This is the case of a baby girl born June 2009 and with CML BCR-ABL1 b2a2 p210 diagnosed in January 2010, at the age of 6 months. She had hepatosplenomegaly on diagnosis with a FBC Hb 6,5g/dL WBC 168x109/L and Plat 1254x109/L , BM cytogenetics 46,XX t(9;22) (q34;11.2).

Treatment was started with oral imatinib given as per the CML-pead-II-study on a dose of 50mg bd. At 3 and 6 months post-treatment RQ-PCRs were respectively 21% and 29%.
Her cord blood was cryopreserved at birth and tested negative for BCR-ABL.

She is the only child of a healthy 36-y-old couple. Although her parents are not related they share HLA antigens so that the patient is homozygotic for HLA A, B, C, DRB1 and DQB1 on high resolution typing.
She was referred for an unrelated allotransplant.

I would like to discuss whether anyone would consider an autologous graft using the cryopreserved CB, advise the parents to try a 2nd child or proceed with an unrelated transplant.

Manuel Abecasis, MD PhD
Director, BMT Program
Instituto Portugues Oncologia
Lisboa Portugal

From my experience as chairman of the pediatric trial CMl PaedII this is one of the youngest cases I am aware of.
Under the assumption of a so far normal development, a six months old baby has a bodyweight of 6 - 7 kg and a body surface aera of 0,3 sqm. No dose recommendations are are availiabe for this age group, but the dose recommended in the protocol (260 - 340 mg/sqm) would turn out into a dose of 100 mg given orally as a SINGLE dose daily. Splitting the dose will result in insufficient blood drug levels. However, pharmacokinetic data in this age group still avait investigation.
You list data on PCR results with a ratio BCR-ABL/ABL of 21% and 29% at month 3 and month 6 respectively. You can hardly expect any change in molecular response within this time frame from diagnosis. More importantly is haematological response at months 3 (what are the data?) and a decline in cytogenetics at months 6 (did you do a cytogenetic examination?). By months 12 the bone marrow should be Ph negative (cytogenetic remission).
As long as there is a treatment response there is no room for transplantation either allogeneic nor autologous. If the parents are interested, a laboratory which I closely cooperate with, can check the Guthrie card or any other material stored away in association with the cord blood banking to check for leukemic cell contamnination on a DNA level (not RT-PCR level as usually done with RNA) which is of much higher sensitivity.
If you have further questions please ring my offic :+49 351 4583522.
With regards
M. Suttorp
Univ Children Hospital
Fetscherstr 74
D01307 Dresden, Germany