Acute Lymphoblastic Leukemia (ALL) - Complete Overview

Definition and Classification

• B-ALL: ~85% of cases; typically childhood leukemias
• T-ALL: ~15%; tends to present in adolescent males as thymic (mediastinal) lymphomas

Epidemiology

• Most common cancer in children; ~6,150 new US cases/year
• Median age at presentation: 35 years (bimodal: peak at age 3-5 years, and a second peak after age 50)
• Slightly more frequent in boys than girls
• Hispanic/Latino children have the highest incidence of any ethnic group in the US
• B-ALL peaks at ~3 years of age; T-ALL peaks in adolescence when the thymus is largest

Pathogenesis

Fig. 13.5 - Origin of lymphoid neoplasms (Robbins Pathology). B-ALL arises from Pre-B lymphoblasts (BLB) in the bone marrow; T-ALL from precursor T-cells (DN/DP) in the thymus.

• T-ALL: NOTCH1 mutations in 50-70% of cases (NOTCH1 is essential for T-cell development)
• B-ALL: Mutations in PAX5, TCF3, ETV6, RUNX1, BCR::ABL1, KMT2A, PBX1 (all required for early hematopoietic differentiation)
• These mutations cause maturation arrest and increased self-renewal (stem cell-like phenotype)
• Complementary mutations activate tyrosine kinase signaling (RAS, BCR-ABL1, JAK2) to drive proliferation
• Fewer than ~10 driver mutations are sufficient to produce full-blown ALL

Cytogenetics and Molecular Biology

Immunophenotyping

• Pro-B ALL (~10%): CD19+/CD22+, CD10-
• Common ALL / Pre-B ALL (~50-60%): CD19+/CD22+, CD10+ (CALLA+) - best outcomes
• Pre-B ALL (~10%): intracytoplasmic immunoglobulin present
• Mature B-ALL (<5%): surface immunoglobulin present

• Early T-cell precursor (ETP-ALL): CD7+, CD1a-, surface CD3-
• Thymic T-ALL: CD1a+, surface CD3-
• Mature T-ALL: surface CD3+

Clinical Manifestations

• Fatigue, pallor, dyspnea (anemia - nearly universal at diagnosis)
• Petechiae, ecchymoses, bleeding gums, epistaxis (thrombocytopenia - ~1/3 have clinical bleeding)
• Recurrent bacterial infections (granulocytopenia)

• Lymphadenopathy and splenomegaly (~20% of cases)
• Mediastinal/thymic mass - particularly in T-ALL (may cause SVC syndrome)
• Bone pain (periosteal infiltration - common in children)
• CNS involvement: headache, nausea, cranial nerve palsies, seizures (<5% at diagnosis but CNS is a major relapse site)
• Leukemia cutis (raised, non-pruritic rash)
• Testicular involvement (a sanctuary site for relapse)

Diagnosis

Laboratory Workup

• CBC: Anemia + thrombocytopenia (nearly universal); WBC highly variable
  • ~25% have WBC >50,000/μL; ~25% have WBC <5,000/μL
• Peripheral smear: Blasts usually present
• LDH: Elevated (cell turnover)
• Uric acid: Elevated - risk of tumor lysis syndrome
• Coagulation: PT/aPTT may be elevated

Definitive Diagnosis

• Bone marrow aspiration/biopsy: ≥20% blasts (hypercellular marrow replacing normal elements)
• Flow cytometry (immunophenotyping): Distinguishes ALL from AML and classifies lineage
• Cytogenetics/FISH/molecular: Essential for risk stratification and guiding therapy
• Lumbar puncture (CSF analysis): Recommended in ALL to assess CNS involvement

Treatment

Phase 1: Induction (~3-4 weeks)

• Core drugs: Vincristine + prednisone/dexamethasone + L-asparaginase + daunorubicin
• Complete remission achieved in 90% of children and 80-90% of adults
• Add rituximab for CD20-positive ALL
• Add BCR-ABL1 TKI (imatinib, dasatinib, ponatinib) for Philadelphia chromosome-positive ALL

Phase 2: Consolidation and Maintenance

• Consolidation: 6-8 courses of intensive chemotherapy (high-dose methotrexate, cytarabine, cyclophosphamide)
• Maintenance: Daily 6-mercaptopurine + weekly methotrexate for up to 2-3 years
• Adolescents and young adults (AYA): Pediatric-inspired regimens (more asparaginase, more CNS prophylaxis) yield better outcomes

Phase 3: CNS Prophylaxis

• Without it, ≥35% of adults develop CNS relapse
• Options: High-dose IV methotrexate + cytarabine, intrathecal chemotherapy, or cranial radiation (2400 cGy)
• CNS relapse reduced to <10% with prophylaxis

Targeted Therapies

Hematopoietic Stem Cell Transplantation (HSCT)

• Allogeneic HSCT considered for high-risk disease and relapsed ALL
• Strategy for relapsed ALL: achieve 2nd complete remission → proceed to allogeneic HSCT

Prognosis

Favorable factors:

• Age 1-9 years (pediatric)
• WBC <50 × 10⁹/L
• Hyperdiploidy
• t(12;21) ETV6::RUNX1
• CALLA-positive (CD10+) B-ALL
• Rapid clearance of minimal residual disease (MRD)

Unfavorable factors:

• Age <1 year or ≥10 years (pediatric); older age in adults
• WBC ≥50 × 10⁹/L at presentation
• Philadelphia chromosome t(9;22)
• Ph-like ALL genotype
• KMT2A (MLL) rearrangement
• Hypodiploidy
• Persistent MRD after induction

• Children: >90% complete remission; long-term cure rates ~85-90%
• Adults: Complete remission 80-90%, but relapse is common; overall survival much lower (~40-50%)
• Relapsed ALL: Generally poor prognosis regardless of age; goal is 2nd CR → allogeneic HSCT

Recent Evidence Update (2024-2025)

1. A 2024 meta-analysis on chemotherapy-free regimens in Ph+ ALL (Ali MA et al., Clin Lymphoma Myeloma Leuk) evaluated TKI-based chemo-free approaches - PMID 38972767
2. A 2025 meta-analysis comparing ponatinib vs. first/second-generation TKIs for Ph+ ALL (Raza MZ et al., Crit Rev Oncol Hematol) - ponatinib (3rd-gen TKI) shows superior outcomes; particularly relevant for T315I mutation - PMID 40517974

Aryabhatta Knowledge University (AKU)

At a Glance

History

Accreditation and Recognition

• UGC (University Grants Commission) approved
• NAAC accredited
• AICTE approved for engineering programs
• PCI (Pharmacy Council of India) approved for pharmacy courses
• AIU (Association of Indian Universities) member
• NIRF Ranking 2024: Band 101-150 (University category)

University Schools

Affiliated Colleges

• 250+ affiliated colleges across Bihar (as per recent data)
• As of 2022-23: 33 educational colleges, 8 community colleges, 11 vocational colleges
• By statutory requirement (from 2022-23), all colleges in Bihar offering professional programs (except medical sciences and engineering, which fall under other regulators) must affiliate with AKU

Programs Offered

Undergraduate (UG)

• B.Tech (Engineering - via JEE Main / BCECE)
• B.Pharm (Pharmacy)
• BPT (Bachelor of Physiotherapy - ~₹1 lakh/year)
• BBA, BCA
• B.Ed (Education)
• B.Sc (Nursing, Agriculture, etc.)
• BA / B.Sc / B.Com (General)
• LLB (Law)
• BJMC (Journalism & Mass Communication)

Postgraduate (PG)

• M.Tech, MBA, MCA
• M.Pharm
• M.Ed
• MA / M.Sc / M.Com
• LLM

Doctoral

• Ph.D. in multiple disciplines (Education, Sciences, Management, etc.)

Admission Process

• UG Engineering: JEE Main scores + BCECE (Bihar Combined Entrance Competitive Examination)
• Medical/Allied Health: NEET mandatory for MBBS, BDS, Nursing
• Other UG programs: 10+2 with 45-50% marks (40-45% for SC/ST)
• PG programs: Bachelor's degree with 50-55% (45-50% for SC/ST)
• Direct university school admissions: AKU entrance exam + merit + interview

Research and Innovation

• Yttrium Aluminum Borate-based functional nanomaterials for LED applications (2026)
• Low-cost eggshell-based water purification system (2026)

Placements

• Average package: ₹3-6 LPA
• High-demand tech roles: ₹12-17 LPA
• University runs a dedicated Placement & Incubation Cell

Student Support

• NSS (National Service Scheme) unit
• Anti-Ragging Cell
• IQAC (Internal Quality Assurance Cell)
• SC/ST and economically weaker section scholarship schemes
• NEP 2020 implementation
• Dean of Students' Welfare
• Student Grievance portal

Contact

• Official Website: akubihar.ac.in
• Admissions Portal: adms.akubihar.ac.in
• Phone: 0612-2351919 / 08102915842
• Location: Mithapur, Patna, Bihar - 800001

MBBS Final Year - Important Topics (Complete Guide)

Subjects in Final Year MBBS (Part II - India / CBME)

1. GENERAL MEDICINE

Cardiology ⭐⭐⭐

• Hypertension - classification, management (JNC/ACC-AHA)
• Heart failure - types (HFrEF vs HFpEF), management
• Acute MI / STEMI / NSTEMI - diagnosis, ECG, management, thrombolysis
• Infective endocarditis - Duke criteria, organisms, treatment
• Rheumatic fever - Jones criteria
• Atrial fibrillation - management, anticoagulation
• Shock - types and management

Respiratory ⭐⭐⭐

• COPD - GOLD staging, management
• Bronchial asthma - classification, stepwise management
• Tuberculosis - types, RNTCP/NTEP regimens, drug side effects
• Pneumonia - classification, organisms, treatment
• Pleural effusion - causes, Light's criteria (exudate vs transudate)
• Lung carcinoma - types, paraneoplastic syndromes

Gastroenterology ⭐⭐⭐

• Peptic ulcer disease - H. pylori, treatment
• Cirrhosis of liver - causes, complications (ascites, variceal bleeding, hepatic encephalopathy, SBP)
• Jaundice - classification, approach
• Inflammatory bowel disease - Crohn's vs UC
• Hepatitis B & C - serology, interpretation, treatment

Nephrology ⭐⭐⭐

• Acute kidney injury (AKI) - causes, RIFLE/KDIGO criteria
• Chronic kidney disease (CKD) - staging, complications
• Glomerulonephritis - types, nephritic vs nephrotic syndrome
• Nephrotic syndrome - causes and management
• Renal tubular acidosis

Neurology ⭐⭐⭐

• Stroke - ischemic vs hemorrhagic, management, thrombolysis window
• Meningitis - bacterial vs viral, CSF findings
• Epilepsy - classification, drug treatment
• Myasthenia gravis - diagnosis, cholinergic vs myasthenic crisis
• Guillain-Barre syndrome
• Parkinson's disease - features and management

Endocrinology ⭐⭐⭐

• Diabetes mellitus - type 1 vs 2, complications, insulin types, oral hypoglycemics
• Diabetic ketoacidosis (DKA) vs HHS - management
• Thyroid disorders - hypothyroidism, hyperthyroidism, thyroid storm
• Cushing's syndrome - causes, investigations
• Addison's disease / adrenal crisis
• Pheochromocytoma

Haematology ⭐⭐⭐

• Iron deficiency anaemia - investigations, treatment
• Megaloblastic anaemia (B12 / Folate)
• Aplastic anaemia
• ITP (Immune Thrombocytopenic Purpura)
• CML - Philadelphia chromosome, imatinib
• Sickle cell disease - pathology, crises
• Coagulation disorders - haemophilia, DIC

Infectious Disease ⭐⭐⭐

• Malaria - P. vivax vs P. falciparum, complications, chloroquine resistance
• Typhoid fever - Widal, complications, treatment
• HIV/AIDS - WHO staging, ART, opportunistic infections
• Dengue - classification (DF, DHF, DSS), NS1, management
• Leptospirosis
• Rabies - post-exposure prophylaxis
• Cholera

Immunology & Rheumatology ⭐⭐

• Rheumatoid arthritis - extra-articular manifestations, treatment (DMARDs)
• SLE - diagnostic criteria (ACR/EULAR), cutaneous manifestations
• Ankylosing spondylitis
• Gout - pathophysiology, management
• Vasculitis syndromes (Wegener's/GPA)

Dermatology (Allied - 15 marks) ⭐⭐

• Psoriasis - types and treatment
• Scabies - treatment
• Leprosy - lepra reactions (Type 1, Type 2/ENL), classification
• Drug eruptions - Stevens-Johnson syndrome, TEN
• Pemphigus vs pemphigoid (bullous lesions)
• Tinea infections
• Atopic dermatitis
• Urticaria and Angioedema

Psychiatry (Allied - 15 marks) ⭐⭐

• Schizophrenia - features, antipsychotics
• Depression - PHQ-9, antidepressants (SSRIs, TCAs)
• Bipolar disorder - mood stabilizers (lithium - toxicity)
• Delirium vs Dementia
• Substance use disorders - alcohol withdrawal, delirium tremens
• Anxiety disorders
• Suicide risk assessment

2. GENERAL SURGERY

General Principles ⭐⭐⭐

• Wound healing - phases, types
• Fluid management and electrolyte disturbances
• Blood transfusion - complications
• Shock - types, management
• Surgical infections (sepsis, necrotizing fasciitis)
• Burns - rule of nines, Parkland formula, fluid management, inhalation burns
• Post-operative complications (DVT, PE, wound dehiscence)

Alimentary Tract ⭐⭐⭐

• Acute appendicitis - Alvarado score, management, complications
• Intestinal obstruction - classification, management
• Peptic ulcer disease - surgical management, complications
• Colorectal carcinoma - staging (Dukes/TNM), management
• Anal canal disorders - haemorrhoids, fistula-in-ano, fissure
• Hernia - direct vs indirect inguinal, femoral, management
• Gallstone disease / Acute cholecystitis / Laparoscopic cholecystectomy
• Pancreatitis (acute) - Ranson's criteria, management

Breast and Endocrine ⭐⭐⭐

• Carcinoma breast - staging, management (lumpectomy vs mastectomy), sentinel node biopsy
• Thyroid - goiter, thyroid carcinoma (papillary - most common, psammoma bodies)
• Thyroglossal cyst
• Pleomorphic adenoma of parotid

Vascular Surgery ⭐⭐

• Varicose veins - clinical features, management
• Deep vein thrombosis (DVT) - Virchow's triad, management, Wells criteria
• Peripheral arterial disease - ABI, management
• Aortic aneurysm

Head and Neck ⭐⭐

• Carcinoma tongue / oral cavity
• Cystic hygroma
• Neck swellings - differential diagnosis

Skin ⭐⭐

• Basal cell carcinoma vs Squamous cell carcinoma vs Melanoma
• Pilonidal sinus
• Carbuncle vs furuncle

Orthopaedics (Allied) ⭐⭐

• Fracture healing - complications (non-union, malunion, compartment syndrome)
• Colles' fracture
• Hip fractures - types, management
• Osteomyelitis - acute vs chronic
• Bone tumours (osteosarcoma, Ewing's)
• Osteoarthritis vs Rheumatoid arthritis (orthopedic perspective)
• Open fractures - management

Anaesthesia (Allied) ⭐⭐

• Spinal vs epidural anaesthesia
• General anaesthesia stages
• Malignant hyperthermia
• Preoperative assessment (ASA grading)

3. OBSTETRICS & GYNAECOLOGY (OBG)

Obstetrics ⭐⭐⭐

• Antenatal care - schedule, investigations, TPAL
• Normal labour - stages, partograph
• Abnormal labour - prolonged labour, shoulder dystocia, cord prolapse
• Pre-eclampsia / Eclampsia - diagnosis (ISSHP criteria), management, magnesium sulfate
• Antepartum haemorrhage (APH) - placenta praevia vs abruption
• Postpartum haemorrhage (PPH) - causes (4 T's), management, bimanual compression
• Preterm labour - management, tocolytics
• Intrauterine growth restriction (IUGR) - types, monitoring
• Multiple pregnancy - complications
• Gestational diabetes - screening (GCT), management
• Fetal distress - CTG interpretation, decelerations
• Caesarean section - indications, types

Gynaecology ⭐⭐⭐

• PCOS (Polycystic Ovarian Syndrome) - Rotterdam criteria, management
• Endometriosis - sites, chocolate cyst, management
• Fibroids (uterine leiomyoma) - types, presentation, management
• Carcinoma cervix - staging (FIGO), Pap smear, HPV, colposcopy
• Carcinoma endometrium - risk factors, staging
• Ovarian tumours - classification, tumor markers (CA-125, AFP, β-hCG)
• Pelvic inflammatory disease (PID) - organisms, treatment
• Ectopic pregnancy - sites, management (salpingectomy vs methotrexate)
• Menstrual disorders - DUB, amenorrhoea, dysmenorrhoea
• Infertility - male and female factors, investigations
• Contraception - OCPs (mechanism, contraindications), IUDs, sterilization
• Prolapse - classification, management

4. PAEDIATRICS

Growth, Development & Nutrition ⭐⭐⭐

• Developmental milestones (motor, speech, social, cognitive) - age-wise
• Failure to thrive
• PEM (Protein Energy Malnutrition) - Kwashiorkor vs Marasmus
• Vitamin deficiencies - Vit D (rickets), Vit A, Vit C (scurvy), Vit B12
• Iron deficiency anaemia in children
• Breast feeding - advantages, complementary feeding

Neonatology ⭐⭐⭐

• Newborn assessment - APGAR score, Ballard score
• Neonatal jaundice - physiological vs pathological, kernicterus, phototherapy
• Respiratory distress syndrome (RDS/HMD) - surfactant deficiency
• Neonatal sepsis - organisms, treatment
• Birth asphyxia - management
• Congenital hypothyroidism
• Neonatal resuscitation (NRP)

Immunisation ⭐⭐⭐

• National Immunisation Schedule (India) - vaccines at each age
• Cold chain
• Contraindications to vaccines
• Adverse events following immunisation (AEFI)

Infectious Diseases ⭐⭐⭐

• Measles, Mumps, Rubella, Varicella - features and complications
• Dengue in children
• Typhoid in children
• Meningitis in children - organisms (age-wise), CSF findings
• Whooping cough (pertussis)

Respiratory ⭐⭐⭐

• Acute respiratory infections (ARI) - WHO classification
• Bronchiolitis - RSV, management
• Bronchial asthma in children - management
• Croup vs Epiglottitis
• Pneumonia in children - treatment by age group

Gastrointestinal ⭐⭐⭐

• Acute diarrhoea - oral rehydration therapy (ORT), PLAN A/B/C
• Dehydration assessment
• Intussusception - features, management
• Pyloric stenosis - projectile vomiting, metabolic alkalosis

Cardiovascular ⭐⭐

• Congenital heart disease - acyanotic (VSD, ASD, PDA) vs cyanotic (TOF, TGA)
• TOF (Tetralogy of Fallot) - 4 features, Tet spells
• Kawasaki disease

Kidney ⭐⭐

• Nephrotic syndrome in children - minimal change disease
• Urinary tract infection (UTI) in children
• Acute glomerulonephritis (APSGN)

Neurology / Developmental ⭐⭐

• Febrile seizures - simple vs complex
• Cerebral palsy - classification, management
• Down syndrome - trisomy 21 features
• Autism spectrum disorder
• Neural tube defects

Haematology / Oncology ⭐⭐

• ALL (Acute Lymphoblastic Leukemia) - most common childhood cancer
• Haemophilia - types, management
• Thalassaemia

5. OPHTHALMOLOGY

6. ENT (Ear, Nose & Throat)

Exam Strategy Tips

1. Medicine - Most vast subject. Start with high-yield systems: Cardiology, Respiratory, Endocrinology, Neurology. Complete one system at a time.
2. Surgery - Read Bailey & Love throughout the year. Focus on long case topics (hernia, thyroid, breast, appendix).
3. OBG - DC Dutta is standard. Prioritize eclampsia, PPH, ectopic pregnancy, carcinoma cervix - these are near-constant long questions.
4. Paediatrics - Most focused subject. Master developmental milestones, immunization chart, and neonatology cold.
5. Ophthalmology & ENT - Relatively concise. Standard textbooks + previous year questions cover 90% of exam content.
6. Clinicals/Viva - Know long case format, short case examination, and instrument identification.

• Medicine: Harrison's / Davidson's / Kumar & Clark
• Surgery: Bailey & Love / SRB
• OBG: DC Dutta (Obs) / DC Dutta (Gynae) / Shaw's
• Paediatrics: Nelson's / O.P. Ghai / Aruchami
• Ophthalmology: Khurana
• ENT: Dhingra