Acute lymphoblastic leukemia (ALL)

Clonal proliferation and accumulation of blast cells from lymphoid series in blood, bone marrow and other organs

Disorder  originates in single B or T lymphocyte progenitor 

B cell type – 80%     T cell type – 20%

Common age group – 5 to 15 yrs

Etiology  - unknown 

Acute leukemias - clinical features

1. Bleeding

2. Fever/infection

3. Fatiguability and pallor

4. Hepatomegaly

5. Splenomegaly

6. Lymphadenopathy

7. CNS involvement

8. Testicular involvement in males

Acute leukemias - laboratory findings 

1. Blood examination - anemia, - thrombocytopenia, - variable leukocyte count, usually increased from 10,000 to 500,000/cmm - blood morphology: presence of blast cells 

2. Bone marrow morphology - presence of blast cells (>20%) - suppression of normal hematopoiesis

3. Cytochemical stains

4. Immunophenotyping

5. Cytogenetics

Immune phenotyping

Cytogenetics

Morphologic subtypes of acute lymphoblastic leukemias  (FAB classification)

Subtype           Morphology       Occurrence (%)
L1   Small round blasts              75
clumped chromatin
L2 Pleomorphic larger blasts     20
clefted nuclei, fine chromatin
L3 Large blasts, nucleoli,       5

vacuolated cytoplasm

Chromosomal/molecular abnormalities with prognostic significance in ALL

Better prognosis
- normal karyotype
- hyperdiploidy
Poor prognosis
- t (8; 14)
- t (4; 11)
Very poor prognosis
- t (9; 22); BCR/ABL (+)


 Treatment strategy in ALL

Remission induction therapy in ALL

1. Antineoplastic treatment
a.Drugs: L-asparaginase, Daunorubicin, Prednisolone, Vincristine
    b/Treatment duration: 4-8 weeks
c/ No of courses: 1- 2
2. CNS prophylaxis – Methotrexate (intrathecal)
3. Supportive care

4. Treatment of complications

Consolidation

Drugs – Etoposide, cytarabine, and Daunorubicn, Methotrexate(I.v.)
+/-

Stem Cell transplantation

Maintenance of remission

• Prednisolone, Vincristine, Mercaptopurine and Methotrexate (oral)
• May need to be continued for 2-3 years

Treatment results in ALL 

Adults
Complete remission  (CR) 80-85%
Leukemia-free survival (LFS)            30-40%

Children
Complete remission (CR) 95-99%
Leukemia-free survival (LFS)            70-80%

Cleft lip and cleft palate

Development

Face develops from 3 processes – frontonasal, maxillary and mandibular

Intermaxillary segment is formed when medial growth of maxillary prominences cause fusion of medial nasal prominences in midline. In adult this segment forms philtrum, 4 incisors and primary palate.

Secondary palate forms from the outgrowth of maxillary prominences called palatine shelves

Primary and secondary palate fuse at the incisive foramen to form the definitive adult palate

Types 

• Cleft lip alone 15%
• Cleft lip and palate 45%
• Cleft palate only 40%
• Sometimes cleft can not be seen externally - submucous

Etiology

• Genetic
• Environmental – maternal epilepsy and drugs like steroids, diazepam and phenytoin
• Syndromic- most common Pierre Robin sequence ( isolated cleft palate , glossoptosis or posteriorly placed tongue and retrognathia). Other syndromes Treacher Collins, down etc

Complications 

• Swallowing 
• Sucking
• Defective speech
• Recurrent URTI and its sequelae
• Cosmetic problem

Primary management

Antenatal diagnosis of cleft lip (not isolated cleft palate) possible at 18 weeks of gestation by USG.

Referred to cleft surgeon if appropriate for counseling to allay fear

Photographs of before and after surgery are invaluable

Most babies born with cleft lip and palate feed and thrive well but some may require assistance

Major respiratory obstruction is uncommon and occurs exclusively in children with Pierre robin sequence

Definitive management

Cleft lip repair is commonly performed between 3-6 months of age whereas cleft palate is frequently performed between 6- 18 months of age.
Millard’s criteria (rule of 10) – cleft lip is repaired when child is 10 weeks old, child gains weight of 10 pounds and its Hb reaches 10g/dl. Millard’s cleft lip repair.
Cleft palate surgery when child is 10 months old weighs 10 kg and HB is 10g/dl. Wardill-kilner push back operation

Secondary management

Following surgery regular review regarding hearing, speech, dental development and facial growth should be done

Extraocular Muscles : Function and Innervation

Eye Movement Control Systems

Extraocular Muscles : Function

Superior Oblique muscle : can depress and abduct the eye from the neutral position. From the adducted position, it is the only muscle that can depress the eye

Inferior Oblique muscle : can elevate and abduct the eye from the neutral position.From the adducted position, it is the only muscle that can elevate the eye

Superior rectus muscle : can elevate and adduct the eye from neutral position. it is the only muscle that can elevate the eye from the abducted position

Inferior rectus muscle : can depress and adduct the eye from the neutral position. From the abducted position , it is the only muscle that can depress the eye.

The Lateral rectus muscle can abduct the eye.

Innervation:

Cranial Nerve III :

• Medial rectus : adducts eye
• Superior rectus : elevate, intorts, adducts eye
• Inferior rectus  : depresses, extorts, adducts eye
• Inferior Oblique: elevates, extorts, abducts eye

Cranial Nerve IV : 

• Superior Oblique : depresses, intorts , abducts eye

Cranial Nerve VI : 

• Lateral rectus: Abducts eye.

Intraperitoneal and Retroperitoneal Organs

Major Intraperitoneal Organs: (suspended by a mesentery)

• Stomach
• Liver and Gallbladder
• Spleen
• Duodenum, 1st part
• Tail of pancreas
• Jejunum
• Ileum
• Appendix
• Transverse colon
• Sigmoid colon

Major Secondary Retroperitoneal Organs : (loss of mesentery during development)

• Duodenum 2 & 3 parts
• Head ,neck, & body of pancreas
• Ascending colon
• Descending colon
• Upper rectum

Major Primary Retroperitoneal Organs : (never had a mesentery)

• Kidneys
• Adrenal glands
• Ureters
• Aorta
• Inferior vena cava
• Lower rectum 
• Anal canal

Germ layer Derivatives Ectoderm (Neural crest)

Neural crest

• Adrenal Medulla

• Ganglia :

-Sensory-pseudounipolar neurons
-Autonomic-postganglionic neurons

• Pigment cells

• Schwann cells

• Meninges- Pia and arachnoid mater

• Pharyngeal arch cartilage

• Odontoblasts

• Parafollicular (C) cells

• Aorticopulmonary septum

• Endocardial cushions