My best guess would be atypical CML or CNL. In these cases the CSF3R mutation can be found in >50% of cases (and this mutation is rarely found anywhere else). Depending on the type of mutation, the disease may be responsive to SRC inhibition (dasatinib) or JAK inhibition (rux). See the Maxon NEJM paper for details. There are trials open exploring this, but I would get HLA typing going, as transplant is likely in the cards down the line.

I am not sure how many places do CSF3R testing, but if you can't find anywhere nearby, let me know and I will try to set something up.



ORIGINAL CASE:
I would appreciated if you can give me some advice about the diagnosis and treatment.
A male 18 year old, presented with fatigue. His CBC showed Hb 5.4 g/dl Hct 17.6 % MCV 106.7 fL WBC 60,050/uL (N 52%, L 6%, Mo 9%, Eo 14%, Band 8%, Blast 6%, Myelocyte 4%, Meta myelocyte 1%)
Peripheral blood smear showed dysmorphic of neutrophil, eosinophil.
Bone marrow aspirate showed increase cellularity 2+, Megakaryocyte decrease 2+, normal erythroid, increase myeloid 2+.
BCR-ABL negative, pending for JAK2 mutation and PDGFR1 mutation
U/S upper abdomen showed splenomegaly; 17.7 cm. No hepatomegaly and lymphadenopathy.
Unfortunately, we do not have laboratory test for other myeloid mutation.
I am thinking about the diagnosis of atypical CML in this case and plan to discuss with his parent in order to go for allogeneic stem cell transplantation.

I would like to ask if you agree with the diagnosis and plan of treatment.

Hello to everybody. I agree with other comments in this case. I believe that we need some more clinical details like platelet count, bone marrow blast and promyelocyte count as well evaluation of dysplastic features within bone marrow if any.
Classical cytogenetic banding can provide essential information but can fail if it is normal. Than all mutations suggested by Prof. Hochhaus can be done if system can support (pay) in local or some reference lab. If karyotype is normal, than also bone marrow biopsy can add some details like degree of fibrosis, architectural displacement within the bone marrow (smth similar to ALIP), blast clusters...
Some of features are similar to MDS/MPN entity especially that patient has monocytes in differential. Even he is to young for CMML but it would be of interest to see morphology of those monocytes in peripheral blood (absolute mono count is around 6000).
Hydroxyurea will calm WBC count but it may also have a detrimental effect to anemia and platelets. If bone marrow blasts are over 10% than his clinical course can be aggressive, hence HLA typing and search for HLA compatible sibling will be also worth to consider.

ORIGINAL CASE:
I would appreciated if you can give me some advice about the diagnosis and treatment.
A male 18 year old, presented with fatigue. His CBC showed Hb 5.4 g/dl Hct 17.6 % MCV 106.7 fL WBC 60,050/uL (N 52%, L 6%, Mo 9%, Eo 14%, Band 8%, Blast 6%, Myelocyte 4%, Meta myelocyte 1%)
Peripheral blood smear showed dysmorphic of neutrophil, eosinophil.
Bone marrow aspirate showed increase cellularity 2+, Megakaryocyte decrease 2+, normal erythroid, increase myeloid 2+.
BCR-ABL negative, pending for JAK2 mutation and PDGFR1 mutation
U/S upper abdomen showed splenomegaly; 17.7 cm. No hepatomegaly and lymphadenopathy.
Unfortunately, we do not have laboratory test for other myeloid mutation.
I am thinking about the diagnosis of atypical CML in this case and plan to discuss with his parent in order to go for allogeneic stem cell transplantation.

I would like to ask if you agree with the diagnosis and plan of treatment.

This is a very young age for a myeloid disorder such as aCML. Is there any family history of myeloid disorders? Or cancer in general?

I agree that there is the need of a more defined diagnosis and that at least cytogenetics is necessary. In any case the clinical presentation appears very aggressive and the patient is very young. Therefore, in my opinion, I would not delay too much the start of the treatment and I would start to consider a classical chemo + transplant approach.

agree with what Andreas has said about additional testing, in particular classical cytogenetics
however, what primers were used for bcr-abl? If in fact, multiplex primers were used, they may have missed an uncommon breakpoint and this case actually is cml with a rarer breakpoint. Would consider sending a sample to a reference lab where this could be examined.
proceeding to allografting without a true diagnosis is premature

Recommended diagnostics to confirm diagnosis of atypical CML:
Most importantly: Metaphase Cytogenetics from BM or PB
Further: FIP1L1-PDGFRA, CSFR mutations, SETBP1 mutations.

Allo SCT should not be done without proper cytogenetic analysis.

I have forwarded name and email details for a local consultation which I am recommending for this case