerloose-UZ Gent).

1.2.5. Stem Cell Transplantation for AML
• Guidelines. (Barbara De Moerloose-UZ Gent).

1.3.CML
• CML registry (I-CML-paed study): International study of chronic myeloid leukemia (CML) :
Treatments and outcomes inn children and adolescents. In preparation. (Barbara De Moerloose- UZ
Gent).
• STOPIMAPED: An international collaborative study to discontinue Imatinib/Glivec® in pediatric CML
patients with sustained complete molecular response. . In preparation (Barbara De Moerloose- UZ
Gent).

2. MDS syndromes and JMML:
• EWOG-MDS 2006: Prospective non–randomized multi-center study for epidemiology and
characterization of Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic Leukemia
(JMML) in childhood. Study Open (Barbara De Moerloose-UZ Gent).
• Guidelines for Hematopoietic Stem Cell Transplantation (HSCT) in Childhood MDS and JMML.

3. Severe Aplastic Anemia

• EWOG-SAA 2010: Genetic and immunologic characterization of Acquired Severe Aplastic Anemia
(SAA) in children and adolescents. An open non-randomized multicenter prospective study. Study
Open (Veerle Labarque – UZ Leuven)
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4. Lymphomas
4.1.Hodgkin’s lymphoma
4.1.1. Classical Hodgkin’s Lymphoma
• EuroNet-PHL-C2 study: Second international Inter-Group study for classical Hodgkin lymphoma in
children and adolescents (Anne Uyttebroeck-UZ Leuven).

4.1.2. Lymphocytic Predominance
• EuroNet-PHL-LP study. Treat as per study protocol. (An Van Damme – UCL).

4.1.3. Relapse Hodgkin’s Lymphoma
• EuroNet-PHL-C1 study: First international Inter-Group Study for classical Hodgkin’s Lymphoma in
Children and Adolescents. Study closed Jan 31st, 2013. EuroNet-PHL-C1 protocol from p89 (Anne
Uyttebroeck-UZ Leuven).

4.2.Non Hodgkin lymphoma
4.2.1. B-NHL: Burkitt/ Burkitt-like, DLBCL
• Low/intermediate risk B-NHL: Therapeutic recommendations for low/intermediate risk B-cell NHL in
children or adolescents
• High risk B-NHL and B-AL: Inter- B-NHL ritux 2010: Intergroup trial for children or adolescents with B-
NHL or B-AL: evaluation of rituximab efficacy and safety in high risk patients. Study Open (Anne
Uyttebroeck – UZ Leuven).

4.2.2.PMLBL
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• Phase II study PMLBL of B-cel ritux 2010. Study closed. To treat PMLBL see recommendations (Anne
Uyttebroeck – UZ Leuven).

4.2.3. Lymphoblastic lymphoma
• Euro-LB 01: Study closed. Treat as per protocol. (Anne Uyttebroeck – UZ Leuven)

4.2.4. ALCL
• ALCL 99: International protocol for the treatment of childhood anaplastic large cell lymphoma. Study
closed. Treat as per protocol. (Anne Uyttebroeck-UZ Leuven).
• ALCL relapse: Treatment protocol for relapsed anaplastic large cell lymphoma of childhood and
adolescence. An European Inter-group Co-operation on Childhood Non-Hodgkin Lymphoma
(EICNHL) International Multicentre Therapy Study. Study closed. Treat as per protocol. (Anne
Uyttebroeck-UZ Leuven).

4.2.5. NHL in DNA repair disorders / immunodeficiencies
4.2.6. Post-transplant lymphoproliferative disease (PTLD)
4.2.7. Other

5. Brain tumors
General information
• As a group, brain tumors are the second most frequent malignancy in childhood.
• Clinical symptoms: depending on age, localization, tumor type, evolution and presence of raised
intracranial pressure. The most frequent complaints are headaches, vomiting, behavioral changes,
changes in level of consciousness, visual problems, motor deficits, cranial nerve deficits, cerebellar
disturbances and endocrine dysfunction.
• Diagnosis:
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 MRI brain + spinal cord (preoperatively for detection of drop metastasis).
 Ophtalmological examination
 Endocrinological evaluation
 Cytology of CSF for detection of tumor cells in case of
medulloblastoma/PNET/ependymoma.
 Tumor markers in blood and CSF (-HCG and -FP) in case of suspicion of germ cell tumor
• Treatment:
 Neurosurgery:
 Diagnostic: biopsy or tumor resection for anatomopathological examination
including fresh frozen tissue for all childhood braintumors
 Treatment of intracranial hypertension
 Tumor reduction: Evaluation of extent of tumor resection within postoperative 72
hours (MRI or CT)
 Radiotherapy:
 General: as little and as late as possible
 Chemotherapy: see protocol section. For rare pathologies, treatment decisions need to be
taken on an individual basis. Referent experts should be contacted or cases can be discussed
on the weekly neuro-oncology webconferences.

5.1. Astrocytomas
5.1.1. Low grade Gliomas
• SIOP-LGG 2004. Cooperative multicenter study for children and adolescents with low grade glioma.
Study not open in Belgium. Treat as per protocol. Standard of care: standard arm. In accordance
with the LGG 2014 protocol (LOGGIC) radiotherapy will be used as second line therapy. There is a
consensus for Belgium to already omit radiotherapy for first line therapy of LGG.
• SIOP-LGG-2014 (LOGGIC): Phase II randomized, international multicenter study for children and
adolescents with non NF-related low grade glioma. In preparation (An Van Damme – UCL)

5.1.2. High grade Gliomas
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• HIT-HGG-2007. International cooperative Phase II trial of the HIT-HGG study group for the
treatment of high grade glioma, diffuse intrinsic pontine glioma and gliomatosis cerebri in children ≥
3 years and adolescents < 18 years. Treat as per protocol.
• Infant HGG protocol: not open in Belgium. Treat as per protocol

5.2. Brain stem
Diffuse intrapontine glioma (DIPG):
• Standard of care: radiotherapy
• Optional: addition of temozolamide. It has not been shown that this prolongs time to relapse. See
HIT-HGG-2007
• Re-irradiation should be considered for relapse dIPG

5.3.Embryonal tumors
5.3.1 Medulloblastoma
The risk stratification for children with a medulloblastoma is according to age and biology
1) Children younger than 5 years
• YC MB LR and HR protocol : In preparation (S. Jacobs – UZ Leuven)

2) Children older than 5 years
• PNET 5: An international prospective study on clinically standard-risk medulloblastoma in children
older than 3 to 5 years with low-risk biological profile (PNET5 MB-LR) or average-risk biological
profile (PNET 5 MB-SR). Trial open in Belgium (S. Jacobs-UZ Leuven).
Patients without residual disease (of ≤1.5cm²), classic MB, desmoplastic or nodular MB and without
metastasis can be included. Other patients can be included in the new HR MB protocol that will be
written.
• HIT-2000: Study closed; treat as per protocol. In the future a new protocol for HR MB in children
older than 5 years will be written.
• Experimental study France: please contact Dr. E. Sariban (HUDERF)
Relapsed medulloblastoma:
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