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Irish Journal of Medical Science

, Volume 182, Issue 3, pp 377–382 | Cite as

In search of Pinkel’s children: unravelling the biological heterogeneity of childhood acute lymphoblastic leukaemia by genotype and treatment molecular response

  • J. Krawczyk
  • S. Maguire
  • N. Sandys
  • J. Kelly
  • C. Ryan
  • A. O’Marcaigh
  • L. Storey
  • S. Rooney
  • C. Phillips
  • O. P. Smith
Original Article
  • 146 Downloads

Abstract

Background

Acute lymphoblastic leukaemia (ALL), the commonest childhood malignancy has seen remarkable progress since the 1960s with cure rates now approaching 85 %. To achieve this patients undergo intensive treatment that usually takes 2.5–3.5 years involving on average 15 different chemotherapeutic drugs. In 1971, Donald Pinkel reported Total Therapy-Protocol V that used 5 drugs and cranial radiation therapy over a similar time period. Today, one half of these patients (Pinkel’s children) remain alive and free of leukaemia.

Aim

The aim of this study was to evaluate the impact post-induction minimal residual disease (MRD) levels had on survival and its relationship with the more established clinical and biological prognostic predictors of outcome in the hope of identifying a subgroup of patients that are at very low risk of failure.

Methods

A retrospective review of 250 Irish children with ALL was carried out. MRD status after 28 days of induction chemotherapy and other known predictors of outcome were correlated with 5 year event-free survival (EFS).

Results

MRD status was the strongest predictor of outcome with 5 year EFS rates greater that 90 % seen in those patients with low-risk MRD and this was associated with TEL/AML1 rearrangement, high hyperdiploidy (HH) karyotype and female gender.

Conclusion

Both MRD and karyotype are powerful determinants of outcome in childhood ALL. Therefore, it is reasonable to conclude that the majority of children cured by Pinkel et al. in the late 1960s were most likely composed of low-risk MRD, TEL/AML1 and HH patients.

Keywords

Pinkel’s children ALL MRD Tel/AML1 High hyperdiploidy EFS 

Notes

Conflict of interest

None.

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Copyright information

© Royal Academy of Medicine in Ireland 2012

Authors and Affiliations

  • J. Krawczyk
    • 1
  • S. Maguire
    • 2
  • N. Sandys
    • 2
  • J. Kelly
    • 3
  • C. Ryan
    • 4
  • A. O’Marcaigh
    • 1
    • 2
  • L. Storey
    • 1
  • S. Rooney
    • 1
  • C. Phillips
    • 1
  • O. P. Smith
    • 1
    • 2
  1. 1.Department of HaematologyOur Lady’s Children’s HospitalDublinIreland
  2. 2.Trinity College, University of DublinDublinIreland
  3. 3.National Centre for Medical GeneticsOur Lady’s Children’s HospitalDublinIreland
  4. 4.Department of HaematologyMercy University HospitalCorkIreland

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