Journal of Haematology and Stem Cell Research

Thalidomide in Transfusion-Dependent Beta-Thalassaemia in Pakistan: A Proposed Framework for Safe Prescribing, Risk-Stratified Monitoring, and Pharmacovigilance

Abdul Mannan, Muhammad Abdul Naeem — Fri, 09 Oct 2026 00:00:00 +0000

Background. Transfusion-dependent beta-thalassaemia (TDT) kills children in Pakistan. Mortality from iron overload complications, cardiac siderosis, and panhypopituitarism is common before adulthood in settings where access to regular transfusion and chelation is poor. In this context, thalidomide has been adopted at multiple centres as an off-label fetal haemoglobin (HbF) inducer to reduce transfusion dependence. It is being used, frequently, without patient registration, without any pregnancy risk assessment, and without pharmacovigilance reporting to the Drug Regulatory Authority of Pakistan (DRAP).

Clinical Context. Unlike Western populations or well-resourced Asian thalassaemia centres, the majority of female TDT patients in Pakistan never reach menarche. Iron-overload-driven hypogonadotrophic hypogonadism is documented in over 80% of Pakistani TDT patients. A framework that applies blanket pregnancy prevention rules to this population is both clinically inappropriate and practically undeliverable in remote settings. It also diverts attention from the patients who genuinely need those protections.

Objectives. To review the evidence for thalidomide in TDT, document its known risks in the Pakistani context, and propose a practical risk-stratified prescribing and monitoring framework adapted from the US S.T.E.P.S. programme.

Proposed Framework. Five components are proposed: (1) prescriber and centre registration; (2) risk-stratified reproductive assessment with targeted pregnancy prevention for those who actually need it; (3) structured haematological, neurological, and endocrine monitoring; (4) response assessment at six months; and (5) compulsory adverse event reporting through DRAP.

Conclusions. Thalidomide offers real benefit to a population with few alternatives. The teratogenic risk is real but applies to a minority of patients in Pakistan's TDT population. A framework that ignores the endocrine reality of Pakistani TDT patients protects no one and will not be followed. One that is honest about who needs protecting, and how, might be.

Association of Iron Overload with Hepatic Function Abnormalities in Transfusion Dependent Beta-Thalassemia Major Children- Insights from a Thalassemia Center in Karachi

Fri, 09 Oct 2026 00:00:00 +0000

Objective: To determine iron overload induced liver function abnormalities in transfusion dependent beta thalassemia major patients and to analyze relationship between serum ferritin levels with liver enzymes.

Methodology: This cross-sectional study was conducted in Baqai Medical University Karachi and Muhammadi Thalassemia Center Karachi from December 2021 to May 2022. Total 100 transfusion dependent beta-thalassemia major patients were included. Lab investigations for serum ferritin and liver function tests were performed on Roche Cobas c111 and e411 analyzers.

Results: Serum ferritin, Bilirubin, ALT, and ALP levels from blood samples of 100 patients with ages ranging from 2 to 16 years were analysed. Females constituted 51 % of the samples. Ferritin levels were not significantly different between genders (p= 0.1429). Patients were divided into two groups according to ferritin levels (<2500ng/mL) and (>2500ng/mL). Median(IQR) for ALT level of group 1 and 2 was 47.0 (34.0–67.0) and 164.0 (89.0–200.0) respectively, whereas median(IQR) ALP level for each group was 125.0 (92.5–161.5) and 200.0 (172.0–224.0) respectively. There was a significant, strong positive correlation of rise in ALT(r=0.675) and ALP(r=0.677) as ferritin levels rose (>2500ng/mL). Bilirubin levels were high in patients with ferritin levels (<2500ng/mL). There was a weak and non-significant correlation of rise in bilirubin levels, with iron overload (>2500ng/mL).

Conclusion: Elevated serum ferritin levels indicate iron overload induced derangement of the liver functions in transfusion dependent beta-thalassemia major children. There is a strong positive association between increased serum ferritin levels and increased liver enzymes levels.

The Emerging Role of Bruton's Tyrosine Kinase Inhibitors in Multiple Myeloma

Irtaza Saeed — Thu, 01 Oct 2026 00:00:00 +0000

Multiple myeloma (MM) remains an essentially incurable plasma cell malignancy despite major advances with proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and autologous transplantation. Bruton’s tyrosine kinase (BTK), a non-receptor kinase central to B-cell receptor signaling, is selectively overexpressed in myeloma stem-like cells and drives both tumor-intrinsic survival pathways and BTK-dependent osteoclast genesis in the bone marrow niche. Ibrutinib, the first covalent BTK inhibitor evaluated in relapsed/refractory MM, showed modest single-agent activity but meaningful responses in combination regimens, though acquired C481S-mediated resistance limited its development. Newer covalent agents improved selectivity without escaping this resistance mechanism, while the non-covalent inhibitor pirtobrutinib and BTK-degrading PROTACs offer mutation-independent strategies. We argue that biomarker selected, combination based, and next generation BTK targeted approaches deserve renewed and focused clinical investigation in multiple myeloma.