Unlucky CBC : What happens when the numbers don’t add up

Dr.Ghaniya KC , Dr.C Jayakumar
Amrita Institute of Medical sciences , Kochi

Five years old male child presented with complaints of high grade intermittent fever and diffuse abdominal pain since three days and two episodes of non-projectile non-bilious vomiting since one day.CBC done out side showed highly elevated Total counts 80K /uL , hence referred to AIMS for further management.

H/o recurrent tooth infection
No h/o outside food intake / sick contact
No h/o bleeding / ecchymosis / thrombotic events.
H/o viral fever one month ago, labs done at that time showed TC – 4.8 K /uL 

2nd child of NCM.1st child , nine years , male, healthy
Antenatal , Natal, Post Natal history – uneventful
Development History – Achieved age appropriate milestones
Immunization history – Immunized for age according to NIS schedule

Family history – No h/o hematological illness in the family

O/E : Child is tired looking
Bilateral cervical lymphadenopathy +
No pallor,icterus,cyanosis,clubbing,edema

Weight – 16 kg
Height – 105 cm 
BMI – 14.5 kg/m2

Systemic examination : 
P/A : mild epigastric tenderness + , Splenomegaly +
RS : AEBE , NVBS
CVS : S1 S2 + no mumumr

Investigations : 
TC – 213 K /uL , N-1% , L- 8% , Monocytes – 85%, Hb – 10.4 , Plt – 99 K/uL , PT/INR – 2.47 , CRP -18 mg/L 
RFT / LFT – normal 
LDH – 1721 U/L 
Ferrtin – 670 ng/ml

USG abdomen – Borderline splenomegaly

Peripheral smear showed – Total count more than 200,000 cells /cumm. Blasts / pro monocytes which are intermediate to large in size with high neutrophil to cytoplasm ratio, irregular nuclear membrane, open chromatin and conspicuous nucleoli.MPO negative

Clinical impression – PBS feautures suggestive of acute leukemia favour acute myeloid leukemia with monocytic differentiation.

Emergency Hematology consult was given , child was shifted to PICU ,started on Hydroxyurea and IV fluids, underwent Leukapheresis.

Flow cytomtery : Acute myeloid leukemia with monocytic differentiation 

AML FISH panel : no evidence of translocation 

FISH for Del(7q) : no evidence of any abnormality 

Bone Marrow Kartotyping : Chromosome analysis revealed an abnormal male chromosome complement with gain of chromonsome 6 in 12 out of 20 cells .

He received 3 doses of cytosine.Child was started on Inj Piptaz and Tab Posaconazole 

Currently TC is – 6000K/uL
Planned to start on AML BFM protocol

Acute Myeloid Leukemia

Acute myeloid (myelogenous, myelocytic, myeloblastic) leukemia (AML) consists of a group of malignant disorders characterized the replacement of normal bone marrow with abnormal, primitive hematopoietic cells. Although the cure rate has improved, treatments are associated with notable morbidity and mortality. 

Symptoms due to a deficiency of normally functioning cells include the following:
• Cytopenias: Can result from a deficiency of normally functioning cell
• Anemia: Characterized pallor, fatigue, tachycardia, and headache
• Hemorrhage: Most commonly, easy bruising, petechiae, epistaxis, gingival bleeding
• Fever: Should initially always be attributed to infection

Symptoms due to the proliferation and infiltration of the abnormal leukemic cell mass and infiltrative disease include the following:
• Extramedullary infiltration: Most commonly in the reticuloendothelial system
• Mediastinal mass: May cause symptoms of respiratory insufficiency or superior vena cava syndrome
• Abdominal masses: May cause pain or obstruct the GI or urogenital tracts
• Gingival hyperplasia, CNS infiltration: Often associated with monoblastic leukemia 

Management

Pharmacotherapy
Pharmacotherapy used in managing AML includes the following medications:
• Chemotherapeutic drugs: Cytarabine (cytosine arabinoside), fludarabine, daunorubicin (daunomycin), etoposide, amsacrine, 6-thioguanine, cyclophosphamide, mitoxantrone, tretinoin, arsenic trioxide, L-asparaginase, gemtuzumab ozogamicin, sorafenib, clofarabine
• Antiemetic drugs: Ondansetron, granisetron, palonosetron, lorazepam, aprepitant, dexamethasone
• Prophylactic broad-spectrum antimicrobials: Trimethoprim-sulfamethoxazole, penicillin
• Prophylactic antifungals: Fluconazole, nystatin, voriconazole, caspofungin, micafungin
• Tumor lysis: Allopurinol, rasburicase
Nonpharmacologic therapy
• Allogeneic or autologous BMT following chemotherapy and irradiation: May reduce relapse rates but doesn’t always improve overall survival
• Radiation treatment: Primarily to treat chloromas and other masses pressing on a vital structure and that may imminently cause irreversible damage; craniospinal irradiation for persistent CNS leukemia
• Transfusion support: To correct anemia and thrombocytopenia until remission is achieved (eg, RBC transfusions); to correct coagulopathies (FFP)