The aim of the study was to analyse the burden of cytomegalovirus (CMV) disease in children undergoing hematopoietic stem cell transplantation (HSCT) and its correlation with all-cause mortality. We ...performed a retrospective study in children up to 18 years of age who underwent allogeneic HSCT between February 2002 to December 2021 in the pediatric blood and marrow transplantation unit. A total of 1035 patients were included where five hundred forty-three (52.4%) patients underwent matched family donor (MFD) HSCT, 213 (20.5%) underwent matched unrelated donor (MUD) HSCT; 279 (26.9%) underwent haploidentical HSCT (T cell replete in 213 and T cell depleted in 66 patients). CMV reactivation was documented in 258 (24.9% patients). CMV was seen in 39 (7.2%) MFD, 77 (36.1%) MUD, 106 T cell replete (49.7%) and 36 T cell depleted (54.5%) transplants. CMV reactivation was predominantly documented in those where donor and recipient were positive (D + /R +) for CMV serostatus (77%)) prior to HSCT. Overall mortality rate was significantly higher in the CMV positive group (103/258, 39.9%), as compared to the CMV negative group (152/777, 19.6%) (
p
value = 0.0001). CMV was the direct cause of death in 13/1035 children (1.2%). GvHD as a cause of death was found to be significantly higher among those with CMV (
n
= 32) as compared to those without CMV (
n
= 14) (35.6 versus 9%,
p
value = 0.0001). The incidence of CMV reactivation was noted in 25% of HSCT recipients, and predominantly in haploidentical HSCTs. CMV reactivation was shown to significantly impact all-cause mortality and there was a significantly increased risk of mortality due to GvHD among those with CMV reactivation.
X‐linked agammaglobulinemia (XLA) is a primary antibody disorder due to a mutation in the Bruton tyrosine kinase gene that requires lifelong immunoglobulin replacement resulting in a significant ...economic burden and treatment abandonment. Hematopoietic stem cell transplantation (HSCT) offers an alternative option for complete cure. In our series, two children with XLA underwent successful HSCT using a myeloablative conditioning with thiotepa, treosulfan, and fludarabine from a matched sibling donor. The second child had rejected his first graft following a busulfan‐based regimen with resultant autologous reconstitution. At 6 months post‐HSCT, serum IgG were normal, off IVIG, and had no infections. Both children after a median follow‐up of 20 months have 100% chimerism. Treosulfan‐based reduced toxicity myeloablative HSCT has encouraging results with a positive impact on the socioeconomics in developing countries.
Background
: Very early-onset inflammatory bowel disease (VEOIBD) is defined as IBD in children under six years of age. We present outcome data of hematopoietic stem cell transplantation (HSCT) in ...the above children.
Patients and methods
: We performed a retrospective study in children under six years of age who underwent HSCT for VEOIBD with an identified monogenic disorder from December 2012 to December 2020.
Results
: Of the 25 children included, the underlying diagnosis was IL10R deficiency (n = 4), Wiskott-Aldrich syndrome (n = 4), Leukocyte adhesion defect (n = 4), Hyper IgM syndrome (n = 3), Chronic granulomatous disease (n = 2), and one each with XIAP deficiency, severe congenital neutropenia, Omenn syndrome, Hyper IgE syndrome, Griscelli syndrome, MHC Class II deficiency, LRBA deficiency, and IPEX syndrome. Donors included a matched family donor in 10(40%); a matched unrelated donor in 8 (32%), haploidentical in 7 (28%) (T depleted 16%, T replete with post-transplant cyclophosphamide12%). Conditioning was myeloablative in 84% ofHSCTs. We documented engraftment in 22 (88%) children, primary graft failure in 2 children (8%), mixed chimerism in 6 (24%) children with mortality in 4/6 children. Children with a sustained chimerism of > 95% did not have recurrence of any features of IBD. Overall survival was 64%, with a median follow-up of 55 months. Mixed chimerism was associated with a significantly increased risk of mortality (p-value = 0.001).
Conclusions
: VEOIBD caused by monogenic disorders can be offered HSCT. Early recognition, optimal supportive care, and complete chimerism are essential components to achieving survival.
We aimed to analyze data in children with primary hemophagocytic lymphohistiocytosis (HLH) who underwent hematopoietic stem cell transplantation (HSCT). We performed a retrospective study where ...children up to 18 years, with primary HLH and who underwent HSCT from January 2011 to December 2019, were included. Twenty-five children with genetic HLH underwent HSCT, including variants (Griscelli syndrome (GS2) 7, Chediak–Higashi syndrome (CHS) 2, XIAP mutation 2). Donors were matched family 8 (32%), umbilical cord blood unit 3 (12%), matched unrelated 2 (8%), haploidentical HSCT 12 (48%), (TCR alpha/beta depletion 2 and post-transplant cyclophosphamide 10). With treosulfan-based conditioning, engraftment was achieved in 23/25 (92%) transplants (100% in haplo-HSCT), with sustained complete chimerism in 87%. Disease-free survival was noted in 2/3 children with stable mixed chimerism. Graft-versus-host disease (GVHD) of grade I/II was noted in 6 (24%), grade III in 3 (13%); chronic limited skin GVHD in 2 (12%) children. Overall survival was 72% (87.5% in matched donor, 66.7% in the haplo-HSCT), 71% in GS2, 50% in CHS, 100% in XIAP. HSCT is curative in primary HLH with acceptable disease-free survival with mixed chimerism. Haplo-HSCT is a viable option for those without matched family or unrelated donors.
We aimed to analyze infections in children undergoing hematopoietic stem cell transplantation (HSCT) until engraftment. The spectrum and risk factors associated will help plan interventions to reduce ...mortality. We performed a retrospective analysis on the infections, associated risk factors, and mortality until engraftment in children up to 18 years of age undergoing HSCT from January 2017 to August 2020. A total of 399 children were included, with a male: female ratio of 1.9:1, with matched related donor HSCT in 36.6%, a matched unrelated donor in 18.3%, and haploidentical HSCT in 38.1% of children. Culture positive bacteremia was documented in 22.1% transplants with gram-negative bacteria (GNB) isolated in 71/88 (80%). Among the GNB, the predominant organism was Klebsiella pneumonia in 38 (53%), E.coli in 16 (22%), Pseudomonas in 9 (12%). Carbapenem resistance was documented in 24/71 (33%). The incidence of possible, probable, and proven fungal infections in the cohort was 63 (15%), 28 (7%), and 6 (1.5%), respectively. Mortality up to engraftment due to sepsis in our cohort is 3.3% (n = 13). There was a significant association between mortality and a perianal focus (30.8%,
p
value 0.029) and the presence of carbapenem resistance (38%,
p
value 0.002). Mortality among those who developed proven fungal infections was significantly higher than those with bacteremia (
p
value 0.004). Our study has identified fungal sepsis and carbapenem-resistant GNB sepsis as high-risk groups for mortality. Risk directed interventions in these groups would help ensure survival and optimal outcomes.
Wolman disease is a rare genetic disorder with an autosomal recessive inheritance. A mutation in the LIPA gene causes lysosomal acid lipase (LAL) deficiency results in lipid storage and adrenal ...insufficiency. Death in early infancy is due to liver failure.
We describe the clinical course of a three-month-old infant diagnosed with Wolman disease. A rapid mutational analysis confirmed a LIPA gene defect.
He underwent matched unrelated donor peripheral blood stem cell hematopoietic stem cell transplantation (HSCT) at 3 months of age, with a treosulfan-based conditioning, which resulted in engraftment with donor-derived hematopoietic cells. He required supportive care for sinusoidal obstruction syndrome and mucositis. He was administered low dose prednisolone for grade I skin graft versus host disease, and a complete donor chimerism was documented on several occasions. At one year post HSCT, his growth and development were optimal, and there was no hepatosplenomegaly. He is maintained on glucocorticoid and mineralocorticoid supplements for primary hypoaldosteronism.
The case emphasizes the timely diagnosis and the potential for successful treatment of Wolman disease by HSCT.
Introduction: Outcome data in pediatric plasma exchange, especially in nonrenal indications are scarce. We aimed to evaluate its role and outcome in our patients.
Subjects and Methods: A ...retrospective study of children admitted in the year 2016 to the Pediatric Intensive Care Unit requiring plasma exchange for nonrenal indications was undertaken. Plasma exchange was given as adjunctive therapy along with primary treatment for the disease concerned. Demographic and clinical data were studied, and descriptive statistical analysis was carried out.
Results: Ten children underwent plasma exchange during this 1-year period with a male: female ratio of 3:2 and a mean age of 10 years (range 3-16 years). The indications were acute disseminated encephalomyelitis (n = 2), acute neuromyelitis optica (n = 1), catastrophic antiphospholipid antibody syndrome secondary to systemic lupus erythematosus (SLE) (n = 1), severe SLE with cerebritis/hemophagocytic lymphohistiocytosis (HLH) (n = 2), severe dengue sepsis with HLH/multi-organ dysfunction syndrome (n = 2), and thrombotic microangiopathy secondary to snake bite envenomation (n = 2). All received either 1.5 or 2 times plasma volume exchange (mean sessions - 4, range = 1-6). The mean duration of stay in hospital was 17.2 days (range = 3-40 days), and follow-up was 78 days (range = 3-180 days), with the majority of children (8/10, 80%) survived from the catastrophic illness at the time of discharge. Two children (2/10, 20%) succumbed due to the disease per se in severe dengue sepsis in one and enterobacteriaceae sepsis (hospital-acquired pneumonia) in another.
Conclusion: Plasma exchange was found to be beneficial as complementary therapy in a critical care setting, especially for nonrenal indications.
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