Treatment of a STAT5b::RARα positive case of APL in a patient not eligible for intensive chemotherapy.

Acute promyelocytic leukaemia (APL) with a STAT5b::RARα gene fusion is an extremely rare subtype of APL characterised by resistance to conventional therapies and extremely poor prognosis. This case highlights that whilst APL with variant RARα translocations are rare, they do pose significant challenges both diagnostically and in their clinical management. This case, in the first instance, demonstrates the importance of using a combination of molecular techniques including next generation sequencing (NGS) for diagnosis particularly in morphological and immunophenotypic typical APL which appears negative by confirmatory testing. Secondly, our patient represents, to the best of our knowledge, the first documented example of this rare disease that has been managed with, and shown sensitivity to low-dose cytarabine (LDAC) in combination with venetoclax (Ven). This case demonstrates that although treatment options are extremely limited for patients not eligible for intensive chemotherapy non-intensive options do show increasing promise.

Effect of the timing of antiretroviral treatment initiation on CD4 count in children and youths living with HIV in North India.

BACKGROUND: Immediate start of antiretroviral treatment (ART) among non-hospitalized outpatient children living with HIV may improve or worsen clinical outcomes due to immune reconstitution. OBJECTIVE: Role of immediate versus post-stabilization start of antiretroviral treatment in children and youths living with HIV on CD4 count and viral load suppression. METHODS: This was a single blinded, randomized controlled trial conducted on outpatients attending a tertiary care hospital associated HIV clinic in North India. We enrolled ART-naive children and youths living with HIV aged 18 months to 21 years in a 1:1 ratio. Block randomization was done using computerized software. Children and youths living with HIV were either started with ART on diagnosis immediately within 24 h (Group A) or post stabilization at 2 weeks (Group B) as per National AIDS Control Organization (NACO) India guidelines. Both groups were comparable for baseline characteristics. RESULTS: There was no significant difference seen in CD4 counts between two groups at 6 months follow up. CD4 count increased significantly in immediate group but not in post-stabilization group at 6 months. No significant changes/differences was seen in WHO clinical staging or anthropometry; one patient developed tuberculosis in both groups. Viral load at 6 months in both the groups did not differ significantly. CONCLUSION: Immediate ART in children and youths living with HIV results in significant increase in CD4 count at 6 months follow up exemplifying immunological response to ART.

Renal Adverse Effects of Tenofovir Containing Regimens in HIV-Infected Children and Adolescents in North India.

OBJECTIVE: To study the prevalence of abnormal renal functions among children living with HIV (CLHIV) receiving tenofovir disoproxil fumarate (TDF) containing antiretroviral therapy (ART). METHODS: A prospective, observational study was conducted among CLHIV aged 10 years to 21 years attending the pediatric HIV clinic. We included CLHIV weighing ≥ 30 kg who had been receiving TDF-containing regimens for at least 6 months, with estimated glomerular filtration rate (eGFR) > 60 ml/min/m2 at enrolment and for whom baseline laboratory parameters were available before starting ART. Clinical and laboratory parameters like serum creatinine, serum phosphate, urinary protein and glucose estimation, CD4 count and viral load were noted from records. The mean change in serum creatinine, estimated glomerular filtration rate (eGFR), creatinine clearance, serum phosphate, and presence of urinary glucose and protein by dipstick were assessed at 3- and 12-months follow-up. RESULTS: We enrolled 70 patients with mean (SD) age 14.99 (2.45) years who had been receiving TDF-based ART for a mean (SD) duration of 14.60 (12.80) months. At 3-months and 12-months follow-up, 32.85% and 41.42% patients, respectively, had eGFR below 90 mL/min/1.73m2, while 4.2% and 2.8% patients, respectively, had eGFR between 50-60 mL/min/1.73m2. One patient had creatinine clearance below 50 mL/min/1.73m2. Four patients had hypophosphatemia at the first and last follow-up respectively, and five patients had proteinuria. There was no statistically significant change in CD4 counts, serum potassium, or serum uric acid during study duration. CONCLUSION: TDF-containing ART regimen is associated with decreased eGFR, creatinine clearance and proteinuria.