Prognostic Performance of the Augmented Hematopoietic Cell Transplantation-Specific Comorbidity/Age Index in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation from Alternative Graft Sources

The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was developed and validated to weigh the burden of pretransplantation comorbidities and estimate their impact on post-transplantation risks of nonrelapse mortality (NRM). Recently, the HCT-CI was augmented by the addition of both age and the values of 3 markers: ferritin, albumin, and platelet count. So far, research involving The HCT-CI has been limited almost exclusively to recipients of allogeneic hematopoietic cell transplantation (HCT) from HLA-matched grafts. To this end, we sought to investigate the discriminative capacity of an augmented comorbidity/age index among 724 recipients of allogeneic HCT from HLA-mismatched (n = 345), haploidentical (n = 117), and umbilical cord blood (UCB; n = 262) grafts between 2000 and 2013. In the overall cohort, the augmented comorbidity/age index had a higher c-statistic estimate for prediction of NRM compared with the original HCT-CI (.63 versus .59). Findings were similar for recipients of HLA-mismatched (.62 versus .59), haploidentical (.60 versus .54), or UCB grafts (.65 versus .61). Compared with patients with an HCT-CI score ≥4, those with a score <4 had a higher survival rate among recipients of HLA-mismatched (55% versus 39%; P < .0008), HLA-haploidentical (58% versus 38%; P = .01), or UCB (67% versus 48%; P = .004) grafts. Our results demonstrate the utility of the augmented comorbidity/age index as a valid prognostic tool among recipients of allogeneic HCT from alternative graft sources.     

Current Practice in Vitamin D Management in Allogeneic Hematopoietic Stem Cell Transplantation: A Survey by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation

Beyond its impact on bone health, numerous studies have investigated the immune-regulatory properties of vitamin D and shown how its deficiency can affect outcomes in allogeneic hematopoietic stem cell transplantation (HSCT), particularly in acute or chronic graft-versus-host disease. This survey, carried out by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation (EBMT), describes the current clinical practice discrepancies across the EBMT HSCT programs. We therefore recommend the development of evidence-based guidelines to standardize evaluation criteria and to harmonize the management of vitamin D deficiency in patients undergoing allogeneic HSCT.     

Fludarabine and Total-Body Irradiation Conditioning before Ablative Haploidentical Transplantation: Long-Term Safety and Efficacy

Although myeloablative conditioning (MAC) before haploidentical donor transplant (HIDT) with post-transplant cyclophosphamide is being increasingly used, the optimal preparative regimen remains unclear. In our initial trial, the feasibility of HIDT following a MAC preparative regimen using fludarabine and 12 Gy of total-body irradiation was demonstrated in 30 patients. We now present long-term outcome results, including an additional 52 patients, now with 47 months (16 to 96) median follow-up. Median patient age was 42 (19 to 61) years. The most common diagnoses were acute myelogenous leukemia (51%) and acute lymphoblastic leukemia (33%), and 39% had a high/very high disease risk index (DRI). Engraftment was universal with no cases of primary or secondary graft failure. Grade 3 to 4 acute graft-versus-host disease (GVHD) and moderate to severe chronic GVHD occurred in 17% and 23%, respectively. Nonrelapse mortality (NRM) was 7% at 1 year and 13% at 4 years. Estimated 4-year overall survival (OS), disease-free survival, and cumulative incidence of relapse (CIR) were 67%, 60%, and 27%, respectively. CIR was significantly higher in patients with high/very high- versus low/intermediate-risk DRI (38% versus 20%, P= .032), which led to inferior 4-year OS (50% versus 77%, P = .001). Median time to systemic immunosuppressive therapy (IST) discontinuation was 7.8 months, with 84% of patients off IST at 2 years post-transplant. Current GHVD-free, relapse-free survival (CGRFS) at 2, 3, and 4 years was 60%, 57%, and 60%, respectively. This approach to MAC HIDT results in universal engraftment; low rates of NRM, infection, and clinically significant GVHD; and relatively rapid IST discontinuation, resulting in high rates of CGRFS and survival.     

Warranting the decision-maker,not the decision: How healthcare practitioners evaluate the legitimacy of patients’ unprompted requests for risk-reducing mastectomy

ObjectiveShared decision-making exists to reconcile healthcare practitioners’ responsibilities to respect patients’ autonomy whilst ensuring well-made decisions. Patients sometimes make unprompted requests for procedures that carry medical and other risks, such as risk-reducing mastectomy (RRM). Faced with pre-formed decisions into which they have had little input, it is unclear how practitioners can reconcile respecting autonomy with ensuring well-made decisions.MethodsQualitative study of linked patient-practitioner interviews in a breast unit in North-West England. We examined how 10 practitioners addressed 19 patients’ unprompted requests for RRM.ResultsPractitioners empathised with patients’ distress about cancer risk, regarded RRM as legitimate to help, but were wary of choices made ‘emotionally’. Practitioners did not seek to establish whether choices were well-made but, instead, ‘warranted’ patients by satisfying themselves that patients were ‘sensible’ and ‘informed’ decision-makers, and thus their decisions could be trusted. Practitioners provided information, and tested patients’ resolve by delaying decisions and presenting ‘what if’ scenarios depicting failure or harm from RRM.ConclusionPatients who present emotionally and with resolution can receive RRM without evidence of a well-made decision.Practice Implications: Argumentation theory proposes an ethically robust and clinically practicable approach, whereby practitioners elicit, examine and, where appropriate, challenge arguments underpinning patients’ decisions.     

Detection of “Candidatus Rickettsia wissemanii” in ticks parasitizing bats (Mammalia: Chiroptera) in the northern Brazilian Amazon

A total of 482 bats representing 32 species and two families were captured in the Amazon forests of the Amapá state in northern Brazil. Nineteen Artibeus planirostris bats (3.9 %) were infested with 160 ticks, all identified as Ornithodoros hasei. Three pools of larvae were screened for rickettsial DNA via polymerase chain reaction (PCR) targeting three rickettsial genes: gltA, ompA and htrA. Only one of them yielded an amplicons of the expected size for all three molecular assays. Comparisons of the obtained sequences including a phylogenetic analysis confirmed the occurrence of “Candidatus Rickettsia wissemanii” in Brazil.

     

A new benzodiazepine pharmacology.

Classical benzodiazepine drugs are in wide clinical use as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. They act by enhancing the gamma-aminobutyric acid(A) (GABA(A)) receptor function in the central nervous system. The pharmacological relevance of the multitude of structurally diverse GABA(A) receptor subtypes has only recently been identified. Based on an in vivo point mutation strategy, alpha(1)-GABA(A) receptors were found to mediate sedation, anterograde amnesia, and part of the seizure protection, whereas alpha(2)-GABA(A) receptors, but not alpha(3)-receptors, mediate anxiolysis. Rational drug targeting to specific receptor subtypes has now become possible. Only restricted neuronal networks will be modulated by the new subtype-selective drugs. Promising new anxiolytics have already been developed. A new pharmacology of the benzodiazepine site is on the horizon.