Incidence and risk factors of pain crisis after hematopoietic cell transplantation for sickle cell disease.

ABSTRACT: Vaso-occlusive episodes (VOC) or pain crises are the most common indications for hematopoietic cell transplantation (HCT) for sickle cell disease (SCD). Elimination of pain crisis after HCT is an important patient-centered outcome and may improve understanding of the natural history of pain syndromes in SCD. We examined deidentified records of 763 patients followed-up for a median of 36.7 months (range, 0.3-168.6 months), with 69.6% patient's age <18 years at HCT, 83.3% patient's Karnofsky-Lansky performance score (KPS) ≥90, overall survival 92.9%, event-free survival 72.4%, graft failure (GF) 22.4%, AGVHD 21.4%, CGVHD 27%, and pain crisis 8.65%. On unadjusted logistic regression, increased risk of pain crisis after HCT was observed in patient's aged >10 years at HCT (range, 11-17 years; OR, 9.43; 95% CI, 3.20-27.79; P < .0001), in age ≥18 years (OR, 16.62; 95% CI, 5.85-47.16; P < .0001), in those with history of pain crisis 2 years before HCT (OR, 13.16; 95% CI, 4.08-42.42; P < .0001), alternate donors (haploidentical [OR, 4.80; 95% CI, 2.48-9.31; P < .0001], unrelated matched [OR, 2.71; 95% CI, 1.23-5.97; P = .0132], and mismatched unrelated [OR, 3.19; 95% CI, 1.44-7.05; P = .0041], and those with GF (n = 41 [5.37%]; OR, 7.15; 95% CI, 4.20-12.18; P < .0001). Pain crisis was less frequent with KPS of ≥90 (OR, 0.31; 95% CI, 0.18-0.55; P < .0001). Multivariable logistic regression models confirmed age at HCT, KPS, graft type, donor type, history of VOC 2 years before HCT, and GF as independent predictors of pain crisis after HCT and generated predictive models and nomograms for pain crisis after HCT for SCD, which can support shared decision making.

Cystic Fibrosis Rapid Response: Translating Multi-omics Data into Clinically Relevant Information.

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients. To track microbial dynamics during acute exacerbations, a CF rapid response (CFRR) strategy was developed. The CFRR relies on viromics, metagenomics, metatranscriptomics, and metabolomics data to rapidly monitor active members of the viral and microbial community during acute CF exacerbations. To highlight CFRR, a case study of a CF patient is presented, in which an abrupt decline in lung function characterized a fatal exacerbation. The microbial community in the patient's lungs was closely monitored through the multi-omics strategy, which led to the identification of pathogenic shigatoxigenic Escherichia coli (STEC) expressing Shiga toxin. This case study illustrates the potential for the CFRR to deconstruct complicated disease dynamics and provide clinicians with alternative treatments to improve the outcomes of pulmonary exacerbations and expand the life spans of individuals with CF.IMPORTANCE Proper management of polymicrobial infections in patients with cystic fibrosis (CF) has extended their life span. Information about the composition and dynamics of each patient's microbial community aids in the selection of appropriate treatment of pulmonary exacerbations. We propose the cystic fibrosis rapid response (CFRR) as a fast approach to determine viral and microbial community composition and activity during CF pulmonary exacerbations. The CFRR potential is illustrated with a case study in which a cystic fibrosis fatal exacerbation was characterized by the presence of shigatoxigenic Escherichia coli The incorporation of the CFRR within the CF clinic could increase the life span and quality of life of CF patients.