diskusi kasus

1. AML M5 with Plasmacytosis
Karina Nilasari
Moderator :
dr. Dian Sukma Hanggara, M Biomed, Sp.PK
1
Case Discussion

2. Data Base
Male / 60 y.o
Chief Complaint : Fever
Present Medical History :
The patient had suffered from fever since 4 days
before admission, and the fever had been spiking in this last
2 days. The fever was getting better with paracetamol.
The patient had lost his body weight about 4 kg in a
week. He also suffering from dry cough for a week, also
shortness of breath when doing activity, accompanied with
cold sweat since the last 5 days. This condition was getting
better when the patient have rest. The patient also had
suffered from pain when take a breath.
2

3. Data Base
Past medical history :
• The pastient had been diagnosed Tuberculosis 6 months before
admission, and already take medicine for 6 months from the
doctor.
• The patient had suffered from hypertension for years and
ussualy take amlodipine 1x 5mg, irregularly.
Family medical History :
- There were no family suffer from the same illness
Social and family history
- Patient is a merchant
3

4. Physical Examination
General status Severely ill, GCS : 4-5-6
BW: 50kg H: 150cm ( BMI:normal)
Vital sign BP : 130/80 mmHg HR : 84 bpm
RR : 20 tpm T : 36,8°C (axilla)
Head & Neck Anemic conjunctiva +/+, Icteric sclera -/-
JVP : R+2 cmH2O
Thorax P : symmetrical, VBS +/+, Rh -/-, Wh -/-
C : ictus at 5th ICS, 1 cm lateral of MCL, single S1/S2, murmur -, gallop -
Abdomen Flat, Soefl (+), Liver : unpalpable, Lien : unpalpable, meteorimus (-),
traube space tympani
Extremities Warm acral, edema -/-
4

5. 5
HEMATOLOG
Y
16-01-20
(15:32:30)
16-01-20
(17:41:29)
17-01-2020
(11:16:31)
Reference
Hemoglobin 8,00 8,00 6,60 13,4 – 17,7 g/dL
Erythrocyte 2,28 2,21 1,81 4,0 – 5,5 . 106 /µL
Leucocyte 20,68 20,50 22,59 4,3 - 10,3 .103 /µL
Hematocrit 22,70 23,20 18,90 40 – 47 %
Thrombocyte 85 74 61 142 – 424 . 103 /µL
MCV 102,70 101,80 104,40 80 - 93 fL
MCH 36,20 35,10 36,50 27 – 31 pg
MCHC 35,20 34,50 34,90 32 - 36 g/dL
RDW 17,20 17,00 17,30 11,5-14,5
Diff.count:
Eo/Baso/Neut/
Lymph/Mono
0/0/0/2/33/65 0/0/0/2/31/67 0/0/0/2/32/66 0-4/0-1/51-67/25-33/2-5

6. 6
HEMATOLOGY
17-01-2020
(13:54:26)
19-01-20 Reference
Hemoglobin 7,20 9,60 13,4 – 17,7 g/dL
Erythrocyte 2,03 2,95 4,0 – 5,5 . 106 /µL
Leucocyte 16,98 12,04 4,3 - 10,3 .103 /µL
Hematocrit 20,80 27,60 40 – 47 %
Thrombocyte 75 76 142 – 424 . 103 /µL
MCV 102,50 93,60 80 - 93 fL
MCH 35,50 32,50 27 – 31 pg
MCHC 34,60 34,80 32 - 36 g/dL
RDW 16,70 20,10 11,5-14,5%
Diff.count:
Eo/Baso/Neut/
Lymph/Mono
0/0/0/2/32/66 0/0/0/2/33/65 0-4/0-1/51-67/25-33/2-5
transf
usi
transf
usi

7. 16-01-2020 17-01-2020
(11:16:31)
17-01-2020
(13:54:26)
Normal range
Retikulo
sit
Absolut
0,0095 . 106
/uL
0,0054 . 106
/uL
0,0106 . 106
/uL
Retikulo
sit
0,43 % 0,30 % 0,52 % 0,5 – 2,5
Immatu
re
Platelet
Fraction
2,2 % 2,2 % 1,1 – 6,1
7

8. Evaluasi Hapusan Darah 16-01-2020 (15:32:30)
Lain-lain Hasil Diff Count: 0/0/0/4/19/24
Sel blas : 45%
Promonosit : 8 %
Eritrosit Normokrom Anisopoikilositosis, Eliptosit (+),
Makroovalosit (+)
Lekosit Kesan Jumlah meningkat, sel blas +
Trombosit Kesan Jumlah menurun
8

9. Evaluasi Hapusan Darah 17-01-2020 (11:16:31)
Lain-lain Hasil Diff Count: 0/0/0/1/25/32
Normoblas : 2/100 leukosit
Mieloblas : 8 %
Monoblas : 15%
Promonosit : 16 %
Limfoplasmasitik : 3%
Eritrosit Normokrom Anisopoikilositosis, Makroovalosit +,
Rouleaux phenomena +, Normoblas dengan displasia
+
Lekosit Kesan Jumlah meningkat, mieloblas +, monoblas +
Trombosit Kesan Jumlah menurun
9

10. BMP (17 Januari 2020)
• Selularitas : Hiperseluler
• Rasio M:E : 80:1
• Eritropoiesis : Aktivitas turun
• Granulopoisis : Aktivitas turun, mieloblas 7-8%
• Megakariopoisis : Aktivitas turun
• Cadangan Fe : Positif
• Lain-lain : Terdapat proliferasi monoblas dan promonosit
65%, monosit 13% dan sel plasma 9%
• Kesimpulan : Acute Monocytic Leukemia (AML M5) dengan
plasmasitosis
10

11. Darah Tepi
11Diseritropoiesis Monoblas +

12. Sumsum Tulang
12
Hiperseluler Monoblas , sel plasma

13. Sumsum Tulang
13
ST : Fe +

14. Clinical chemistry 16-01-20 17-01-20 Normal reference
Urea 34,5 26,2 16,6 – 48,5 mg/dL
Creatinine 1,08 0,92 < 1,2 mg/dL
Uric acid 6,7 3,4 – 7 mg/dL
Fe 129 53-167 μg/dL
TIBC 157 300-400 μg/dL
Saturasi Transferin 82 16-45%
RBS 172 < 200mg/dL
Albumin 3,53 3,5- 5,5 g/dL
14

15. Clinical chemistry 17-12 Normal reference
AST/SGOT 43 0 – 32 U/L
ALT/SGPT 71 0 – 33 U/L
LDH 627 240-480 U/L
RBG 172 <200 mg/dL
15

16. LABORATORY RESULT
16
Electrolyte 06-09 Normal reference
Natrium 132 133- 148 mmol/L
Kalium 3,32 3,5 – 5,0 mmol/L
Chloride 105 101 – 105 mmol/L
Calsium 8,6 7,6-11,0 mg/dL
Phosphor 4,1 2,7-4,5 mg/dL

17. 17
BGA 16-01 Reference
pH 7.37 7.35 – 7.45
pCO2 36.0 35 – 45 mmHg
pO2 51.3 80 – 100 mmHg
HCO3 21.2 21 – 28 mmol/L
BE -4.2
(-3) – (+3)
mmol/L
SpO2 86.4 % > 95%
Normal (mix vein?)

18. 16/01/20 Reference
PPT (sec) 10,70 9,3 – 11,4 sec
Control (sec) 10,9
INR 1,03 < 1,5
APTT 26,80 24,6 – 30,6 sec
Control (sec) 25,1
Conclusion Normal

19. Immunoserology Value Normal Range
HEPATITIS B
HBsAg Non- reactive
COI : 0,472
COI < 0,9 : Non reactive
COI ≥ 0,9 - <1,0 :
Borderline
COI ≥ 1,0 : Reactive
HEPATITIS C
Anti HCV Non- reactive
COI : 0,177
COI < 0,9 : Non reactive
COI ≥ 0,9 - <1,0 :
Borderline
COI ≥ 1,0 : Reactive
19

20. DATA INTERPRETATION
This is a case of a 60-year old male, with laboratory tests showed:
 Normochrom anisopoikilocytosis anemia, low reticulocyte, leukocytosis,
trombocytopenia
 Compensated Metabolic acidosis  normal
 Hyponatremia, hypokalemia, normal chloride
 Increased of Transferin Saturation and low TIBC
 Blood smear : rouleaux phenomenon, myeloblast, monoblast
 Increased LDH
 BMP conclusion: Acute Monocytic Leukemia (AML M5) with plasmacytosis
Based on medical history, physical & other supporting examinations showed :
1. AML-M5
2. Suspect a Reactive Plasmacytosis ddx MM concomitant with AML M5
20

21. Data Interpretations
• Suggestion: SPE, urinalysis, chest x ray
• Monitoring : CBC, SI, TIBC, BMP
21

22. Establishment of diagnosis
Reactive Plasmacytosis in
AML
22

23. Establishment of
diagnosis
23

24. AML
• Acute myeloid leukemia (AML) is a malignant disease of the bone
marrow in which hematopoietic precursors are arrested in an early
stage of development.
• Most AML subtypes are distinguished from other related blood
disorders by the presence of more than 20% blasts in the bone
marrow.

25. The workup for acute myeloid leukemia (AML)
includes the following:
• Blood tests
• Bone marrow aspiration and biopsy (the definitive diagnostic tests)
• Analysis of genetic abnormalities
• Diagnostic imaging

26. • Immunophenotyping by flow cytometry of bone marrow or
peripheral blood samples can be used to help distinguish AML
from acute lymphocytic leukemia (ALL) and further classify the
subtype of AML
• Cytogenetic studies performed on bone marrow provide important
prognostic information and can guide treatment by confirming a
diagnosis of acute promyelocytic leukemia (APL).
• Perform human leukocyte antigen (HLA) or DNA typing in patients
who are potential candidates for allogeneic transplantation.

27. • In patients with signs or symptoms suggesting central nervous system
(CNS) involvement, computed tomography (CT) or magnetic
resonance imaging (MRI) should be performed. Lumbar puncture is
indicated in those patients if no CNS mass or lesion is detected on CT
or MRI.
• Evaluation of myocardial function is needed once the diagnosis of
AML is confirmed because many of the chemotherapeutic agents
used in treatment are cardiotoxic.
[Guideline] NCCN Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. National Comprehensive Cancer Network. Available
at https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Version 3.2020 — December 23, 2019; Accessed: May 26, 2020.

28. FAB classification of Acute Myeloid Leukimia
M0 AML, minimally differentiated
M1 AML, without maturation
M2 AML, with maturation
M3 Acute promyelocytic leukemia, hypergranular
M3v Acute promyelocytic leukemia, variant, microgranular
M4 Acute myelomonocytic leukemia
M4eo Acute myelomonocytic leukemia with eosinophilia
M5a Acute monoblastic leukemia, poorly differentiated
M5b Acute monoblastic leukemia, differentiated
M6 Acute erythroleukemia
M7 Acute megakaryoblastic leukemia

29. Acute monoblastic and acute monocytic
leukemia (AML M5)
• The subtype of acute myeloid leukemia (AML) classified by the French-
AmericanBritish (FAB) Classification as M5 or acute monocytic leukemia, is a
distinct subtype with characteristic clinical features
• AML FAB M5 is frequently associated with specific chromosomal
translocations
• Clinically, the disease is associated with hyperleukocytosis extramedullary
involvement and coagulation abnormalities including disseminated
intravascular coagulation.
• The disease has been reported to have a poor prognosis compared to other
subtypes of AML, although this has not been clearly established.
TALLMAN, Martin S., et al. Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid
leukemia: a report from the Eastern Cooperative Oncology Group. Journal of clinical oncology, 2004, 22.7: 1276-1286.

30. • AML- M5 is defined by more than 20% (WHO clasification) or more
than 30% (French-American British (FAB) classification) of myeloblast
in the bone marrow aspirate
• Bone marrow monocytic cells comprise more than 80% of non-
erythroid cells
• In AML-M5a, more than 80% of monocytic cells are monoblasts,
whereas in AML-M5b less than 80% of monocytic cells are
monoblasts, other show (pro)monocytic differentiation.
TALLMAN, Martin S., et al. Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid
leukemia: a report from the Eastern Cooperative Oncology Group. Journal of clinical oncology, 2004, 22.7: 1276-1286.

31. This Patient
• Male 60 y.o
• Fever, lost his body weight
• Normochrom anisopoikilocytosis anemia, low reticulocyte, leukocytosis,
trombocytopenia
• Increased of Transferin Saturation and low TIBC
• Blood smear : rouleaux phenomenon, myeloblast, monoblast
• Increased LDH
• BMP conclusion: Acute Monocytic Leukemia (AML M5) with plasmacytosis
31
AML-M5 with plasmacytosis
• Suggestion : -
• Monitoring: Complete blood Count, SI, TIBC, BMP

32. Reactive
Plasmacytosis in
AML
32

33. Plasmacytosis in this patient
• Plasmacytosis : abnormal increased of plasma cells in
circulation or tissues.
• Laboratory test: bicytopenia
• BMA results: mieloblas 7-8%, monoblas dan
promonosit 65%, monosit 13% dan sel plasma 9%
AML concomitant with
Multiple Myeloma
AML with reactive
plasmacytosis
?

34. Multiple Myeloma
• A neoplastic proliferation of a single clone of plasma cells →
production of a monoclonal protein
• Incidence: 4 per 100,000 persons per year
• The cause is unknown
• Clinical features: bone pain (back/chest), renal insufficiency,
hypercalcemia, ↑ susceptibility for bacterial infection
• Predisposing factors: radiation, exposure to industrial or agricultural
toxins, or a genetic element may have a role
Manual of Clinical Hematology, 3rd ed

35. Diagnosis of MM from The International
Myeloma Working Group (IMWG)
Symptomatic Myeloma
Presence of an monoclonal immunoglobulin* in serum and/or urine
plus clonal plasma cells in the marrow and /or a documented clonal
plasmacytoma
PLUS one or more of the following:
Calcium elevation (>11.5 mg/dL)
Renal insufficiency (creatinine >2 mg/dL)
Anemia (hemoglobin <10 g/dL)
Bone disease (lytic lesions or osteopenia)

36. Reactive Plasmacytosis
Reactive plasmacytosis in bone marrow can be seen in both
neoplastic and non-neoplastic conditions:
• myeloproliferative neoplasms, myelodysplastic syndromes,
mastocytosis or other malignancies
• Seen in polyclonal hypergammaglobulinemia, systemic polyclonal
B immunoblastic proliferation, autoimmune disorders (e.g. SLE ),
immunocompromise (e.g. HIV infection), and infections.
J Hematol Thromb Dis 2013, 1:4

37. JIIMC 2016 Vol. 11, No.4, Akhtar Y, Ahmad SQ, Jamal S. Acute Myeloid Leukaemia with Plasmacytosis.

38. Reactive Plasmacytosis (RP) in AML
• Reactive BM plasmacytosis is characterized by an increase in the percentage
of plasma cells above the normal, i.e. more than 3% but generally it does not
exceed 20%
• It is seen in chronic infections, autoimmune diseases, connective tissue
disorders, diabetes mellitus and malignancies
• In AML , reactive BM plasmacytosis may be due to the presence of either
some concomitant, or preceding inflammatory or infectious disorder and the
plasma cells are considered to proliferate due to persistent antigenic
stimulation
• Paracrine stimulation by interleukin (IL)‐6 secreted by leukaemias cells has
also been proposed as a cause.
JIIMC 2016 Vol. 11, No.4, Akhtar Y, Ahmad SQ, Jamal S. Acute Myeloid Leukaemia with Plasmacytosis.

39. Reactive Plasmacytosis (RP) in AML
• Plasma cells usually do not exceed 10%.
• Pathogenic mechanism for this plasmacytosis is unclear.
• Could be due to high production of IL-6 by leukemic
blast cells → paracrine growth stimulation of plasma
cells → marrow plasmacytosis
• To establish: need other tests to exclude causes of RP
• Serum protein electrophoresis (SPE): polyclonal
expansion of gamma globulins.
Rangan A, Arora B, Rangan P, Dadu T. Florid plasmacytosis in a case of acute myeloid leukemia: A diagnostic dilemma. Indian journal of
medical and paediatric oncology: official journal of Indian Society of Medical & Paediatric Oncology. 2010 Jan;31(1):36.

40. This Patient
• Male 60 y.o
• Fever, lost his body weight, dry cough
• Normochrom anisopoikilocytosis anemia, low reticulocyte, leukocytosis,
trombocytopenia
• Blood smear : rouleaux phenomenon, myeloblast, monoblast
• BMP : Proliferation of monoblast dan promonocyte 65%, monocyte 13% and
plasma cells 9%
• Tuberculosis infection
40
Suspected a Reactive Plasmacytosis ddx MM concomitant
with AML M5
• Suggestion : SPE, Bence Jones Protein, Calsium serum

41. CONCLUSION
• It has been discussed, male 60 years old with AML-M5 and Suspected
Reactive Plasmacytosis ddx suspected MM concomitant with AML M5
• Plasmacytosis in this patient due to suspected reactive plasmacytosis
or suspected MM concomitant with AML M5
• AML with plasmacytosis is a heterogenous phenomenon. Reactive
plasmacytosis in AML must be differentiated from AML with MM as
the latter requires different therapeutic approach.
• Suggestion : SPE, Bence Jones Protein, Calsium serum
• Monitoring: Complete blood Count, SI, TIBC, BMP
41

42. THANK YOU