Pulmonary Complications After Pediatric Stem Cell Transplant

Abstract

The number of disorders that benefit from hematopoietic stem cell transplantation (HSCT) has increased, causing the overall number of HSCT to increase accordingly. Disorders treated by HSCT include malignancy, benign hematologic disorders, bone marrow failure syndromes, and certain genetic diagnoses. Thus, understanding the complications, diagnostic workup of complications, and subsequent treatments has become increasingly important. One such category of complications includes the pulmonary system. While the overall incidence of pulmonary complications has decreased, the morbidity and mortality of these complications remain high. Therefore, having a clear differential diagnosis and diagnostic workup is imperative. Pulmonary complications can be subdivided by time of onset and whether the complication is infectious or non-infectious. While most infectious complications have clear diagnostic criteria and treatment courses, the non-infectious complications are more varied and not always well understood. This review article discusses pulmonary complications of HSCT recipients and outlines current knowledge, gaps in knowledge, and current treatment of each complication. This article includes some adult studies, as there is a significant paucity of pediatric data.

New Applications of JAK/STAT Inhibitors in Pediatrics: Current Use of Ruxolitinib

“…Clinical evidence in the pediatric population has demonstrated the significant preventive anti-inflammatory capacity of ruxolitinib when administered at a minimum dosage (2.5 mg twice daily); at the molecular level, this condition corresponds to a partial blockage of JAK receptors, which limits the hyper-inflammation associated with STAT phosphorylation ( Figure 3 ). The anti-inflammatory role played by ruxolitinib has allowed the repositioning of this drug in other areas clinically characterized by cytokine storm, e.g., severe cases of COVID-19 [ 40 , 41 ]. Finding modulators of target cytokines specific for cGVHD that involve inflammatory activation has been very important, as it has allowed the application of precision medicine in this field.…”

“…Similarly, in cGVHD, which is historically associated with steroid-dependence or refractoriness, PR varies between 80 and 89%, with, however, only 8% of patients achieving a complete response [ 40 ]. Although this may be a limitation in JAK inhibitor use, it must be taken into account that severe cGVHD, particularly with lung involvement, often had a poor prognosis, with an ineluctable decline in lung function until respiratory insufficiency [ 41 ]. Ruxolitinib, in small case series, shows a partial improvement or stabilization of lung function, with an overall reduction of steroid and other immunosuppressor use and better overall survival [ 42 ].…”

Pulmonary complications after hematopoietic stem cell transplantation in children: a functional and tomographic evaluation

“…O transplante de células-tronco hematopoiéticas (TCTH) é o tratamento de escolha para doenças neoplásicas e não neoplásicas em crianças, (1,2) e, apesar dos cuidados avançados de suporte e tratamentos específicos, complicações pulmonares ainda ocorrem em uma grande proporção de todos os receptores de células-tronco hematopoiéticas, sendo responsável por considerável morbidade e mortalidade. (1,2,4) Etiologicamente, essas complicações podem ser classificadas de acordo com o tempo decorrido desde o transplante. Na fase pré-enxerto (primeiros 30 dias após o procedimento), complicações não infecciosas e pneumonia fúngica são mais comuns.…”

“…Já na fase tardia (após os primeiros 100 dias), as principais complicações estão associadas às doenças do enxerto contra o hospedeiro (DECH) crônicas, como bronquiolite obliterante (BO) e BO com pneumonia em organização. (1)(2)(3)(4) Testes de função pulmonar (TFPs) podem ajudar a identificar o nível de deterioração no período pós-TCTH. (7) Embora a tomografia computadorizada (TC) seja o método de escolha para detectar anormalidades pulmonares, os achados tomográficos geralmente são inespecíficos e requerem correlações temporais baseadas no estado imune do paciente.…”

“…As infecções virais e fúngicas foram os agentes causadores mais prevalentes, contrariando outros estudos (2)(3)(4)9) em que as infecções bacterianas foram as mais comuns. Tal divergência pode estar relacionada ao grande número de transplantes autólogos em outros estudos; nosso estudo incluiu apenas transplantes alogênicos, onde as infecções oportunistas são mais comuns devido à terapia imunossupressora prolongada.…”