4.2.1. Leukaemias

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells Acute myeloid leukaemia

Despite intensive chemotherapy, less than half of all patients with acute myeloid leukaemia (AML) will survive in the long term (Gibson et al., 2005). Disease recurrence and treatment-related toxicities still account for approximately 40% of deaths in paediatric patients with de novo AML. Allogeneic HSCT may provide a GVL effect in such patients (Table 4.1).

Current indicators of HSCT in AML include: relapsed AML in second complete remission (CR2); relapsed AML in first complete remission (CR1) with high-risk features such as FLT3/ITD+ with a high allelic ratio of >0.4 (HR FLT3/ITD+ ); presence of monosomy 7, monosomy 5 or del5q; lack of evidence of low-risk cytogenetics; evidence of residual AML (MRD = 0.1%) at end of induction; and lack of low-risk cytogenetics with radiographic evidence of progressive extramedullary AML at end of induction (Kelly et al., 2014). Currently, low-risk AML (defined as an inversion (16)/t(16;16) or t(8,21),NPM1 mutation, Down syndrome or acute promyelocytic leukaemia (APL) in CR1) is not considered for transplantation, as survival is >60% with just chemotherapy. Acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) in children is a heterogeneous disease with different molecular and chromosomal abnormalities. Current indicators of HSCT in ALL in children include ultra-high-risk ALL in CR1, in which estimated survival with chemotherapy is <50%. The ultra-high-risk group includes: hypodiploidy with <45 chromosomes; T cell precursor ALL; very-high-risk infants with myelomonocytic leukaemia (MML) rearrangement at age < 6 months and either poor response to glucocorticoid treatment or initial leukocyte count =300 Ч 109 /l; and poor early responders with =1% minimal residual disease at the end of 46 days of induction therapy (Pulsipher et al., 2011).

Table 4.1. Common indications for allogeneic HSCT in children.

Category Diseases
Malignant disorders ALL in CR1 ultra-high-risk; ALL with medullary relapse within 30 months of diagnosis; multiple-relapsed extramedullary disease; relapsed T-cell ALLAML in CR1 with high-risk features; relapsed AMLPrimary or secondary myelodysplastic syndrome (MDS)

Recurrent Hodgkin’s lymphoma and NHL

Haematological disorders Idiopathic aplastic anaemia with matched sibling or immunotherapy resistance without sibling; other bone marrow failure syndromes, including Fanconi anaemia, dyskeratosis congenita, haemoglobinopathies sickle cell disease, beta thalassemia
Immunodeficiency disorders SCIDS; CD40 ligand Def.; Wiskott – Aldrich syndrome; chronic granulomatous disease; congenital neutropenia; familial HLH
Metabolic disorders Hurler syndrome; Maroteaux – Lamy syndrome (MPS VI); adrenal leukodystrophy (ALD); Krabbe disease; metachromatic leucodystrophy; congenital erythropoietic porphyria (CEP); malignant osteopetrosis
Autoimmune disorders IPEX; infantile-onset Crohn’s disease

HSCT is a treatment option for relapsed ALL based on the sites of relapse and on the duration of first remission. Indications for treatment include relapsed T cell ALL, early bone marrow relapse within 30 months of diagnosis and multiple extramedullay relapses. Estimated long-term survival after transplantation is currently around 60% (Fagioli et al., 2013). Juvenile myelomonocytic leukaemia and chronic myeloid leukaemia

Juvenile myelomonocytic leukaemia (JMML) is a rare type of leukaemia that occurs in young children. Allogenic HSCT is the only curative option. Pretransplant chemotherapy does not change outcome, so current practice is to undertake transplantation as soon as an appropriate donor is available (Yoshida et al., 2012). Long-term survival after transplantation is around 70% and relapse is a significant problem (Loh, 2011).

Currently, HSCT in children with chronic myeloid leukaemia (CML) in the chronic phase is reserved to those who fail tyrosine kinase inhibitor therapy. Two-year overall survival in children remains high, at 80%, after the HSCT chronic phase (Hamidieh et al., 2013).


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