The patient was 47/M, referred to me in June 2014 by private haematologist for treatment of Ph+ CML.
The patient was originally seen by private haematologist for incidental findings of aneamia, thrombocytopenia and slight increase in WBC (Hb 9.4 g/dL, Plt 65 x 10^9/L, WBC 10.1 x 10^9/L). No immature cells seen in peripheral blood. RBCs showed hypochromasia, polychromasia, microcytosis, anisocytosis, poikilocytosis, and some target cells, and tear drop cells. Moderate thrombocytopenia with no giant plt.
BM in private on 20/3/2014 showed normocellular with active trilineage haemopoiesis. No dysplastic changes seen in erythroid and granulopeisis. Blasts 1%. However, Mega was increased in number, and hypolobulated nucleus and dysplastic changes were observed. Cytogenetic of marrow showed t(9;22)(q34,q11,2) [4] was detected in a subpopulation of cells. PCR x BCR-ABL in peripheral blood was positive for BCR-ABL p210 fusion transcript.
When I saw the patient, he was asymptomatic. On further enquiry, patient was a known B-thalassaemia trait but he had plt level for some years. I went through his medical history through the electronic records and previous blood tests (for other reasons). Thrombocytopenia was present at least since 2003 without proper investigations. Apart from mild anaemia, the rest of the CBP and other lab were unremarkable. He had no splenomegaly.
CBP repeated- Hb 9, Plt 60, WBC 8 with normal D/C and no blasts. Hb pattern confirmed B-Thal trait. qPCR x BCR-AB (IS)= 5.6%. As the patient had no symptoms and expressed concerns of cost and SE of TKI, I suggested observation for now and repeat BCR-ABL in 3 months time.
I saw him again in early August. He was well. CBP stable, Plt 69, WBC 7.9, no blasts. qPCR x BCR-ABL was pending.
I think this patient has B-Thal Trait and asymptomatic ITP for some years. The incidental finding of molecular Ph+ CML was rather unexpected. For patient with known Ph+CML, we would aim to eradicate Ph+ clone and achieve MMR as early as possible. However, I am not sure what the nature history of this case. The disease may eventually evolve to clinical CML and require TKI. Yet, early treatment may not have any impact on OS. Would you observe or start TKI now as treating someone has already achieved CHR?
Also, would the presence of thrombocytopenia affect your treatment decision?
Grateful if you can share your thoughts with me.

With best regards,

Kenny

An interesting case. It is hard to predict the natural history of such an unusual case of CML. The risk of blast crisis if left untreated may be lower than the 10-20% we normally see in untreated patients but I am not sure I would be confident enough about that to leave him untreated, now that we have such effective treatment. He may look great up until the day he presents in frank blast crisis. The cytopenia will probably make it difficult to treat him but I would still start imatinib perhaps at a lower dose and tolerate platelet counts down to 30. These patients with cytopenia are never easy to treat but with perseverance you often get adequate molecular control even with quite low doses of TKI and even with enforced interruptions. Of course if he insists on watching and waiting that is fine, as long as he is fully aware of the risk he is taking.


(case repeated here for reader reference)
The patient was 47/M, referred to me in June 2014 by private haematologist for treatment of Ph+ CML.
The patient was originally seen by private haematologist for incidental findings of aneamia, thrombocytopenia and slight increase in WBC (Hb 9.4 g/dL, Plt 65 x 10^9/L, WBC 10.1 x 10^9/L). No immature cells seen in peripheral blood. RBCs showed hypochromasia, polychromasia, microcytosis, anisocytosis, poikilocytosis, and some target cells, and tear drop cells. Moderate thrombocytopenia with no giant plt.
BM in private on 20/3/2014 showed normocellular with active trilineage haemopoiesis. No dysplastic changes seen in erythroid and granulopeisis. Blasts 1%. However, Mega was increased in number, and hypolobulated nucleus and dysplastic changes were observed. Cytogenetic of marrow showed t(9;22)(q34,q11,2) [4] was detected in a subpopulation of cells. PCR x BCR-ABL in peripheral blood was positive for BCR-ABL p210 fusion transcript.
When I saw the patient, he was asymptomatic. On further enquiry, patient was a known B-thalassaemia trait but he had plt level for some years. I went through his medical history through the electronic records and previous blood tests (for other reasons). Thrombocytopenia was present at least since 2003 without proper investigations. Apart from mild anaemia, the rest of the CBP and other lab were unremarkable. He had no splenomegaly.
CBP repeated- Hb 9, Plt 60, WBC 8 with normal D/C and no blasts. Hb pattern confirmed B-Thal trait. qPCR x BCR-AB (IS)= 5.6%. As the patient had no symptoms and expressed concerns of cost and SE of TKI, I suggested observation for now and repeat BCR-ABL in 3 months time.
I saw him again in early August. He was well. CBP stable, Plt 69, WBC 7.9, no blasts. qPCR x BCR-ABL was pending.
I think this patient has B-Thal Trait and asymptomatic ITP for some years. The incidental finding of molecular Ph+ CML was rather unexpected. For patient with known Ph+CML, we would aim to eradicate Ph+ clone and achieve MMR as early as possible. However, I am not sure what the nature history of this case. The disease may eventually evolve to clinical CML and require TKI. Yet, early treatment may not have any impact on OS. Would you observe or start TKI now as treating someone has already achieved CHR?
Also, would the presence of thrombocytopenia affect your treatment decision?
Grateful if you can share your thoughts with me.
With best regards,

Kenny

Most of these cases have a different type of BCR-ABL junction like BCR exon 19 - ABL exon a2. The low % of p210 transcripts observed may indeed suggest that it may derive from an alternative splicing, particularly if the cytogenetic or FISH analysis reveals that 100% f the cells are Ph-psitive. I would in any case start imatinib therapy at 400 mg per day as also these cases may progress.

(original case repeated here for reader reference)

The patient was 47/M, referred to me in June 2014 by private haematologist for treatment of Ph+ CML.
The patient was originally seen by private haematologist for incidental findings of aneamia, thrombocytopenia and slight increase in WBC (Hb 9.4 g/dL, Plt 65 x 10^9/L, WBC 10.1 x 10^9/L). No immature cells seen in peripheral blood. RBCs showed hypochromasia, polychromasia, microcytosis, anisocytosis, poikilocytosis, and some target cells, and tear drop cells. Moderate thrombocytopenia with no giant plt.
BM in private on 20/3/2014 showed normocellular with active trilineage haemopoiesis. No dysplastic changes seen in erythroid and granulopeisis. Blasts 1%. However, Mega was increased in number, and hypolobulated nucleus and dysplastic changes were observed. Cytogenetic of marrow showed t(9;22)(q34,q11,2) [4] was detected in a subpopulation of cells. PCR x BCR-ABL in peripheral blood was positive for BCR-ABL p210 fusion transcript.
When I saw the patient, he was asymptomatic. On further enquiry, patient was a known B-thalassaemia trait but he had plt level for some years. I went through his medical history through the electronic records and previous blood tests (for other reasons). Thrombocytopenia was present at least since 2003 without proper investigations. Apart from mild anaemia, the rest of the CBP and other lab were unremarkable. He had no splenomegaly.
CBP repeated- Hb 9, Plt 60, WBC 8 with normal D/C and no blasts. Hb pattern confirmed B-Thal trait. qPCR x BCR-AB (IS)= 5.6%. As the patient had no symptoms and expressed concerns of cost and SE of TKI, I suggested observation for now and repeat BCR-ABL in 3 months time.
I saw him again in early August. He was well. CBP stable, Plt 69, WBC 7.9, no blasts. qPCR x BCR-ABL was pending.
I think this patient has B-Thal Trait and asymptomatic ITP for some years. The incidental finding of molecular Ph+ CML was rather unexpected. For patient with known Ph+CML, we would aim to eradicate Ph+ clone and achieve MMR as early as possible. However, I am not sure what the nature history of this case. The disease may eventually evolve to clinical CML and require TKI. Yet, early treatment may not have any impact on OS. Would you observe or start TKI now as treating someone has already achieved CHR?
Also, would the presence of thrombocytopenia affect your treatment decision?
Grateful if you can share your thoughts with me.

With best regards,

Kenny

Interesting case and I have a couple of questions. Bone marrow morphology suggests increased megas, yet patient is thrombocytopenic and has tear drops on the peripheral blood film. There were no comments on marrow fibrosis. Is there any? Wonder if there is an element of myelofibrosis secondary to burned out ET here and secondary thrombocytopenia. Has JAK2 been looked at? I have in very rare cases of what appears to be hypersplenism, considered splenectomy in order to sustain blood counts and therapy.
I agree with started therapy with a TKI at slightly lower dose. I would not wait.


(original case repeated here for reader reference)
The patient was 47/M, referred to me in June 2014 by private haematologist for treatment of Ph+ CML.
The patient was originally seen by private haematologist for incidental findings of aneamia, thrombocytopenia and slight increase in WBC (Hb 9.4 g/dL, Plt 65 x 10^9/L, WBC 10.1 x 10^9/L). No immature cells seen in peripheral blood. RBCs showed hypochromasia, polychromasia, microcytosis, anisocytosis, poikilocytosis, and some target cells, and tear drop cells. Moderate thrombocytopenia with no giant plt.
BM in private on 20/3/2014 showed normocellular with active trilineage haemopoiesis. No dysplastic changes seen in erythroid and granulopeisis. Blasts 1%. However, Mega was increased in number, and hypolobulated nucleus and dysplastic changes were observed. Cytogenetic of marrow showed t(9;22)(q34,q11,2) [4] was detected in a subpopulation of cells. PCR x BCR-ABL in peripheral blood was positive for BCR-ABL p210 fusion transcript.
When I saw the patient, he was asymptomatic. On further enquiry, patient was a known B-thalassaemia trait but he had plt level for some years. I went through his medical history through the electronic records and previous blood tests (for other reasons). Thrombocytopenia was present at least since 2003 without proper investigations. Apart from mild anaemia, the rest of the CBP and other lab were unremarkable. He had no splenomegaly.
CBP repeated- Hb 9, Plt 60, WBC 8 with normal D/C and no blasts. Hb pattern confirmed B-Thal trait. qPCR x BCR-AB (IS)= 5.6%. As the patient had no symptoms and expressed concerns of cost and SE of TKI, I suggested observation for now and repeat BCR-ABL in 3 months time.
I saw him again in early August. He was well. CBP stable, Plt 69, WBC 7.9, no blasts. qPCR x BCR-ABL was pending.
I think this patient has B-Thal Trait and asymptomatic ITP for some years. The incidental finding of molecular Ph+ CML was rather unexpected. For patient with known Ph+CML, we would aim to eradicate Ph+ clone and achieve MMR as early as possible. However, I am not sure what the nature history of this case. The disease may eventually evolve to clinical CML and require TKI. Yet, early treatment may not have any impact on OS. Would you observe or start TKI now as treating someone has already achieved CHR?
Also, would the presence of thrombocytopenia affect your treatment decision?
Grateful if you can share your thoughts with me.

With best regards,

Kenny