Antimicrobial prophylaxis and the rate of blood stream infections and Clostridioides difficile in pediatric stem cell transplantation: A single-center retrospective study.

BACKGROUND: The use of prophylactic antibiotics in the pre-engraftment period to minimize the risk of bacteremia is debatable given concerns of Clostridioides difficile (C. diff), antibiotics resistance, and disruption of gut microbiota. METHODS: We retrospectively reviewed the rate and characteristics of bacteremia and C. diff infections within the first 100 days post-HSCT in all pediatric patients who received routine antibacterial prophylaxis during HSCT from 2015 to 2018. C. diff infection was defined by the presence of three or more unformed stools in 24 h and positive stool test for C. diff or its toxins. RESULTS: One hundred and thirty-five (100 allogeneic and 35 autologous) transplants in 123 patients were eligible for analysis. Median age at transplant was 7.1 (range 0.2-13.7), 67 (55%) were women, and diagnosis was malignant condition in 68 patients. Median time to neutrophil engraftment was 18 days (13-23). Cefepime or piperacillin-tazobactam prophylaxis was used in 105 (78%) and 28 (21%) of patients, respectively. Only five (3%) patients had bacteremia during the pre-engraftment period, and 13 (11%) patients developed bacteremia postengraftment. Septic shock was present in only one patient pre-engraftment and was due to gram-negative bacteria. All patients who developed bacteremia received MAC. Thirteen patients (10%) of patients fulfilled C. diff infection definition. There was no mortality related to bacterial infections among our patients. CONCLUSIONS: The use of antibiotic prophylaxis was associated with low rate of bacteremia in the pre-engraftment period and a 10% risk of C. diff infections. More studies are needed to better evaluate the efficacy of antibiotic prophylaxis in HSCT patients.

The effect of intensity of conditioning regimen on the outcome of HSCT in children with sickle cell disease.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) provides a cure for patients with sickle cell disease (SCD). This study describes the effect of conditioning regimen intensity on HSCT outcomes among children younger than 14 years with SCD. METHODS: Transplants from HLA-matched related donors (MRD) and unrelated donors (MUD) using either myeloablative conditioning (MAC) regimens or reduced intensity conditioning (RIC) regimens were considered. Event-free survival (EFS) was the primary endpoint. Secondary endpoints included overall survival (OS) and occurrence of GVHD. RESULTS: 48 SCD patients underwent HSCT, 45 (93.8%) patients had MRD, 1 (2.1%) had 9/10 related donor, and 2 (4.1%) had MUD. The median age at transplant was 8.6 years (range, 3.1-13.8). Conditioning regimens were myeloablative (MAC) in 41 (85.4%) patients and of reduced intensity in 7 (14.6%) patients. EFS at 2 years was 100% among MAC group compared to 29% in the RIC group (p < .001). The median follow-up was 43.4 months (range 26.8-134). All events in the RIC group were secondary graft failure. However, OS was 100% in both groups at 2 years. Acute GVHD II-IV was diagnosed in 2 (4.1%) patients. Chronic GVHD occurred in 2 (4.1%) patients. GVHD did not occur in patients who underwent MUD HSCT. CONCLUSIONS: MAC in children with SCD is well tolerated and associated with an excellent outcome for HLA-matched HSCT in SCD. There was a high rate of secondary graft failure with the use of RIC. Future studies are needed to optimize RIC regimens in HSCT of children with SCD.

Successful hematopoietic stem cell transplant in leukocyte adhesion deficiency type III presenting primarily as malignant infantile osteopetrosis.

Leukocyte adhesion deficiency type III (LAD-III) is caused by mutations in FERMT3 that encodes Kindlin-3 which regulates integrins activation. LAD-III predisposes to infections and bleeding. Osteopetrosis was reported in some cases. We report three patients who presented as malignant infantile osteopetrosis. One had recurrent infections and none had bleeding. Exome sequencing revealed a novel homozygous mutation in FERMT3 c.1555C > T (p.Gln519Ter). Two patients underwent successful hematopoietic stem cell transplant (HSCT) from matched siblings with resolution of osteopetrosis. The third patient died secondary to sepsis prior to HSCT. Our results support early HSCT in LAD-III prior to the occurrence of life-threatening complications.