Worldwide, acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy, of which B-cell ALL comprises approximately 85% of cases.^1,2 Although the 5-year survival rate for B-ALL exceeds 90% in some countries, approximately 15% – 20% of patients experience relapse after achieving remission with standard chemotherapy. Despite treatment intensification with salvage chemotherapy and subsequent haematopoietic stem cell transplantation (HSCT), overall survival (OS) in these patients remains poor with little improvement over the past few decades.^1,2,3,4,5

Up to 20% of paediatric patients with B-ALL will demonstrate minimal residual disease (MRD) following induction and consolidation chemotherapy. Minimal residual disease is defined as the presence of leukaemic cells not detectable by microscopy but measured using standardised methods such as flow cytometry, with a sensitivity of 10⁻⁴ (0.01%).^1,3,4,5 Minimal residual disease is the most important risk factor, not only in predicting haematological relapse but also in predicting OS in patients with relapsed disease, highlighting its prognostic value.^1,2,3,5,6,7

Thus, prioritising the treatment of MRD-positive disease is essential to improving OS in refractory and/or relapsed (R/R) B-ALL.^2,3,5

One such promising therapy, which reduces MRD by eradicating the leukaemic clone, is blinatumomab, a bispecific T-cell engager construct. Blinatumomab redirects cluster of differentiation (CD)3-expressing T-cells towards CD19-expressing B-lineage cells (expressed on all B-cell leukaemic blasts), which facilitates cell lysis and eliminates leukaemic clones seemingly resistant to conventional chemotherapy.^2,3,5,8,9

To date, there are only a few published studies on the use of blinatumomab in paediatric B-ALL in the outpatient setting.^10,11,12

South Africa (SA) is an upper-middle-income country with a population of approximately 63.1 million people.¹³ It has a two-tiered healthcare system, with privately funded insurance-based services alongside state-run care.¹⁴ This system leads to inconsistent access to specialised medical services and novel medications such as blinatumomab. Only 15.5% of the South African (SA) population is privately funded with potential access to these agents.^13,15

Even with medical insurance, families often face personal hardships during prolonged hospital stays, including financial strain, risk of job loss, increased stress and emotional anxiety.

All paediatric patients (< 18 years of age) with R/R B-ALL who received blinatumomab at a single privately funded paediatric oncology unit (POU) from February 2022 to April 2025 were included. February 2022 was the date of the first paediatric blinatumomab infusion.

A total of seven patients received blinatumomab from February 2022 to April 2025. Five patients had relapsed disease, and blinatumomab formed part of their salvage therapy. The remaining two patients had refractory B-ALL after induction and consolidation chemotherapy (MRD positivity) and received blinatumomab immediately thereafter (Table 1 and Figure 1).

Blinatumomab was administered as a continuous infusion over 28 days, followed by a 14-day treatment-free period. All seven patients received a minimum of two cycles. Dose incrementation was not performed. Six patients (< 45 kg) received blinatumomab at a dose of 15 mcg/m² per day, while one patient (> 45 kg) received a fixed dose of 28 mcg per day. A priming dose of dexamethasone (10 mg/m² – 15 mg/m²) was given prior to the first infusion bag. Each infusion bag was constituted to run over 48 h. Blinatumomab was infused through an ambulatory infusion pump using either an implantable port (six patients) or a peripherally inserted central catheter in one patient. The intravenous tubing contained an in-line filter and was primed with blinatumomab prior to connection. Flushing of lines was strictly avoided when changing infusion bags, and blinatumomab was infused through a dedicated lumen.

The POU nursing staff completed comprehensive in-house training before initiating blinatumomab therapy, with a pharmaceutical sales representative available to address any questions or administration-related issues; no urgent administration-related issues were encountered.

A bone marrow (BM) biopsy was performed by a paediatric oncologist at the start of each cycle, with a lumbar puncture and intrathecal methotrexate performed twice per cycle.

Two patients remained in hospital for the duration of their blinatumomab infusions (citing logistical and socioeconomic reasons). The remaining five patients were admitted for a median of 3 days at the start of each cycle and were then followed up every 48 h – 96 h in the POU outpatient clinic. Prior to discharge, all caregivers received intensive training to manage home infusions safely. They were provided with the POU contact numbers to call at any time for assistance with infusion-related issues.

At outpatient visits, patients were clinically assessed, any side effects were managed and additional training was provided as needed. Up to two infusion bags were dispensed per visit to facilitate home-based bag changes and to allow for the continuous infusion of the drug. Notably, no patient required hospital readmission during this period.

Adverse events were documented and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.^16,17

Three patients experienced Grade 1 cytokine release syndrome (CRS) during the first week of cycle 1. None exhibited haemodynamic instability, and all were successfully managed with oral antipyretics and additional dexamethasone.

One patient also developed Grade 1 immune effector cell-associated neurotoxicity syndrome, presenting with significant tremors and notable fatigue. Symptoms resolved following treatment for CRS. No adverse events were observed beyond cycle 1.

No patient required the temporary or permanent discontinuation of the drug as a result of an adverse event. In one instance, a patient’s blinatumomab infusion bag was depleted at home without a replacement, resulting in a 4-h delay between bag changes. A repeat dose of dexamethasone was administered as an outpatient prior to restarting the new infusion bag, with no adverse effects reported.

Six patients (n = 6/7) had an M1 marrow (< 5% blasts), while one had an M2 marrow (5% – 25% blasts) at the start of blinatumomab. All patients were MRD negative after the first cycle.

Two of the five patients with relapsed B-ALL underwent matched unrelated donor HSCT following blinatumomab therapy. One patient experienced an isolated BM relapse within 100 days post-transplant and was not salvageable. The second patient, with relapsed infant B-ALL, received four cycles while confirming HSCT donor availability. She underwent an uneventful transplant and remains in remission.

One patient, who had previously undergone HSCT, did not proceed to a second transplant because of complications from chronic gastrointestinal graft-versus-host disease and cytomegalovirus colitis following her initial HSCT. She received three cycles of blinatumomab instead.

Another patient, while awaiting her third cycle as a bridge to transplant, experienced a combined relapse. She did not receive further blinatumomab and, despite salvage attempts, demised from her disease.

One patient is currently awaiting HSCT after completing his second cycle of blinatumomab.

The two patients with refractory B-ALL at the end of induction chemotherapy achieved MRD negativity following the first cycle of blinatumomab. Both received two cycles in total and subsequently transitioned back to standard frontline chemotherapy, without proceeding to upfront HSCT.

This case series included privately funded paediatric patients with R/R B-ALL treated with blinatumomab at a single POU in SA.

In keeping with the published date, blinatumomab was shown to be safe and effective in children with R/R B-ALL, with all patients achieving MRD negativity and experiencing no severe adverse effects. Notably, all patients had a low pre-treatment tumour burden, which significantly reduced the risk of CRS and neurotoxicity.^3,7

The patients with relapsed B-ALL were considered for HSCT following blinatumomab bridging therapy, in line with current standard practice.^3,4,8 The two patients with refractory B-ALL achieved MRD negativity after the first cycle of blinatumomab. They both received a further cycle and are continuing standard B-ALL chemotherapy without an upfront HSCT.

The majority of infusions were successfully administered in the outpatient setting. Outpatient treatment empowered families to take greater ownership of care, significantly reducing anxiety and improving overall well-being. It lowered hospital and chemotherapy administration costs and preserved valuable family time. Additionally, this approach provided financial benefits for both insurance providers and patient families.

Compared to conventional chemotherapy for R/R-ALL, which often involves prolonged hospitalisation and significant toxicity, blinatumomab is highly effective in eliminating MRD. When administered in the context of low upfront disease burden, it offers a cost-effective, home-based treatment option with low toxicity, benefiting both patients and their families.^10,11,12