Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potentially curative therapy for high-risk acute leukemias, including B-cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). However, real-world data from low-resource settings remain scarce. This study aimed to describe transplant outcomes and assess the impact of early cyclosporine A (CsA) exposure on post-transplant complications.

Methods We conducted a retrospective analysis of patients with acute leukemia who underwent allo-HSCT at a referral center in Mexico between 2018 and 2024. CsA levels were monitored from day 0 to +100 post-transplant, with a target therapeutic range of 200–300 ng/mL. Time in therapeutic range (TTR) and time in supratherapeutic range (TToxR, >300 ng/mL) were calculated for the first four weeks and extended up to twelve weeks post-transplant. Outcomes included acute graft-versus-host disease (aGVHD), CMV reactivation, graft pathology, and relapse. Statistical analyses included descriptive statistics, Chi-square or Fisher's exact test, and Student's t-test or Mann-Whitney U test, as appropriate.

Results A total of 91 patients were included: 54 adolescents and young adults (AYA) with high-risk B-ALL (median age: 24 years; 51.9% female), and 37 with AML (median age: 43 years; 51.4% male), 75.7% of whom had high-risk disease.

Before HSCT, 49.4% had received one prior line of therapy, and 50.5% had received two or more lines. All patients were in complete remission at the time of transplant. Transplants were haploidentical in 53.8% and matched-related in 46.2%. Myeloablative conditioning (MAC) was used in 59.3% of cases.

aGVHD occurred in 44.4% of B-ALL patients (median onset: 25 days) and in 45.9% of AML patients (median onset: 29 days), with cutaneous involvement predominating in both groups.

Subtherapeutic CsA levels (<200 ng/mL) during the first 4 weeks were more frequent in patients who developed aGVHD (61.1% vs 38.9%, p=0.05), and were associated with haploidentical donors (p=0.014) and higher CD34+ cell doses (p=0.03).

CMV reactivation occurred in 56% of patients, most of whom were at intermediate risk. Among viremic patients, 72% had CsA levels <200 ng/mL vs 42% of non-viremic patients (p=0.039).

The highest CsA area under the curve (AUC) was observed during the first 4 weeks post-transplant. In B-ALL patients a lower CsA AUC at 8 weeks post-transplant was associated with CMV reactivation (p=0.012), while a lower AUC at 12 weeks showed a trend toward association with aGVHD (p = 0.09). In AML patients a lower CsA AUC at 4 weeks post-transplant was associated with graft failure (p=0.021).

Graft pathology (failure or poor graft function) occurred in 9.8% (9/91) of patients, more frequently among those with low TTR (30.3% vs 13.2%, p=0.041). TToxR was significantly higher in patients who began CsA before graft infusion (p=0.027), suggesting a higher risk of early supratherapeutic exposure.

Relapse occurred in 18.5% of B-ALL patients (median 165 days post-HSCT) and in 16.2% of AML patients (median 301 days). Risk factors for relapse included ≥3 prior lines of therapy (p=0.024) and absence of maintenance therapy (p=0.009) in B-ALL, and post-HSCT minimal residual disease (MRD) positivity in AML (p=0.023). Mortality among relapsed patients was 90% for B-ALL and 27% for AML.

Conclusions This real-world study highlights the challenges of managing high-risk acute leukemias with allo-HSCT in a resource-limited setting. Early subtherapeutic CsA exposure was associated with increased risk of aGVHD and CMV reactivation. Early initiation of CsA led to higher TToxR, while poor TTR was linked to graft complications.

Relapse was associated with ≥3 prior treatment lines and lack of maintenance therapy in B-ALL, and with MRD positivity post-transplant in AML. These findings underscore the importance of optimizing immunosuppression, implementing therapeutic drug monitoring, and developing robust post-transplant strategies.

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2025
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