(a) (i) How do you differentiate between acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) based on…

(a)(i)

ALL and AML are differentiated by lineage of blasts on peripheral smear and marrow, using FAB morphology and WHO immunophenotypic and cytogenetic criteria. FAB classifies ALL as L1-L3 and AML as M0-M7, but WHO adds immunophenotype and cytogenetics. In ALL, peripheral smear shows lymphoblasts with high nuclear-to-cytoplasmic ratio, scant agranular cytoplasm, condensed chromatin and no Auer rods; immunophenotyping is TdT positive, with B-cell or T-cell markers. In AML, myeloblasts have more cytoplasm, fine chromatin, nucleoli, primary granules and Auer rods; they are myeloperoxidase and Sudan black B positive and express CD13/CD33. Peripheral smear may show circulating blasts in both, but morphology and immunophenotype identify lineage; marrow shows suppression of normal trilineage maturation. Bone marrow is hypercellular with maturation arrest in both, and marrow aspirate is required to quantify blasts. The WHO 2016 and ICC criteria use a blast threshold of 20% or more; the WHO 5th edition (2022) removed the blast cut-off for most AML with defining genetic abnormalities (such as t(15;17) PML::RARA, t(8;21) RUNX1::RUNX1T1, inv(16) CBFB::MYH11 and NPM1 mutation), which are diagnosed irrespective of blast percentage, whereas ALL is usually diagnosed with at least 20% (commonly 25%) lymphoblasts. Flow cytometry is now the key discriminator: ALL expresses TdT with CD19, CD10, CD22 and cytoplasmic CD79a (B-ALL) or cytoplasmic CD3 and CD7 (T-ALL), while AML expresses MPO, CD13, CD33, CD117 and, in monocytic types, CD14 and CD64. Cytogenetics further separate them: Philadelphia chromosome/BCR-ABL1 is characteristic of some ALL, while t(8;21) and inv(16) are recurrent AML abnormalities.

(a)(ii)

Current ALL therapy is age- and risk-stratified and guided by measurable residual disease (MRD) measured by flow cytometry or PCR at the end of induction and consolidation, which is the strongest prognostic factor; cure rates now approach 90% in children but only 40–50% in older adults. In children, protocols (COG, BFM, UKALL; in India ICiCLe) based on NCI risk criteria use induction with vincristine, a corticosteroid (dexamethasone or prednisolone) and pegylated L-asparaginase, adding an anthracycline (daunorubicin or doxorubicin) for higher-risk disease, followed by consolidation, delayed intensification, CNS prophylaxis with intrathecal methotrexate, and prolonged maintenance with daily oral 6-mercaptopurine and weekly methotrexate for about 2 years in total; cranial irradiation is now limited to overt CNS disease or very high risk. Blinatumomab added to consolidation improves survival in standard-risk B-ALL (COG AALL1731). Risk groups are defined by age, presenting white-cell count, CNS involvement and cytogenetics. Remission is assessed by marrow, and therapy is continued according to response and risk. In adolescents and young adults (up to about 39 years), paediatric-inspired regimens give better results than adult regimens; older adults receive hyper-CVAD or GRAALL-type regimens, and blinatumomab added to consolidation improves survival in MRD-negative B-ALL (E1910 trial); Ph+ ALL is treated with a tyrosine kinase inhibitor (imatinib, dasatinib or ponatinib) combined with low-intensity chemotherapy or, increasingly, chemotherapy-free with blinatumomab, and allogeneic haematopoietic stem-cell transplantation is considered in high-risk or Ph+ disease, often in first remission. For relapsed or refractory B-ALL, blinatumomab, inotuzumab ozogamicin and CAR-T cell therapy, especially tisagenlecleucel in children and young adults, are used to achieve remission before transplant where eligible.

(b)

The National Immunization Schedule under the Universal Immunization Programme protects against 12 diseases. For infants and children it includes BCG, OPV-0 and hepatitis B birth dose at birth; bOPV, pentavalent vaccine (DPT + hepatitis B + Hib) and rotavirus vaccine at 6, 10 and 14 weeks; fractional IPV at 6 and 14 weeks and 9 months; PCV at 6 and 14 weeks with a booster at 9 months; measles-rubella (MR) at 9–12 and 16–24 months; JE vaccine at 9–12 and 16–24 months in endemic districts; DPT booster and OPV booster at 16–24 months; DPT second booster at 5–6 years; and Td at 10 and 16 years (Td replaced TT in 2019). Vitamin A is given with MR, though it is not a vaccine. These include live attenuated vaccines such as BCG, OPV, MR and JE, and inactivated, subunit or conjugate vaccines such as IPV, hepatitis B, DPT, pentavalent and PCV. An adverse event following immunization is any untoward medical occurrence after vaccination, whether or not causally related to the vaccine. The WHO classifies AEFIs by cause into vaccine product-related reactions, vaccine quality defect-related reactions, immunization error-related reactions (programmatic errors, such as a non-sterile injection causing abscess), immunization anxiety-related reactions, and coincidental events. Serious AEFIs (death, hospitalization, disability, or cluster) must be reported and investigated by the district AEFI committee, and AEFI reporting supports vaccine safety surveillance. Examples: DPT may cause local sterile abscess, high febrile reaction, hypotonic-hyporesponsive episode or encephalopathy; measles/MMR may cause fever, febrile seizures, rash or thrombocytopenia; OPV may cause vaccine-associated paralytic poliomyelitis (about 1 in 2.7 million doses, mostly with the first dose); BCG may cause local ulceration, suppurative lymphadenitis, and rarely disseminated BCG disease in immunodeficient infants; and rotavirus vaccine carries a small risk of intussusception.

(c)

Renovascular hypertension (about 1–5% of hypertension; 90% atherosclerotic renal artery stenosis in older adults, 10% fibromuscular dysplasia in young women, and Takayasu arteritis as an important cause in young Indians) is suspected when hypertension begins before 30 or after 55 years, is resistant, has an abdominal bruit, or presents with flash pulmonary oedema, unexplained kidney injury, a rise in creatinine of more than 30% after starting an ACE inhibitor or ARB, or asymmetric kidney size (difference of more than 1.5 cm). Screening is usually Doppler ultrasound of renal arteries (peak systolic velocity >180–200 cm/s, renal–aortic ratio >3.5, and a resistive index that also predicts response to revascularization); CTA or MRA confirms stenosis, while catheter-based renal angiography remains the gold standard and allows intervention. Management depends on aetiology. In fibromuscular dysplasia, percutaneous transluminal renal angioplasty, with stenting if needed, is curative and first-line. In atherosclerotic renal artery stenosis, the ASTRAL and CORAL trials showed no added benefit of routine stenting over medical therapy, so optimal medical therapy with antihypertensives, ACE inhibitors or ARBs with caution in bilateral stenosis, statins, antiplatelet therapy and risk-factor control is the cornerstone; revascularization is reserved for refractory hypertension, recurrent flash pulmonary oedema, acute kidney injury, or severe bilateral/solitary-kidney disease, and may be endovascular or surgical. Surgical revascularization is considered for selected atherosclerotic lesions, such as long-segment or complex stenosis, or failed endovascular therapy. In Takayasu arteritis, immunosuppression to achieve remission precedes angioplasty or bypass.