Haploidentical Stem Cell Transplantation With TCR αß+/CD19+ Depletion in Children With Nonmalignant Hematologic Disorders: Outcomes From a Referral Center in Peru.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with TCR αß+/CD19+ cell depletion is a promising therapeutic alternative for children with nonmalignant hematologic disorders, especially in low-income countries where finding a compatible donor is challenging. The use of this transplantation approach for nonmalignant hematologic disorders has not been previously described in the Peruvian pediatric population. METHODS: We present the outcomes of children under 19 with nonmalignant hematologic disorders who underwent haplo-HSCT with TCR αß+/CD19+ cell depletion between 2018-2022 at a referral center in Lima, Peru. Survival probabilities and cumulative incidence functions were calculated using the Kaplan-Meier method. RESULTS: A total of 17 children aged between 1 to 18.6 years (median = 9.7 years) were included. The follow-up period ranged from 10 days to 66.20 months, with a median of 4.34 months. The probability of overall survival, event-free survival, and failure-free survival was 33.70%, 31.40%, and 68.8%, respectively. The incidence rate of graft failure was 49.80%, while the mortality rate not associated with graft failure was 18.8%. The incidence rate of acute graft-versus-host disease (GvHD) was 25.60%, and the incidence rate of viral infections was 59.40%. CONCLUSIONS: The high incidence rates of graft failure and viral infections suggest that these factors may negatively impact the survival of children with nonmalignant hematologic disorders who undergo haplo-HSCT with TCR αß+/CD19+ cell depletion. Therefore, optimizing the current conditioning regimens and ensuring timely access to first, second, and third-line antivirals is crucial to improve the survival of these patients.

Refractory human cytomegalovirus infection without evidence of genetic resistance in the UL-54 and UL-97 genes in a pediatric hematopoietic stem cell transplant recipient: a case report.

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Management of refractory CMV infections, especially in developing countries, can be challenging due to the limited availability of second and third-line antiviral drugs or alternative treatments. Here, we present a case of an 8 years-old patient diagnosed with acute myeloid leukemia. Eight months post-diagnosis, the patient underwent TCR-αß+/CD19+-depleted haploidentical HSCT. Both the donor and recipient tested positive for anti-CMV IgG and negative for IgM antibodies. Before transplantation, the patient received CMV prophylaxis in the form of intravenous ganciclovir. Post-transplantation, the patient exhibited oscillating CMV viral loads and was diagnosed with a refractory infection. Treatment with ganciclovir, foscarnet, and cidofovir was unsuccessful. Sequencing of UL-54 and UL-97 genes was performed to rule out potential resistance to first-line treatment. Ten months after the HSCT, the child died from hypovolemic shock due to gastrointestinal bleeding. This is the first case reported in Peru and Latin America of a refractory CMV infection in a pediatric HSCT recipient without evidence of clinical symptoms and CMV genetic resistance. This case demonstrates the need for alternative treatments to manage refractory CMV infections, especially in haploidentical HSCT cases where drug resistance is frequent (~15%). Furthermore, this case highlights the importance of using highly sensitive genetic tools to detect mutations associated with virus resistance in a broader range of the viral genome.