A INTERESTING CASE OF ABDOMINAL PAIN

BY DR.ANIRUDH J SHETTYPROF.DR.G.ELANGOVAN’S UNIT

28 yr male patient came with c/o abdominal pain-1 week in duration involving predominantly the left upper and centre of the abdomen vague dragging pain assoc with fullness of abd no h/o any aggravating or relieving factors

h/o early satiety + h/o loss of appetite + No h/o loss of weight No h/o jaundice No h/o haematemesis No h/o altered bowel habits No h/o bleeding tendencies

PAST h/o -> No h/o Tb/HTN/DM

PERSONAL h/o -> consumes alcohol occasionally not a smoker

O/E – Pt conscious oriented afebrile anemic no Cyanosis,clubbing,icterus, lymphadenopathy B.P-110/70 mmHG P.R -80 min

P/A –mild distention of abdomen+ no dialated viens,scars or sinuses massive spleenomegaly(+) crossing the umbilicus no hepatomegaly no FF+

CVS – S1S2(+) NO murmurs

RS – NVBS+ no added sounds

CNS - NFND

BASELINE INVESTIGATIONSCBC Hb – 14

TC – 9300

P69,L31

ESR – 15

PLATLETS – 1,50,000

RFT

RBS -152 UREA – 32 CREAT – 1.0

SODIUM; 135 K+ - 6.0 CL – 105 HCO- 19

ECG – WNL

CHEST X – RAY - WNL

GGH HEMATOLOGY

CBCTC – 1,60,000 SHIFT TO LEFT

BLAST 1%

HB – 9.2

PLATLET -1,80,000

Chronic phase of CML

P/S

Markedly increased TC, showsMYELOBLAST,PROMYELOCYTE,METAMYELOCYTE,BAND FORMS

BONE MARROW ASPIRATION

BONE MARROW FRAGMENT SHOWING A DENSLLY CELLULAR MARROW FRAGMENT WITH ABSENT FAT CELLS

LOW POWER MICROSCOPE: MYELOID HYPERPLASIA WITH RELATIVELY REDUCED ERYTHROID PROGENITORS

Patient was started on Imatinib mesylate 400mg 1-0-0

Chronic Myelogenous Leukemia CML accounts for 15% of all cases of

leukemia.

More common in men

Peak incidence : fourth and fifth decade

In CML the c-ABL gene is translocated from its normal abode on chromosone 9 to chromosone 22,where it fuses with bcr gene.

As a consequence of the fusion, c-ABL loses a region that controls tyrosine kinase activity. Thus the BCR-ABL protien,the product of the fusion gene has potent and constitutive tyrosine kinase activity.

CML PHASES

1. CHRONIC PHASE

2. ACCELARATED PHASE

3. BLAST CRISIS

SYMPTOMS EASY FATIGABILITY

DECREASE TOLERANCE TO EXERTION

ABDOMINAL DISCOMFORT AND EARLY SATIETY( DUE TO SPLENIC ENLARGEMENT)

WIEGHT LOSS AND EXCESSIVE SWEATING The symptoms are vague, nonspecific and

gradual in onset

A physical examination may detect pallor and

splenomegaly.The latter was present in 90% of patients.

UNCOMMON PRESENTATIONS : Dramatic hypermetabolism(night sweats,wt

loss,heat intolerance) Acute gouty arthritis(due to hyperurecemia) Priapism,tinnitus Lt upper quadrant n lt shoulder pain due to

splenic infarction and perisplenitis.

CML is often suspected on the basis on the complete blood count, which shows increased granulocytes of all types, typically including maturemyeloid cells. 

Basophils and eosinophils are almost universally increased; this feature may help differentiate CML from a leukemoid reaction.

A bone marrow biopsy is often performed as part of the evaluation for CML, and CML is diagnosed by detecting the Philadelphia chromosome. 

Lab findings

10–19% myeloblasts in the blood or bone marrow.

>20% basophils in the blood or bone marrow

Platelet count <100,000, unrelated to therapy

Cytogenetic evolution with new abnormalities in addition to the Philadelphia chromosome

Increasing splenomegaly or white blood cell count, unresponsive to therapy

ACCELERATED PHASE

Blast crisis is the final phase in the evolution of CML, and behaves like an acute leukemia, with rapid progression and short survival.

 Blast crisis is diagnosed if any of the following are present in a patient with CML:

>20% myeloblasts or lymphoblasts in the blood or bone marrow.

Large clusters of blasts in the bone marrow on biopsy.

Development of a chloroma (solid focus of leukemia outside the bone marrow)

BLAST CRISIS

IMATINIB MESYLATE

STEM CELL TRANSPLANTATION

IFN-ALPHA

HYDROXYUREA

SECOND GENERATION TK INHIBITOR-DASATINIB AND NILOTINIB

THERAPEUTIC OPTIONS

INITIAL CYTOREDUCTION IMTINIB NOW IS USED AS INITIAL THERAPY

IN ALMOST ALL PATIENTS WITH CML.

IN CASES WHERE WBC COUNT IS MARKEDLY ELEVATED HYDROXYUREA CAN BE USED TO PREVENT HYPERLEUKOCYTIC SYNDROME.

MOA OF IMATINIB The bcr abl oncoprotien

with a molecule of ATP in d kinase pocket.

Phosphorylation - > substrate .Activates downstream molecules

Imatinib occcupies d kinase pocket preventing phosphorylation of its substrates

HAEMATOLOGICRESPONSE

CYTOGENETIC RESPONSE

MOLECULAR RESPONSE(BCR ABL TO CONTROL GENE RATIO ACCORDING TO IS SCALE)

FREQUENCY .Every 2 weeks until a complete response has been achieved and confirmed.every 3 months unless othwise required

every 6 months until a complete response has been achieved and confirmed.then every 12 months

EVERY 3 MONTHS

METHOD complete blood count (CBC) with differential

Conventional cytogenetic examination

.FISH (fluorescene in situ hybridisation) (only before treatment)

.RQ-PCR(Reverse transcription quantitative polymerase chain reaction)

DEFINITION OF RESISTANCE

ASSESSMENT METHODSUBOPTIMAL RESPONSE FAILURE

Hematologic No Complete hematologic response(CHR) within 3 months

No hematologic response within 3 monthsLoss of CHR at any time

Cytogenetic No MCyR (Major cytogenetic response )within 6 monthsNo CCyR(Complete cytogenetic response) within 18 months

.No cytogenetic response within 6 monthsNo MCyR within 12 monthsNo CCyR within 18 monthsLoss of CCyR at any timeNot applicable.

MOLECULAR No MMR(Major molecular response) within 8 monthsLoss of MMR at any time

TREATMENT FAILURE Second generation TKI like DASATINIB NILOTINIB

Allogenic human stem cell transplant

Well tolerated compared to other treatment options in CML

Superficial edema Nausea,muscle cramps Rash,Diarrhea

Uncommon side effects:tumour lysis in accelerated phase,splenic rupture,cerebral edema,Varicella Zoster infections

SIDE EFFECTS

Imatinib is not recommended during pregnancy.

Hydroxyurea has the lowest mutagenic potential among the cytotoxic agents.

IFN can also be safely used during pregnancy.

TREATMENT OF CHRONIC PHASE CML DURING PREGNANCY

Patients who are younger than 65 yrs and who have a identical twin or a histocompatible sibling can be transplanted after intensive therapy usually with cyclophosphamide.

GVHD is common.

ALLOGENIC STEM CELL TRANSPLANTATION

THANK YOU