Siramizu Et Al 2015.docx

SIRAMIZU et al 2015 Assessment of response to treatment  Criteria for reliable assessment o Malignant vs normal cells o Tumour-specific markers stable o Sensitivity at least 1 malignant cell/10^4 normal cells  Established methods in leukaemia o Flow cyt for aberrant immunophenotypes o PCR amplification of fusion transcripts or AgR genes  Recent studies showing good prognostic indicator for ALCL (ALK fusions) and T-LBL Criteria for diagnosis  Histopath and immunophenotyping being replaced by genetic profiling  Sehn and Gascoyne 2015 - several drugs may only be effective in subtypes (e.g. of DLBCL) in adults - but whether applies to paeds is controversial as more homogenous however, poor outcome if relapse Management  EFS for NHL approach 90% for mature B-NHL  Studies for less toxic therapy for BL contributes to higher risk of relapse - Cairo et al. 2007, Woessmann et al 2005; less intensive therapy equally effective for standard risk but not for high-risk  Inhibitory factors for development of new therapies for children o High cure rate o Unknown late effects on development o Different subtypes in paediatrics compared to adults New possibilities  CAR-T - relapsed/refractory ALL approved but not yet for refractory B-NHL  Blinatumomab - CD19 - again with refractory pre-B cell leukaemia

Table 4. FAB/LMB and BFM Staging Schemas for B-cell NHL

Stratum FAB/LMB International Study[19,20,23]

Disease Manifestation

A

Completely resected stage I and abdominal stage II

Ba

Multiple extra-abdominal sites Nonresected stage I and II, III, IV (marrow <25% blasts, no CNS disease); epidural masses (stage III Murphy staging) are treated as group B unless there is evidence of dural invasion

BFM Group [24]

C

Mature B-cell ALL (>25% blasts in marrow) and/or CNS disease

R1

Completely resected stage I and abdominal stage II

R2

Nonresected stage I or II and stage III with LDH <500 IU/L

R3

Stage III with LDH 500–999 IU/L Stage IV, B-ALL (>25% blasts), no CNS disease, and LDH <1,000 IU/L

R4

Stage III, IV, B-cell ALL with LDH >1,000 IU/L Any CNS disease