Clinical Case Discussion Forum
To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML cases here. Physicians submit a brief history of the patient and the case for discussion using this forum.
10-years old girl who presented CML as bilineage blast crisis
Dear colleagues,
May I ask you to share your opinion on my patient with bilineage blast crisis of CML as initial presentation.
The 10 years old girl was admitted with hyperleukocytosis of 60 000/mcl with 60% of blast cells, mild anemia and normal platelets. Immunophenotyping of blast population revealed 40% of B-lineage leukemic precursors and 10% of myeloid blasts. Cytogenetics demonstrated Ph1-chromosome and molecular genetic analysis was positive for bcr/abl p 210. She received ALL-directed induction (Vc x 5 doses, peg-asparaginase on day 3, dexametasone 6 mg/msq for 5 weeks and 2 doses of daunorubicin) together with dasatinib.
After recovery from chemotherapy-induced aplasia CR was confirmed and bcr/abl:abl ratio dropped to <0.01% in concordance with MRD(-) status by FCM. Although I have at least 1 patient who is now 22 years in MMR after lymphoid blast crisis of CML, treated with high-risk ALL "blocks" with imatinib, bilineage nature of blast crisis tells in favor of SCT.
May I ask to share your opinion about this case, taking into account that parents are asking about possibility of deferring SCT. Thank you!
Thank you for sharing the case. I think the approach really depends on the underlying diagnosis. In general, I would manage Ph+ MPAL similarly to Ph+ ALL—that is, ALL directed chemotherapy with a TKI, and if MRD negativity is achieved, I would not pursue transplant.
For CML-BP with a biphenotypic phenotype, I would be more inclined to recommend transplant. In this case, however, the BCR::ABL1 level is concordant with the lymphoblast population, which argues against CML-BP.
On the other hand, if I am reading it correctly, the disease appears bilineal rather than biphenotypic, which can still be seen in MPAL, but overall makes CML-BP somewhat more likely.
Given the ambiguity, I would lean toward recommending BMT, but if the parents decline, I would continue treatment as for Ph+ ALL.
The case you describe represents bilineage blast crisis in CML (not biphenotypic where both myeloid and lymphatic markers are expressed simultaneously on a blast cell). One may speculate that in your case out of CML in chronic phase at an advanced stage (10 % myeloblasts) a lymphoid blast cell population evolved (40 % lympoid blasts).
Following ALL-treatment and dasatinib, the 10-year old girl is now in deep molecular remission (0.01% BCR::ABL1 transcript rate). My personal experience comprises a a 5-year-old girl in CML-BP who was treated because of a missing donor ongoingly with imatinib without SCT. She is in ongoing deep molecular remission for 11 years by now. This case may be similar to your 22-year-long observation of a case. But such cases may be rare exceptions. The general recommendations to treat CML-BP is to perform SCT without delay.
Whether close monitoring (every 6 weeks) by PCR (not by FACS because of lower sensitivity) under ongoing dasatinib treatment is an alternative to SCT, nobody presently knows, because of missing pediatric (and adult) data.
Any treatment decision must take into account the local availability of dasatinib for long term treatment, the adherence of the patient/family to close monitoring (at least during the next two years in 6 to 8 weeks intervals), the availability of a perfectly matched SCT donor and the conditioning regimen to be used (fully myeloablative vs reduced intensity).
Sorry for not providing you with a clear recommendation - but the rarity of pediatric CML and the weak pediatric CML networking in many countries from a global viewpoint are real obstacles.
Kind regards and all the best for your patient.