1. Myeloid Neoplasm and Hematopoietic Stem Cell Disorders
Zartash Gul, MD
Associate Professor of Medicine
Division of Hematology & Oncology
University of Cincinnati College of Medicine
2/4/2018

2. Overview CML (BCR/ABL+ve)
Myeloproliferative neoplasms (JAK2 +ve PV, ET, Myelofibrosis)
AML-APL
MDS
Hematopoietic stem cell transplant
MPD

3. CML (Chronic Myeloid Leukemia)
Myeloproliferative disorder with overproduction of myeloid cells that differentiate.
Philadelphia chromosome positive t(9:22)
Presentation
Chronic phase- <10% blasts asymptomatic, splenomegaly
accelerated phase-10-20% blasts
Blast phase >20% blasts and/or extramedullary disease , s/s of acute leukemia (anemia, leukopenia, leukocytosis, thrombocytopenia)

4. CML
Treatment: Imatinib, Dasatinib, Nilotinib– all inhibitors of BCR/ABL tyrosine kinase.
Most patients in chronic phase do not need upfront consideration for allogeneic transplant.
Patients who present in blast phase, accelerated phase or develop mutations on TKIs or are intolerant will need consideration for transplant.

5. Which of the following statements regarding CML are false?
CML is myeloproliferative disorder and represents a clonal disorder of the pluripotential hematopoietic stem cell
The CBC often reveals thrombocytosis, neutrophilic leukocytosis and basophilia.
The presence of Philadelphia chromosome is characteristic of CML and is a poor prognostic sign.
The three main phases of CML are chronic, accelerated and blast phase.

6. Answer
C) Up to 95% of patients with CML express Philadelphia chromosome which results from a reciprocal translocation between long arms of chromosome 9 and 22. Patients with CML who do not have this translocation have a considerably worse prognosis than patients who do.

7. Myeloproliferative disorders (JAK2 positive)
Polycythemia Vera –Increase in RBC mass , Increase in granulocytes and platelets. r/o gaisbock’s syndrome or other causes of erthrocytosis.
Presentation –hyper viscosity-headache, dizziness
Thrombosis
Bleeding
Pruritis (inc histamine form basophils)
Splenomegaly
Evaluation-Erythropoietin , inc WBC, basophils,, Vit B12 LAP
Treatment: Phlebotomy (HCT men <45% and females<42%), Aspirin, Hydrea (if prior h/o thrombosis, age >60 or plt >1.5 million)

8. Essential Thrombocytosis
Increase in platelets >600,000/ul
r/o reactive thrombocytosis –inflammation, post splenectomy, iron deficiency etc.
Presentation: asymptomatic;thrombosis, erythromelalgia
Diagnosis:Peripheral smear-large hypogranular plts.
Bone marrow bx:megakaryocytic hyperplasia
Treatment: low risk –asprin, high risk add hydrea plt goal<400,000

9. Which of the following statements about ET is false?
In patients with ET an elevation in the platelet count is caused by increased production by megakaryocytes in conjunction with normal platelet survival.
To diagnose ET, iron deficiency, malignancies, inflammatory conditions and infections must be excluded.
The platelets in patients with ET are functional and haemorrhage rarely happens.
Unlike PV,ET rarely progresses;only 3-4% patients develop leukemia.

10. Answer
C) hemorrhagic events can occur in upto 40% patients with ET

11. Myelofibrosis
clonal myeloproliferation with reactive marrow fibrosis and extramedullary hematopoiesis.
Presentation: massive splenomegaly, fatigue weight loss
Diagnosis: anemia, leucoerythroblastic picture on smear, bone marrow bx- dry tap
Treatment: Allogeneic transplant, ruxolitinib.
Prognosis: median survival <5 years.

12. Leukoerythroblastic peripheral blood smear showing the presence of nucleated red cells and immature white cells

13. AML
Clonal proliferation of hematopoietic precursors with decreased ability to differentiate into mature cells.
Risk factors: prior radiation and chemotherapy.
Presentation: anemia, thrombocytopenia, leukopenia, leukostais, DIC, TLS.
Diagnosis: Peripheral smear, Bone marrow biopsy
Treatment: Induction with 7+3 (anthracycine and cytarabine)
Prognosis: age, cytogenetics.

14. Question
55 year old male presents with fever, malaise for a month. On work up WBC count is 45000, Hgb is 7.9 and Platelet count is 90,000, ANC is peripheral smear most of the white count consist of following type of cells.

15. What is your next step in management?
Obtain blood cultures
Start broad spectrum antibiotics.
Start allopurinol
Consult hematology/oncology

16. Answer C) start allopurinol
While obtaining blood cultures, starting antibiotics and consulting hematology/oncology are all important steps in managing the patient as an internist prevention of tumor lysis syndrome in a patient with acute leukemia is of utmost importance and therefore early institution of allopurinol.

17. APL
Biologically and clinically distinct variant of AML. APL -AML-M3 -(FAB) classification system
Acute Promyelocytic Leukemia with t(15;17); PML-RARA in the World Health Organization classification system.
Induction: All-Trans Retinoic Acid (ATRA) •Resulted in the highest cure rates.
High-risk patients: •Combination of ATRA and chemotherapy
Low-risk patients (WBC ≤ 10): •Combination of ATRA and Arsenic Trioxide for induction and consolidation therapy.
DIC well known complication-start therapy and supportive care.

18. Discontinue ATRA and start high dose dexamethasone.
33 year old male with APL started on ATRA. A few days later his WBC countis up from 4600/ul36,240/ul. He has low grade fever and a mild cough. Which of the following would be an appropriate next step in management of this patient?
Discontinue ATRA
Discontinue ATRA and start high dose dexamethasone.
Continue current therapy.
Start antibiotics.

19. Answer C) discontinue ATRA and start steroids.
Recognize ATRA syndrome. Fever, hyper leukocytosis, respiratory symptoms.

20. MDS
It is a heterogeneous group that shares 3 common features- dysplastic looking marrow, peripheral blood cytopenia and a tendency to evolve into AML.
About 25% can progress to AML esp those with poor karyotype and >10% blasts.
Cause of death in most patients is infections.
In older patients we can use supportive care or hypomethylating agents.
Only curative therapy is allogeneic transplant.
Lenalidomide therapy is effective in patients with del 5q.

21. Hematopoietic stem cell transplant
Autologous stem cell transplant
Patient is his own donor
No risk of GVHD
Used mostly in Multiple myeloma, lymphoma and immune mediated disorders
Allogeneic stem cell transplant
Patient needs a donor related, unrelated, fully HLA matched, mismatched donor, Haploidentical donor or cord blood transplant.
Risk of GVHD, VOD, infections
Mostly done for leukemias or lymphomas that relapse after autologous transplant

22. Complications of allogeneic transplant.
Early<30 days:
Mucositis,GI toxicity,
VOD,
Infection,
Agvhd
>30 days and long term
acute and chronic GVHD
infertility,
second malignancy,
cardiovascular disease.

23. Complications of transplant

24. AGVHD Skin GI tract- Liver- Diarrhea Nausea/Vomiting, GI bleeding
Increased liver enzymes
Increased bilirubin

25. CGVHD

26. CGVHD

27. VOD
Occurs acutely within first 3-4 weeks of allogeneic transplant

28. Late complications of allogeneic transplant include:
Acute GVHD
Mucositis
Second malignancies
VOD

29. Answer
Second malignancies.

30. Thank you