Transcript Introduction to Critical Care Medicine

Hematologic Malignancy
for Internist 2014
Chinadol Wanitpongpun MD.
Cancer treatment
Chemotherapy & Targeted therapy
 Radiotherapy
 Surgery
 Other : Bone Marrow transplantation
(BMT) / Tumor vaccine

BSA
BSA = √Ht X BW /3600
 Actual BW (JCO2012)
 Overweight (conditioning regimens)



Actual > 40% IDW : Adjust BW
Adjust BW = IBW + 0.5(Actual-Ideal)
Male 50 + 2.3 X (inch > 60)
 Female 45 + 2.3 X (inch > 60)

Hematologic Malignancy
Myeloid Neoplasms
 Lymphoid Neoplasms
 Histiocytic & Dendritic neoplasms

The Must Known
Acute Leukemia especially M3
 MPNs : PV / ET / CML / AMM
 Lymphoma : HD / DLBCL / BL
 Multiple Myeloma

Scope for each Diseases
Criteria Diagnosis
 Clinical features or manifestations
 Classification
 Staging
 Prognostic score
 Treatment

Myeloid Neoplasms
Myeloid Neoplasms
Differentiation Proliferation
Maturation
Absent
Increase
Dysplasia
Normal
Dysplasia
Increase
Normal
Increase
Disease
AML
MDS
CMMoL
MPNs
AML (1)
FAB classification : morphology M0-M7
 WHO classification : cytogenetic
 Acute marrow failure within 8 weeks
 Hepatosplenomegaly rare in de novo
 WBC usually high (leukemic profile) except
aleukemic or hypoplastic leukemia

AML (2)
Diagnosis by
Blast > 20% in PBS and BM
except t(8;21) / t(15;17) / inv(16)
t(16;16) or erythroleukemia
Flow cytometry : blast gate >20%
M0-M7 by CD marker
Mass biopsy : Granulocytic sarcoma
 DDX : ALL

AML-M6
2 forms
 Pure erythroid leukemia



Erythroid > 80% minimal myeloblast
Acute erythroid/myeloid leukemia
Erythroid > 50%
 Blast > 20% of all non erythroid cell

Flow Cytometry for AML
1. Blast gate : Acute Leukemia
2. AML / ALL : MPO / TdT / CD19 /
CD 34 / CD117
3. M3 / Non M3 : CD34 - & HLADR –
4. M6 (GPA) / M7 (CD41/61)
5. M4/M5 (CD11c / CD14 / CD64)
6. M0-2 (MPO / CD15) -/-, +/-, +/+
AML (3)
Feature
Incidence
Mean age
L+S+LN+
Special organ
AML
80%
Any
40%
CNS (M4 or M5)
Gum / Skin (M5)
Hypokalemia M5
Chloromas (M2)
DIC (M3)
ALL
20%
20-30 (<50)
50%
CNS
Joint
Testis
Mediastinum
(ATLL and LBL)
AML (4)
Myeloblast
Size 3-5X RBC
Low N:C ratio
Blue-gray cytoplasm
3-5 Nucleoli
Granule present
Auer rod or Faggot
MPO + / TDT-
Lymphoblast
Size < 3X RBC
High N:C ratio
Blue-purple cytoplasm
0-2 Nucleoli
Granule absent
Absent
MPO- / TDT+
AML (5)
ALL
Cytogenetic in AML
Normal Cytogenetic AML
AML (6)
AML (7)

Mutation associated with prognosis
Favorable + c-kit mutation = intermediate
 Normal karyotype + NPM1 = favorable
 Normal karyotype + CEBPA = favorable
 Normal karyotype + FLT3/ITD = unfavorable

AML (8)
Treatment 2 phases
 Induction : 3+7 regimen
(Idarubicin 3 + Ara-C 7)
 Post remission therapy or consolidation
depend on cytogenetic
Favorable : CMT (HDAC 3-4 cycles)
Intermediate / Unfavorable : ALBMT

Cytarabine (Ara-C) SE
Neutrophilic Eccrine Hydradenitis
 Pyoderma Gangrnosum
 Keratitis / Conjunctivitis
 Cytarabine syndrome : seizure &
cerebellar toxicity

APL (1)
Acute promyelocytic leukemia
 Abnormal promyelocyte

APL (2)
Present with bleeding (DIC) or BM
failure
 Diagnosis by PBS / BMA
 Abnormal promyelocyte or blast > 30%
 2 subtypes

Hypergranular or Typical : Low WBC
 Hypogranular (Microgranular) : High WBC

APL (3)
APL (4)
Flow cytometry dual low or absence
expression of HLA-DR and CD34 and
bright expression of CD33
 Cytogenetic : t(15;17)
 Other : t(5;17) or t(11;17) poor response
to ATRA just only t(11;17) associated
PLZF-RARA

APL (5)

Treatment


APL with PLZF-RARA treat as AML non M3
3 phases
Induction : Idarubicin + ATRA
 Consolidation

 1st
and 3rd cycle : Idarubicin + ATRA + Ara-C
 2nd cycle : Idarubicin + Mitoxanthone

Maintenance : 6-MP + MTX + ATRA 2 yr.
Ara-C in Consolidation
Depend on risk group
 High risk

Initial WBC > 10,000
 Initial Platelet < 40,000

APL (6)
ATRA side effects
 Differentiation syndrome : fever + weight
gain + dyspnea + pleural effusion and
ascites + leukocytosis
treat by stop ATRA + IV steroid
 Hepatitis
 Pseudotumor cerebri
 Dry mouth

APL (7)

ATO3
SE as ATRA
 QTc prolong
 Hypokalemia / Hypomagnesemia

MDS (1)
Subacute to chronic cytopenia
 Elderly
 80% involve erythroid (anemia)
 No organomegaly
 Dysplastic features > 10% of lineage
 Diagnosis by PBS + BMA + Chromosome

DDX. Erythroid Hyperplasia
Acute Blood loss
 Hemolysis
 Megaloblastic anemia
 Myelodysplastic syndrome (MDS)
 AML-M6

MDS (2)

Dysplastic features
Erythroid : nucleus-multiple / budding
Ring sideroblast (>15% erythroid series)
 Myeloid : bilobed / Pelger-Huet
Incease myeloblast
 Megakaryocyte : micro-hypolobated


Cellularity mostly increase with eythroid
hyperplasia
MDS (3)

WHO Classification
RA / RCMD + RS
 RN / RT
 5q- syndrome
 RAEB-I / RA EB-II
 MDS/MPD
 AML
 Unclassified

MDS (5)

Treatment
Transfusion / Iron chelation
 5q- syndrome : lenalidomide RR 67%
 Hypoplastic / HLADR-15 / PNH : treat as AA
 RN / RT : hypomethylating agent
 IPSS score

 Low
risk : Growth factors EPO + G-CSF
 High risk : BMT / Hypomethylating agent
Predictive Factor for EPO resp.
EPO level > 200 (500) U/L
 RBC Transfusion > 2 units/month
0 RR 74%
1 RR 23%
2 RR 7%
 IPSS score / RAEB / Cytogenetic

CMMoL
Chronic myelomonocytic Leukemia
 Persistent of PBS monocytosis > 1,000
 Ph chromosome negative
 Dysplastic change and blast < 20%
 Most common presentation :
leukocytosis / splenomegaly / arthralgia
 Treatment : supportive or cytoreductive

Thrombophilia both A. & V.

DDX (5)
Antiphospholipid syndrome
 Hyperhomocysteinemia
 Heparin induced thrombocytopenia (HIT)
 Myeloproliferative neoplasm (MPD)
 Dysfibrinogenemia

Polycythemia Vera (1)
Present with arterial and venous thrombosis
/ headache or dizziness / post bathing
pruritus / erythromelagia / splenomegaly /
gout / (false PT/PTT prolong)
 20% turn AMM / AML and death
 Awareness in Low MCV with Normal Hb
 Diagnostic criteria


2 major + 1 minor or first major + 2 minor
PV (2)

Major criteria
Hb > 18.5 in men and 16.5 in women or 17 / 15 +
sustain increase Hb2 g/dl /RBC mass >25% NPV
 JAK2 V617F mutation (95%)or other ex. exon12


Minor criteria
BM : panmyelosis
 Low EPO level
 In vitro endogenous erythroid colony formation

PV (3)
Polycythemia Vera
Reactive Erythrocytosis
Insidious onset
Thrombohemorrhagic
Erythromelagia
Post bathing pruritus
Absent causes
Splenomegaly
JAK2 V617F 95%
Acute / abrupt onset
Absent
Absent
Absent
Present
Absent
Negative
PV (4)

Reactive setting

Tissue hypoxia
 Cyanotic
heart disease
 Lung disease : COPD
 Abnormal Hb : CO / Met / Tak
EPO producing tumor
 Renal artery stenosis
 Therapy related : EPO / Androgen

PV (5)

Treatment
ASA in all patients if no contraindicated and
effective for treatment erythromelagia
 Cytoreductive in high risk

 Age
> 60 yr. /previous thrombosis
 CAD risk or Platelet > 1,500,000

Blood letting
keep Hct < 45 in men and 42 in women and
39 in pregnancy
PV (6)

Cytoreductive agents
Hydroxyurea
 Interferon : young patient or pregnancy

Caution
Hydroxyurea combination with ddc /
AZT / indinavir show median decline in
CD4 approximately 100/mm3
 Increase risk peripheral neuropathy /
hepatotoxicity and pancreatitis in ddc /
AZT
 Megaloblastoid change RBC

Essential Thrombocytosis (ET)
Thrombocytosis
 Thrombosis > hemorrhage
 JAK2 V617F + 50%
 Normal life expectancy / mild S++
 Diagnostic criteria


4 of all Platelet > 450,000 + BMBX high MK
+ R/O other MPN + JAK2 or no reactive cause
ET (2)
ET
Thrombosis
Hemorrhage
Insidious onset
No causes
May be splenomegaly
Reactive
Absent
Absent
Acute / Abrupt
Present causes
Absent
ET (3)

Reactive thrombocytosis
Iron deficiency anemia
 Splenectomy
 Hemolysis or bleeding
 Infection or inflammation
 Tissue damage
 Malignancy
 Rebound phenomenon

ET (4)

Treatment
ASA in high risk or CAD risk
 Cytoreductive in high risk

 Hydroxyure
 Analgrelide
No blood letting
 Pregnancy : IFN-α

Chronic Myeloid Leukemia (1)
Pluripotent stem cell disorder
 Philadelphia or Bcr-Abl + 100%
 Most common p210 KD chimeric fusion
protein
 p190 KD in Ph+ ALL / p230 KD in CNL
 Leukocytosis relate with spleen size
 DDX : other MPN and CNL

CML (2)
CML
Hyperviscosity-priapism
Leukemic infiltration
Insidious onset
No causes
Splenomegaly
Platelet / Basophil / Eo
PBS:Blast-promyelocyte
Philadelphia + / LAP low
Leukemoid reaction
Absent
Absent
Acute Onset
Severe stress / Sepsis
Absent
Normal
Left shift
Absent / LAP high
CML (3)

Chronic Neutrophilic Leukemia (CNL)
WBC > 25,000
 Segmented PMN + Band > 80%
 Myeloblast < 1 %
 Immature granulocyte < 10%
 Hepatosplenomegaly
 No causes
 Ph negative

CML (4)
Chronic
Blast < 5-10%
Basophil < 20%
Response to TKI
Accelerated
Blast 10-19%
Basophil > 20%
Persist Plt↑ or ↓
Progressive S++
Increase WBC
Clonal evolution
Blastic
Blast > 20%
Any
BMX : cluster
of blast
Extramedullary
blast prol.
DDX
CML -BP
Ph+ AML
Previous history
Splenomegaly
Platelet normal
Basophilia
Eosinophilia
Ph+ t(9;22)
Bcr-Abl 210 kD
Absent
Rare
Almost always decrease
Absent
Absent
Ph+ t(9;22)
Bcr-Abl 190 kD
CML (5)
Treatment
 CP : Imatinib 400 mg/day / Nilotinib /
Dasatinib
 AP : Imatinib 600-800 mg/day / N / D
 BP : Imatinib 600-800 mg /day or D /
CMT then Allogeneic BMT
 Evaluate response and F/U follow by
milestone
Treatment Failure
Poor Adherence / Compliance
 Overproduction Bcr-Abl
 Alternative TK pathway
 Mutation analysis

ELN 2013
Time
3 mo.
6 mo.
12 mo.
Any time
Optimal
Bcr < 10%
Ph+ < 65%
Ph+ < 35%
Bcr < 1 %
Ph+ 0
> MMR
Warning
>10%
65-95%
Ph+ 35-65
1-10 %
Ph+ 1-35%
CCA/Ph
-7 -7q
Bcris>0.1%
Failure
No CHR
> 95% / M
Ph+ > 65%
>10%
>35% / M
Loss CHR
Loss CCyR
MMR / M
Primary Myelofibrosis (PMF)
Or Agnogenic myeloid metaplasia
 MK and Histiocyte proliferation 
PDGF and FGF  fibroblast
 Mean age : 60 yr.
 Present with anemia and splenomegaly
 Osteosclerosis / Portal HT-EV
 JAK2 + 50%

PMF (2)

Diagnostic criteria : all major + 2 minor
Major : BM change + R/O other MPN +
clonal marker
 Minor : PBS + increase LDH + anemia + S+

Prognostic score : Lille score
 Treatment

Allogeneic BMT / JAKII inh.(Ruxolitinib)
 Supportive / HU / Splenic RT / Transfusion

Conclusion MPNs
PV
Elderly
Polycythemia
S+
Thrombosis
Panmyelosis
JAK2 V617F
JAK2 exon12
ASA
HU / IFN
Blood letting
ET
Elderly
Thrombocytosis
S+ or SThrombosis
Increase MK
JAK2 V617F
MPLW151L/K
ASA
HU / IFN
Analgrelide
CML
Yound adult
Leukocytosis
S++ WBC
Splenomegaly
High M:E
Philadelphia
t(9;22)
TKI
BMT
AMM
Elderly
Anemia
S++  Hb
Anemia
Dry tap
JAK2
MPL
BMT
HU / JAKI
Supportive
Lymphoid Neoplasms
Lymphoid Neoplasms

Precursor :
Acute Lymphoblastic Leukemia (ALL)
 Lymphoblastic lymphoma (LBL)


Mature :

Lymphoma
ALL (1)
20% of adult leukemia
 Acute BM failure
 Tissue infiltrate : CNS / testis
 Mediastinal mass in ATLL / T-LBL
 Poor prognosis in adult 5yr. OS 30%
 Diagnosis by flow cytometry and BMA

ALL (2)

Risk classification
Ultrahigh risk : Ph+
 High risk : 1 of all following

 Age
> 35 or Poor PS
 WBC > 30,000 in B 100,000 in T
 Pro-B CD10- / Early and mature T
 Cytogenetic : t(4;11) / -7 / +8 / 11q23 / t(1;19) / hypoploidy
 CR after 4 wk. or MRD + > 0.01%

Standard risk : negative above marker
ALL (3)
Treatment
 Ultrahigh risk and high risk



Induction to CR then Allogeneic BMT
Standard risk

ALL protocol or HyperCVAD regimen +
upfront BMT
Lymphoma
Hodgkin Lymphoma
Nodal presentation
CLN / Mediastinal LN
Contiguous LN involve
Alcoholic induced pain
Pel-Epstein fever
BM involvement 15%
Reed-Sternburg cell
Non Hodgkin Lymphoma
Nodal or Extranodal
Any area
Skip lesion
Absent
B symptom
BM involvement 30%
Absent
Hodgkin Lymphoma (1)

Classical HD 95%

Nodular sclerosis 70%
 Young

female / CLN & mediastinal mass / limited
Mixed cellularity
 Advanced
stage / splenic involvement 60%
Lymphocyte –rich elderly present with advanced
 Lymphocyte-depletion elderly associated HIV


Nodular lymphocyte predominance HD 5%
HL (2)
Staging by Ann Arbor
 Prognostic score

Stage I-II : favorable risk score
 Stage III-IV : IPS score


Treatment for CHL
I/II : ABVD X4 + IFRT (2+20 / 4+30)
 III/IV : ABVD X6-8 + IFRT / ESC BEACOPP
 NLPHD : RT / R / Observe

NHL (1)
B cell Lymphoma
PCNSL / IVL / PHL / Bone
Testicular involvement
Immunologic phenomena
Less common
Lung : LN / nodule (LG)
M protein
IHC : CD20 / 79a / CD138
T cell lymphoma
Skin / other extranodal
Rare except in NK-T cell
Less common
Leukopenia / HPS
Lung : interstitial infiltrate
Absent except AITL
IHC : CD3 / CD45Ro
NHL (2)
Indolent Lymphoma
Insidious onset > 6 mo.
Slow progressive in size
Waxes and wanes
No or Late B symptom
Absent / Low Ki-67
Low or High normal LDH
Mostly involve BM
Difficult to cure
Aggressive Lymphoma
Acute-Subacute in 6 mo.
Rapid progressive in size
Absent
At presentation
Tumor lysis syndrome
High LDH
About 30%
Cure or Die
NHL (3)

Lymphoma in Thailand
HD
15-20%
 NHL 80-85%

B
cell 90%




T
DLBCL
35%
FL
30%
MCL 10% MALT 10% / CLL 10%
Others
5%
cell 10%

PTCL NOS 30% + AITL 20% and other
B-cell Lymphoma
Indolent
CLL / SLL
HCL
MZL
FL
LPL
Aggressive
DLBCL
PCNSL
PMBL
IVL
LG
PBL
PEL
MM
MCL
Very Aggressive
LBL
BL
PCL
Chronic Lymphocytic Leukemia /
Small Lymphocytic Lymphoma
CLL (leukemia) / SLL (lymphoma)
 Same IHC but difference presentation
 Asymptomatic / LN++ / L+S+
 AIHA / ITP / CIDP
 M protein maybe found / HypoGammaGlb
 Absolute lymphocytosis > 5,000
 Flow : + CD5 / CD23 and – FMC7

CLL/SLL Treatment
SLL stage I : IFRT
 SLL stage II-IV / CLL stage 0-2 : Ind

Organ dysfunction / Bulky disease
 Anemia / Thrombocytopenia not resp. steroid
 Lymphocyte doubling < 6 mo.


CLL stage III-IV or Binet C
FCR / R-CHOP / R-CVP
 R / R + alkylating agent

Hairy cell Leukemia (HCL)
Elderly present with splenomegaly and
pancytopenia with monocytopenia
 PBS : lymphocyte with cytoplasmic hairy
projection
 BMA : dry tap (myelofibrosis)
 BMBX : fried-egg appearance
 IHC : CD5- CD23- / + Cd11C,25,103,
TRAP and Annexin A1

HCL Treatment

Indication for treatment
Systemic symptom / Splenic discomfort
 Hb < 12 / ANC < 1,000 / Plt < 100,000
 Recurrent infection


Regimen
Cladribine / Pentostatin
 CHOP / CVP
 R / IFN

Marginal zone Lymphoma (MZL)
Nodal : LN ++
 MALT

Gastric (ulcer in stomach) ass. H. pylori
 Non gastric MALT

Orbital (mass) ass. C. psiitaci
 Thyroid (mass) ass. Hashimoto’s thyroiditis
 Salivary gland (mass) ass. Sjogren syndrome


Splenic MZL (s+++) ass. HCV infection
MZL Treatment
Nodal : treat as FL
 Splenic MZL

Asymptomatic : observe
 Symptomatic : treat HCV / Splenectomy / R


MALT

Gastric : I/II : H.p / R / RT, III-IV : Ind
 R-CHOP

/ R-CVP
Non Gastric : I/II : Local RT, III-IV as FL
Follicular Lymphoma (FL)
Elderly in 6th decade
 LN ++ / S++
 Skin / GI tract- duodenum / Ocular / Breast
 40-70% BM involvement
 IHC : + CD10 and BCL6 /t(14;18)

FL Treatment

Grade
III : treat as DLBCL
 I-II
 Stage Ia/IIa : IFRT + R
 Stage IIb-IV : Indication :

 Organ
dysfunction
 Cytopenia /
 Bulky disease / Compressive symptom
 Regimen : R-CHOP / R-CVP + R maintenance 2 yr.
Lymphoplasmacytic Lymphoma /
Waldenstrom Macroglobulinemia
Median age 60 yr.
 Associated genetic or HCV infection
 IgM production >> IgG >>>>IgA
 30% present with hyperviscosity synd.
 AIHA or Cryoglobulinemia
 Diarrhea and coagulopathy
 BX : Dutcher bodies

LPL Treatment

Indication for treatment
As other indolent
 Cold agglutinin disease
 Cryoglobulinemia
 Amyloidosis
 Hyperviscosity


Regimen

R-CHOP / R-CVP
Flow cytometry
Disease
CLL/SLL
MCL
FL
LPL
MZL
HCL
CD5
+
+
-
CD23
+
-
Other
FMC7CCD1+
CD10+ 60%
CD138
t(11;18)
CD11c/25/
103/AXA1
Conclusion Treatment of
Indolent Lymphoma
Followed by stage / prognosis score and
indication for treatment
 Wait and watch
 Radiation
 Chemotherapy

DLBCL (1)
Most common NHL subtype
 Nodal or extranodal mass
 11-27% BM involvement


Discordant > concordant
Nucleus > macrophage or > 2X Lymphocyte
 Staging by Ann arbor
 Prognostic score : IPI

DLBCL (2)

Treatment
Stage I-II IPI = 0 : R-CHOP 3 + RT or 6 cycles
 Stage I-II IPI > 1 or stage III-IV

 R-CHOP
6-8 cycles + RT in bulky lesion
CNs prophylaxis in testicular and sinonasal / high
LDH / > 1 extranodal site / extensive BM involvement
/ Breast / IOL / Paraspinal / HIV
 RT : Compression-X / CNS/SN/BR/PS/T/W
 G-CSF prophylaxis : >60 / BM / Malnut / ECOG > 2

Primary CNS Lymphoma
Almost all DLBCL in CNS without
evidence of systemic disease
 Intracerebral or intraocular mass
 Supratentorial homogenous lesion
 90% intraocular lesion develop
contralateral tumor
 Treatment : high dose MTX regimen +
RT + IT CMT

PCNSL Treatment
ECOG > 2 : Palliative care / WBRT
 ECOG 0-2

< 60 yr : HDMTX + HDAC + RT + IT
 >60 yr : HDMTX + RT + IT

Primary Mediastinal LBCL
Young adult female
 DLBCL in mediastinum
 Absent other LN and BM
 DDX : Nodular sclerosis HL / LBL /
ALCL / BL and ATLL
 Treatment :

PMBL Treatment

Stage Ia / IIa
R-CHOP + RT
 R-ICE + RT


Stage IIb/IIx / III-IV
R-CHOP
 DA-EOPOCHR

Intravascular Lymphoma (IVL)
Selective growth within vessels
 2 forms
 Western form : neurocutaneous
 Asian form : multiple organ failure / L+S+
pancytopenia / hemophagocytic synd.
 Diagnosis by skin biopsy
 Poor prognosis

Lymphomatoid Granulomatosis
Rare
 90% pulmonary involvement
 Other : brain / kidney / liver and skin
 Rare LN and BM involvement
 CXR : vary in size multiple pulmonary
nodule
 Poor prognosis

Plasmablastic Lymphoma
High incidence in HIV patient
 Present with oral cavity mass
 Associated with EBV infection 100%

Primary Effusion Lymphoma
Lymphoma that present with effusion
without tumor mass
 Pleural / pericardial and ascites
 Associated with HHV8 in HIV patient

Infection and Lymphoma
H. pylori : Gastric MALT
 C. psittaci : Orbital MALT
 HCV : Splenic MZL
 HTLV1 : ATLL
 HHV8 : PEL
 EBV : PBL / BL / NKT / PCNSL etc.
 HIV : distinct clinical course

Multiple Myeloma (1)
Clonal plasma cell disorder
 Clinical manifestation

Chronic anemia or BM failure
 Bone pain / osteoporosis / compression fracture
 Mass with compressive symptom
 Hyperviscosity syndrome
 Hypercalcemia and renal failure
 Amyloidosis : IgA / λ light chain

MM (2)

Classification
MGUS  Smoldering
 Symptomatic MM
 Non secretory MM : no M protein
 Solitary / extraosseous plasmacytoma
 Plasma cell leukemia : > 2,000 or 20%
 AL amyloidosis
 POEMS

MM (3)

Diagnosis all of 3 criteria

M protein (except non secretory MM)
 SPEP
or SFLCR
BM plasma cell > 10% or plasmacytoma
 CRAB or related organ / tissue impairment

 Ca
> 11.5 / Hb < 10 / Cr > 2
 Bone : osteolytic / severe osteopenia / fracture
Normal ALP no osteoblastic activity except IgD type
 Recurrent
infection / Hyperviscosity / Amyloidosis
MM (4)
Common type : IgG > Light chain / IgA
> >> IgD / IgE / IgM / biclonal MM
 SPEP negative can’t be R/O MM should
be evaluate SFLCR / IF
 SFLCR (κ/λ ratio) normal 0.26-1.65


If out of proportion : light chain disease
Immunofixation
 PBS : Rouleaux formation

MM (5)

Staging by ISS
B2microGb
Alb
Stage I
< 3.5
> 3.5
 Stage II
Nor I or III
 Stage III
> 5.5
Any
Predict median survival 60 / 45 / 30 mo.


Risk classification by cytogenetic
MM (6)
Treatment (8)
 Chemotherapy


Transplant candidate
 Bortezomib
(velcade ) based : Vel-Dex X 4
then Autologous BMT + consol / M
 Non transplant candidate
 Any
regimen ex.VMP until best response + 2 +
consolidation & maintenance therapy
MM (7)
Transplantation
 Bisphosphonate
 EPO : Disease status at least VGPR
 Infectious prophylaxis : PCP / HZV

+ vaccine Pneumococcal / IF / HIB
Thromboprophylaxis : Thal / Len
 Radiation prevent fracture
 Tumor vaccine

Mantle cell Lymphoma (MCL)
Aggressive form
 Lymphomatous polyposis of large bowel
 Flow : + CD5 / FMC7 and –CD23
 Cyclin-D1 positive ass. t(11;14)
 Treatment

MCL Treatment

Stage I/II : CMT alone


R-CHOP / R-HyperCVAD / CALGB
Stage III-IV :
R-CHOP / R-HyperCVAD
 Trasnplant candidate : Autologous BMT
 Non transplant candidate : + R maintenance

Burkitt Lymphoma
Short doubling time tumor
 Tumor lysis syndrome
 Distal ileum and cecal mass / testis
 Most common translocation : t(8;14)



Associated with c-myc gene
Treatment :
Low risk : CODOX-M X 3 cycles
 High risk : CODOX/IVAC or HyperCVAD 8 cycle

Low risk Burkitt
All of these criteria
 Completely resected abdominal lesion or
single extraabdominal lesion < 10 cm.
 Normal LDH

T-cell Lymphoma
Extranodal
NKTCL
ETCL
HSTCL
Nodal
ALCL
AITL
PTCL, NOS
Cutaneous
MF & SS
SPLTCL
Leukemic presentation of TCL : PLL / ATLL / LGL
Extranodal NK/T cell
Lymphoma, nasal type
Lethal midline granuloma
 Strongly EBV association
 Mass in NP and Paranasal sinus
 CD56 and CD45Ro +
 Treatment : Radiosensitive

CHOP is not enough
Highly expression P-glycoprotein
Efflux CMT esp. Doxorubicin
ENNKTCL, Nasal type TX

Extranasal / Nasal stage III-IV
Systemic CMT : SMILE / AspaMetDex
 Autologous BMT

Nasal stage I without risk factor : RT alone
 Nasal stage I with risk factor /II


CCRT or Sequential CMT + RT
Enteropathic T cell lymphoma
Associated celiac disease
 Most commonly in jejunum or ileum
 Present with intestinal perforation
 Chronic diarrhea with malabsorption
 Treatment : CHOP or EPOCH

γδ-Hepatosplenic T cell
Lymphoma
Young adult male
 20% arise in pt. with long term
immunosuppressive drug for solid
organ transplant
 L+++S++
 Aggressive and poor prognosis

Anaplastic Large cell (ALCL)
ALK + good prognosis
 Treatment : CHOP

Angioimmunoblastic (AITL)
Generalized LN++ / L+S+
 Systemic symptom
 Polyclonal gammopathy
 Pleural effusion / arthritis / ascites
 Cold agglutinin disease
 RF + Anti-SMA +
 Treatment : CHOP / EPOCH

PTCL, NOS
Nodal form
 Not compatible with AITL / ALCL
 Advanced disease
 Paraneoplastic : eosinophilia / pruritus
and hemophagocytic syndrome
 Treatment : CHOP / EPOCH + BMT

Mycosis Fungoides (MF) and
Sezary syndrome
Most common cutaneous T cell lymphoma
 Limited to skin with wide spread
 Skin lesion : patch / plaque or tumor
 Intraepidermal collection of cell
(Pautrier abscess)
 Treatment : PUVA / CSA / CMT

SCPLTCL
Subcutaneous paniculitis
 20% associated SLE
 Present with multiple subcutaneous nodule
on extremities and trunk
 May cytopenia / hepatitis / HPS
 Hepatosplenomegaly

ATLL
HTLV-1 associated
 Acute variant

High WBC / rash / LN++ / hypercalcemia
 T cell impairment  OI


Lymphomatous variant


LN ++
Chronic variant

Exfolliative skin rash
Large granular lymphocytic
leukemia (LGL)
Associated AI disease : RA
 Persistent LGL 2,000 > 6 mo.
 Neutropenia
 Hypergammaglobulinemia

Conclusion TX T-NHL

CMT
CHOP is not enough except ALK+ ALCL
 CHOEP / EPOCH / CEOP
 NK-T : SMILE / AspaMetDex

RT esp. NKT
 If possible : BMT in all patients


Except easily controlled Cutaneous form and
ALK+ ALCL
Common sites of Lymphoma (1)
CNS : DLBCL
 Orbital : MALT / FL / DLBCL
 Sinus : DLBCL / NKT
 Oral cavity : PBL
 Testis : DLBCL / BL / LBL / NK
 Lung : LG
 Mediastinum : NS / PMBL / ALCL /
T-LBL / BL

Common sites of Lymphoma (2)

GI tract
Stomach : MALT / DLBCL
 Duodenum : FL / DLBCL
 Jejunum : ETCL / IPSID / DLBCL
 Ileum : BL / DLBCL
 Colon : MCL / DLBCL


Effusion : PEL
The Must Known
Acute Leukemia especially M3
 MPNs : PV / ET / CML / AMM
 Lymphoma : HD / DLBCL / BL
 Multiple Myeloma

Question and Answer
THE END